NEJM -- Management of Stable Coronary Disease -- Polling Results
Management of Stable Coronary Disease — Polling Results
Susan Cheng, M.D., and John Jarcho, M.D.
In late October, we presented the case of a patient with stable coronary artery disease in Clinical Decisions,1 an interactive feature designed to assess how readers would manage a clinical problem for which there may be more than one appropriate treatment. Our patient was a 65-year-old man with hypertension, obesity, and type 2 diabetes who presented with a 2-week history of exertional angina. He underwent an exercise-tolerance test on a treadmill, along with myocardial perfusion imaging, which showed a fixed anterior defect and a reversible anterolateral defect, both of moderate size. His subsequent cardiac catheterization revealed an occluded first diagonal branch, a long lesion with 70% stenosis in the midportion of the left anterior descending coronary artery, a calcified lesion with 80% stenosis in the proximal left circumflex coronary artery, and 50% stenosis of the posterior descending coronary artery. These findings were accompanied by anterior-wall hypokinesis and an ejection fraction of 45% by left ventriculography.
Of the three management options proposed, the most popular — receiving 3282 votes (43.0% of the 7632 votes cast) — was to initiate appropriate medical therapy and follow the patient closely for adherence and efficacy. A close second, with 3066 votes (40.2% of the votes cast), was the option to initiate appropriate medical therapy and to refer the patient for coronary-artery bypass grafting (CABG). The remaining option, to initiate appropriate medical therapy and refer the patient for percutaneous coronary intervention (PCI), received 1284 votes (16.8% of the votes cast). The 7632 participants who voted were from 111 distinct countries and regions and indicated that they were physicians (84.9%), students (7.7%), or other health professionals (5.0%). Detailed results are displayed according to country in an interactive map. The percentage of participants who selected a given treatment option varied only slightly when responses were stratified by participants' self-reported locations
Friday, November 30, 2007
NEJM -- Management of Stable Coronary Disease
NEJM -- Management of Stable Coronary Disease
Management of Stable Coronary Disease
Case Vignette
A 65-year-old man with hypertension, obesity, and type 2 diabetes mellitus has been under your care for the past 5 years. He has been receiving hydrochlorothiazide (25 mg daily) and metformin (500 mg twice daily); his blood pressure is 130/82 mm Hg, his body-mass index (the weight in kilograms divided by the square of the height in meters) is 32, and his glycated hemoglobin is 7.5%. He comes to your office seeking advice about the management of his recently diagnosed coronary artery disease. Two weeks earlier, he had presented with chest tightness and shortness of breath after walking two blocks. His symptoms resolved within a few minutes at rest. An exercise-tolerance test on a treadmill was performed according to the Bruce protocol, along with myocardial perfusion imaging. The patient exercised for 8 minutes, stopping because of chest pressure and dyspnea; his peak systolic blood pressure was 160 mm Hg, and his peak heart rate was 140 beats per minute. Electrocardiography showed ST-segment depression of 1 mm in the anterolateral leads. The perfusion study revealed a fixed perfusion defect of moderate size in the anterior wall and a reversible defect of moderate size in the anterolateral wall.
The patient underwent cardiac catheterization and was found to have multivessel coronary artery disease, with occlusion of the first diagonal branch of the left anterior descending coronary artery, a long lesion with 70% stenosis in the midportion of the left anterior descending coronary artery, 80% stenosis with a calcified lesion in the proximal left circumflex coronary artery, and 50% stenosis of the posterior descending coronary artery. A left ventriculogram obtained during the procedure showed anterior-wall hypokinesis and a left ventricular ejection fraction of 45%. The patient was advised to discuss management of his coronary artery disease with you before making a decision about how to proceed; you have received the results of his exercise test and his catheterization report.
Management of Stable Coronary Disease
Case Vignette
A 65-year-old man with hypertension, obesity, and type 2 diabetes mellitus has been under your care for the past 5 years. He has been receiving hydrochlorothiazide (25 mg daily) and metformin (500 mg twice daily); his blood pressure is 130/82 mm Hg, his body-mass index (the weight in kilograms divided by the square of the height in meters) is 32, and his glycated hemoglobin is 7.5%. He comes to your office seeking advice about the management of his recently diagnosed coronary artery disease. Two weeks earlier, he had presented with chest tightness and shortness of breath after walking two blocks. His symptoms resolved within a few minutes at rest. An exercise-tolerance test on a treadmill was performed according to the Bruce protocol, along with myocardial perfusion imaging. The patient exercised for 8 minutes, stopping because of chest pressure and dyspnea; his peak systolic blood pressure was 160 mm Hg, and his peak heart rate was 140 beats per minute. Electrocardiography showed ST-segment depression of 1 mm in the anterolateral leads. The perfusion study revealed a fixed perfusion defect of moderate size in the anterior wall and a reversible defect of moderate size in the anterolateral wall.
The patient underwent cardiac catheterization and was found to have multivessel coronary artery disease, with occlusion of the first diagonal branch of the left anterior descending coronary artery, a long lesion with 70% stenosis in the midportion of the left anterior descending coronary artery, 80% stenosis with a calcified lesion in the proximal left circumflex coronary artery, and 50% stenosis of the posterior descending coronary artery. A left ventriculogram obtained during the procedure showed anterior-wall hypokinesis and a left ventricular ejection fraction of 45%. The patient was advised to discuss management of his coronary artery disease with you before making a decision about how to proceed; you have received the results of his exercise test and his catheterization report.
Cholesterol seen tied to heart disease, not stroke
Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths
The Lancet 2007; 370:1829-1839
Summary
Background
Age, sex, and blood pressure could modify the associations of total cholesterol (and its main two fractions, HDL and LDL cholesterol) with vascular mortality. This meta-analysis combined prospective studies of vascular mortality that recorded both blood pressure and total cholesterol at baseline, to determine the joint relevance of these two risk factors.
Methods
Information was obtained from 61 prospective observational studies, mostly in western Europe or North America, consisting of almost 900 000 adults without previous disease and with baseline measurements of total cholesterol and blood pressure. During nearly 12 million person years at risk between the ages of 40 and 89 years, there were more than 55 000 vascular deaths (34 000 ischaemic heart disease [IHD], 12 000 stroke, 10 000 other). Information about HDL cholesterol was available for 150 000 participants, among whom there were 5000 vascular deaths (3000 IHD, 1000 stroke, 1000 other). Reported associations are with usual cholesterol levels (ie, corrected for the regression dilution bias).
Findings
1 mmol/L lower total cholesterol was associated with about a half (hazard ratio 0·44 [95% CI 0·42–0·48]), a third (0·66 [0·65–0·68]), and a sixth (0·83 [0·81–0·85]) lower IHD mortality in both sexes at ages 40–49, 50–69, and 70–89 years, respectively, throughout the main range of cholesterol in most developed countries, with no apparent threshold. The proportional risk reduction decreased with increasing blood pressure, since the absolute effects of cholesterol and blood pressure were approximately additive. Of various simple indices involving HDL cholesterol, the ratio total/HDL cholesterol was the strongest predictor of IHD mortality (40% more informative than non-HDL cholesterol and more than twice as informative as total cholesterol). Total cholesterol was weakly positively related to ischaemic and total stroke mortality in early middle age (40–59 years), but this finding could be largely or wholly accounted for by the association of cholesterol with blood pressure. Moreover, a positive relation was seen only in middle age and only in those with below-average blood pressure; at older ages (70–89 years) and, particularly, for those with systolic blood pressure over about 145 mm Hg, total cholesterol was negatively related to haemorrhagic and total stroke mortality. The results for other vascular mortality were intermediate between those for IHD and stroke.
Interpretation
Total cholesterol was positively associated with IHD mortality in both middle and old age and at all blood pressure levels. The absence of an independent positive association of cholesterol with stroke mortality, especially at older ages or higher blood pressures, is unexplained, and invites further research. Nevertheless, there is conclusive evidence from randomised trials that statins substantially reduce not only coronary event rates but also total stroke rates in patients with a wide range of ages and blood pressures.
The Lancet 2007; 370:1829-1839
Summary
Background
Age, sex, and blood pressure could modify the associations of total cholesterol (and its main two fractions, HDL and LDL cholesterol) with vascular mortality. This meta-analysis combined prospective studies of vascular mortality that recorded both blood pressure and total cholesterol at baseline, to determine the joint relevance of these two risk factors.
Methods
Information was obtained from 61 prospective observational studies, mostly in western Europe or North America, consisting of almost 900 000 adults without previous disease and with baseline measurements of total cholesterol and blood pressure. During nearly 12 million person years at risk between the ages of 40 and 89 years, there were more than 55 000 vascular deaths (34 000 ischaemic heart disease [IHD], 12 000 stroke, 10 000 other). Information about HDL cholesterol was available for 150 000 participants, among whom there were 5000 vascular deaths (3000 IHD, 1000 stroke, 1000 other). Reported associations are with usual cholesterol levels (ie, corrected for the regression dilution bias).
Findings
1 mmol/L lower total cholesterol was associated with about a half (hazard ratio 0·44 [95% CI 0·42–0·48]), a third (0·66 [0·65–0·68]), and a sixth (0·83 [0·81–0·85]) lower IHD mortality in both sexes at ages 40–49, 50–69, and 70–89 years, respectively, throughout the main range of cholesterol in most developed countries, with no apparent threshold. The proportional risk reduction decreased with increasing blood pressure, since the absolute effects of cholesterol and blood pressure were approximately additive. Of various simple indices involving HDL cholesterol, the ratio total/HDL cholesterol was the strongest predictor of IHD mortality (40% more informative than non-HDL cholesterol and more than twice as informative as total cholesterol). Total cholesterol was weakly positively related to ischaemic and total stroke mortality in early middle age (40–59 years), but this finding could be largely or wholly accounted for by the association of cholesterol with blood pressure. Moreover, a positive relation was seen only in middle age and only in those with below-average blood pressure; at older ages (70–89 years) and, particularly, for those with systolic blood pressure over about 145 mm Hg, total cholesterol was negatively related to haemorrhagic and total stroke mortality. The results for other vascular mortality were intermediate between those for IHD and stroke.
Interpretation
Total cholesterol was positively associated with IHD mortality in both middle and old age and at all blood pressure levels. The absence of an independent positive association of cholesterol with stroke mortality, especially at older ages or higher blood pressures, is unexplained, and invites further research. Nevertheless, there is conclusive evidence from randomised trials that statins substantially reduce not only coronary event rates but also total stroke rates in patients with a wide range of ages and blood pressures.
Thursday, November 29, 2007
Possible association between 3,4-methylenedioxymethamphetamine abuse and valvular heart disease.
Possible association between 3,4-methylenedioxymethamphetamine abuse and valvular heart disease.
THE AMERICAN JOURNAL OF CARDIOLOGY Vol. 100 Issue 9 Nov 2007
Abstract: Valvular heart disease, inducing valvular regurgitation, has been described in users of drugs such as anorectic agents and ergot derivates. 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") also leads in vitro to the proliferation of cardiac valvular interstitial cells by activation of the 5-hydroxytryptamine 2B receptor.
The aim of this study was to determine the occurrence of valvulopathy in young adults taking MDMA.
Twenty-nine subjects using or having used MDMA and 29 gender- and age-matched controls were blindly evaluated with echocardiography.
Eight subjects (28%) who took MDMA had abnormal echocardiographic results using the United States Food and Drug Administration's criteria for appetite suppressant-induced valvular heart disease, compared with none in the control group (p = 0.0045).
Six (21%) subjects had mitral regurgitation of 1/4 and 4 (14%) of > or =2/4, compared with none in the control group (p = 0.002). The mean mitral regurgitant area ratios (jet/atrium) were 12 +/- 9.8% and 5 +/- 1.3%, respectively (p = 0.007). Tricuspid regurgitation > or =2/4 was present in 13 MDMA users (45%) and absent in controls (p <0.001). The mean tricuspid regurgitant area ratios were 19 +/- 9.5% and 9 +/- 4.5%, respectively (p <0.001). Four MDMA users (14%) had mild aortic regurgitation (p = 0.11). Valvular "strands" were present in 6 MDMA users (21%) and in none of the controls (p = 0.02).
In conclusion, MDMA may lead to mild to moderate valvular heart disease and valvular strands.
THE AMERICAN JOURNAL OF CARDIOLOGY Vol. 100 Issue 9 Nov 2007
Abstract: Valvular heart disease, inducing valvular regurgitation, has been described in users of drugs such as anorectic agents and ergot derivates. 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") also leads in vitro to the proliferation of cardiac valvular interstitial cells by activation of the 5-hydroxytryptamine 2B receptor.
The aim of this study was to determine the occurrence of valvulopathy in young adults taking MDMA.
Twenty-nine subjects using or having used MDMA and 29 gender- and age-matched controls were blindly evaluated with echocardiography.
Eight subjects (28%) who took MDMA had abnormal echocardiographic results using the United States Food and Drug Administration's criteria for appetite suppressant-induced valvular heart disease, compared with none in the control group (p = 0.0045).
Six (21%) subjects had mitral regurgitation of 1/4 and 4 (14%) of > or =2/4, compared with none in the control group (p = 0.002). The mean mitral regurgitant area ratios (jet/atrium) were 12 +/- 9.8% and 5 +/- 1.3%, respectively (p = 0.007). Tricuspid regurgitation > or =2/4 was present in 13 MDMA users (45%) and absent in controls (p <0.001). The mean tricuspid regurgitant area ratios were 19 +/- 9.5% and 9 +/- 4.5%, respectively (p <0.001). Four MDMA users (14%) had mild aortic regurgitation (p = 0.11). Valvular "strands" were present in 6 MDMA users (21%) and in none of the controls (p = 0.02).
In conclusion, MDMA may lead to mild to moderate valvular heart disease and valvular strands.
Patent Foramen Ovale and Cryptogenic Stroke in Older Patients
Patent Foramen Ovale and Cryptogenic Stroke in Older Patients
Michael Handke, M.D., Andreas Harloff, M.D., Manfred Olschewski, M.Sc., Andreas Hetzel, M.D., and Annette Geibel, M.D.
NEW ENGLAND JOURNAL OF MEDICINE
Volume 357 — November 29, 2007 — Number 22
ABSTRACT
Background Studies to date have shown an association between the presence of patent foramen ovale and cryptogenic stroke in patients younger than 55 years of age. This association has not been established in patients 55 years of age or older.
Methods We prospectively examined 503 consecutive patients who had had a stroke, and we compared the 227 patients with cryptogenic stroke and the 276 control patients with stroke of known cause. We examined the prevalences of patent foramen ovale and of patent foramen ovale with concomitant atrial septal aneurysm in all patients, using transesophageal echocardiography. We also compared data for the 131 younger patients (<55 years of age) and those for the 372 older patients (55 years of age).
Results The prevalence of patent foramen ovale was significantly greater among patients with cryptogenic stroke than among those with stroke of known cause, for both younger patients (43.9% vs. 14.3%; odds ratio, 4.70; 95% confidence interval [CI], 1.89 to 11.68; P<0.001) and older patients (28.3% vs. 11.9%; odds ratio, 2.92; 95% CI, 1.70 to 5.01; P<0.001). Even stronger was the association between the presence of patent foramen ovale with concomitant atrial septal aneurysm and cryptogenic stroke, as compared with stroke of known cause, among both younger patients (13.4% vs. 2.0%; odds ratio, 7.36; 95% CI, 1.01 to 326.60; P=0.049) and older patients (15.2% vs. 4.4%; odds ratio, 3.88; 95% CI, 1.78 to 8.46; P<0.001). Multivariate analysis adjusted for age, plaque thickness, and presence or absence of coronary artery disease and hypertension showed that the presence of patent foramen ovale was independently associated with cryptogenic stroke in both the younger group (odds ratio, 3.70; 95% CI, 1.42 to 9.65; P=0.008) and the older group (odds ratio, 3.00; 95% CI, 1.73 to 5.23; P<0.001).
Conclusions There is an association between the presence of patent foramen ovale and cryptogenic stroke in both older patients and younger patients. These data suggest that paradoxical embolism is a cause of stroke in both age groups.
Michael Handke, M.D., Andreas Harloff, M.D., Manfred Olschewski, M.Sc., Andreas Hetzel, M.D., and Annette Geibel, M.D.
NEW ENGLAND JOURNAL OF MEDICINE
Volume 357 — November 29, 2007 — Number 22
ABSTRACT
Background Studies to date have shown an association between the presence of patent foramen ovale and cryptogenic stroke in patients younger than 55 years of age. This association has not been established in patients 55 years of age or older.
Methods We prospectively examined 503 consecutive patients who had had a stroke, and we compared the 227 patients with cryptogenic stroke and the 276 control patients with stroke of known cause. We examined the prevalences of patent foramen ovale and of patent foramen ovale with concomitant atrial septal aneurysm in all patients, using transesophageal echocardiography. We also compared data for the 131 younger patients (<55 years of age) and those for the 372 older patients (55 years of age).
Results The prevalence of patent foramen ovale was significantly greater among patients with cryptogenic stroke than among those with stroke of known cause, for both younger patients (43.9% vs. 14.3%; odds ratio, 4.70; 95% confidence interval [CI], 1.89 to 11.68; P<0.001) and older patients (28.3% vs. 11.9%; odds ratio, 2.92; 95% CI, 1.70 to 5.01; P<0.001). Even stronger was the association between the presence of patent foramen ovale with concomitant atrial septal aneurysm and cryptogenic stroke, as compared with stroke of known cause, among both younger patients (13.4% vs. 2.0%; odds ratio, 7.36; 95% CI, 1.01 to 326.60; P=0.049) and older patients (15.2% vs. 4.4%; odds ratio, 3.88; 95% CI, 1.78 to 8.46; P<0.001). Multivariate analysis adjusted for age, plaque thickness, and presence or absence of coronary artery disease and hypertension showed that the presence of patent foramen ovale was independently associated with cryptogenic stroke in both the younger group (odds ratio, 3.70; 95% CI, 1.42 to 9.65; P=0.008) and the older group (odds ratio, 3.00; 95% CI, 1.73 to 5.23; P<0.001).
Conclusions There is an association between the presence of patent foramen ovale and cryptogenic stroke in both older patients and younger patients. These data suggest that paradoxical embolism is a cause of stroke in both age groups.
Wednesday, November 28, 2007
Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease
Endogenous Testosterone and Mortality Due to All Causes, Cardiovascular Disease, and Cancer in Men. European Prospective Investigation Into Cancer in Norfolk (EPIC-Norfolk) Prospective Population Study
Circulation. 2007
Published online before print November 26, 2007
Kay-Tee Khaw MBBChir, FRCP*, Mitch Dowsett PhD, Elizabeth Folkerd PhD, Sheila Bingham PhD, Nicholas Wareham MBBS, PhD, Robert Luben BSc, Ailsa Welch PhD, and Nicholas Day PhD
From the Department of Public Health and Primary Care (K.-T.K., R.L., A.W., N.D.), Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK; Academic Department of Biochemistry (M.D., E.F.), Royal Marsden Hospital, London, UK; and MRC Dunn Human Nutrition Unit (S.B.) and MRC Epidemiology Unit (N.W.), Cambridge, UK.
Background—The relation between endogenous testosterone concentrations and health in men is controversial.
Methods and Results—We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all causes, cardiovascular disease, and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men who subsequently died were compared with a control group of 1489 men still alive, matched for age and date of baseline visit. Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths). Odds ratios (95% confidence intervals) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to 1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively (P<0.001 for trend after adjustment for age, date of visit, body mass index, systolic blood pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol intake, physical activity, social class, education, dehydroepiandrosterone sulfate, androstanediol glucuronide, and sex hormone binding globulin). An increase of 6 nmol/L serum testosterone (1 SD) was associated with a 0.81 (95% confidence interval 0.71 to 0.92, P<0.01) multivariable-adjusted odds ratio for mortality. Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years.
Conclusions—In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease.
Circulation. 2007
Published online before print November 26, 2007
Kay-Tee Khaw MBBChir, FRCP*, Mitch Dowsett PhD, Elizabeth Folkerd PhD, Sheila Bingham PhD, Nicholas Wareham MBBS, PhD, Robert Luben BSc, Ailsa Welch PhD, and Nicholas Day PhD
From the Department of Public Health and Primary Care (K.-T.K., R.L., A.W., N.D.), Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK; Academic Department of Biochemistry (M.D., E.F.), Royal Marsden Hospital, London, UK; and MRC Dunn Human Nutrition Unit (S.B.) and MRC Epidemiology Unit (N.W.), Cambridge, UK.
Background—The relation between endogenous testosterone concentrations and health in men is controversial.
Methods and Results—We examined the prospective relationship between endogenous testosterone concentrations and mortality due to all causes, cardiovascular disease, and cancer in a nested case-control study based on 11 606 men aged 40 to 79 years surveyed in 1993 to 1997 and followed up to 2003. Among those without prevalent cancer or cardiovascular disease, 825 men who subsequently died were compared with a control group of 1489 men still alive, matched for age and date of baseline visit. Endogenous testosterone concentrations at baseline were inversely related to mortality due to all causes (825 deaths), cardiovascular disease (369 deaths), and cancer (304 deaths). Odds ratios (95% confidence intervals) for mortality for increasing quartiles of endogenous testosterone compared with the lowest quartile were 0.75 (0.55 to 1.00), 0.62 (0.45 to 0.84), and 0.59 (0.42 to 0.85), respectively (P<0.001 for trend after adjustment for age, date of visit, body mass index, systolic blood pressure, blood cholesterol, cigarette smoking, diabetes mellitus, alcohol intake, physical activity, social class, education, dehydroepiandrosterone sulfate, androstanediol glucuronide, and sex hormone binding globulin). An increase of 6 nmol/L serum testosterone (1 SD) was associated with a 0.81 (95% confidence interval 0.71 to 0.92, P<0.01) multivariable-adjusted odds ratio for mortality. Inverse relationships were also observed for deaths due to cardiovascular causes and cancer and after the exclusion of deaths that occurred in the first 2 years.
Conclusions—In men, endogenous testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease.
Tuesday, November 27, 2007
Increased Mortality, Postoperative Morbidity, and Cost After Red Blood Cell Transfusion in Patients Having Cardiac Surgery
Increased Mortality, Postoperative Morbidity, and Cost After Red Blood Cell Transfusion in Patients Having Cardiac Surgery
Gavin J. Murphy, Barnaby C. Reeves, Chris A. Rogers, Syed I.A. Rizvi, Lucy Culliford, and Gianni D. Angelini
Circulation. 2007;116:2544-2552; published online before print November 12 2007
Background— Red blood cell transfusion can both benefit and harm. To inform decisions about transfusion, we aimed to quantify associations of transfusion with clinical outcomes and cost in patients having cardiac surgery.
Methods and Results— Clinical, hematology, and blood transfusion databases were linked with the UK population register. Additional hematocrit information was obtained from intensive care unit charts. Composite infection (respiratory or wound infection or septicemia) and ischemic outcomes (myocardial infarction, stroke, renal impairment, or failure) were prespecified as coprimary end points. Secondary outcomes were resource use, cost, and survival. Associations were estimated by regression modeling with adjustment for potential confounding. All adult patients having cardiac surgery between April 1, 1996, and December 31, 2003, with key exposure and outcome data were included (98%). Adjusted odds ratios for composite infection (737 of 8516) and ischemic outcomes (832 of 8518) for transfused versus nontransfused patients were 3.38 (95% confidence interval [CI], 2.60 to 4.40) and 3.35 (95% CI, 2.68 to 4.35), respectively. Transfusion was associated with increased relative cost of admission (any transfusion, 1.42 times [95% CI, 1.37 to 1.46], varying from 1.11 for 1 U to 3.35 for >9 U). At any time after their operations, transfused patients were less likely to have been discharged from hospital (hazard ratio [HR], 0.63; 95% CI, 0.60 to 0.67) and were more likely to have died (0 to 30 days: HR, 6.69; 95% CI, 3.66 to 15.1; 31 days to 1 year: HR, 2.59; 95% CI, 1.68 to 4.17; >1 year: HR, 1.32; 95% CI, 1.08 to 1.64).
Conclusions— Red blood cell transfusion in patients having cardiac surgery is strongly associated with both infection and ischemic postoperative morbidity, hospital stay, increased early and late mortality, and hospital costs.
Gavin J. Murphy, Barnaby C. Reeves, Chris A. Rogers, Syed I.A. Rizvi, Lucy Culliford, and Gianni D. Angelini
Circulation. 2007;116:2544-2552; published online before print November 12 2007
Background— Red blood cell transfusion can both benefit and harm. To inform decisions about transfusion, we aimed to quantify associations of transfusion with clinical outcomes and cost in patients having cardiac surgery.
Methods and Results— Clinical, hematology, and blood transfusion databases were linked with the UK population register. Additional hematocrit information was obtained from intensive care unit charts. Composite infection (respiratory or wound infection or septicemia) and ischemic outcomes (myocardial infarction, stroke, renal impairment, or failure) were prespecified as coprimary end points. Secondary outcomes were resource use, cost, and survival. Associations were estimated by regression modeling with adjustment for potential confounding. All adult patients having cardiac surgery between April 1, 1996, and December 31, 2003, with key exposure and outcome data were included (98%). Adjusted odds ratios for composite infection (737 of 8516) and ischemic outcomes (832 of 8518) for transfused versus nontransfused patients were 3.38 (95% confidence interval [CI], 2.60 to 4.40) and 3.35 (95% CI, 2.68 to 4.35), respectively. Transfusion was associated with increased relative cost of admission (any transfusion, 1.42 times [95% CI, 1.37 to 1.46], varying from 1.11 for 1 U to 3.35 for >9 U). At any time after their operations, transfused patients were less likely to have been discharged from hospital (hazard ratio [HR], 0.63; 95% CI, 0.60 to 0.67) and were more likely to have died (0 to 30 days: HR, 6.69; 95% CI, 3.66 to 15.1; 31 days to 1 year: HR, 2.59; 95% CI, 1.68 to 4.17; >1 year: HR, 1.32; 95% CI, 1.08 to 1.64).
Conclusions— Red blood cell transfusion in patients having cardiac surgery is strongly associated with both infection and ischemic postoperative morbidity, hospital stay, increased early and late mortality, and hospital costs.
Glucose-Insulin-Potassium Therapy in Patients With ST-Segment Elevation Myocardial
Title: Glucose-Insulin-Potassium Therapy in Patients With ST-Segment Elevation Myocardial
InfarctionTopic: General CardiologyDate Posted: 11/27/2007
Author(s): Diaz R, Goyal A, Mehta S, et al.Citation: JAMA. 2007;298:2399-2405.
Clinical Trial: No
Study Question: What is the impact of glucose-insulin-potassium (GIK) therapy on outcome of patients presenting with ST-segment elevation myocardial infarction (STEMI)?
Methods: The authors present primary outcome data on 2,748 patients randomized in the OASIS-6 GIK study to GIK versus no infusion. They also present a pooled analysis of the OASIS-6 GIK study and the CREATE-ECLA GIK trial (n = 22,943 patients).
Results: In the OASIS-6 GIK trial, there was no difference in the 6-month mortality (10.8% vs. 10.4%; hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.83-1.31; p = 0.72); heart failure (11.1% vs. 13.5%; HR, 0.83; 95% CI, 0.67-1.02; p = 0.08); or composite of heart failure or mortality (17.5% vs. 19.2%; HR, 0.91; 95% CI, 0.76-1.08; p = 0.27) among patients randomized to GIK compared with controls. Within the pooled trial cohort, there was higher mortality in the GIK group at 3 days (6.2% vs. 5.5%; HR, 1.13; 95% CI, 1.02-1.26; p = 0.03), but there was no difference in the 30-day mortality (9.7% vs. 9.3%; HR, 1.04; 95% CI, 0.96-1.13; p = 0.33). GIK therapy was associated with an increase in glucose and potassium levels, along with a positive volume state in some patients. Patients with one or more of these metabolic derangements after GIK were more likely to have an adverse clinical outcome.
Conclusions: GIK does not provide any clinical benefit in patients with STEMI.
Perspective: Prior preclinical studies and meta-analysis had suggested impressive benefits of GIK in patients with STEMI. While some of the small, randomized trials had suggested impressive survival benefits, a possible increase in mortality in others (e.g., Pol-GIK trial) was dismissed as possibly related to chance. The results of the CREATE-ECLA GIK trial and the current analysis clearly establish the lack of benefit (and possible early harm) of GIK: Another beautiful hypothesis slain by an ugly randomized controlled trial (with apologies to Thomas Huxley). Hitinder S. Gurm, M.B.B.S., F.A.C.C.
InfarctionTopic: General CardiologyDate Posted: 11/27/2007
Author(s): Diaz R, Goyal A, Mehta S, et al.Citation: JAMA. 2007;298:2399-2405.
Clinical Trial: No
Study Question: What is the impact of glucose-insulin-potassium (GIK) therapy on outcome of patients presenting with ST-segment elevation myocardial infarction (STEMI)?
Methods: The authors present primary outcome data on 2,748 patients randomized in the OASIS-6 GIK study to GIK versus no infusion. They also present a pooled analysis of the OASIS-6 GIK study and the CREATE-ECLA GIK trial (n = 22,943 patients).
Results: In the OASIS-6 GIK trial, there was no difference in the 6-month mortality (10.8% vs. 10.4%; hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.83-1.31; p = 0.72); heart failure (11.1% vs. 13.5%; HR, 0.83; 95% CI, 0.67-1.02; p = 0.08); or composite of heart failure or mortality (17.5% vs. 19.2%; HR, 0.91; 95% CI, 0.76-1.08; p = 0.27) among patients randomized to GIK compared with controls. Within the pooled trial cohort, there was higher mortality in the GIK group at 3 days (6.2% vs. 5.5%; HR, 1.13; 95% CI, 1.02-1.26; p = 0.03), but there was no difference in the 30-day mortality (9.7% vs. 9.3%; HR, 1.04; 95% CI, 0.96-1.13; p = 0.33). GIK therapy was associated with an increase in glucose and potassium levels, along with a positive volume state in some patients. Patients with one or more of these metabolic derangements after GIK were more likely to have an adverse clinical outcome.
Conclusions: GIK does not provide any clinical benefit in patients with STEMI.
Perspective: Prior preclinical studies and meta-analysis had suggested impressive benefits of GIK in patients with STEMI. While some of the small, randomized trials had suggested impressive survival benefits, a possible increase in mortality in others (e.g., Pol-GIK trial) was dismissed as possibly related to chance. The results of the CREATE-ECLA GIK trial and the current analysis clearly establish the lack of benefit (and possible early harm) of GIK: Another beautiful hypothesis slain by an ugly randomized controlled trial (with apologies to Thomas Huxley). Hitinder S. Gurm, M.B.B.S., F.A.C.C.
Friday, November 23, 2007
UK guidelines for chronic AF called into question
UK guidelines for chronic AF called into question
By Caroline Price
23 November 2007
Br Med J 2007; 335: 1057-1058
MedWire News: The departure from recommending digoxin as the first-line treatment in patients with chronic atrial fibrillation (AF) by current UK guidelines is premature, conclude investigators in a review of available evidence in the British Medical Journal.
The UK National Institute for Clinical Excellence last year published guidelines that replaced digoxin with beta blockers or calcium antagonists as the recommended initial monotherapy for the control of heart rate in patients with chronic AF.
“Digoxin has been the mainstay of treatment for many years, so new recommendations relegating digoxin should be evidence based and safe,” write Theodora Nikolaidou and Kevin Channer, from Royal Hallamshire Hospital in Sheffield, UK.
But the reviewers found little evidence to support replacing digoxin with either of the other treatments as monotherapy. Rather, they found that improvements in both heart rate variability and exercise tolerance have been shown only with the combination of digoxin and a beta blocker or calcium channel blocker. Indeed, they found some evidence that beta blockers used alone may worsen exercise capacity.
Nikolaidou and Channer reviewed a total of 57 studies, including 25 randomized double blind controlled trials, assessing digoxin, beta blockers, calcium antagonists, and combinations for rate control in chronic AF.
They found that beta-blocker monotherapy was better than digoxin alone at controlling heart rate at rest in just one out of 10 studies, although it improved rate control during exercise in four of the studies. Nevertheless, in six other studies, beta blocker use alone did not improve exercise capacity.
Several studies showed that the combination of beta blocker and digoxin gave greater improvements in heart rate control at rest and during exercise compared with digoxin alone.
The combination’s effect on exercise capacity was inconsistent, causing deterioration in some studies, but improvement or no change in others.
The calcium channel blocker diltiazem was found in five studies to be better than digoxin at controlling heart rate during exercise, but not during rest, and it failed to improve exercise capacity. However, most of the eleven studies assessing the combination of diltiazem and digoxin showed that it provided better heart rate control at rest and during exercise than digoxin alone, and two studies showed the combination gave improved exercise tolerance.
Similar results were seen with the calcium antagonist verapamil as monotherapy in comparison with digoxin, although exercise tolerance improved with verapamil in two of three studies that assessed this outcome. Again, the combination of verapamil with digoxin improved rate control at rest and during exercise compared with digoxin alone, but, despite this, exercise tolerance was not consistently improved.
Nikolaidou and Channer note that use of both verapamil and diltiazem is limited by their negative inotropic effects and “considerable” dose-related side effects.
They conclude: “We believe that the combination of digoxin and a beta blocker or calcium antagonist should be recommended as first-line management. We would emphasize that it is safest to start treatment with digoxin first.”
Journal
By Caroline Price
23 November 2007
Br Med J 2007; 335: 1057-1058
MedWire News: The departure from recommending digoxin as the first-line treatment in patients with chronic atrial fibrillation (AF) by current UK guidelines is premature, conclude investigators in a review of available evidence in the British Medical Journal.
The UK National Institute for Clinical Excellence last year published guidelines that replaced digoxin with beta blockers or calcium antagonists as the recommended initial monotherapy for the control of heart rate in patients with chronic AF.
“Digoxin has been the mainstay of treatment for many years, so new recommendations relegating digoxin should be evidence based and safe,” write Theodora Nikolaidou and Kevin Channer, from Royal Hallamshire Hospital in Sheffield, UK.
But the reviewers found little evidence to support replacing digoxin with either of the other treatments as monotherapy. Rather, they found that improvements in both heart rate variability and exercise tolerance have been shown only with the combination of digoxin and a beta blocker or calcium channel blocker. Indeed, they found some evidence that beta blockers used alone may worsen exercise capacity.
Nikolaidou and Channer reviewed a total of 57 studies, including 25 randomized double blind controlled trials, assessing digoxin, beta blockers, calcium antagonists, and combinations for rate control in chronic AF.
They found that beta-blocker monotherapy was better than digoxin alone at controlling heart rate at rest in just one out of 10 studies, although it improved rate control during exercise in four of the studies. Nevertheless, in six other studies, beta blocker use alone did not improve exercise capacity.
Several studies showed that the combination of beta blocker and digoxin gave greater improvements in heart rate control at rest and during exercise compared with digoxin alone.
The combination’s effect on exercise capacity was inconsistent, causing deterioration in some studies, but improvement or no change in others.
The calcium channel blocker diltiazem was found in five studies to be better than digoxin at controlling heart rate during exercise, but not during rest, and it failed to improve exercise capacity. However, most of the eleven studies assessing the combination of diltiazem and digoxin showed that it provided better heart rate control at rest and during exercise than digoxin alone, and two studies showed the combination gave improved exercise tolerance.
Similar results were seen with the calcium antagonist verapamil as monotherapy in comparison with digoxin, although exercise tolerance improved with verapamil in two of three studies that assessed this outcome. Again, the combination of verapamil with digoxin improved rate control at rest and during exercise compared with digoxin alone, but, despite this, exercise tolerance was not consistently improved.
Nikolaidou and Channer note that use of both verapamil and diltiazem is limited by their negative inotropic effects and “considerable” dose-related side effects.
They conclude: “We believe that the combination of digoxin and a beta blocker or calcium antagonist should be recommended as first-line management. We would emphasize that it is safest to start treatment with digoxin first.”
Journal
Do Diet, Folic Acid, and Vitamins Matter?
Title
Do Diet, Folic Acid, and Vitamins Matter?: What Did We Learn From The Women's Health Initiative, The Women's Health Study, The Women's Antioxidant and Folic Acid Cardiovascular Study, and Other Clinical Trials?[Review]
Author
Wenger, Nanette K. MD
Institution
From the Department of Medicine, Division of Cardiology, Emory University School of Medicine; the Division of Cardiology, Grady Memorial Hospital; and the Emory Heart and Vascular Center, Atlanta, Georgia.
Source
Cardiology in Review. 15(6):288-290, November/December 2007.
Abstract
Data from recent randomized clinical trials have contributed substantially to our understanding of appropriate interventions for coronary heart disease in women. Addressed in this monograph are issues of diet, folic acid, and antioxidant vitamins. Importantly, these randomized clinical trials have helped to clarify conflicting information from observational data, and to aid clinicians and their women patients in making appropriate choices of coronary and cardiovascular preventive therapy.
The 2007 update to the AHA women's prevention guidelines concludes that antioxidant vitamin supplements (eg, vitamins C, E, and beta carotene) should not be used for the primary or secondary prevention of CVD, a class III recommendation.
Do Diet, Folic Acid, and Vitamins Matter?: What Did We Learn From The Women's Health Initiative, The Women's Health Study, The Women's Antioxidant and Folic Acid Cardiovascular Study, and Other Clinical Trials?[Review]
Author
Wenger, Nanette K. MD
Institution
From the Department of Medicine, Division of Cardiology, Emory University School of Medicine; the Division of Cardiology, Grady Memorial Hospital; and the Emory Heart and Vascular Center, Atlanta, Georgia.
Source
Cardiology in Review. 15(6):288-290, November/December 2007.
Abstract
Data from recent randomized clinical trials have contributed substantially to our understanding of appropriate interventions for coronary heart disease in women. Addressed in this monograph are issues of diet, folic acid, and antioxidant vitamins. Importantly, these randomized clinical trials have helped to clarify conflicting information from observational data, and to aid clinicians and their women patients in making appropriate choices of coronary and cardiovascular preventive therapy.
The 2007 update to the AHA women's prevention guidelines concludes that antioxidant vitamin supplements (eg, vitamins C, E, and beta carotene) should not be used for the primary or secondary prevention of CVD, a class III recommendation.
Venous thromboembolism and subsequent hospitalisation due to acute arterial cardiovascular events: a 20-year cohort study
Venous thromboembolism and subsequent hospitalisation due to acute arterial cardiovascular events: a 20-year cohort study
The Lancet, Current Issue, Volume 370, Number 9601, 24 November 2007
Henrik Toft Sørensen, Erzsebet Horvath-Puho, Lars Pedersen, John A Baron, Paolo Prandoni
Summary
Background
In some studies, venous thromboembolism has been associated with atherosclerosis and with the risk of arterial cardiovascular events such as myocardial infarction and stroke. Other studies, however, do not show this association. To help clarify these discrepant findings, we aimed to investigate the risk of arterial cardiovascular events in patients who were diagnosed with venous thromboembolism.
Methods
We undertook a 20-year population-based cohort study using data from nationwide Danish medical databases. After excluding those with known cardiovascular disease, we assessed the risk of myocardial infarction and stroke in 25 199 patients with deep venous thrombosis, 16 925 patients with pulmonary embolism, and 163 566 population controls.
Findings
For patients with deep venous thrombosis, the relative risks varied from 1·60 for myocardial infarction (95% CI 1·35–1·91) to 2·19 (1·85–2·60) for stroke in the first year after the thrombotic event. For patients with pulmonary embolism, the relative risks in that year were 2·60 (2·14–3·14) for myocardial infarction and 2·93 (2·34–3·66) for stroke. The relative risks were also raised, though less markedly, during the subsequent 20 years of follow-up, with 20–40% increases in risk for arterial cardiovascular events. Relative risks were similar for those with provoked and unprovoked deep venous thrombosis and pulmonary embolism.
Interpretation
Patients with venous thromboembolism have a substantially increased long-term risk of subsequent arterial cardiovascular events.
The Lancet, Current Issue, Volume 370, Number 9601, 24 November 2007
Henrik Toft Sørensen, Erzsebet Horvath-Puho, Lars Pedersen, John A Baron, Paolo Prandoni
Summary
Background
In some studies, venous thromboembolism has been associated with atherosclerosis and with the risk of arterial cardiovascular events such as myocardial infarction and stroke. Other studies, however, do not show this association. To help clarify these discrepant findings, we aimed to investigate the risk of arterial cardiovascular events in patients who were diagnosed with venous thromboembolism.
Methods
We undertook a 20-year population-based cohort study using data from nationwide Danish medical databases. After excluding those with known cardiovascular disease, we assessed the risk of myocardial infarction and stroke in 25 199 patients with deep venous thrombosis, 16 925 patients with pulmonary embolism, and 163 566 population controls.
Findings
For patients with deep venous thrombosis, the relative risks varied from 1·60 for myocardial infarction (95% CI 1·35–1·91) to 2·19 (1·85–2·60) for stroke in the first year after the thrombotic event. For patients with pulmonary embolism, the relative risks in that year were 2·60 (2·14–3·14) for myocardial infarction and 2·93 (2·34–3·66) for stroke. The relative risks were also raised, though less markedly, during the subsequent 20 years of follow-up, with 20–40% increases in risk for arterial cardiovascular events. Relative risks were similar for those with provoked and unprovoked deep venous thrombosis and pulmonary embolism.
Interpretation
Patients with venous thromboembolism have a substantially increased long-term risk of subsequent arterial cardiovascular events.
Thursday, November 22, 2007
Treatment delays in reperfusion therapy increase mortality in STEMI patients
Treatment delays in reperfusion therapy increase mortality in STEMI patients
By Sara Carrillo de Albornoz
22 November 2007
Heart 2007; 93: 1552-1555
MedWire News: Patients presenting with ST-segment elevation myocardial infarction (STEMI) who experience long reperfusion therapy delays are at increased risk for death at 6 months, study findings indicate.
This higher 6-month mortality rate is more "critical" in patients receiving fibrinolytic therapy than in those undergoing primary percutaneous coronary intervention (PCI), Kim Eagle (University of Michigan Cardiovascular Center, Ann Arbor, USA) and colleagues add.
"Understanding the overall association between treatment delays and outcomes in reperfusion therapy for STEMI is critical for improving the selection and delivery of both fibrinolytic therapy and primary PCI in individual patients," the authors write in the journal Heart.
Eagle and team analyzed data from the multinational GRACE (Global registry of acute coronary events) trial to determine the association between treatment delays and 6-month mortality in 3959 STEMI patients treated with reperfusion therapy.
Of these, 1786 (45.1%) received fibrinolytic therapy and 2173 (54.9%) underwent primary PCI.
Patients receiving fibrinolytic therapy had a mean door-to-needle time of 35 minutes, while patients undergoing PCI had a mean door-to-balloon time of 78 minutes.
Multivariate analysis accounting for mortality risk factors such as age, cardiac arrest, and ST-changes showed that reperfusion treatment delays were associated with an increased 6-month mortality rate in both treatment groups (p<0.001).
Patients receiving fibrinolytic therapy had an 0.30% increase in 6-month mortality per 10-minute delay in door-to-needle time between 30 and 60 minutes, and those who underwent PCI had a 0.18% increased 6-month mortality per 10-minute delay in door-to-balloon time between 90 and 150 minutes.
Eagle et al conclude: "Although treatment delays are longer in primary PCI, their relationship with clinical outcomes is more gradual than that seen with fibrinolytic therapy.
"This important differential effect of treatment delays on outcome may influence the selection between these two reperfusion strategies in STEMI patients."
Free abstract
By Sara Carrillo de Albornoz
22 November 2007
Heart 2007; 93: 1552-1555
MedWire News: Patients presenting with ST-segment elevation myocardial infarction (STEMI) who experience long reperfusion therapy delays are at increased risk for death at 6 months, study findings indicate.
This higher 6-month mortality rate is more "critical" in patients receiving fibrinolytic therapy than in those undergoing primary percutaneous coronary intervention (PCI), Kim Eagle (University of Michigan Cardiovascular Center, Ann Arbor, USA) and colleagues add.
"Understanding the overall association between treatment delays and outcomes in reperfusion therapy for STEMI is critical for improving the selection and delivery of both fibrinolytic therapy and primary PCI in individual patients," the authors write in the journal Heart.
Eagle and team analyzed data from the multinational GRACE (Global registry of acute coronary events) trial to determine the association between treatment delays and 6-month mortality in 3959 STEMI patients treated with reperfusion therapy.
Of these, 1786 (45.1%) received fibrinolytic therapy and 2173 (54.9%) underwent primary PCI.
Patients receiving fibrinolytic therapy had a mean door-to-needle time of 35 minutes, while patients undergoing PCI had a mean door-to-balloon time of 78 minutes.
Multivariate analysis accounting for mortality risk factors such as age, cardiac arrest, and ST-changes showed that reperfusion treatment delays were associated with an increased 6-month mortality rate in both treatment groups (p<0.001).
Patients receiving fibrinolytic therapy had an 0.30% increase in 6-month mortality per 10-minute delay in door-to-needle time between 30 and 60 minutes, and those who underwent PCI had a 0.18% increased 6-month mortality per 10-minute delay in door-to-balloon time between 90 and 150 minutes.
Eagle et al conclude: "Although treatment delays are longer in primary PCI, their relationship with clinical outcomes is more gradual than that seen with fibrinolytic therapy.
"This important differential effect of treatment delays on outcome may influence the selection between these two reperfusion strategies in STEMI patients."
Free abstract
Inflammation key factor in low socioeconomic status link with CVD
Inflammation key factor in low socioeconomic status link with CVD
By Caroline Price
22 November 2007
Circulation 2007; 116: 2383-2390
MedWire News: Low socioeconomic status is linked to increased levels of serum inflammatory markers, which may explain why it is associated with higher rates of cardiovascular disease (CVD), according to a report in the journal Circulation.
The study of over 6000 men and women revealed that lower income was associated with higher concentrations of interleukin (IL)-6, and C-reactive protein (CRP) in several race and ethnic groups.
"This study helps to explain some of the puzzle as to why poor people have more heart disease," commented Nalini Ranjit (University of Michigan, Ann Arbor, USA), who led the study group.
The researchers reviewed data on 6814 US adults aged 45 to 84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). They conducted race- and ethnicity-stratified analyses to estimate the associations of household income and education with IL-6 and CRP before and after adjustment for factors such as infection and medication use, psychosocial factors, behaviors, adiposity, and diabetes.
Household income was inversely associated with levels of the markers in all race/ethnic groups. Each standard-deviation decrease in income, the equivalent of around US$40,000 (€27,000), was associated with between 6% and 9% higher IL-6 and CRP levels, with the greatest increase in risk among White individuals.
By contrast, the association between education and income was inconsistent across race/ethnic groups. Each standard-deviation decrease in education level was associated with 6-14% higher levels of IL-6 and CRP in White and Black groups, whereas no association was seen for Chinese and Hispanic populations.
"When we adjusted the model for other possible confounding markers such as infection, there was no significant effect on the findings," Ranijit noted. "But when you look at body mass index, it shrinks the effect of income or education on IL-6 and CRP, meaning the associations are mediated by adiposity."
Other factors contributing to the observed associations included a generalized attitude of cynical distrust, which explained some of the link between education and IL-6 levels in all groups, and smoking, which partly accounted for this association in Black and White populations.
"Our results suggest that persons of lower socioeconomic position have greater inflammatory burden that those of high socioeconomic position as a result of the cumulative effects of multiple behavioral psychosocial and metabolic characteristics," the authors write.
"If the role of inflammation in causing multiple chronic diseases is confirmed, inflammation may represent a common element through which low socioeconomic position is related to CVD and other chronic diseases of aging."
Free abstract
By Caroline Price
22 November 2007
Circulation 2007; 116: 2383-2390
MedWire News: Low socioeconomic status is linked to increased levels of serum inflammatory markers, which may explain why it is associated with higher rates of cardiovascular disease (CVD), according to a report in the journal Circulation.
The study of over 6000 men and women revealed that lower income was associated with higher concentrations of interleukin (IL)-6, and C-reactive protein (CRP) in several race and ethnic groups.
"This study helps to explain some of the puzzle as to why poor people have more heart disease," commented Nalini Ranjit (University of Michigan, Ann Arbor, USA), who led the study group.
The researchers reviewed data on 6814 US adults aged 45 to 84 years in the Multi-Ethnic Study of Atherosclerosis (MESA). They conducted race- and ethnicity-stratified analyses to estimate the associations of household income and education with IL-6 and CRP before and after adjustment for factors such as infection and medication use, psychosocial factors, behaviors, adiposity, and diabetes.
Household income was inversely associated with levels of the markers in all race/ethnic groups. Each standard-deviation decrease in income, the equivalent of around US$40,000 (€27,000), was associated with between 6% and 9% higher IL-6 and CRP levels, with the greatest increase in risk among White individuals.
By contrast, the association between education and income was inconsistent across race/ethnic groups. Each standard-deviation decrease in education level was associated with 6-14% higher levels of IL-6 and CRP in White and Black groups, whereas no association was seen for Chinese and Hispanic populations.
"When we adjusted the model for other possible confounding markers such as infection, there was no significant effect on the findings," Ranijit noted. "But when you look at body mass index, it shrinks the effect of income or education on IL-6 and CRP, meaning the associations are mediated by adiposity."
Other factors contributing to the observed associations included a generalized attitude of cynical distrust, which explained some of the link between education and IL-6 levels in all groups, and smoking, which partly accounted for this association in Black and White populations.
"Our results suggest that persons of lower socioeconomic position have greater inflammatory burden that those of high socioeconomic position as a result of the cumulative effects of multiple behavioral psychosocial and metabolic characteristics," the authors write.
"If the role of inflammation in causing multiple chronic diseases is confirmed, inflammation may represent a common element through which low socioeconomic position is related to CVD and other chronic diseases of aging."
Free abstract
Ozone modifies heart disease risk associated with high temperature
Ozone modifies heart disease risk associated with high temperature
By Caroline Price
22 November 2007
Occup Environ Med 2007; Advance online publication
MedWire News: High ozone levels in the atmosphere exacerbate the increase in cardiovascular (CV) mortality due to hot weather, study findings reveal.
"Concentrations of air pollutants, particularly ozone, are correlated with temperature.
Therefore, temperature and air pollution may interact to affect morbidity and mortality," explain C Ren (University of California, Irvine, USA) and colleagues.
Having previously demonstrated that air particulate matter modifies the association between temperature and morbidity and mortality, the researchers specifically examined the effect of ozone on this relationship.
They analyzed data from the US National Morbidity, Mortality, and Air Pollution Study for 95 different geographical regions, containing nearly 100 million people, between June and September each year for the period 1987-2000.
As reported in the journal Occupational and Environmental Medicine, ozone levels ranged from a daily average of 36.74 to 142.85 parts per billion and average daily temperatures ranged from 20°C to around 42°C.
A total of 4 million myocardial infarctions or strokes occurred, and plotting daily deaths against temperature fluctuations during 1 day revealed that ozone was a common factor.
In general, ozone positively modified the associations between temperature and CV mortality, ie, the increase in CV risk with rising temperature was greater the higher the ozone level.
For all 95 communities, a 10°C increase in average maximum temperature on the current day was associated with an increase in CV mortality on the same day of 1.17%, 4.35%, 4.31%, and 8.31% across quartiles of ozone levels, from the lowest to the highest.
Corresponding increases in CV mortality after a 1-day lag across ozone quartiles were 0.80%, 3.73%, 4.35%, and 8.62%.
The authors reason that exposure to ozone may affect the airways and autonomic nervous system, making people more susceptible to temperature fluctuations.
They say that public health warnings should alert people to stay indoors and avoid exposure on days with high temperature and high ozone.
Rising temperatures and the impact of ozone are likely to become increasingly important as the world heats up as a result of global warming, they add.
Journal
By Caroline Price
22 November 2007
Occup Environ Med 2007; Advance online publication
MedWire News: High ozone levels in the atmosphere exacerbate the increase in cardiovascular (CV) mortality due to hot weather, study findings reveal.
"Concentrations of air pollutants, particularly ozone, are correlated with temperature.
Therefore, temperature and air pollution may interact to affect morbidity and mortality," explain C Ren (University of California, Irvine, USA) and colleagues.
Having previously demonstrated that air particulate matter modifies the association between temperature and morbidity and mortality, the researchers specifically examined the effect of ozone on this relationship.
They analyzed data from the US National Morbidity, Mortality, and Air Pollution Study for 95 different geographical regions, containing nearly 100 million people, between June and September each year for the period 1987-2000.
As reported in the journal Occupational and Environmental Medicine, ozone levels ranged from a daily average of 36.74 to 142.85 parts per billion and average daily temperatures ranged from 20°C to around 42°C.
A total of 4 million myocardial infarctions or strokes occurred, and plotting daily deaths against temperature fluctuations during 1 day revealed that ozone was a common factor.
In general, ozone positively modified the associations between temperature and CV mortality, ie, the increase in CV risk with rising temperature was greater the higher the ozone level.
For all 95 communities, a 10°C increase in average maximum temperature on the current day was associated with an increase in CV mortality on the same day of 1.17%, 4.35%, 4.31%, and 8.31% across quartiles of ozone levels, from the lowest to the highest.
Corresponding increases in CV mortality after a 1-day lag across ozone quartiles were 0.80%, 3.73%, 4.35%, and 8.62%.
The authors reason that exposure to ozone may affect the airways and autonomic nervous system, making people more susceptible to temperature fluctuations.
They say that public health warnings should alert people to stay indoors and avoid exposure on days with high temperature and high ozone.
Rising temperatures and the impact of ozone are likely to become increasingly important as the world heats up as a result of global warming, they add.
Journal
Wednesday, November 21, 2007
Regular Exercise Reduces Risk Of Blood Clots
Regular Exercise Reduces Risk Of Blood Clots
21 Nov 2007
According to a new study published in Journal of Thrombosis and Haemostasis, regular participation in sports reduces the risk of developing blood clots by 39 percent in women and 22 percent in men.
Researchers from Leiden University Medical Center in the Netherlands evaluated 7,860 people aged 18-70. Patients who had suffered their first blood clot in a leg vein or lung artery were compared with control subjects who had never experienced blood clots. 31 percent of the patients and 40 percent of the control group participated in sports on a regular basis.
Overall figures for both sexes showed that participating in sports at least once per week, regardless of the type of sport or its intensity, reduced the risk of developing a blood clot in a lung artery by 46 percent and a blood clot in a leg vein by 24 percent. "Women were shown to be even more likely to reap the benefits of regular sporting activities than men," says F.R. Rosendaal, co-author of the study. "When we excluded women who were pregnant or receiving oral contraceptive or hormone replacement therapy - all possible causes of blood clots - the risk for women was reduced by 55 percent."
The authors note that, while strenuous activity is known to increase the risk of blood clot development in the elderly, regular exercise is also shown to greatly benefit the heart, and that the net effect of elderly sports participation may be positive.
The findings also show that people who did not participate in sports were more than four-times as likely to develop a blood clot if they were obese (with a body mass index of 30 or greater) than lean (with a body mass index of less than 25). "When we looked at the results, we found that, overall, the mere fact that people took part in a sporting activity at least once a week was enough to lower their risk of blood clots," say the authors.
Article adapted by Medical News Today from original press release.
21 Nov 2007
According to a new study published in Journal of Thrombosis and Haemostasis, regular participation in sports reduces the risk of developing blood clots by 39 percent in women and 22 percent in men.
Researchers from Leiden University Medical Center in the Netherlands evaluated 7,860 people aged 18-70. Patients who had suffered their first blood clot in a leg vein or lung artery were compared with control subjects who had never experienced blood clots. 31 percent of the patients and 40 percent of the control group participated in sports on a regular basis.
Overall figures for both sexes showed that participating in sports at least once per week, regardless of the type of sport or its intensity, reduced the risk of developing a blood clot in a lung artery by 46 percent and a blood clot in a leg vein by 24 percent. "Women were shown to be even more likely to reap the benefits of regular sporting activities than men," says F.R. Rosendaal, co-author of the study. "When we excluded women who were pregnant or receiving oral contraceptive or hormone replacement therapy - all possible causes of blood clots - the risk for women was reduced by 55 percent."
The authors note that, while strenuous activity is known to increase the risk of blood clot development in the elderly, regular exercise is also shown to greatly benefit the heart, and that the net effect of elderly sports participation may be positive.
The findings also show that people who did not participate in sports were more than four-times as likely to develop a blood clot if they were obese (with a body mass index of 30 or greater) than lean (with a body mass index of less than 25). "When we looked at the results, we found that, overall, the mere fact that people took part in a sporting activity at least once a week was enough to lower their risk of blood clots," say the authors.
Article adapted by Medical News Today from original press release.
Heart Disease Deaths Among Younger Women Might Be on the Rise
Heart Disease Deaths Among Younger Women Might Be on the Rise
After decades of steady decline, deaths from coronary heart disease in women under 54 may be increasing, according to findings published in the Journal of the American College of Cardiology.
Using CDC and U.S. Census data, researchers found that from 2000 to 2002, the death rate due to CHD in women aged 35 to 54 increased by 1.5% annually. Among the youngest of these women (aged 35-44), the mortality rate had begun to rise in 1997 — averaging a 1.3% increase each year.
In addition, the decline in the CHD death rate among men under 54 appeared to slow — from 2000 to 2002, the rate decreased by only 0.5% annually.
The authors remind physicians to use prevailing guidelines to prevent CHD in patients with one or more risk factors. They conclude, "Complacency runs a high risk: mortality rates among younger adults may represent the leading edge of a brewing storm."
LINK(S):
Journal of the American College of Cardiology article (Free PDF)
Journal of the American College of Cardiology editorial (Subscription required)
Published in Physician's First Watch November 21, 2007
After decades of steady decline, deaths from coronary heart disease in women under 54 may be increasing, according to findings published in the Journal of the American College of Cardiology.
Using CDC and U.S. Census data, researchers found that from 2000 to 2002, the death rate due to CHD in women aged 35 to 54 increased by 1.5% annually. Among the youngest of these women (aged 35-44), the mortality rate had begun to rise in 1997 — averaging a 1.3% increase each year.
In addition, the decline in the CHD death rate among men under 54 appeared to slow — from 2000 to 2002, the rate decreased by only 0.5% annually.
The authors remind physicians to use prevailing guidelines to prevent CHD in patients with one or more risk factors. They conclude, "Complacency runs a high risk: mortality rates among younger adults may represent the leading edge of a brewing storm."
LINK(S):
Journal of the American College of Cardiology article (Free PDF)
Journal of the American College of Cardiology editorial (Subscription required)
Published in Physician's First Watch November 21, 2007
Friday, November 16, 2007
Obesity Paradox in Patients with Hypertension and Coronary Artery Disease
Obesity Paradox in Patients with Hypertension and Coronary Artery Disease
The American Journal of Medicine
Volume 120, Issue 10, October 2007, Pages 863-870
Abstract
Purpose
An obesity paradox, a “paradoxical” decrease in morbidity and mortality with increasing body mass index (BMI), has been shown in patients with heart failure and those undergoing percutaneous coronary intervention. However, whether this phenomenon exists in patients with hypertension and coronary artery disease is not known.
Methods
A total of 22,576 hypertensive patients with coronary artery disease (follow-up 61,835 patient years, mean age 66 ± 9.8 years) were randomized to a verapamil-SR or atenolol strategy. Dose titration and additional drugs (trandolapril and/or hydrochlorothiazide) were added to achieve target blood pressure control according to the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure targets. Patients were classified into 5 groups according to baseline BMI: less than 20 kg/m2 (thin), 20 to 25 kg/m2 (normal weight), 25 to 30 kg/m2 (overweight), 30 to 35 kg/m2 (class I obesity), and 35 kg/m2 or more (class II-III obesity). The primary outcome was first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke.
Results
With patients of normal weight (BMI 20 to <25 kg/m2) as the reference group, the risk of primary outcome was lower in the overweight patients (adjusted hazard ratio [HR] 0.77, 95% confidence interval [CI], 0.70-0.86, P <.001), class I obese patients (adjusted HR 0.68, 95% CI, 0.59-0.78, P <.001), and class II to III obese patients (adjusted HR 0.76, 95% CI, 0.65-0.88, P <.001). Class I obese patients had the lowest rate of primary outcome and death despite having smaller blood pressure reduction compared with patients of normal weight at 24 months (−17.5 ± 21.9 mm Hg/−9.8 ± 12.4 mm Hg vs −20.7 ± 23.1 mm Hg /−10.6 ± 12.5 mm Hg, P <.001).
Conclusion
In a population with hypertension and coronary artery disease, overweight and obese patients had a decreased risk of primary outcome compared with patients of normal weight, which was driven primarily by a decreased risk of all-cause mortality. Our results further suggest a protective effect of obesity in patients with known cardiovascular disease in concordance with data in patients with heart failure and those undergoing percutaneous coronary intervention.
The American Journal of Medicine
Volume 120, Issue 10, October 2007, Pages 863-870
Abstract
Purpose
An obesity paradox, a “paradoxical” decrease in morbidity and mortality with increasing body mass index (BMI), has been shown in patients with heart failure and those undergoing percutaneous coronary intervention. However, whether this phenomenon exists in patients with hypertension and coronary artery disease is not known.
Methods
A total of 22,576 hypertensive patients with coronary artery disease (follow-up 61,835 patient years, mean age 66 ± 9.8 years) were randomized to a verapamil-SR or atenolol strategy. Dose titration and additional drugs (trandolapril and/or hydrochlorothiazide) were added to achieve target blood pressure control according to the Sixth Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure targets. Patients were classified into 5 groups according to baseline BMI: less than 20 kg/m2 (thin), 20 to 25 kg/m2 (normal weight), 25 to 30 kg/m2 (overweight), 30 to 35 kg/m2 (class I obesity), and 35 kg/m2 or more (class II-III obesity). The primary outcome was first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke.
Results
With patients of normal weight (BMI 20 to <25 kg/m2) as the reference group, the risk of primary outcome was lower in the overweight patients (adjusted hazard ratio [HR] 0.77, 95% confidence interval [CI], 0.70-0.86, P <.001), class I obese patients (adjusted HR 0.68, 95% CI, 0.59-0.78, P <.001), and class II to III obese patients (adjusted HR 0.76, 95% CI, 0.65-0.88, P <.001). Class I obese patients had the lowest rate of primary outcome and death despite having smaller blood pressure reduction compared with patients of normal weight at 24 months (−17.5 ± 21.9 mm Hg/−9.8 ± 12.4 mm Hg vs −20.7 ± 23.1 mm Hg /−10.6 ± 12.5 mm Hg, P <.001).
Conclusion
In a population with hypertension and coronary artery disease, overweight and obese patients had a decreased risk of primary outcome compared with patients of normal weight, which was driven primarily by a decreased risk of all-cause mortality. Our results further suggest a protective effect of obesity in patients with known cardiovascular disease in concordance with data in patients with heart failure and those undergoing percutaneous coronary intervention.
Long term pharmacotherapy for obesity and overweight: updated meta-analysis
Long term pharmacotherapy for obesity and overweight: updated meta-analysis -- Rucker et al., 10.1136/bmj.39385.413113.25 -- BMJ
Abstract
Objective To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.
Design Updated meta-analysis of randomised trials.
Data sources Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006.
Studies reviewed Double blind randomised placebo controlled trials of approved anti-obesity dugs used in adults (age over 18) for one year or longer.
Results 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365). Of these, 14 trials were new and 16 had previously been identified. Attrition rates averaged 30-40%. Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg). Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds. Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein. Sibutramine lowered concentrations of high density lipoprotein cholesterol and triglycerides but raised blood pressure and pulse rate. Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
Conclusions Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.
Abstract
Objective To summarise the long term efficacy of anti-obesity drugs in reducing weight and improving health status.
Design Updated meta-analysis of randomised trials.
Data sources Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006.
Studies reviewed Double blind randomised placebo controlled trials of approved anti-obesity dugs used in adults (age over 18) for one year or longer.
Results 30 trials of one to four years' duration met the inclusion criteria: 16 orlistat (n=10 631 participants), 10 sibutramine (n=2623), and four rimonabant (n=6365). Of these, 14 trials were new and 16 had previously been identified. Attrition rates averaged 30-40%. Compared with placebo, orlistat reduced weight by 2.9 kg (95% confidence interval 2.5 kg to 3.2 kg), sibutramine by 4.2 kg (3.6 kg to 4.7 kg), and rimonabant by 4.7 kg (4.1 kg to 5.3 kg). Patients receiving active drug treatment were significantly more likely to achieve 5% and 10% weight loss thresholds. Orlistat reduced the incidence of diabetes and improved concentrations of total cholesterol and low density lipoprotein cholesterol, blood pressure, and glycaemic control in patients with diabetes but increased rates of gastrointestinal side effects and slightly lowered concentrations of high density lipoprotein. Sibutramine lowered concentrations of high density lipoprotein cholesterol and triglycerides but raised blood pressure and pulse rate. Rimonabant improved concentrations of high density lipoprotein cholesterol and triglycerides, blood pressure, and glycaemic control in patients with diabetes but increased the risk of mood disorders.
Conclusions Orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects.
Angioplasty vs. Bypass Surgery
Surgery for Heart Disease: Angioplasty vs. Bypass Surgery
Johns Hopkins Health Alerts: Heart Health
Johns Hopkins experts discuss these two life-saving procedures and reviews the advantages and risks of each.
The pain of angina, usually experienced in the chest, is caused by a shortage of blood and oxygen to the heart muscle due to partial blockage of a coronary artery. The two goals in treating angina symptoms are to decrease the heart’s demand for oxygen and to increase its blood supply.
Several types of drugs can often help control angina pain. But when medication is not successful, revascularization—bypass surgery or angioplasty—may be necessary.
Since neither bypass surgery or angioplasty is a cure for atherosclerosis, it is essential to continue dietary and other preventive lifestyle measures and, in many cases, to take lipid-lowering drugs, blood pressure-lowering drugs, and aspirin after undergoing one of these procedures.
Angioplasty and Bypass Surgery -- Two Techniques to Improve Blood FlowEach year more than 300,000 people in the United States undergo coronary artery bypass graft surgery (often called CABG or, simply, bypass surgery). During bypass surgery, a blood vessel from elsewhere in the body is used to reroute blood around a segment of a coronary artery narrowed by atherosclerosis. When needed, five or more bypass grafts can be performed during a single bypass surgery.
About 90%of people who undergo bypass surgery experience relief of angina symptoms after the procedure. Bypass surgery is extremely successful, even for people with extensive heart disease or who are elderly. But bypass surgery is arduous for patients, requiring general anesthesia and four to six days of hospitalization. And bypass surgery is usually performed with the help of a heart-lung machine that maintains blood circulation while the heart is stopped.
About 640,000 Americans a year undergo percutaneous transluminal coronary angioplasty (often called PTCA or, simply, angioplasty). Angioplasty involves inserting a balloon-tipped catheter into an artery; the balloon is guided to the diseased section of the coronary artery and inflated to break up and compress artery-clogging plaque.
Conventional angioplasty does not remove atherosclerotic plaque from the coronary arteries but instead widens the channel (lumen) through which blood flows by squeezing the plaque against the artery wall, cracking the hard part of the plaque, and/or stretching the artery.
About 90% of people notice an immediate improvement in symptoms when the artery lumen is at least 50% open after angioplasty. In about 85% of cases, a small, scaffold-like device called a stent is permanently placed in the artery during angioplasty to help keep the artery open. This helps reduce the rate of restenosis (further narrowing of the artery) to 10% to 20% (compared to 20% to 40% without a stent).
Angioplasty is performed in a cardiac catheterization laboratory and generally takes about one to two hours. Angioplasty does not require general anesthesia and usually involves no more than a night’s stay in the hospital. The risks associated with angioplasty are low.
Factors To Weigh in Choosing Angioplasty or Bypass SurgeryAngioplasty has several advantages over bypass surgery. Angioplasty is a relatively simple procedure, there is no need for general anesthesia, and the rigors of open heart surgery are avoided.
A major disadvantage of angioplasty is restenosis in the first six months after the procedure. People who undergo angioplasty must accept the risk that a repeat angioplasty or, ultimately, bypass surgery may become necessary.
Recurring angina is another consideration. These risks are considerably decreased with the implantation of a stent. Another disadvantage to angioplasty is that many people with coronary heart disease are not suitable candidates for angioplasty.
Bypass surgery may keep arteries open longer and improve blood flow through the coronary arteries more than angioplasty. Bypass surgery generally provides good relief of angina for at least five years.
In addition, bypass surgery is generally favored over angioplasty in people with one or more of the following:
· Disease in the left main coronary artery. This vessel is the main artery supplying blood to the heart, and even a brief period of blockage could damage heart muscle or be fatal.
· Diffuse coronary heart disease. Angioplasty is not effective for the treatment of multiple blockages in several vessels.
· Blockages at an arterial branch. If the blockage is at a point where one artery meets another, angioplasty may move the plaque into the adjacent artery, causing a new blockage.
· Diabetes. In the Bypass Angioplasty Revascularization Investigation (BARI) study, seven-year survival for people with diabetes was significantly better in those who underwent bypass surgery (76%) than angioplasty (56%). However, this study was conducted before traditional and drug-coated stents were available, and if the study were repeated today the results may be different.
Other factors. Other factors that make bypass surgery a better choice than angioplasty include severe disease of the three major coronary arteries (especially in people with reduced left ventricular function) and a history of heart failure.
Two drawbacks to bypass surgery are longer hospital stays and rehabilitation time than with angioplasty. In addition, a recent study of 261 bypass surgery patients found that about 40% of them had a decline in cognitive function that persisted five years after surgery. It is possible, however, that this decline was caused by underlying vascular disease in these patients and not the bypass surgery itself.
Johns Hopkins Health Alerts: Heart Health
Johns Hopkins experts discuss these two life-saving procedures and reviews the advantages and risks of each.
The pain of angina, usually experienced in the chest, is caused by a shortage of blood and oxygen to the heart muscle due to partial blockage of a coronary artery. The two goals in treating angina symptoms are to decrease the heart’s demand for oxygen and to increase its blood supply.
Several types of drugs can often help control angina pain. But when medication is not successful, revascularization—bypass surgery or angioplasty—may be necessary.
Since neither bypass surgery or angioplasty is a cure for atherosclerosis, it is essential to continue dietary and other preventive lifestyle measures and, in many cases, to take lipid-lowering drugs, blood pressure-lowering drugs, and aspirin after undergoing one of these procedures.
Angioplasty and Bypass Surgery -- Two Techniques to Improve Blood FlowEach year more than 300,000 people in the United States undergo coronary artery bypass graft surgery (often called CABG or, simply, bypass surgery). During bypass surgery, a blood vessel from elsewhere in the body is used to reroute blood around a segment of a coronary artery narrowed by atherosclerosis. When needed, five or more bypass grafts can be performed during a single bypass surgery.
About 90%of people who undergo bypass surgery experience relief of angina symptoms after the procedure. Bypass surgery is extremely successful, even for people with extensive heart disease or who are elderly. But bypass surgery is arduous for patients, requiring general anesthesia and four to six days of hospitalization. And bypass surgery is usually performed with the help of a heart-lung machine that maintains blood circulation while the heart is stopped.
About 640,000 Americans a year undergo percutaneous transluminal coronary angioplasty (often called PTCA or, simply, angioplasty). Angioplasty involves inserting a balloon-tipped catheter into an artery; the balloon is guided to the diseased section of the coronary artery and inflated to break up and compress artery-clogging plaque.
Conventional angioplasty does not remove atherosclerotic plaque from the coronary arteries but instead widens the channel (lumen) through which blood flows by squeezing the plaque against the artery wall, cracking the hard part of the plaque, and/or stretching the artery.
About 90% of people notice an immediate improvement in symptoms when the artery lumen is at least 50% open after angioplasty. In about 85% of cases, a small, scaffold-like device called a stent is permanently placed in the artery during angioplasty to help keep the artery open. This helps reduce the rate of restenosis (further narrowing of the artery) to 10% to 20% (compared to 20% to 40% without a stent).
Angioplasty is performed in a cardiac catheterization laboratory and generally takes about one to two hours. Angioplasty does not require general anesthesia and usually involves no more than a night’s stay in the hospital. The risks associated with angioplasty are low.
Factors To Weigh in Choosing Angioplasty or Bypass SurgeryAngioplasty has several advantages over bypass surgery. Angioplasty is a relatively simple procedure, there is no need for general anesthesia, and the rigors of open heart surgery are avoided.
A major disadvantage of angioplasty is restenosis in the first six months after the procedure. People who undergo angioplasty must accept the risk that a repeat angioplasty or, ultimately, bypass surgery may become necessary.
Recurring angina is another consideration. These risks are considerably decreased with the implantation of a stent. Another disadvantage to angioplasty is that many people with coronary heart disease are not suitable candidates for angioplasty.
Bypass surgery may keep arteries open longer and improve blood flow through the coronary arteries more than angioplasty. Bypass surgery generally provides good relief of angina for at least five years.
In addition, bypass surgery is generally favored over angioplasty in people with one or more of the following:
· Disease in the left main coronary artery. This vessel is the main artery supplying blood to the heart, and even a brief period of blockage could damage heart muscle or be fatal.
· Diffuse coronary heart disease. Angioplasty is not effective for the treatment of multiple blockages in several vessels.
· Blockages at an arterial branch. If the blockage is at a point where one artery meets another, angioplasty may move the plaque into the adjacent artery, causing a new blockage.
· Diabetes. In the Bypass Angioplasty Revascularization Investigation (BARI) study, seven-year survival for people with diabetes was significantly better in those who underwent bypass surgery (76%) than angioplasty (56%). However, this study was conducted before traditional and drug-coated stents were available, and if the study were repeated today the results may be different.
Other factors. Other factors that make bypass surgery a better choice than angioplasty include severe disease of the three major coronary arteries (especially in people with reduced left ventricular function) and a history of heart failure.
Two drawbacks to bypass surgery are longer hospital stays and rehabilitation time than with angioplasty. In addition, a recent study of 261 bypass surgery patients found that about 40% of them had a decline in cognitive function that persisted five years after surgery. It is possible, however, that this decline was caused by underlying vascular disease in these patients and not the bypass surgery itself.
Wednesday, November 14, 2007
More evidence of the primacy of chest compressions over ventilation in cardiopulmonary resuscitation
More evidence of the primacy of chest compressions over ventilation in cardiopulmonary resuscitation
November 14, 2007 By Benjamin A. Olenchock, M.D. Ph.D.
The 2005 AHA guidelines for cardiopulmonary resuscitation (CPR) changed the recommended ratio of chest compressions to ventilations from 15:2 to 30:2, based mostly on expert opinion that circulatory support is more critical than ventilatory support.
Researchers at the University of Arizona have performed CPR on 64 domestic pigs which were randomized to receive either the recommended 30:2 CPR or continuous chest compression without ventilations. Their findings, published in the journal Circulation, suggest that continuous chest compressions might lead to improved outcomes.
The investigators used a temporary pacing wire to initiate ventricular fibrillation in anesthetized, intubated pigs. They allowed the non-perfusing rhythm to continue between 3 to 6 minutes and then initiated either continuous chest compressions or 30:2 compressions to breaths. At 12 minutes after initiation of ventricular fibrillation, a first 150 J biphasic shock was delivered, and then resuscitation was continued via advanced cardiac life support guidelines. The primary outcome measure was neurologically normal survival at 24-hours.
Although it was impossible to blind the providers, chest compressions were similarly effective between the two groups as measured by mean arterial pressure. The integrated coronary perfusion pressure, which is known to predict survival following cardiac arrest, was significantly increased in the continuous chest compression group (23 mm vs. 10 mm, p =0.001). Neurologically normal survival was also significantly increased in the continuous chest compression group (70% vs 42%, p=0.025). The benefit of continuous chest compression was greater for those pigs that had non-perfusing rhythms for 6 minutes than for those not perfusing for 2 minutes.
These findings stress the primacy of adequate chest compressions during CPR to maintain a perfusing blood pressure. They also bring to attention the problem of long breaks in chest compressions that occurs when rescuers deliver breaths. Whether this technique would translate into improved outcome in humans will be much more difficult to demonstrate. Perhaps future recommendations from the AHA will continue to move away from rescue breaths towards continuous chest compressions
November 14, 2007 By Benjamin A. Olenchock, M.D. Ph.D.
The 2005 AHA guidelines for cardiopulmonary resuscitation (CPR) changed the recommended ratio of chest compressions to ventilations from 15:2 to 30:2, based mostly on expert opinion that circulatory support is more critical than ventilatory support.
Researchers at the University of Arizona have performed CPR on 64 domestic pigs which were randomized to receive either the recommended 30:2 CPR or continuous chest compression without ventilations. Their findings, published in the journal Circulation, suggest that continuous chest compressions might lead to improved outcomes.
The investigators used a temporary pacing wire to initiate ventricular fibrillation in anesthetized, intubated pigs. They allowed the non-perfusing rhythm to continue between 3 to 6 minutes and then initiated either continuous chest compressions or 30:2 compressions to breaths. At 12 minutes after initiation of ventricular fibrillation, a first 150 J biphasic shock was delivered, and then resuscitation was continued via advanced cardiac life support guidelines. The primary outcome measure was neurologically normal survival at 24-hours.
Although it was impossible to blind the providers, chest compressions were similarly effective between the two groups as measured by mean arterial pressure. The integrated coronary perfusion pressure, which is known to predict survival following cardiac arrest, was significantly increased in the continuous chest compression group (23 mm vs. 10 mm, p =0.001). Neurologically normal survival was also significantly increased in the continuous chest compression group (70% vs 42%, p=0.025). The benefit of continuous chest compression was greater for those pigs that had non-perfusing rhythms for 6 minutes than for those not perfusing for 2 minutes.
These findings stress the primacy of adequate chest compressions during CPR to maintain a perfusing blood pressure. They also bring to attention the problem of long breaks in chest compressions that occurs when rescuers deliver breaths. Whether this technique would translate into improved outcome in humans will be much more difficult to demonstrate. Perhaps future recommendations from the AHA will continue to move away from rescue breaths towards continuous chest compressions
ARBs could reduce effort myocardial ischemia
ARBs could reduce effort myocardial ischemia
By Caroline Price - MedwireNews
13 November 2007
Am J Cardiol 2007; 100: 1517-1521
MedWire News: Treatment with the angiotensin receptor blocker (ARB) losartan decreased electrocardiographic measures of ischemia in patients with stable coronary artery disease (CAD), suggesting a possible role for this class of drugs in effort myocardial ischemia, report US researchers.
"Our results showed that losartan 100 mg is able to decrease transient exercise-induced myocardial ischemia by decreasing time to onset of 1-mm ST segment depression, ST-segment depression at peak exercise, and time to recovery of ST-segment depression and increasing exercise duration and maximal workload," report Giancarlo Longobardi (Scientific Institute of Telese Terme, Italy).
The researchers randomly assigned 28 CAD patients to receive losartan 100 mg or placebo for 28 days, followed by 1 week of placebo in both groups and then cross-over to the alternative regimen for a further 28 days.
All patients had reproducible positive exercise test results at the beginning of the study and were normotensive and in sinus rhythm. None of the patients had evidence of left ventricular hypertrophy or conduction defects, or a history of myocardial infarction.
Patients underwent an exercise stress test at the end of each phase of the study.
The results, published in the American Journal of Cardiology, showed that patients' systolic blood pressure (SBP) levels were significantly decreased with losartan compared with placebo (p<0.05). SBP and rate-pressure product were lower after losartan treatment than after placebo at submaximal exercise (both p<0.005), at 1-mm ST depression (p<0.001 and p<0.02, respectively), and at peak exercise (p<0.001 and p<0.005, respectively).
Patients had significantly delayed time to 1-mm ST-depression onset after losartan treatment compared with placebo treatment (479 vs 475 seconds, p<0.01) as well as decreased ST-segment depression at peak exercise (1.3 vs 1.0, p<0.05) and time to recovery of ST-segment depression (120 vs 177, p<0.01).
Furthermore, losartan treatment significantly increased exercise duration (603 vs 565 seconds, p<0.001) and maximal workload (4208 vs 3742 kg, p<0.001) during exercise stress testing compared with placebo.
The team speculates that the mechanism of action, similar to that of nitrates, is likely related to vasodilation in conductive arteries, with a relative decrease in afterload, and vasodilator effects on epicardial and resistance vessels in the coronary circulation.
Free abstract
By Caroline Price - MedwireNews
13 November 2007
Am J Cardiol 2007; 100: 1517-1521
MedWire News: Treatment with the angiotensin receptor blocker (ARB) losartan decreased electrocardiographic measures of ischemia in patients with stable coronary artery disease (CAD), suggesting a possible role for this class of drugs in effort myocardial ischemia, report US researchers.
"Our results showed that losartan 100 mg is able to decrease transient exercise-induced myocardial ischemia by decreasing time to onset of 1-mm ST segment depression, ST-segment depression at peak exercise, and time to recovery of ST-segment depression and increasing exercise duration and maximal workload," report Giancarlo Longobardi (Scientific Institute of Telese Terme, Italy).
The researchers randomly assigned 28 CAD patients to receive losartan 100 mg or placebo for 28 days, followed by 1 week of placebo in both groups and then cross-over to the alternative regimen for a further 28 days.
All patients had reproducible positive exercise test results at the beginning of the study and were normotensive and in sinus rhythm. None of the patients had evidence of left ventricular hypertrophy or conduction defects, or a history of myocardial infarction.
Patients underwent an exercise stress test at the end of each phase of the study.
The results, published in the American Journal of Cardiology, showed that patients' systolic blood pressure (SBP) levels were significantly decreased with losartan compared with placebo (p<0.05). SBP and rate-pressure product were lower after losartan treatment than after placebo at submaximal exercise (both p<0.005), at 1-mm ST depression (p<0.001 and p<0.02, respectively), and at peak exercise (p<0.001 and p<0.005, respectively).
Patients had significantly delayed time to 1-mm ST-depression onset after losartan treatment compared with placebo treatment (479 vs 475 seconds, p<0.01) as well as decreased ST-segment depression at peak exercise (1.3 vs 1.0, p<0.05) and time to recovery of ST-segment depression (120 vs 177, p<0.01).
Furthermore, losartan treatment significantly increased exercise duration (603 vs 565 seconds, p<0.001) and maximal workload (4208 vs 3742 kg, p<0.001) during exercise stress testing compared with placebo.
The team speculates that the mechanism of action, similar to that of nitrates, is likely related to vasodilation in conductive arteries, with a relative decrease in afterload, and vasodilator effects on epicardial and resistance vessels in the coronary circulation.
Free abstract
Mitochondria Send Death Signal To Cardiac Cells, Study Shows
Mitochondria Send Death Signal To Cardiac Cells, Study Shows
13 Nov 2007
Scientists have determined how cardiac cells die just as emergency treatments restore blood flow to a heart in distress, a paradox that has long puzzled doctors who are able to relieve pain in patients suffering from blocked arteries but can't stop the damage caused by the renewed rush of blood.
The discovery may lead to new ways to save that dying tissue.
It is the stoppage of blood flow and resulting loss of oxygen to the heart that causes chest pain during cardiac events. Clinicians' first order of business is restoring that flow with medicine or other noninvasive procedures, or even an invasive procedure, such as placement of a stent or balloon to open a blocked vessel.
But the rush of blood - and the oxygen it carries - that restores a heart's beat and relieves the pain can also damage tissue and weaken the heart's function because cardiac cells die in the process. And like brain cells, cardiac cells take a long time for the body to replace, so the damage is difficult to repair.
Researchers at Ohio State University Medical Center have traced this cell-death signal to the mitochondria, the principal energy source of cells, through a specialized technique. In experiments, cardiac cell mitochondria were isolated and subjected to ischemia and reperfusion - the blockage and restart of blood flow. The researchers hope that identifying the origin of the cell-death signal will improve the chances of finding a way to stop the signal, reducing the damage associated with restored blood flow to the heart.
The results were published in the October issue of the Journal of Molecular and Cellular Cardiology. "This form of cardiac cell death is a major medical and health issue. The patient has severe pain from the loss of blood flow and oxygen to the heart, so we cannot do anything other than clear that artery to restore the blood and oxygen. But when that is done, the patient loses cardiac cells. It's a paradox," said senior study author Pedram Ghafourifar, associate professor of surgery and pharmacology and director of basic science research in the division of vascular surgery at Ohio State 's Medical Center.
"The mitochondria have been suspected in this process, but to date, we haven't known for sure." Ghafourifar's lab developed a technique allowing researchers to watch isolated mitochondria in real time during this process. Using chemical probes and a novel technique called dual-wavelengths excitation spectrophotofluorometry, they saw that after the mitochrondria were subjected to ischemia followed by reoxygenation, a boost of calcium occurred in the mitochondria.
"Calcium levels went up like never before, which is unusual, because mitochrondria typically are able to tightly maintain a low level of calcium," said Ghafourifar, also an investigator in the Davis Heart and Lung Research Institute. That glut of calcium, in turn, triggered an enzyme to begin churning out toxic levels of the free radical nitric oxide - much more than the mitochondria could handle. And that excess of nitric oxide led to the release of a mitochondrial protein that sends the death signal to the cell.
The enzyme at work in this process is called mitochondrial nitric oxide synthase, discovered and reported by Ghafourifar's lab in 1997. Because researchers don't know the cause of the calcium increase during reoxygenation of the heart, Ghafourifar and his colleagues have focused on the enzyme as a therapeutic target to stop the production of nitric oxide that leads to cell death. "The next immediate step is finding whether we can inhibit this enzyme so it doesn't generate excess nitric oxide during the reoxygenation phase," Ghafourifar said. "We're trying to develop experimental drugs that can be delivered at the time of reperfusion or just before. Some seem to be successful at selectively inhibiting the enzyme." The experimental therapies will soon be tested in animal studies. The identification of the enzyme as a target to stop cell death could influence a range of therapeutic options, Ghafourifar said, by applying to disease processes characterized by cell death, or, in the case of cancer, the refusal of cells to die when they should.
"Cell death is involved in a variety of diseases that don't seem to be related," he said. "In cancer, cells do not die. In Parkinson's and Alzheimer's disease, cells die earlier than we want them to. If we figure out how cell death happens, we can put up a fight against a number of diseases."
Ohio State University
13 Nov 2007
Scientists have determined how cardiac cells die just as emergency treatments restore blood flow to a heart in distress, a paradox that has long puzzled doctors who are able to relieve pain in patients suffering from blocked arteries but can't stop the damage caused by the renewed rush of blood.
The discovery may lead to new ways to save that dying tissue.
It is the stoppage of blood flow and resulting loss of oxygen to the heart that causes chest pain during cardiac events. Clinicians' first order of business is restoring that flow with medicine or other noninvasive procedures, or even an invasive procedure, such as placement of a stent or balloon to open a blocked vessel.
But the rush of blood - and the oxygen it carries - that restores a heart's beat and relieves the pain can also damage tissue and weaken the heart's function because cardiac cells die in the process. And like brain cells, cardiac cells take a long time for the body to replace, so the damage is difficult to repair.
Researchers at Ohio State University Medical Center have traced this cell-death signal to the mitochondria, the principal energy source of cells, through a specialized technique. In experiments, cardiac cell mitochondria were isolated and subjected to ischemia and reperfusion - the blockage and restart of blood flow. The researchers hope that identifying the origin of the cell-death signal will improve the chances of finding a way to stop the signal, reducing the damage associated with restored blood flow to the heart.
The results were published in the October issue of the Journal of Molecular and Cellular Cardiology. "This form of cardiac cell death is a major medical and health issue. The patient has severe pain from the loss of blood flow and oxygen to the heart, so we cannot do anything other than clear that artery to restore the blood and oxygen. But when that is done, the patient loses cardiac cells. It's a paradox," said senior study author Pedram Ghafourifar, associate professor of surgery and pharmacology and director of basic science research in the division of vascular surgery at Ohio State 's Medical Center.
"The mitochondria have been suspected in this process, but to date, we haven't known for sure." Ghafourifar's lab developed a technique allowing researchers to watch isolated mitochondria in real time during this process. Using chemical probes and a novel technique called dual-wavelengths excitation spectrophotofluorometry, they saw that after the mitochrondria were subjected to ischemia followed by reoxygenation, a boost of calcium occurred in the mitochondria.
"Calcium levels went up like never before, which is unusual, because mitochrondria typically are able to tightly maintain a low level of calcium," said Ghafourifar, also an investigator in the Davis Heart and Lung Research Institute. That glut of calcium, in turn, triggered an enzyme to begin churning out toxic levels of the free radical nitric oxide - much more than the mitochondria could handle. And that excess of nitric oxide led to the release of a mitochondrial protein that sends the death signal to the cell.
The enzyme at work in this process is called mitochondrial nitric oxide synthase, discovered and reported by Ghafourifar's lab in 1997. Because researchers don't know the cause of the calcium increase during reoxygenation of the heart, Ghafourifar and his colleagues have focused on the enzyme as a therapeutic target to stop the production of nitric oxide that leads to cell death. "The next immediate step is finding whether we can inhibit this enzyme so it doesn't generate excess nitric oxide during the reoxygenation phase," Ghafourifar said. "We're trying to develop experimental drugs that can be delivered at the time of reperfusion or just before. Some seem to be successful at selectively inhibiting the enzyme." The experimental therapies will soon be tested in animal studies. The identification of the enzyme as a target to stop cell death could influence a range of therapeutic options, Ghafourifar said, by applying to disease processes characterized by cell death, or, in the case of cancer, the refusal of cells to die when they should.
"Cell death is involved in a variety of diseases that don't seem to be related," he said. "In cancer, cells do not die. In Parkinson's and Alzheimer's disease, cells die earlier than we want them to. If we figure out how cell death happens, we can put up a fight against a number of diseases."
Ohio State University
Tuesday, November 13, 2007
AHA - 2007: Oral contraceptives increase risk of plaques
Oral contraceptives increase risk of plaques
Orlando, FL - A team of Belgian researchers has made the surprise discovery that women who have used oral contraceptives (OCs) for some time appear to be at increased risk of atherosclerosis in the carotid and femoral arteries. They also found that those taking the pill had three times higher C-reactive protein (CRP) levels than those not using it.
Dr Ernest Rietzschel (Ghent University, Belgium) reported the findings at the American Heart Association (AHA) 2007 Scientific Sessions last week. He told heartwire: "This is the first time that this has been documented. It was an accidental finding. We were stunned by the large elevations in CRP that you see in women taking the pill, so we then performed a safety analysis to see whether there was a link between past pill use and atherosclerosis measured by echo in both the carotid and femoral arteries. Our null hypothesis was that we would see no effect, but in hindsight that was probably naive."
He stressed, however, that this research should not mean that women should cease using oral contraceptives: "I'm certainly not advocating stopping use of the pill," he noted. First, the findings need to be replicated, "that's really important," he said, "and then we need more research. It's staggering that for a drug that is being used by 80% of women, there is so little information about the long-term safety. That's really incredible."
OCs an important factor in global atherosclerotic burden
Rietzschel and colleagues started out by assessing novel risk factors for atherosclerosis in women participating in the Asklepios study, a blinded sample of men and women volunteers aged 35 to 55 years in the Belgian population who were free from overt cardiovascular disease. Rietzschel said that there has been one prior report of increased CRP in OC users, from the Cardiovascular Risk in Young Finns study.
Of 1301 women (mean age 45.7 years) in Asklepios, 27.4% were taking OCs and 10.0% were taking hormone replacement therapy (HRT). Past OC use was much higher, however, with 81% of women having taken it for at least one year, with a median exposure of 13 years.
After multivariate adjustment, women who were not taking OCs or HRT had high-sensitivity CRP of 1.0 mg/L compared with 1.2 for those currently taking HRT and 3.3 for women currently taking OCs. Effects on other inflammatory markers, such as interleukin-6, were far less pronounced, the researchers note.
"Contraceptive therapy is a major cause of CRP rise. The magnitude of CRP rise (threefold) far exceeds other population-prevalent noninfectious stimuli and is much larger than the CRP rise for HRT. Future research should take into account this effect when reporting CRP data in women, aim to qualify its biological significance, and assess the potential of CRP as a tool to select those women at high thrombotic risk under hormonal therapy," Rietzschel et al say.
This finding spurred Rietzschel and his team to look at past OC use, "something we might not have considered a plausible candidate for atherosclerosis," he explained to heartwire. After multivariate adjustment, they found the odds ratios (OR) per 10 years of OC exposure were 1.17 for carotid plaque and 1.28 for femoral plaque. They also looked at prevalence of bilateral disease as a more stringent phenotype of atherosclerosis and found ORs per 10 years of OC exposure of 1.42 for carotid plaque and 1.34 for femoral plaque.
"Use of contraceptive therapy is very common and is associated with an unexpected increase in the prevalence of carotid and femoral atherosclerosis in otherwise young, apparently healthy women. Our data suggest a 20% to 30% increased prevalence of plaque in the carotid and femoral arteries per 10 years of OC exposure. In the light of widespread and usually prolonged OC use, these results suggest OC use could be an important factor in the global atherosclerotic burden," the scientists observe.
A unique opportunity to intervene
While Rietzschel stresses that women should not stop taking the pill on the basis of this research, he says, "Perhaps women should be wary of taking the pill for longer than they need to. At a certain point, don't prolong it out of habit."
Women seeking oral contraception also present a unique opportunity for doctors to give advice on the prevention of cardiovascular disease at an early age, he notes. "Young women have an idea that they won't succumb to cardiovascular disease, which is entirely wrong, because more women die of cardiovascular disease than men. Maybe this is a good time to start talking with young women. Okay, you want to take the pill, but think about the long-term implications. You should stop smoking, check your weight, and be more physically active. Also, we know the pill has effects on blood pressure and lipid profiles, so these should be checked."
The pharmaceutical industry must also contribute, Rietzschel says: "We would like to ask them to develop safer pills." He says he has been approached by some OC manufacturers following his presentation last week but declined to say which ones.
At this time, it is also impossible to say whether any specific type of pill is more hazardous than any other, he noted. "We know that estrogen has a beneficial effect on lipid profiles and it is probably the progestin component of the pill that has adverse effects on lipids, but with regard to the blood-pressure rises seen, it's not clear what raises BP."
Orlando, FL - A team of Belgian researchers has made the surprise discovery that women who have used oral contraceptives (OCs) for some time appear to be at increased risk of atherosclerosis in the carotid and femoral arteries. They also found that those taking the pill had three times higher C-reactive protein (CRP) levels than those not using it.
Dr Ernest Rietzschel (Ghent University, Belgium) reported the findings at the American Heart Association (AHA) 2007 Scientific Sessions last week. He told heartwire: "This is the first time that this has been documented. It was an accidental finding. We were stunned by the large elevations in CRP that you see in women taking the pill, so we then performed a safety analysis to see whether there was a link between past pill use and atherosclerosis measured by echo in both the carotid and femoral arteries. Our null hypothesis was that we would see no effect, but in hindsight that was probably naive."
He stressed, however, that this research should not mean that women should cease using oral contraceptives: "I'm certainly not advocating stopping use of the pill," he noted. First, the findings need to be replicated, "that's really important," he said, "and then we need more research. It's staggering that for a drug that is being used by 80% of women, there is so little information about the long-term safety. That's really incredible."
OCs an important factor in global atherosclerotic burden
Rietzschel and colleagues started out by assessing novel risk factors for atherosclerosis in women participating in the Asklepios study, a blinded sample of men and women volunteers aged 35 to 55 years in the Belgian population who were free from overt cardiovascular disease. Rietzschel said that there has been one prior report of increased CRP in OC users, from the Cardiovascular Risk in Young Finns study.
Of 1301 women (mean age 45.7 years) in Asklepios, 27.4% were taking OCs and 10.0% were taking hormone replacement therapy (HRT). Past OC use was much higher, however, with 81% of women having taken it for at least one year, with a median exposure of 13 years.
After multivariate adjustment, women who were not taking OCs or HRT had high-sensitivity CRP of 1.0 mg/L compared with 1.2 for those currently taking HRT and 3.3 for women currently taking OCs. Effects on other inflammatory markers, such as interleukin-6, were far less pronounced, the researchers note.
"Contraceptive therapy is a major cause of CRP rise. The magnitude of CRP rise (threefold) far exceeds other population-prevalent noninfectious stimuli and is much larger than the CRP rise for HRT. Future research should take into account this effect when reporting CRP data in women, aim to qualify its biological significance, and assess the potential of CRP as a tool to select those women at high thrombotic risk under hormonal therapy," Rietzschel et al say.
This finding spurred Rietzschel and his team to look at past OC use, "something we might not have considered a plausible candidate for atherosclerosis," he explained to heartwire. After multivariate adjustment, they found the odds ratios (OR) per 10 years of OC exposure were 1.17 for carotid plaque and 1.28 for femoral plaque. They also looked at prevalence of bilateral disease as a more stringent phenotype of atherosclerosis and found ORs per 10 years of OC exposure of 1.42 for carotid plaque and 1.34 for femoral plaque.
"Use of contraceptive therapy is very common and is associated with an unexpected increase in the prevalence of carotid and femoral atherosclerosis in otherwise young, apparently healthy women. Our data suggest a 20% to 30% increased prevalence of plaque in the carotid and femoral arteries per 10 years of OC exposure. In the light of widespread and usually prolonged OC use, these results suggest OC use could be an important factor in the global atherosclerotic burden," the scientists observe.
A unique opportunity to intervene
While Rietzschel stresses that women should not stop taking the pill on the basis of this research, he says, "Perhaps women should be wary of taking the pill for longer than they need to. At a certain point, don't prolong it out of habit."
Women seeking oral contraception also present a unique opportunity for doctors to give advice on the prevention of cardiovascular disease at an early age, he notes. "Young women have an idea that they won't succumb to cardiovascular disease, which is entirely wrong, because more women die of cardiovascular disease than men. Maybe this is a good time to start talking with young women. Okay, you want to take the pill, but think about the long-term implications. You should stop smoking, check your weight, and be more physically active. Also, we know the pill has effects on blood pressure and lipid profiles, so these should be checked."
The pharmaceutical industry must also contribute, Rietzschel says: "We would like to ask them to develop safer pills." He says he has been approached by some OC manufacturers following his presentation last week but declined to say which ones.
At this time, it is also impossible to say whether any specific type of pill is more hazardous than any other, he noted. "We know that estrogen has a beneficial effect on lipid profiles and it is probably the progestin component of the pill that has adverse effects on lipids, but with regard to the blood-pressure rises seen, it's not clear what raises BP."
Study says nitrite/nitrate-rich foods may help in heart attack survival
Study says nitrite/nitrate-rich foods may help in heart attack survival
Preclinical study by UT-Houston
Public release date: 12-Nov-2007
EurekAlert
HOUSTON – (NOV. 12, 2007)—Nitrite/nitrate found in vegetables, cured meats and drinking water may help you survive a heart attack and recover quicker, according to a pre-clinical study led by a cardiovascular physiologist at The University of Texas Health Science Center at Houston. Findings appear in the Nov. 12 early online edition of the Proceedings of the National Academy of Sciences.
Mice fed an extra helping of nitrite and nitrate fared much better following a heart attack than those on a regular diet. The mice with extra nitrite had 48 percent less cell death in the heart following heart attack. Mice with a low nitrite/nitrate diet had 59 percent greater injury.
Mice with extra nitrite were also more likely to survive a heart attack or myocardial infarction. They had a survival rate of 77 percent compared to 58 percent for the mice that were nitrite deficient.
“This is a very significant finding given the fact that simple components of our diet – nitrite and nitrate – that we have been taught to fear and restrict in food can now protect the heart from injury. Simple changes in our daily dietary habits such as eating nitrite and nitrate rich foods such as fruits and vegetables and some meats in moderation can drastically improve outcome following a heart attack,” said lead author Nathan S. Bryan, Ph.D., an assistant professor at UT-Houston’s Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM).
The study, “Effects of dietary nitrite and nitrate on myocardial ischemia/reperfusion injury” includes co-authors from the Albert Einstein College of Medicine of Yeshiva University: John W. Calvert, Ph.D.; John W. Elrod, Ph.D.; Susheel Gundewar, M.D.; Sang Yong Ji; and David J. Lefer, Ph.D.
The next logical step, according to Bryan, is to potentially monitor patients with known cardiovascular risk factors to determine if supplemental nitrite/nitrate in the diet can decrease the incidence and severity of heart attack and stroke or enhance recovery.
Nitrite forms nitric oxide gas during a heart attack which reopens closed or clogged arteries, thereby reducing the amount of permanent injury to the heart muscle, he said. “This paper provides the first demonstration of the consequences of changes in dietary nitrite and nitrate on nitric oxide biochemistry and the outcome of heart attack,” Bryan said.
This year about 1.2 million Americans will have a first or recurrent heart attack, the American Heart Association reports. About 452,000 of these people will die. Coronary heart disease is the nation’s single leading cause of death.
“Interestingly, formulations of topical nitrite preparations are effective in wound and burn healing. Clinical trials for such uses as well as diabetic skin ulcers are also underway. It appears that dietary supplementation of nitrites and their topical uses will be effective and inexpensive therapies due to their conversion to nitric oxide,” said Ferid Murad, M.D., Ph.D., the 1998 Nobel Laureate for Physiology or Medicine, which he shared for the discovery of nitric oxide as a signaling molecule. He also is director of the IMM’s Center for Cell Signaling.
Although nitric oxide is metabolized to produce nitrite, which in turn produces nitrate, the process can be reversed in the body, allowing nitrite/nitrate laden plasma and heart tissue to create the vessel-widening, nitric oxide gas during oxygen deprivation, Bryan said.
Not limited to heart disease, Bryan believes dietary nitrite/nitrate will also help with other conditions characterized by a sudden disruption of blood or oxygen including stroke or peripheral vascular disease. He is aware of seven clinical trials involving nitrite/nitrate therapy but suggests that nitrite and nitrate should be investigated in terms of preventing disease as well as potential treatments.
Much maligned following a report in the 1960s linking nitrite/nitrate to cancer, according to Bryan, these nitrogen compounds should not be completely excluded from our diets and may one day even be viewed as nutrients. “The public perception is that nitrite/nitrate are carcinogens but they are not,” he said. “Many studies implicating nitrite and nitrate in cancer are based on very weak epidemiological data. If nitrite and nitrate were harmful to us, then we would not be advised to eat green leafy vegetables or swallow our own saliva, which is enriched in nitrate.”
Nitrite and nitrate are natural molecules produced in our body and our main dietary source of circulating nitrite, and nitrate in our body comes from eating vegetables and not cured or processed meats, Bryan pointed out. “Vegetables have up to 100 times more nitrate than processed meats—so, the amount of nitrite and nitrate one may consume in processed or cured meats is far less than one consumes by eating, for example, a spinach salad,” he said.
Bryan recently co-authored a second study also published in the Proceedings of the National Academy of Sciences demonstrating that the body produces massive amounts of nitrite from nitric oxide when oxygen is short supply. Tibetans, living nearly three miles above sea level, have 50 to 100 times more nitrite in their system than people at sea level. “This demonstrates that increasing nitrite availability is a natural, adaptive physiological response to low oxygen and does not cause cancer,” he said.
Bryan also is a faculty member of the Department of Integrative Biology and Pharmacology at the UT Medical School at Houston and a member of the Nitric Oxide Society, Society for Free Radical Biology and Medicine, and the American Heart Association.
Preclinical study by UT-Houston
Public release date: 12-Nov-2007
EurekAlert
HOUSTON – (NOV. 12, 2007)—Nitrite/nitrate found in vegetables, cured meats and drinking water may help you survive a heart attack and recover quicker, according to a pre-clinical study led by a cardiovascular physiologist at The University of Texas Health Science Center at Houston. Findings appear in the Nov. 12 early online edition of the Proceedings of the National Academy of Sciences.
Mice fed an extra helping of nitrite and nitrate fared much better following a heart attack than those on a regular diet. The mice with extra nitrite had 48 percent less cell death in the heart following heart attack. Mice with a low nitrite/nitrate diet had 59 percent greater injury.
Mice with extra nitrite were also more likely to survive a heart attack or myocardial infarction. They had a survival rate of 77 percent compared to 58 percent for the mice that were nitrite deficient.
“This is a very significant finding given the fact that simple components of our diet – nitrite and nitrate – that we have been taught to fear and restrict in food can now protect the heart from injury. Simple changes in our daily dietary habits such as eating nitrite and nitrate rich foods such as fruits and vegetables and some meats in moderation can drastically improve outcome following a heart attack,” said lead author Nathan S. Bryan, Ph.D., an assistant professor at UT-Houston’s Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM).
The study, “Effects of dietary nitrite and nitrate on myocardial ischemia/reperfusion injury” includes co-authors from the Albert Einstein College of Medicine of Yeshiva University: John W. Calvert, Ph.D.; John W. Elrod, Ph.D.; Susheel Gundewar, M.D.; Sang Yong Ji; and David J. Lefer, Ph.D.
The next logical step, according to Bryan, is to potentially monitor patients with known cardiovascular risk factors to determine if supplemental nitrite/nitrate in the diet can decrease the incidence and severity of heart attack and stroke or enhance recovery.
Nitrite forms nitric oxide gas during a heart attack which reopens closed or clogged arteries, thereby reducing the amount of permanent injury to the heart muscle, he said. “This paper provides the first demonstration of the consequences of changes in dietary nitrite and nitrate on nitric oxide biochemistry and the outcome of heart attack,” Bryan said.
This year about 1.2 million Americans will have a first or recurrent heart attack, the American Heart Association reports. About 452,000 of these people will die. Coronary heart disease is the nation’s single leading cause of death.
“Interestingly, formulations of topical nitrite preparations are effective in wound and burn healing. Clinical trials for such uses as well as diabetic skin ulcers are also underway. It appears that dietary supplementation of nitrites and their topical uses will be effective and inexpensive therapies due to their conversion to nitric oxide,” said Ferid Murad, M.D., Ph.D., the 1998 Nobel Laureate for Physiology or Medicine, which he shared for the discovery of nitric oxide as a signaling molecule. He also is director of the IMM’s Center for Cell Signaling.
Although nitric oxide is metabolized to produce nitrite, which in turn produces nitrate, the process can be reversed in the body, allowing nitrite/nitrate laden plasma and heart tissue to create the vessel-widening, nitric oxide gas during oxygen deprivation, Bryan said.
Not limited to heart disease, Bryan believes dietary nitrite/nitrate will also help with other conditions characterized by a sudden disruption of blood or oxygen including stroke or peripheral vascular disease. He is aware of seven clinical trials involving nitrite/nitrate therapy but suggests that nitrite and nitrate should be investigated in terms of preventing disease as well as potential treatments.
Much maligned following a report in the 1960s linking nitrite/nitrate to cancer, according to Bryan, these nitrogen compounds should not be completely excluded from our diets and may one day even be viewed as nutrients. “The public perception is that nitrite/nitrate are carcinogens but they are not,” he said. “Many studies implicating nitrite and nitrate in cancer are based on very weak epidemiological data. If nitrite and nitrate were harmful to us, then we would not be advised to eat green leafy vegetables or swallow our own saliva, which is enriched in nitrate.”
Nitrite and nitrate are natural molecules produced in our body and our main dietary source of circulating nitrite, and nitrate in our body comes from eating vegetables and not cured or processed meats, Bryan pointed out. “Vegetables have up to 100 times more nitrate than processed meats—so, the amount of nitrite and nitrate one may consume in processed or cured meats is far less than one consumes by eating, for example, a spinach salad,” he said.
Bryan recently co-authored a second study also published in the Proceedings of the National Academy of Sciences demonstrating that the body produces massive amounts of nitrite from nitric oxide when oxygen is short supply. Tibetans, living nearly three miles above sea level, have 50 to 100 times more nitrite in their system than people at sea level. “This demonstrates that increasing nitrite availability is a natural, adaptive physiological response to low oxygen and does not cause cancer,” he said.
Bryan also is a faculty member of the Department of Integrative Biology and Pharmacology at the UT Medical School at Houston and a member of the Nitric Oxide Society, Society for Free Radical Biology and Medicine, and the American Heart Association.
Primary Aldosteronism Common in Patients With Type 2 DM and Resistant Htn
Primary Aldosteronism Common in Patients With Type 2 DM and Resistant Htn
Study Highlights:
Included were 100 consecutive patients aged 18 to 75 years with type 2 diabetes for more than 3 months and treated for hypertension with at least 3 antihypertensive medications.
Resistant hypertension was defined as blood pressure greater than 140/90 mm Hg despite the use of 3 or more antihypertensive agents.
Excluded were those treated with spironolactone or eplerenone; those with glycated hemoglobin value greater than 9%, severe uncontrolled hypertension (blood pressure > 180/110 mm Hg), a history of heart failure, angina, a serum creatinine level greater than 1.8 mg/dL, hepatic disease, Cushing's disease, hyperthyroidism, or pheochromocytoma; and those who were pregnant or lactating.
Patients were screened for primary aldosteronism while taking their usual medications, because stopping blood pressure medications was considered unethical.
Blood samples were drawn in the morning after 30 minutes of rest in the sitting position.
Patients with serum potassium levels of less than 3.5 mmol/L received KCl (40 mEq) daily for 1 week and were rescreened once the potassium level was at least 3.5 mmol/L.
Screening studies included measurement of PAC and PRA and the calculation of the PAC/PRA ratio.
Patients with hypertension and a PAC/PRA ratio greater than 30 ng/mL/hour underwent further studies to confirm a diagnosis of primary aldosteronism.
Salt loading was used to confirm the diagnosis.
Urinary aldosterone was measured 3 days after a salt load or PAC was measured after an intravenous salt load of 2 L of 0.9% saline infused for 4 hours at 500 mL/hour.
Primary aldosteronism was diagnosed if the 24-hour urinary aldosterone concentration was 12 µg or greater during the third day of salt load or if PAC was 5.0 ng/dL or greater after the intravenous load.
93 patients were black, 5 were white, 1 was Hispanic, and 1 was Native American.
Mean age was 59 years, mean duration of diabetes was 8.9 years, mean duration of hypertension was 16 years, and mean body mass index was 34.4 kg/m2 with 75% having a body mass index greater than 30 kg/m2.
The mean number of antihypertensive agents taken was 3.7.
98% were taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 92% were taking a diuretic agent, 73% were taking a β-blocker, 62% were talking a calcium channel blocker, and 31% were taking an α-blocker.
Mean potassium level was 4.0 mmol/L with 15 subjects having levels below 3.5 mmol/L.
34% had an increased PAC/PRA ratio and received additional testing.
Primary aldosteronism was diagnosed in 14% of patients.
There were no differences in age, years of hypertension, years of diabetes, body mass index, blood pressure, glycated hemoglobin level, or numbers or types of antihypertensive agents used between those with and without primary aldosteronism.
Mean systolic and diastolic blood pressures were 157 and 93 mm Hg in those with primary aldosteronism and 158 and 89 mm Hg, respectively, in those without.
Those with primary aldosteronism had a lower potassium level (3.7 vs 4.0 mmol/L), lower serum creatinine level (0.9 vs 1.0 mg/dL), a higher PAC, a lower PRA, and higher PAC/PRA ratio vs those without primary aldosteronism.
Of those with resistant hypertension, 55% had suppressed PRA or salt-sensitive hypertension.
The authors concluded that patients with diabetes and poorly controlled hypertension should be screened for primary aldosteronism using the PAC/PRA ratio followed by salt-suppression testing in those with a positive ratio.
Pearls for Practice:
Resistant hypertension in patients with type 2 diabetes is defined as a persistent blood pressure of 140/90 mm Hg or higher despite treatment with at least 3 antihypertensive agents.
The prevalence of primary aldosteronism among patients with type 2 diabetes with resistant hypertension is 14%.
Study Highlights:
Included were 100 consecutive patients aged 18 to 75 years with type 2 diabetes for more than 3 months and treated for hypertension with at least 3 antihypertensive medications.
Resistant hypertension was defined as blood pressure greater than 140/90 mm Hg despite the use of 3 or more antihypertensive agents.
Excluded were those treated with spironolactone or eplerenone; those with glycated hemoglobin value greater than 9%, severe uncontrolled hypertension (blood pressure > 180/110 mm Hg), a history of heart failure, angina, a serum creatinine level greater than 1.8 mg/dL, hepatic disease, Cushing's disease, hyperthyroidism, or pheochromocytoma; and those who were pregnant or lactating.
Patients were screened for primary aldosteronism while taking their usual medications, because stopping blood pressure medications was considered unethical.
Blood samples were drawn in the morning after 30 minutes of rest in the sitting position.
Patients with serum potassium levels of less than 3.5 mmol/L received KCl (40 mEq) daily for 1 week and were rescreened once the potassium level was at least 3.5 mmol/L.
Screening studies included measurement of PAC and PRA and the calculation of the PAC/PRA ratio.
Patients with hypertension and a PAC/PRA ratio greater than 30 ng/mL/hour underwent further studies to confirm a diagnosis of primary aldosteronism.
Salt loading was used to confirm the diagnosis.
Urinary aldosterone was measured 3 days after a salt load or PAC was measured after an intravenous salt load of 2 L of 0.9% saline infused for 4 hours at 500 mL/hour.
Primary aldosteronism was diagnosed if the 24-hour urinary aldosterone concentration was 12 µg or greater during the third day of salt load or if PAC was 5.0 ng/dL or greater after the intravenous load.
93 patients were black, 5 were white, 1 was Hispanic, and 1 was Native American.
Mean age was 59 years, mean duration of diabetes was 8.9 years, mean duration of hypertension was 16 years, and mean body mass index was 34.4 kg/m2 with 75% having a body mass index greater than 30 kg/m2.
The mean number of antihypertensive agents taken was 3.7.
98% were taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, 92% were taking a diuretic agent, 73% were taking a β-blocker, 62% were talking a calcium channel blocker, and 31% were taking an α-blocker.
Mean potassium level was 4.0 mmol/L with 15 subjects having levels below 3.5 mmol/L.
34% had an increased PAC/PRA ratio and received additional testing.
Primary aldosteronism was diagnosed in 14% of patients.
There were no differences in age, years of hypertension, years of diabetes, body mass index, blood pressure, glycated hemoglobin level, or numbers or types of antihypertensive agents used between those with and without primary aldosteronism.
Mean systolic and diastolic blood pressures were 157 and 93 mm Hg in those with primary aldosteronism and 158 and 89 mm Hg, respectively, in those without.
Those with primary aldosteronism had a lower potassium level (3.7 vs 4.0 mmol/L), lower serum creatinine level (0.9 vs 1.0 mg/dL), a higher PAC, a lower PRA, and higher PAC/PRA ratio vs those without primary aldosteronism.
Of those with resistant hypertension, 55% had suppressed PRA or salt-sensitive hypertension.
The authors concluded that patients with diabetes and poorly controlled hypertension should be screened for primary aldosteronism using the PAC/PRA ratio followed by salt-suppression testing in those with a positive ratio.
Pearls for Practice:
Resistant hypertension in patients with type 2 diabetes is defined as a persistent blood pressure of 140/90 mm Hg or higher despite treatment with at least 3 antihypertensive agents.
The prevalence of primary aldosteronism among patients with type 2 diabetes with resistant hypertension is 14%.
Monday, November 12, 2007
AHA - 2007: Heart Institute of Japan Candesartan Randomized Trial for evaluation of Coronary Artery Disease: HIJ-CREATE
Heart Institute of Japan Candesartan Randomized Trial for evaluation of Coronary Artery Disease: HIJ-CREATE
Vijay Kunadian MBBS MD MRCP
ORLANDO, Nov. 7: The HIJ-CREATE trial was presented by Dr. Hiroshi Kasanuki, M.D. from Tokyo Women’s Medical University at the American Heart Association, Scientific Sessions 2007.
This study demonstrated that the use of candesartan was not associated with a significant difference in major cardiovascular events at a median follow-up of 4.2 years compared to standard medical therapy without the use of candesartan in patients with coronary artery disease and hypertension.
Briefly, this study evaluated the use of candesartan (angiotensin receptor blocker-ARB) compared to standard medical therapy without the use of an ARB in patients with a history of coronary artery disease and hypertension to determine if there was a reduction in cardiovascular events using candesartan.
In this study patients were randomized to treatment with candesartan or standard medical therapy without the use of the ARB in an open-label manner. The target blood pressure was 130/85 mmHg. Patients were followed up at 6, 12, 24, 36, 48 and 60-month intervals. In total 1024 patients were in the candesartan group and 1025 patients were in the standard medical therapy group. Patients were recruited from 14 sites in Japan between June 2001 and April 2004. The primary endpoint of the study was to determine the time to occurrence of first major adverse cardiovascular event. The major secondary endpoints included the incidence of coronary revascularization and new-onset diabetes.
About 35% of the patients had suffered a prior acute coronary syndrome and 38% had suffered a prior myocardial infarction. The ARB-based approach was associated with significantly fewer drug-related adverse events (p=0.027), and fewer patients discontinued the ARB than the ACE inhibitor (p<0.001). Patients in the ARB group had significantly less cough (p<0.001). There were no differences in development of dizziness, hyperkalemia, or liver dysfunction. There were 552 primary events during a mean follow-up of 4.2 years: 264 (25.8%) in the candesartan group and 288 (28.1%) in the non-ARB group (relative risk 0.89 [95% CI 0.76-1.06], p=0.19). There was no difference in the occurrence of revascularization between the candesartan and the standard therapy groups [25% vs. 26.6%, RR 0.92 (0.77-1.12), p=0.41]. There was a difference in the occurrence of new-onset diabetes in the ARB and the standard therapy groups [1.1% vs. 2.9%, RR 0.37 (0.15-0.94), p=0.04]. In patients with creatinine clearance <60ml/min, the HR was 0.79 (0.63-0.99), p=0.039.
Therefore, the HIJ CREATE study demonstrated that candesartan did not significantly improve the occurrence of major adverse cardiac events compared to standard medical therapy at a median follow-up of 4.2 years. However, candesartan was associated with fewer adverse effects. Treatment with candesartan may be beneficial in patients with glucose metabolism abnormalities and those with mild to moderate renal dysfunction. These findings are comparable to the VALIANT study which was conducted in patients with acute myocardial infarction.
References: Originally presented at AHA Scientific Sessions 2007.
Vijay Kunadian MBBS MD MRCP
ORLANDO, Nov. 7: The HIJ-CREATE trial was presented by Dr. Hiroshi Kasanuki, M.D. from Tokyo Women’s Medical University at the American Heart Association, Scientific Sessions 2007.
This study demonstrated that the use of candesartan was not associated with a significant difference in major cardiovascular events at a median follow-up of 4.2 years compared to standard medical therapy without the use of candesartan in patients with coronary artery disease and hypertension.
Briefly, this study evaluated the use of candesartan (angiotensin receptor blocker-ARB) compared to standard medical therapy without the use of an ARB in patients with a history of coronary artery disease and hypertension to determine if there was a reduction in cardiovascular events using candesartan.
In this study patients were randomized to treatment with candesartan or standard medical therapy without the use of the ARB in an open-label manner. The target blood pressure was 130/85 mmHg. Patients were followed up at 6, 12, 24, 36, 48 and 60-month intervals. In total 1024 patients were in the candesartan group and 1025 patients were in the standard medical therapy group. Patients were recruited from 14 sites in Japan between June 2001 and April 2004. The primary endpoint of the study was to determine the time to occurrence of first major adverse cardiovascular event. The major secondary endpoints included the incidence of coronary revascularization and new-onset diabetes.
About 35% of the patients had suffered a prior acute coronary syndrome and 38% had suffered a prior myocardial infarction. The ARB-based approach was associated with significantly fewer drug-related adverse events (p=0.027), and fewer patients discontinued the ARB than the ACE inhibitor (p<0.001). Patients in the ARB group had significantly less cough (p<0.001). There were no differences in development of dizziness, hyperkalemia, or liver dysfunction. There were 552 primary events during a mean follow-up of 4.2 years: 264 (25.8%) in the candesartan group and 288 (28.1%) in the non-ARB group (relative risk 0.89 [95% CI 0.76-1.06], p=0.19). There was no difference in the occurrence of revascularization between the candesartan and the standard therapy groups [25% vs. 26.6%, RR 0.92 (0.77-1.12), p=0.41]. There was a difference in the occurrence of new-onset diabetes in the ARB and the standard therapy groups [1.1% vs. 2.9%, RR 0.37 (0.15-0.94), p=0.04]. In patients with creatinine clearance <60ml/min, the HR was 0.79 (0.63-0.99), p=0.039.
Therefore, the HIJ CREATE study demonstrated that candesartan did not significantly improve the occurrence of major adverse cardiac events compared to standard medical therapy at a median follow-up of 4.2 years. However, candesartan was associated with fewer adverse effects. Treatment with candesartan may be beneficial in patients with glucose metabolism abnormalities and those with mild to moderate renal dysfunction. These findings are comparable to the VALIANT study which was conducted in patients with acute myocardial infarction.
References: Originally presented at AHA Scientific Sessions 2007.
Rethinking a “healthy weight”: New study finds that being overweight is not associated with increased mortality from cardiovascular causes
Rethinking a “healthy weight”: New study finds that being overweight is not associated with increased mortality from cardiovascular causes
November 9, 2007 By Benjamin A. Olenchock, M.D. Ph.D.
Bethesda, MD
A new study has examined disease-specific mortality rates based on body mass index (BMI) using data from the National Health and Nutrition Examination Survey (NHANES) databases.
The findings, published in the Journal of the American Medical Association, suggest that individuals defined as overweight (BMI between 25 and 30) do not have increased cardiovascular mortality. Obesity (BMI > 30), however, was associated with excess cardiovascular mortality, although to a much lesser extent than in previous years. Under-weight (BMI<18.5) was associated with higher non-CVD/non-cancer mortality. This research is a continuation of work published in 2005 that examined all-cause mortality.
The previous study reported that over-weight individuals had decreased all-cause mortality compared to normal weight individuals, while obesity and under-weight were found to have increased all-cause mortality.
The statistical analyses required to do such a study were quite complex. The study used the NHANES databases to gather baseline data in representative cross-sectional samples of the United States population. Cause of death was divided into three categories: cardiovascular, cancer, and all other. They used a Cox proportional hazard model to calculate the relative disease-specific risk for the different BMI classes, separating the analysis by age for statistical reasons. The model included sex, smoking status, race, and alcohol consumptions as other covariates. To estimate the excess disease-specific mortality in 2004 attributable to BMI class, they applied their relative risk data to mortality data from the United States vital statistics in 2004, estimating the current distribution of covariates using the NHANES 1999-2002 cross-sectional data set.
Obesity was associated with 81,072 [CI 51,433 to 110,710] excess deaths from cardiovascular disease but no statistically significant increase in cancer deaths (14,930, [CI -13,721 to 43,582]). Obesity was, however, associated with increased obesity-related cancers, defined as colon, breast, esophageal, uterine, ovarian, kidney and pancreatic (13,839 excess deaths, CI 1920 to 25,758). The authors analyzed longitudinal changes in attributable deaths by using relative risk estimates for individual NHANES databases. They found that using NHANES I (1971-1975) relative risk estimates, obesity was associated with 161,290 excess deaths from cardiovascular causes, much more than the current estimate of 81,072.
Overweight was associated with no excess deaths from cardiovascular causes (-17,074, CI -50,407 to 16,259) or cancer (-13,533, CI -44364 to 17298), but significantly decreased deaths from all-other causes (-107674, CI -148738 to -66610). Underweight, in contrast, was associated with excess deaths from all-other causes (23,455, CI 11,848 to 35,061). Looking closer at the over-weight category, the authors did find that both overweight and obese individuals had excess deaths from kidney disease and diabetes.
This data adds significantly to their previous work, which demonstrated differences in all-cause mortality based on BMI. One interesting finding is that over-weight is associated with less all-cause mortality and no difference in cardiovascular mortality. Also, the data are notable for the apparent change in the excess cardiovascular deaths associated with obesity over time, perhaps reflecting improvements in medical care in recent years. These data are sure to bring commentaries on the statistical methods used, changes in BMI class over time as a consequence rather than cause of disease, concerns about cause of death reporting bias, etc. Nonetheless, this work is an important contribution to our current understanding of healthy body weight and the relationship between cardiovascular disease mortality and excess body weight.
November 9, 2007 By Benjamin A. Olenchock, M.D. Ph.D.
Bethesda, MD
A new study has examined disease-specific mortality rates based on body mass index (BMI) using data from the National Health and Nutrition Examination Survey (NHANES) databases.
The findings, published in the Journal of the American Medical Association, suggest that individuals defined as overweight (BMI between 25 and 30) do not have increased cardiovascular mortality. Obesity (BMI > 30), however, was associated with excess cardiovascular mortality, although to a much lesser extent than in previous years. Under-weight (BMI<18.5) was associated with higher non-CVD/non-cancer mortality. This research is a continuation of work published in 2005 that examined all-cause mortality.
The previous study reported that over-weight individuals had decreased all-cause mortality compared to normal weight individuals, while obesity and under-weight were found to have increased all-cause mortality.
The statistical analyses required to do such a study were quite complex. The study used the NHANES databases to gather baseline data in representative cross-sectional samples of the United States population. Cause of death was divided into three categories: cardiovascular, cancer, and all other. They used a Cox proportional hazard model to calculate the relative disease-specific risk for the different BMI classes, separating the analysis by age for statistical reasons. The model included sex, smoking status, race, and alcohol consumptions as other covariates. To estimate the excess disease-specific mortality in 2004 attributable to BMI class, they applied their relative risk data to mortality data from the United States vital statistics in 2004, estimating the current distribution of covariates using the NHANES 1999-2002 cross-sectional data set.
Obesity was associated with 81,072 [CI 51,433 to 110,710] excess deaths from cardiovascular disease but no statistically significant increase in cancer deaths (14,930, [CI -13,721 to 43,582]). Obesity was, however, associated with increased obesity-related cancers, defined as colon, breast, esophageal, uterine, ovarian, kidney and pancreatic (13,839 excess deaths, CI 1920 to 25,758). The authors analyzed longitudinal changes in attributable deaths by using relative risk estimates for individual NHANES databases. They found that using NHANES I (1971-1975) relative risk estimates, obesity was associated with 161,290 excess deaths from cardiovascular causes, much more than the current estimate of 81,072.
Overweight was associated with no excess deaths from cardiovascular causes (-17,074, CI -50,407 to 16,259) or cancer (-13,533, CI -44364 to 17298), but significantly decreased deaths from all-other causes (-107674, CI -148738 to -66610). Underweight, in contrast, was associated with excess deaths from all-other causes (23,455, CI 11,848 to 35,061). Looking closer at the over-weight category, the authors did find that both overweight and obese individuals had excess deaths from kidney disease and diabetes.
This data adds significantly to their previous work, which demonstrated differences in all-cause mortality based on BMI. One interesting finding is that over-weight is associated with less all-cause mortality and no difference in cardiovascular mortality. Also, the data are notable for the apparent change in the excess cardiovascular deaths associated with obesity over time, perhaps reflecting improvements in medical care in recent years. These data are sure to bring commentaries on the statistical methods used, changes in BMI class over time as a consequence rather than cause of disease, concerns about cause of death reporting bias, etc. Nonetheless, this work is an important contribution to our current understanding of healthy body weight and the relationship between cardiovascular disease mortality and excess body weight.
Medications for COPD: A Review of Effectiveness - October 15, 2007 -- American Family Physician
Medications for COPD: A Review of Effectiveness - October 15, 2007 -- American Family Physician
Abstracts:
Chronic obstructive pulmonary disease (COPD) is a common problem among patients presenting to primary care. This condition has multiple individual and combined treatment regimens. The goals of treatment are to improve quality of life, exercise tolerance, sleep quality, and survival; and to reduce dyspnea, nocturnal symptoms, exacerbations, use of rescue medications, and hospitalizations. All patients benefit from bronchodilator medications as needed. Long-acting inhaled anticholinergics are probably more beneficial than short-acting formulations. Use of inhaled corticosteroids might benefit patients with mild COPD who have an inflammatory component or significant reversibility on spirometry. Patients with moderate to severe disease benefit from the use of long-acting inhaled anticholinergics, inhaled corticosteroids, and possibly a long-acting beta2 agonist or mucolytics. For rescue therapy, short-acting beta2 agonists or combination anticholinergics with a short-acting beta2 agonist should be used. Inhaled corticosteroids should be considered before initiating a long-acting beta2 agonist. Caution should be used if a long-acting beta2 agonist is discontinued before initiation of an inhaled corticosteroid because this may precipitate exacerbations. Evidence to support the use of mucolytics, oral theophylline, and oral corticosteroids is limited. Patients with severe hypoxemia (i.e., arterial oxygen pressure less than 55 mm Hg or oxygen saturation less than 88 percent) should be given continuous oxygen. (Am Fam Physician 2007;76:1141-8, 1151-2. Copyright © 2007 American Academy of Family Physicians.)
Abstracts:
Chronic obstructive pulmonary disease (COPD) is a common problem among patients presenting to primary care. This condition has multiple individual and combined treatment regimens. The goals of treatment are to improve quality of life, exercise tolerance, sleep quality, and survival; and to reduce dyspnea, nocturnal symptoms, exacerbations, use of rescue medications, and hospitalizations. All patients benefit from bronchodilator medications as needed. Long-acting inhaled anticholinergics are probably more beneficial than short-acting formulations. Use of inhaled corticosteroids might benefit patients with mild COPD who have an inflammatory component or significant reversibility on spirometry. Patients with moderate to severe disease benefit from the use of long-acting inhaled anticholinergics, inhaled corticosteroids, and possibly a long-acting beta2 agonist or mucolytics. For rescue therapy, short-acting beta2 agonists or combination anticholinergics with a short-acting beta2 agonist should be used. Inhaled corticosteroids should be considered before initiating a long-acting beta2 agonist. Caution should be used if a long-acting beta2 agonist is discontinued before initiation of an inhaled corticosteroid because this may precipitate exacerbations. Evidence to support the use of mucolytics, oral theophylline, and oral corticosteroids is limited. Patients with severe hypoxemia (i.e., arterial oxygen pressure less than 55 mm Hg or oxygen saturation less than 88 percent) should be given continuous oxygen. (Am Fam Physician 2007;76:1141-8, 1151-2. Copyright © 2007 American Academy of Family Physicians.)
Treatment of pulmonary embolism in critical illness
Treatment of pulmonary embolism in critical illness
A very helpful review appeared recently in Chest. Key points follow:
Assessment
Get a bigger bang for the buck with CT by measuring RV and LV diameters. RV/LV diameter ratios over 0.9 are concerning for right ventricular dysfunction.
Echocardiography is useful in the assessment of RV function.
Biomarkers (troponin, BNP, ProBNP) are potentially useful indicators of RV damage and wall stress. Given the shorter half life of BNP and ProBNP these markers are more useful than troponin for assessment of patient progress in real time. Q 12 hour determinations are suggested by the authors.
Assessment of RV function by any means is useful for assessing risk. Negative predictive power exceeds positive predictive power.
Hemodynamic support
Judicious volume infusion can improve RV function. Theoretical adverse effects of RV over distension are cited.
Norepinephrine is favored for vasopressor support. However, this is based largely on animal data. High level comparative clinical studies are not available.
Antithrombotic and antiembolic strategiesIntravenous anticoagulants are favored over subcutaneously administered anticoagulants if the patient is critically ill.
Concerning contraindications the authors state: Only rarely is anticoagulant treatment flatly contraindicated (eg, active hemorrhage in the brain or another vital organ, uncontrolled bleeding threatening tissue perfusion); but in those situations, consideration of prompt placement of a vena cava filter (see below) and clot removal (see above) should be undertaken.
The established indication for intravenous thrombolytic therapy is PE causing shock. Potential indications are deterioration despite standard treatment and normotensive patients with RV dysfunction.
Link: http://doctorrw.blogspot.com/
A very helpful review appeared recently in Chest. Key points follow:
Assessment
Get a bigger bang for the buck with CT by measuring RV and LV diameters. RV/LV diameter ratios over 0.9 are concerning for right ventricular dysfunction.
Echocardiography is useful in the assessment of RV function.
Biomarkers (troponin, BNP, ProBNP) are potentially useful indicators of RV damage and wall stress. Given the shorter half life of BNP and ProBNP these markers are more useful than troponin for assessment of patient progress in real time. Q 12 hour determinations are suggested by the authors.
Assessment of RV function by any means is useful for assessing risk. Negative predictive power exceeds positive predictive power.
Hemodynamic support
Judicious volume infusion can improve RV function. Theoretical adverse effects of RV over distension are cited.
Norepinephrine is favored for vasopressor support. However, this is based largely on animal data. High level comparative clinical studies are not available.
Antithrombotic and antiembolic strategiesIntravenous anticoagulants are favored over subcutaneously administered anticoagulants if the patient is critically ill.
Concerning contraindications the authors state: Only rarely is anticoagulant treatment flatly contraindicated (eg, active hemorrhage in the brain or another vital organ, uncontrolled bleeding threatening tissue perfusion); but in those situations, consideration of prompt placement of a vena cava filter (see below) and clot removal (see above) should be undertaken.
The established indication for intravenous thrombolytic therapy is PE causing shock. Potential indications are deterioration despite standard treatment and normotensive patients with RV dysfunction.
Link: http://doctorrw.blogspot.com/
Sunday, November 11, 2007
AHA - 2007: More Evidence of Cardiovascular Safety of Second-Generation Sulfonylureas
AHA: More Evidence of Cardiovascular Safety of Second-Generation Sulfonylureas
By Peggy Peck, Executive Editor, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor University of Pennsylvania School of Medicine.
November 09, 2007
Primary source: American Heart Association
Source reference:
Patch RK, et al "Treatment of diabetes and outcome after myocardial infarction: a community study" AHA Meeting 2007; Abstract 3588.
ORLANDO, Nov. 9 -- Diabetes patients who used second- generation sulfonylureas had no excess one-year mortality after a myocardial infarction, researchers said here.
A community study of patients treated for MI found that the 12-month survival for diabetes patients using second-generation sulfonylureas was about 95%, versus a one-year survival of 90% for non-diabetic MI patients (P0.001), Richard K. Patch, III, M.D., of the Mayo Clinic in Rochester, Minn., and colleagues, reported at the American Heart Association meeting.
Moreover, diabetes patients treated with second-generation sulfonylureas also had significantly better one-year survival than diabetes patients using diet alone or insulin (P0.001).
After adjusting for age, sex, reperfusion, and duration of diabetes, only use of insulin was associated with excess mortality and the risk was greatest among patients with the longest history of diabetes, he said. "There was no association between sulfonylurea use and excess mortality," he said.
The concern about increased cardiovascular mortality with sulfonylureas emerged in the early 1970s, when first-generation drugs in this class began to be widely used. The likely mechanism for increased mortality was the drug's ability to bind to adenosine triphospate-sensitive potassium channels in pancreatic beta cells -- ironically the same mechanism that made the drug effective in treating diabetes.
In pancreatic cells, binding ATP keeps the potassium channels closed, which triggers an influx of calcium ions into the cell, promoting increased release of insulin via exocytosis of insulin-containing granules.
The downside to the first-generation sulfonylurea drugs was that they were not specific to ATP-sensitive potassium channels in the pancreas, but also binded to ATP-sensitive potassium channels in heart cells and vascular smooth-muscle cells. In the heart and the vasculature, this binding action impairs coronary blood flow, which limits control of ischemic damage during myocardial infarction.
But studies of second-generation sulfonylureas have reported that the drugs may reduce the risk of MI.
Against that background, Dr. Patch and colleagues studied the question of the impact of second-generation sulfonylurea on survival following MI.
They analyzed outcomes data from 2,732 MIs that occurred in Olmsted County, Minn., from 1979 through 2002. The average age of patients was 70, and women made up 56% of the cohort.
Four hundred and eighty-six of the MI patients had diabetes and 24% of them used second-generation sulfonylureas, 47% used insulin, while 22% relied on diet alone for management of diabetes.
Five hundred and eight MI patients died within a year of the incident MI.
Compared with non-diabetic MI patients, patients with diabetes were more likely to be overweight or obese, hyperlipidemic, and to have received urgent reperfusion therapy during hospitalization for treatment of the incident MI.
By Peggy Peck, Executive Editor, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor University of Pennsylvania School of Medicine.
November 09, 2007
Primary source: American Heart Association
Source reference:
Patch RK, et al "Treatment of diabetes and outcome after myocardial infarction: a community study" AHA Meeting 2007; Abstract 3588.
ORLANDO, Nov. 9 -- Diabetes patients who used second- generation sulfonylureas had no excess one-year mortality after a myocardial infarction, researchers said here.
A community study of patients treated for MI found that the 12-month survival for diabetes patients using second-generation sulfonylureas was about 95%, versus a one-year survival of 90% for non-diabetic MI patients (P0.001), Richard K. Patch, III, M.D., of the Mayo Clinic in Rochester, Minn., and colleagues, reported at the American Heart Association meeting.
Moreover, diabetes patients treated with second-generation sulfonylureas also had significantly better one-year survival than diabetes patients using diet alone or insulin (P0.001).
After adjusting for age, sex, reperfusion, and duration of diabetes, only use of insulin was associated with excess mortality and the risk was greatest among patients with the longest history of diabetes, he said. "There was no association between sulfonylurea use and excess mortality," he said.
The concern about increased cardiovascular mortality with sulfonylureas emerged in the early 1970s, when first-generation drugs in this class began to be widely used. The likely mechanism for increased mortality was the drug's ability to bind to adenosine triphospate-sensitive potassium channels in pancreatic beta cells -- ironically the same mechanism that made the drug effective in treating diabetes.
In pancreatic cells, binding ATP keeps the potassium channels closed, which triggers an influx of calcium ions into the cell, promoting increased release of insulin via exocytosis of insulin-containing granules.
The downside to the first-generation sulfonylurea drugs was that they were not specific to ATP-sensitive potassium channels in the pancreas, but also binded to ATP-sensitive potassium channels in heart cells and vascular smooth-muscle cells. In the heart and the vasculature, this binding action impairs coronary blood flow, which limits control of ischemic damage during myocardial infarction.
But studies of second-generation sulfonylureas have reported that the drugs may reduce the risk of MI.
Against that background, Dr. Patch and colleagues studied the question of the impact of second-generation sulfonylurea on survival following MI.
They analyzed outcomes data from 2,732 MIs that occurred in Olmsted County, Minn., from 1979 through 2002. The average age of patients was 70, and women made up 56% of the cohort.
Four hundred and eighty-six of the MI patients had diabetes and 24% of them used second-generation sulfonylureas, 47% used insulin, while 22% relied on diet alone for management of diabetes.
Five hundred and eight MI patients died within a year of the incident MI.
Compared with non-diabetic MI patients, patients with diabetes were more likely to be overweight or obese, hyperlipidemic, and to have received urgent reperfusion therapy during hospitalization for treatment of the incident MI.
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