Thiazolidinediones and Cardiovascular Outcomes in Older Patients With Diabetes
Lorraine L. Lipscombe, MD, MSc; Tara Gomes, MHSc; Linda E. Lévesque, BScPhm, MSc; Janet E. Hux, MD, MSc; David N. Juurlink, BPhm, MD, PhD; David A. Alter, MD, PhD
JAMA. 2007;298(22):2634-2643.
Context Thiazolidinediones (TZDs), used to treat type 2 diabetes, are associated with an excess risk of congestive heart failure and possibly acute myocardial infarction. However, the association between TZD use and cardiovascular events has not been adequately evaluated on a population level.
Objective To explore the association between TZD therapy and congestive heart failure, acute myocardial infarction, and mortality compared with treatment with other oral hypoglycemic agents.
Design, Setting, and Patients Nested case-control analysis of a retrospective cohort study using health care databases in Ontario. We included diabetes patients aged 66 years or older treated with at least 1 oral hypoglycemic agent between 2002 and 2005 (N = 159 026) and followed them up until March 31, 2006.
Main Outcome Measures The primary outcome consisted of an emergency department visit or hospitalization for congestive heart failure; secondary outcomes were an emergency department visit or hospitalization for acute myocardial infarction and all-cause mortality. The risks of these events were compared between persons treated with TZDs (rosiglitazone and pioglitazone) and other oral hypoglycemic agent combinations, after matching and adjusting for prognostic factors.
Results During a median follow-up of 3.8 years, 12 491 patients (7.9%) had a hospital visit for congestive heart failure, 12 578 (7.9%) had a visit for acute myocardial infarction, and 30 265 (19%) died. Current treatment with TZD monotherapy was associated with a significantly increased risk of congestive heart failure (78 cases; adjusted rate ratio [RR], 1.60; 95% confidence interval [CI], 1.21-2.10; P < .001), acute myocardial infarction (65 cases; RR, 1.40; 95% CI, 1.05-1.86; P = .02), and death (102 cases; RR, 1.29; 95% CI, 1.02-1.62; P = .03) compared with other oral hypoglycemic agent combination therapies (3478 congestive heart failure cases, 3695 acute myocardial infarction cases, and 5529 deaths). The increased risk of congestive heart failure, acute myocardial infarction, and mortality associated with TZD use appeared limited to rosiglitazone.
Conclusion In this population-based study of older patients with diabetes, TZD treatment, primarily with rosiglitazone, was associated with an increased risk of congestive heart failure, acute myocardial infarction, and mortality when compared with other combination oral hypoglycemic agent treatments.
Showing posts with label Risks. Show all posts
Showing posts with label Risks. Show all posts
Wednesday, December 12, 2007
Tuesday, October 9, 2007
New Prediction Model To Guide Prevention Of Heart Disease
New Prediction Model To Guide Prevention Of Heart Disease
09 Oct 2007
A University of Rochester Medical Center researcher has been awarded a National Institutes of Health grant to study whether accounting for social risk factors, in addition to traditional predictors, can be useful in assessing patients' risk and ultimately preventing coronary heart disease.
Kevin A. Fiscella, M.D., M.P.H., associate professor in the Department of Family Medicine, was awarded $823,199 by the National Heart, Lung and Blood Institute, part of the NIH, to demonstrate that inclusion of social risk factors -- socioeconomic status, race, ethnicity and marital status -- into overall risk assessment and preventive treatment guidelines offers the potential for reducing disparities in coronary heart disease (CHD).
Traditional tools to make predictions -- indicators such as age and gender, whether a patient is a smoker, diabetic or has high blood pressure -- have been used for decades by health care professionals to calculate a patient's risk of heart disease, Fiscella said. Such predictions ultimately drive treatment.
A large body of research shows that a socioeconomic component also predicts risk in determining heart disease. Disparities in coronary heart disease mortality by socioeconomic status, race and ethnicity, have been extensively documented, but translating them into clinical practice to reduce CHD disparities has proven challenging and the data is not yet incorporated into formal health assessments, Fiscella said.
"We're proposing to modify the risk tools to include socioeconomic factors and calculate the impact on prediction. If you're less educated or make less money, you have a much higher risk of heart disease. An inaccurate estimate impacts what tests and therapies a patient receives, and when." As a result, more intensive behavioral interventions focusing on diet, exercise, smoking cessation and medical adherence may be implemented.
Fiscella's three-year study will use a database containing more than 30,000 adult patient cases representative of the nation's population. It will compare the performance of predicting risk using only existing tools, to a formula that incorporates socioeconomic factors with conventional tools. His team will determine whether persons of lower economic position could be more appropriately treated using an updated, supplemented risk model.
Risk scoring using traditional criteria is currently available electronically. When a physician sees a patient, their risk factor is determined with just a few clicks.
"If we're successful in validating our prediction model, in the future physicians may see it available through a paper version or through a handheld device," Fiscella said.
A handful of studies have been done in Europe regarding the issue of social risk factors. Findings show that adding social class into the equation of risk prediction models does help to identify those in a lower social class who are at higher risk of CHD, even in the UK, where there is universal health care access.
"We know intuitively that social risk factors have a significant impact on the care of a patient but no one has said how can we apply this to decision-making at the bedside."
Article adapted by Medical News Today from original press release.
Source: Karin Christensen University of Rochester Medical Center
09 Oct 2007
A University of Rochester Medical Center researcher has been awarded a National Institutes of Health grant to study whether accounting for social risk factors, in addition to traditional predictors, can be useful in assessing patients' risk and ultimately preventing coronary heart disease.
Kevin A. Fiscella, M.D., M.P.H., associate professor in the Department of Family Medicine, was awarded $823,199 by the National Heart, Lung and Blood Institute, part of the NIH, to demonstrate that inclusion of social risk factors -- socioeconomic status, race, ethnicity and marital status -- into overall risk assessment and preventive treatment guidelines offers the potential for reducing disparities in coronary heart disease (CHD).
Traditional tools to make predictions -- indicators such as age and gender, whether a patient is a smoker, diabetic or has high blood pressure -- have been used for decades by health care professionals to calculate a patient's risk of heart disease, Fiscella said. Such predictions ultimately drive treatment.
A large body of research shows that a socioeconomic component also predicts risk in determining heart disease. Disparities in coronary heart disease mortality by socioeconomic status, race and ethnicity, have been extensively documented, but translating them into clinical practice to reduce CHD disparities has proven challenging and the data is not yet incorporated into formal health assessments, Fiscella said.
"We're proposing to modify the risk tools to include socioeconomic factors and calculate the impact on prediction. If you're less educated or make less money, you have a much higher risk of heart disease. An inaccurate estimate impacts what tests and therapies a patient receives, and when." As a result, more intensive behavioral interventions focusing on diet, exercise, smoking cessation and medical adherence may be implemented.
Fiscella's three-year study will use a database containing more than 30,000 adult patient cases representative of the nation's population. It will compare the performance of predicting risk using only existing tools, to a formula that incorporates socioeconomic factors with conventional tools. His team will determine whether persons of lower economic position could be more appropriately treated using an updated, supplemented risk model.
Risk scoring using traditional criteria is currently available electronically. When a physician sees a patient, their risk factor is determined with just a few clicks.
"If we're successful in validating our prediction model, in the future physicians may see it available through a paper version or through a handheld device," Fiscella said.
A handful of studies have been done in Europe regarding the issue of social risk factors. Findings show that adding social class into the equation of risk prediction models does help to identify those in a lower social class who are at higher risk of CHD, even in the UK, where there is universal health care access.
"We know intuitively that social risk factors have a significant impact on the care of a patient but no one has said how can we apply this to decision-making at the bedside."
Article adapted by Medical News Today from original press release.
Source: Karin Christensen University of Rochester Medical Center
Wednesday, August 8, 2007
Warfarin: Prescribe with Care in the Elderly
Journal Watch CardiologyJune 13, 2007
Warfarin: Prescribe with Care in the Elderly
Mark S. Link, MD
Journal Watch. 2007;6(6) ©2007 Massachusetts Medical Society
In a real-world cohort of elderly patients, the hazards of warfarin therapy were found to be greater than previously reported.
Summary
Randomized controlled trials have shown that warfarin significantly reduces the risk for stroke in patients with atrial fibrillation. Therefore, warfarin has become a standard component of the armamentarium for patients with AF and a CHADS2 (congestive heart failure, hypertension, age ≥75, diabetes, previous stroke or transient ischemic attack) score of 1 or 2 (depending on individual patient characteristics) or higher. However, these trials have generally included few individuals older than 80, and the investigators may have preselected, whether by design or unintentionally, participants at a lower risk for bleeding during warfarin treatment. Recently, researchers at an anticoagulation clinic studied a real-world cohort of 472 patients (including 153 aged ≥ 80 years) who were taking warfarin. Prospectively tracked outcomes were major hemorrhage, time to discontinuation of warfarin, and physician-stated reason for warfarin termination.
Within 1 year, 26 patients experienced a major hemorrhage. Patients aged ≥80 years had a markedly increased risk for major hemorrhage (13.10 events per 100 person-years, vs. 4.75 per 100 person-years in patients aged <80>
Comment
Prevention of cerebrovascular accidents in elderly patients with AF is an important and laudable goal. Unfortunately, the hazards of prophylactic warfarin are heightened by advanced age, recent initiation, and higher INRs. Aspirin use, a predisposition to falls, and frailty are also likely to increase the risk for hemorrhage. An accompanying editorial emphasizes the difficulties of treating AF in the elderly and the apparent increase in major bleeding reported in recent trials. Careful analysis of the risks and benefits of anticoagulation is essential in managing such patients.
References:
Hylek EM et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007 May 29; 115:2689-96.
Wyse DG. Bleeding while starting anticoagulation for thromboembolism prophylaxis in elderly patients with atrial fibrillation: From bad to worse. Circulation 2007 May 29; 115:2684-6.
Warfarin: Prescribe with Care in the Elderly
Mark S. Link, MD
Journal Watch. 2007;6(6) ©2007 Massachusetts Medical Society
In a real-world cohort of elderly patients, the hazards of warfarin therapy were found to be greater than previously reported.
Summary
Randomized controlled trials have shown that warfarin significantly reduces the risk for stroke in patients with atrial fibrillation. Therefore, warfarin has become a standard component of the armamentarium for patients with AF and a CHADS2 (congestive heart failure, hypertension, age ≥75, diabetes, previous stroke or transient ischemic attack) score of 1 or 2 (depending on individual patient characteristics) or higher. However, these trials have generally included few individuals older than 80, and the investigators may have preselected, whether by design or unintentionally, participants at a lower risk for bleeding during warfarin treatment. Recently, researchers at an anticoagulation clinic studied a real-world cohort of 472 patients (including 153 aged ≥ 80 years) who were taking warfarin. Prospectively tracked outcomes were major hemorrhage, time to discontinuation of warfarin, and physician-stated reason for warfarin termination.
Within 1 year, 26 patients experienced a major hemorrhage. Patients aged ≥80 years had a markedly increased risk for major hemorrhage (13.10 events per 100 person-years, vs. 4.75 per 100 person-years in patients aged <80>
Comment
Prevention of cerebrovascular accidents in elderly patients with AF is an important and laudable goal. Unfortunately, the hazards of prophylactic warfarin are heightened by advanced age, recent initiation, and higher INRs. Aspirin use, a predisposition to falls, and frailty are also likely to increase the risk for hemorrhage. An accompanying editorial emphasizes the difficulties of treating AF in the elderly and the apparent increase in major bleeding reported in recent trials. Careful analysis of the risks and benefits of anticoagulation is essential in managing such patients.
References:
Hylek EM et al. Major hemorrhage and tolerability of warfarin in the first year of therapy among elderly patients with atrial fibrillation. Circulation 2007 May 29; 115:2689-96.
Wyse DG. Bleeding while starting anticoagulation for thromboembolism prophylaxis in elderly patients with atrial fibrillation: From bad to worse. Circulation 2007 May 29; 115:2684-6.
Saturday, July 7, 2007
QRISK accurately predicts cardiovascular risk
QRISK accurately predicts cardiovascular risk
06 July 2007
Br Med J 2007; Advance online publication
MedWire News:
The cardiovascular disease risk score QRISK identifies people at risk more accurately than the Framingham model or the Scottish score ASSIGN, say UK researchers.
"QRISK includes additional variables that allow better tailoring of management to the individual patient and will help minimize health inequalities," the authors write in an advance online publication by the British Medical Journal.
Julia Hippisley-Cox (University of Nottingham) and colleagues derived a new cardiovascular risk score, the QRISK, and validated its performance against the Framingham algorithm and the ASSIGN score.
The derivation cohort consisted of 1.28 million patients, aged 35-74 years, who were free of diabetes and cardiovascular disease, and registered at 318 practices between 1995 and 2007. The validation cohort consisted of 0.61 million patients from 160 practices.
The Framingham algorithm over-predicted cardiovascular disease risk at 10 years by 35%, ASSIGN by 36%, and QRISK by 0.4%.
QRISK predicted 8.5% of patients aged 35-74 years to be at high risk compared with predictions of 12.8% for the Framingham algorithm and 14.0% for ASSIGN.
Using QRISK, 34.5% of women and 72.9% of men aged 64-75 years were considered at high risk compared with 24.1% and 86.0%, respectively, using the Framingham model.
"Measures of discrimination tended to be higher for QRISK than for the Framingham algorithm and it was better calibrated to the UK population than either the Framingham or ASSIGN models," the team comments.
UK estimates based on QRISK give 3.2 million patients as being at high risk, 4.7 million based on the Framingham algorithm, and 5.1 million with ASSIGN.
Overall, 9% of the patients would be reclassified as being high-to-low risk or vice versa using QRISK, compared with the Framingham algorithm.
Hippisley-Cox et al conclude: "We think that QRISK is likely to provide more appropriate estimates of cardiovascular disease risk in contemporary UK populations and better discriminate those at high risk on the basis of their age, sex, and social deprivation as well as existing antihypertensive treatment.
"It is likely therefore to be a more equitable tool to inform patient management decisions."
Luc Bonneux (Netherlands Interdisciplinary Demographic Institute, The Hague) commented in a related editorial: "There is little medical of scientific justification that risk calculations with arbitrary thresholds should supersede informed choice. Absolute risk scores do not offer an easy escape from moral choices."
Journal
Thursday, June 14, 2007
Unanimous "No" to Rimonabant: Safety Not Demonstrated, FDA Advisory Panel Says
Heartwire 2007. © 2007 Medscape
June 13, 2007 (Silver Spring, MD) - In a blow to the drug maker, as well as millions of overweight and obese Americans hoping for a new weight-loss medication, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted unanimously to send Sanofi-Aventis back to gather more detailed safety information about rimonabant over the long term, in larger patient numbers.
After a day of discussion and presentations, all 14 members of the advisory committee agreed that rimonabant did not demonstrate a risk/benefit profile to enable it to be approved for the indication the sponsor was seeking: weight management in individuals with a body-mass index of >30 kg/m2 or in individuals with a BMI of >27 kg/m2 when accompanied by at least one comorbid condition.
The committee's concerns centered on what many concluded was a "clear" signal of increased risk of neurological side effects—seizures, depression, anxiety, aggressiveness, and suicidal thoughts among patients randomized to rimonabant. Many were also concerned about the low number of patients—441 in total—who had actually been taking the 20-mg dose for out to two years. Several panel members stated that even current, ongoing studies of rimonabant, including the CRESCENDO study, are not appropriately designed to clarify the types of adverse events occurring in people taking the drug.
A more detailed report on the rimonabant hearing will be posted by heartwire on Thursday.
June 13, 2007 (Silver Spring, MD) - In a blow to the drug maker, as well as millions of overweight and obese Americans hoping for a new weight-loss medication, the FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted unanimously to send Sanofi-Aventis back to gather more detailed safety information about rimonabant over the long term, in larger patient numbers.
After a day of discussion and presentations, all 14 members of the advisory committee agreed that rimonabant did not demonstrate a risk/benefit profile to enable it to be approved for the indication the sponsor was seeking: weight management in individuals with a body-mass index of >30 kg/m2 or in individuals with a BMI of >27 kg/m2 when accompanied by at least one comorbid condition.
The committee's concerns centered on what many concluded was a "clear" signal of increased risk of neurological side effects—seizures, depression, anxiety, aggressiveness, and suicidal thoughts among patients randomized to rimonabant. Many were also concerned about the low number of patients—441 in total—who had actually been taking the 20-mg dose for out to two years. Several panel members stated that even current, ongoing studies of rimonabant, including the CRESCENDO study, are not appropriately designed to clarify the types of adverse events occurring in people taking the drug.
A more detailed report on the rimonabant hearing will be posted by heartwire on Thursday.
Preoperative Hematocrit Linked with Postoperative Outcome in Older Patients
Physician's First Watch for June 13, 2007
David G. Fairchild, MD, MPH, Editor-in-Chief
Preoperative Hematocrit Linked with Postoperative Outcome in Older Patients
In older patients, preoperative hematocrit levels outside the normal range are associated with higher mortality after noncardiac surgery, a study in JAMA finds.
Researchers examined Veterans Health Administration data from some 310,000 mostly male patients aged at least 65 years who underwent major noncardiac surgery. They stratified the cohort by preoperative hematocrit level and then determined 30-day postoperative mortality.
The 30-day mortality for the entire cohort was 3.9%. Patients with preoperative anemia (hematocrit levels <39.0%)>for each percentage-point departure from the normal range.
Editorialists highlight the strengths of the large observational database used in this study, but write that clinicians should not use these findings "to justify interventions — use of transfusion, erythropoietic agents, iron supplementation — outside the research setting."
JAMA article (Free)
JAMA editorial (Subscription required)
David G. Fairchild, MD, MPH, Editor-in-Chief
Preoperative Hematocrit Linked with Postoperative Outcome in Older Patients
In older patients, preoperative hematocrit levels outside the normal range are associated with higher mortality after noncardiac surgery, a study in JAMA finds.
Researchers examined Veterans Health Administration data from some 310,000 mostly male patients aged at least 65 years who underwent major noncardiac surgery. They stratified the cohort by preoperative hematocrit level and then determined 30-day postoperative mortality.
The 30-day mortality for the entire cohort was 3.9%. Patients with preoperative anemia (hematocrit levels <39.0%)>for each percentage-point departure from the normal range.
Editorialists highlight the strengths of the large observational database used in this study, but write that clinicians should not use these findings "to justify interventions — use of transfusion, erythropoietic agents, iron supplementation — outside the research setting."
JAMA article (Free)
JAMA editorial (Subscription required)
Tuesday, June 12, 2007
Cardiovascular Disease and Subsequent Kidney Disease
Cardiovascular Disease and Subsequent Kidney Disease
Essam F. Elsayed, MD; Hocine Tighiouart, MS; John Griffith, PhD; Tobias Kurth, MD, ScD; Andrew S. Levey, MD; Deeb Salem, MD; Mark J. Sarnak, MD, MS; Daniel E. Weiner, MD, MS
Arch Intern Med. 2007;167:1130-1136.
ABSTRACT
Background
Chronic kidney disease is a risk factor for cardiovascular disease (CVD); however, it is uncertain if CVD is a risk factor for progression or development of kidney disease.
Methods
Individual patient data were pooled from 2 longitudinal, community-based, limited-access studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Baseline CVD was defined by stroke, angina, claudication, transient ischemic attack, coronary angioplasty or bypass, and recognized or silent myocardial infarction. Study outcomes included kidney function decline, defined by an increase in serum creatinine level of at least 0.4 mg/dL (35.4 µmol/L), and development of kidney disease, defined by an increase in serum creatinine level of at least 0.4 mg/dL (35.4 µmol/L) in which the baseline serum creatinine level was less than 1.4 mg/dL (<123.8 µmol/L) in men and less than 1.2 mg/dL (<106.1 µmol/L) in women and the final serum creatinine levels exceeded these levels. Secondarily, kidney function decline was defined by an estimated glomerular filtration rate (eGFR) reduction of at least 15 mL/min per 1.73 m2, and development of kidney disease was defined by an eGFR reduction of at least 15 mL/min per 1.73 m2 in which the baseline eGFR was at least 60 mL/min per 1.73 m2 and the final eGFR was below these levels. Multivariate logistic regression analysis was used to determine the association between CVD and outcomes.
Results
Among 13 826 individuals, the mean ± SD baseline serum creatinine level was 0.9 ± 0.2 mg/dL (79.6 ± 17.7 µmol/L), and the mean ± SD baseline eGFR was 89.8 ± 20.1 mL/min per 1.73 m2. In serum creatinine level–based models, 520 individuals (3.8%) experienced kidney function decline, and 314 individuals (2.3%) developed kidney disease during a mean ± SD of 9.3 ± 0.9 years of follow-up. Baseline CVD, present in 1787 individuals (12.9%), was associated with an increased risk of all outcomes (odds ratio, 1.70; 95% confidence interval, 1.36-2.13), an odds ratio of 1.75 (95% confidence interval, 1.32-2.32) for serum creatinine level, and odds ratios of 1.28 (95% confidence interval, 1.13-1.45) and 1.54 (95% confidence interval, 1.26-1.89) for eGFR for kidney function decline and development of kidney disease, respectively.
Conclusion
Cardiovascular disease is independently associated with kidney function decline and with the development of kidney disease.
Essam F. Elsayed, MD; Hocine Tighiouart, MS; John Griffith, PhD; Tobias Kurth, MD, ScD; Andrew S. Levey, MD; Deeb Salem, MD; Mark J. Sarnak, MD, MS; Daniel E. Weiner, MD, MS
Arch Intern Med. 2007;167:1130-1136.
ABSTRACT
Background
Chronic kidney disease is a risk factor for cardiovascular disease (CVD); however, it is uncertain if CVD is a risk factor for progression or development of kidney disease.
Methods
Individual patient data were pooled from 2 longitudinal, community-based, limited-access studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Baseline CVD was defined by stroke, angina, claudication, transient ischemic attack, coronary angioplasty or bypass, and recognized or silent myocardial infarction. Study outcomes included kidney function decline, defined by an increase in serum creatinine level of at least 0.4 mg/dL (35.4 µmol/L), and development of kidney disease, defined by an increase in serum creatinine level of at least 0.4 mg/dL (35.4 µmol/L) in which the baseline serum creatinine level was less than 1.4 mg/dL (<123.8 µmol/L) in men and less than 1.2 mg/dL (<106.1 µmol/L) in women and the final serum creatinine levels exceeded these levels. Secondarily, kidney function decline was defined by an estimated glomerular filtration rate (eGFR) reduction of at least 15 mL/min per 1.73 m2, and development of kidney disease was defined by an eGFR reduction of at least 15 mL/min per 1.73 m2 in which the baseline eGFR was at least 60 mL/min per 1.73 m2 and the final eGFR was below these levels. Multivariate logistic regression analysis was used to determine the association between CVD and outcomes.
Results
Among 13 826 individuals, the mean ± SD baseline serum creatinine level was 0.9 ± 0.2 mg/dL (79.6 ± 17.7 µmol/L), and the mean ± SD baseline eGFR was 89.8 ± 20.1 mL/min per 1.73 m2. In serum creatinine level–based models, 520 individuals (3.8%) experienced kidney function decline, and 314 individuals (2.3%) developed kidney disease during a mean ± SD of 9.3 ± 0.9 years of follow-up. Baseline CVD, present in 1787 individuals (12.9%), was associated with an increased risk of all outcomes (odds ratio, 1.70; 95% confidence interval, 1.36-2.13), an odds ratio of 1.75 (95% confidence interval, 1.32-2.32) for serum creatinine level, and odds ratios of 1.28 (95% confidence interval, 1.13-1.45) and 1.54 (95% confidence interval, 1.26-1.89) for eGFR for kidney function decline and development of kidney disease, respectively.
Conclusion
Cardiovascular disease is independently associated with kidney function decline and with the development of kidney disease.
Thursday, June 7, 2007
Cardiac Mortality Drop Attributed to Therapies and Risk Factor Reductions
Cardiac Mortality Drop Attributed to Therapies and Risk Factor Reductions
By Neil Osterweil, Senior Associate Editor, MedPage TodayReviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco June 06, 2007
ATLANTA, June 6 -- Credit for the near halving of the rate of coronary disease deaths in the U.S, from 1980 to 2000, belongs equally to reductions in risk factors and to the rise of evidence-based therapies, found CDC and British researchers.
There were 341,745 fewer deaths from coronary heart disease in 2000 than in 1980, and about 47% of that decline can be attributed to primary and secondary medical therapies and interventions, they reported in the June 7 issue of the New England Journal of Medicine.
Reductions in risk factors such as smoking, high cholesterol, hypertension and inactivity get the nod for an additional 44% of the drop in coronary heart disease mortality, according to Earl S. Ford, M.D., M.P.H., of the National Center for Chronic Disease Prevention and Health Promotion, and colleagues.
But they also found that two major factors prevented the decreases in deaths from being even greater.
Our analysis estimated that increases in the body-mass index accounted overall for about 26,000 additional deaths from coronary heart disease in 2000, and increases in the prevalence of diabetes for about 33,500 additional deaths; both figures are consistent with the results of other recent studies they wrote. "Efforts to address these two risk factors should therefore receive particular attention in future measures to improve the public health."
The investigators used a previously validated statistical model called IMPACT to analyze the relative contributions of risk factor reduction, medical therapies, and interventions such as coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty to the decline in coronary disease-related deaths. The analyses were conducted at the University of Liverpool in England.
The difference between the expected and actual number of deaths from coronary heart disease in 2000 versus 1980 was distributed proportionally among the various treatments and risk factors included in the analyses.
They employed primarily data sources that were specific to the U.S. population, using the most up-to-date, least biased, and most representative sources whenever possible.
They found that the age-adjusted death rate for coronary heart disease among men fell from 542.9 deaths per 100,000 in 1980 to 266.8 per 100,000 in 2000. Among women, the rate fell from 263.3 per 100,000 in 1980 to 134.4 deaths per 100,000 in 2000. The total difference in observed vs. expected deaths in 2000 was 341,745.
About 47% of the decrease (159,330 fewer deaths) was attributed to treatments as follows:
Secondary preventive therapies after myocardial infarction or revascularization, 11%,
Initial treatments for acute myocardial infarction or unstable angina 10%,
Treatments for heart failure, 9%,
Revascularization for chronic angina, 5%,
Other therapies 12%.
In additional 44% of the drop could be attributed to the following changes in risk factors (numbers represent percentage of total reduction, and overlap):
Reductions in total cholesterol, 24%,
Decrease in systolic blood pressure, 20%,
Decline in smoking prevalence, 12%,
Reduction in physical inactivity, 5%.
Progress in risk factor reductions was partially offset, however, by an 8% increase in body-mass index over the two decades, by a 10% rise in the prevalence of diabetes, the authors noted.
"Irrespective of the assumptions used, we found that the largest contributions from medical therapies consistently came from secondary prevention, followed by treatments for acute coronary syndromes, then heart failure," they wrote. "Revascularization by means of CABG or angioplasty for stable or unstable disease together accounted for approximately 7% of the overall drop in deaths from coronary heart disease, a finding that is consistent with the results of previous studies in the United States and elsewhere."
They noted that possible study limitations included the use of data from various sources, including some studies that might have been limited by ethnic, geographic, or selections biases. They also noted that most of varying quality o and the averaging of interactions across broad groups, although the analyses were limited only to reductions in deaths, and did not include quality-of-life measures.
Funding source for the study was not specified. The authors reported that they had no conflicts of interest.
Primary source: New England Journal of Medicine
Source reference:
Ford ES et al.
Explaining the Decrease in U.S. Deaths from Coronary Disease, 1980-2000. N Engl J Med 2007;356:2388-98.
By Neil Osterweil, Senior Associate Editor, MedPage TodayReviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco June 06, 2007
ATLANTA, June 6 -- Credit for the near halving of the rate of coronary disease deaths in the U.S, from 1980 to 2000, belongs equally to reductions in risk factors and to the rise of evidence-based therapies, found CDC and British researchers.
There were 341,745 fewer deaths from coronary heart disease in 2000 than in 1980, and about 47% of that decline can be attributed to primary and secondary medical therapies and interventions, they reported in the June 7 issue of the New England Journal of Medicine.
Reductions in risk factors such as smoking, high cholesterol, hypertension and inactivity get the nod for an additional 44% of the drop in coronary heart disease mortality, according to Earl S. Ford, M.D., M.P.H., of the National Center for Chronic Disease Prevention and Health Promotion, and colleagues.
But they also found that two major factors prevented the decreases in deaths from being even greater.
Our analysis estimated that increases in the body-mass index accounted overall for about 26,000 additional deaths from coronary heart disease in 2000, and increases in the prevalence of diabetes for about 33,500 additional deaths; both figures are consistent with the results of other recent studies they wrote. "Efforts to address these two risk factors should therefore receive particular attention in future measures to improve the public health."
The investigators used a previously validated statistical model called IMPACT to analyze the relative contributions of risk factor reduction, medical therapies, and interventions such as coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty to the decline in coronary disease-related deaths. The analyses were conducted at the University of Liverpool in England.
The difference between the expected and actual number of deaths from coronary heart disease in 2000 versus 1980 was distributed proportionally among the various treatments and risk factors included in the analyses.
They employed primarily data sources that were specific to the U.S. population, using the most up-to-date, least biased, and most representative sources whenever possible.
They found that the age-adjusted death rate for coronary heart disease among men fell from 542.9 deaths per 100,000 in 1980 to 266.8 per 100,000 in 2000. Among women, the rate fell from 263.3 per 100,000 in 1980 to 134.4 deaths per 100,000 in 2000. The total difference in observed vs. expected deaths in 2000 was 341,745.
About 47% of the decrease (159,330 fewer deaths) was attributed to treatments as follows:
Secondary preventive therapies after myocardial infarction or revascularization, 11%,
Initial treatments for acute myocardial infarction or unstable angina 10%,
Treatments for heart failure, 9%,
Revascularization for chronic angina, 5%,
Other therapies 12%.
In additional 44% of the drop could be attributed to the following changes in risk factors (numbers represent percentage of total reduction, and overlap):
Reductions in total cholesterol, 24%,
Decrease in systolic blood pressure, 20%,
Decline in smoking prevalence, 12%,
Reduction in physical inactivity, 5%.
Progress in risk factor reductions was partially offset, however, by an 8% increase in body-mass index over the two decades, by a 10% rise in the prevalence of diabetes, the authors noted.
"Irrespective of the assumptions used, we found that the largest contributions from medical therapies consistently came from secondary prevention, followed by treatments for acute coronary syndromes, then heart failure," they wrote. "Revascularization by means of CABG or angioplasty for stable or unstable disease together accounted for approximately 7% of the overall drop in deaths from coronary heart disease, a finding that is consistent with the results of previous studies in the United States and elsewhere."
They noted that possible study limitations included the use of data from various sources, including some studies that might have been limited by ethnic, geographic, or selections biases. They also noted that most of varying quality o and the averaging of interactions across broad groups, although the analyses were limited only to reductions in deaths, and did not include quality-of-life measures.
Funding source for the study was not specified. The authors reported that they had no conflicts of interest.
Primary source: New England Journal of Medicine
Source reference:
Ford ES et al.
Explaining the Decrease in U.S. Deaths from Coronary Disease, 1980-2000. N Engl J Med 2007;356:2388-98.
Tuesday, June 5, 2007
Coronary Heart Disease (CHD)--One or Several Diseases?
[This article proposes an alternative causation for the emergence and decline of the coronary heart disease "epidemic" experienced by many developed countries. A consistent explanation by the authors addressing the emergence of CHD in developing countries would be that many populations of developing countries have had high prevalence of infectious diseases and malnutrition which has created a vulnerability to CHD when these people later in their lives are exposed to tobacco smoking and other risky behaviors.]
Title: Coronary Heart Disease (CHD)--One or Several Diseases?
Author: MI Azambuja, R Levins
Reference: Perspectives in Biology and Medicine 2007; 50(2): 228,
http://muse.jhu.edu/journals/perspectives_in_biology_and_medicine/toc/pbm50.2.html
Reviewer: Carlos Mendoza Montano, PhD, APRECOR, Guatemala, ProCOR contributing editor, e-mail: projhouse@intelnet.net.gt
The current article presents an interesting perspective about the causation of CHD. It revisits evidence that may have been overlooked or misinterpreted during the heights of the CHD epidemic in the United States and other developed countries due to the prevalent framework of multicausality, and the hegemony of the lipid over alternative hypotheses to CHD causation. The authors of the article propose a fresh look at some old evidence which leads to new ways of thinking about CHD, its trends and its causes, and new ways of thinking about chronic disease occurrence in general.
According to the multifactorial model of causality, CHD is conceived as resulting from possible alternative and interconnected chains of exposures component causes) that would eventually become sufficient to initiate the disease in an individual. Azambuja and Levins argue that, 40 years after its introduction, we still lack a sound biologic theory to explain the development of CHD and its progression to death, which allows them to question both this causal model and the degenerative idea behind it.
The article pointed out that during the rise in CHD mortality (1931-1935), the odds of finding hypertensive disease among cases of CHD was 5:1. In 1951-1955, the degree of atherosclerosis in males from all age categories was considerably greater, but the odds of finding hypertensive disease among cases had reversed to 1:2.5. Since there is no reason for assuming that the incidence of hypertensive disease had significantly decreased over this period, the authors felt justified in concluding that these findings indicate a considerable increase in CHD that is independent of hypertension as a factor in its pathogenesis. During the 20th century, then, the profile of the CHD cases varied from the pre-epidemic period (until the 1920s and 1930s) to the height of the epidemic period (1950s and 1960s), and again during the decline in CHD mortality (1980s to date). Cases described during the pre- and post-epidemic periods were mostly associated with "inflammation" and an individual phenotype suggestive of insulin-resistance (obesity, diabetes), hypertension, and/or smoking. During the epidemic period, hypercholesterolemia became the hallmark of CHD cases. The authors wondered how these trends should be interpreted.
Azambuja and Levins conceive CHD as encompassing different diseases associated with vulnerabilities and triggers with varying distributions over time and space. Therefore, they suggest that changes in CHD features accompanying the changes in CHD occurrence resulted from expansions and retractions of sub-populations of CHD cases over time. According to them, the steep rise in CHD mortality seen after the 1920s resulted from a huge expansion of a particular subpopulation of cases, characterized by high cholesterol levels and high case fatality.
While individual vulnerability is routinely considered in modeling infectious diseases, it is frequently ignored with respect to chronic diseases. Vulnerability to chronic "degenerative" diseases is usually conceived as a genetic attribute and, as such, not subject to short-term variation. Over the past years, different pathways have been postulated that could change individuals phenotypically and favor vulnerability to chronic diseases and CHD, including autoimmunity upon infection, metabolic reprogramming upon infection, and metabolic reprogramming associated with nongenomic mechanisms of inheritance. An alternative explanation of the huge expansion of a specific subpopulation of CHD cases occurring from the 1920s to the 1960s could depend not as much on changes in exposure to CHD risk factors as on an acquired window of vulnerability to the disease opened in the middle of the 20th century.
The article pointed out that during the rise in CHD mortality (1931-1935), the odds of finding hypertensive disease among cases of CHD was 5:1. In 1951-1955, the degree of atherosclerosis in males from all age categories was considerably greater, but the odds of finding hypertensive disease among cases had reversed to 1:2.5. Since there is no reason for assuming that the incidence of hypertensive disease had significantly decreased over this period, the authors felt justified in concluding that these findings indicate a considerable increase in CHD that is independent of hypertension as a factor in its pathogenesis. During the 20th century, then, the profile of the CHD cases varied from the pre-epidemic period (until the 1920s and 1930s) to the height of the epidemic period (1950s and 1960s), and again during the decline in CHD mortality (1980s to date). Cases described during the pre- and post-epidemic periods were mostly associated with "inflammation" and an individual phenotype suggestive of insulin-resistance (obesity, diabetes), hypertension, and/or smoking. During the epidemic period, hypercholesterolemia became the hallmark of CHD cases. The authors wondered how these trends should be interpreted.
Azambuja and Levins conceive CHD as encompassing different diseases associated with vulnerabilities and triggers with varying distributions over time and space. Therefore, they suggest that changes in CHD features accompanying the changes in CHD occurrence resulted from expansions and retractions of sub-populations of CHD cases over time. According to them, the steep rise in CHD mortality seen after the 1920s resulted from a huge expansion of a particular subpopulation of cases, characterized by high cholesterol levels and high case fatality.
While individual vulnerability is routinely considered in modeling infectious diseases, it is frequently ignored with respect to chronic diseases. Vulnerability to chronic "degenerative" diseases is usually conceived as a genetic attribute and, as such, not subject to short-term variation. Over the past years, different pathways have been postulated that could change individuals phenotypically and favor vulnerability to chronic diseases and CHD, including autoimmunity upon infection, metabolic reprogramming upon infection, and metabolic reprogramming associated with nongenomic mechanisms of inheritance. An alternative explanation of the huge expansion of a specific subpopulation of CHD cases occurring from the 1920s to the 1960s could depend not as much on changes in exposure to CHD risk factors as on an acquired window of vulnerability to the disease opened in the middle of the 20th century.
The article postulates that both hypercholesterolemia and coronary thrombosis reported frequently among the CHD cases registered from the 1920s to the 1960s were secondary to an autoimmune response to influenza (re)infection developed among a specific subgroup of vulnerable individuals (those 15 to 45 years old in 1918) marked by the 1918 influenza pandemic virus. This vulnerability may be due to autoimmune disruption of low-density lipoprotein-receptor interactions.
One subgroup of CHD cases, however, has grown since the 1980s: that associated with inflammation and insulin resistance. The growth of this subtype of CHD cases does not seem to be merely relative or secondary to the impressive fall in the number of hypercholesterolemic cases. We need to ask what caused the emergence of the vulnerable (insulin-resistant) phenotype underlying the rising rates of obesity, diabetes, and their associated pool of CHD cases in the population. An important contribution may come from Barker\'s hypothesis and from other theories of nongenetic inheritance of vulnerability across generations. Evidence suggests that the interaction of genes and the pre- and postnatal environments, against a heterogeneous background of vulnerability, could operate to produce metabolic programming effects across generations and result in obesity, diabetes, and cardiovascular diseases later in life.
Comments: This article proposes an alternative causation for the emergence and decline of the CHD "epidemic" experienced by many developed countries during the 20th century. The authors of the article did not address the emergence of CHD currently observed in most developing countries, although a consistent explanation with their argument would be that many populations of developing countries have had high prevalence of infectious diseases and malnutrition which has created a vulnerability to CHD when these people later in their lives are exposed to tobacco smoking and other risky behaviors.
Another issue not addressed in the article is the implications of the proposed theory of CVD causation on the prevention of CHD. The cornerstone of CHD prevention and control is the reduction of traditional risk factors such as blood cholesterol and hypertension. These prevention strategies have proved to be very effective to prevent or delay the onset of CVD outcomes in diverse populations of the world and many studies have indicated that the reduction of CHD mortality rates observed in many countries was associated to the reduction of mean cholesterol levels, fat consumption and other risk factors of populations. It would be interesting that Azambuja and Levins discuss these issues to reconcile their theory with the large evidence regarding effective CHD prevention.
The article postulates that both hypercholesterolemia and coronary thrombosis reported frequently among the CHD cases registered from the 1920s to the 1960s were secondary to an autoimmune response to influenza (re)infection developed among a specific subgroup of vulnerable individuals (those 15 to 45 years old in 1918) marked by the 1918 influenza pandemic virus. This vulnerability may be due to autoimmune disruption of low-density lipoprotein-receptor interactions.
One subgroup of CHD cases, however, has grown since the 1980s: that associated with inflammation and insulin resistance. The growth of this subtype of CHD cases does not seem to be merely relative or secondary to the impressive fall in the number of hypercholesterolemic cases. We need to ask what caused the emergence of the vulnerable (insulin-resistant) phenotype underlying the rising rates of obesity, diabetes, and their associated pool of CHD cases in the population. An important contribution may come from Barker's hypothesis and from other theories of nongenetic inheritance of vulnerability across generations. Evidence suggests that the interaction of genes and the pre- and postnatal environments, against a heterogeneous background of vulnerability, could operate to produce metabolic programming effects across generations and result in obesity, diabetes, and cardiovascular diseases later in life.
Comments: This article proposes an alternative causation for the emergence and decline of the CHD "epidemic" experienced by many developed countries during the 20th century. The authors of the article did not address the emergence of CHD currently observed in most developing countries, although a consistent explanation with their argument would be that many populations of developing countries have had high prevalence of infectious diseases and malnutrition which has created a vulnerability to CHD when these people later in their lives are exposed to tobacco smoking and other risky behaviors.
Another issue not addressed in the article is the implications of the proposed theory of CVD causation on the prevention of CHD. The cornerstone of CHD prevention and control is the reduction of traditional risk factors such as blood cholesterol and hypertension. These prevention strategies have proved to be very effective to prevent or delay the onset of CVD outcomes in diverse populations of the world and many studies have indicated that the reduction of CHD mortality rates observed in many countries was associated to the reduction of mean cholesterol levels, fat consumption and other risk factors of populations. It would be interesting that Azambuja and Levins discuss these issues to reconcile their theory with the large evidence regarding effective CHD prevention
Title: Coronary Heart Disease (CHD)--One or Several Diseases?
Author: MI Azambuja, R Levins
Reference: Perspectives in Biology and Medicine 2007; 50(2): 228,
http://muse.jhu.edu/journals/perspectives_in_biology_and_medicine/toc/pbm50.2.html
Reviewer: Carlos Mendoza Montano, PhD, APRECOR, Guatemala, ProCOR contributing editor, e-mail: projhouse@intelnet.net.gt
The current article presents an interesting perspective about the causation of CHD. It revisits evidence that may have been overlooked or misinterpreted during the heights of the CHD epidemic in the United States and other developed countries due to the prevalent framework of multicausality, and the hegemony of the lipid over alternative hypotheses to CHD causation. The authors of the article propose a fresh look at some old evidence which leads to new ways of thinking about CHD, its trends and its causes, and new ways of thinking about chronic disease occurrence in general.
According to the multifactorial model of causality, CHD is conceived as resulting from possible alternative and interconnected chains of exposures component causes) that would eventually become sufficient to initiate the disease in an individual. Azambuja and Levins argue that, 40 years after its introduction, we still lack a sound biologic theory to explain the development of CHD and its progression to death, which allows them to question both this causal model and the degenerative idea behind it.
The article pointed out that during the rise in CHD mortality (1931-1935), the odds of finding hypertensive disease among cases of CHD was 5:1. In 1951-1955, the degree of atherosclerosis in males from all age categories was considerably greater, but the odds of finding hypertensive disease among cases had reversed to 1:2.5. Since there is no reason for assuming that the incidence of hypertensive disease had significantly decreased over this period, the authors felt justified in concluding that these findings indicate a considerable increase in CHD that is independent of hypertension as a factor in its pathogenesis. During the 20th century, then, the profile of the CHD cases varied from the pre-epidemic period (until the 1920s and 1930s) to the height of the epidemic period (1950s and 1960s), and again during the decline in CHD mortality (1980s to date). Cases described during the pre- and post-epidemic periods were mostly associated with "inflammation" and an individual phenotype suggestive of insulin-resistance (obesity, diabetes), hypertension, and/or smoking. During the epidemic period, hypercholesterolemia became the hallmark of CHD cases. The authors wondered how these trends should be interpreted.
Azambuja and Levins conceive CHD as encompassing different diseases associated with vulnerabilities and triggers with varying distributions over time and space. Therefore, they suggest that changes in CHD features accompanying the changes in CHD occurrence resulted from expansions and retractions of sub-populations of CHD cases over time. According to them, the steep rise in CHD mortality seen after the 1920s resulted from a huge expansion of a particular subpopulation of cases, characterized by high cholesterol levels and high case fatality.
While individual vulnerability is routinely considered in modeling infectious diseases, it is frequently ignored with respect to chronic diseases. Vulnerability to chronic "degenerative" diseases is usually conceived as a genetic attribute and, as such, not subject to short-term variation. Over the past years, different pathways have been postulated that could change individuals phenotypically and favor vulnerability to chronic diseases and CHD, including autoimmunity upon infection, metabolic reprogramming upon infection, and metabolic reprogramming associated with nongenomic mechanisms of inheritance. An alternative explanation of the huge expansion of a specific subpopulation of CHD cases occurring from the 1920s to the 1960s could depend not as much on changes in exposure to CHD risk factors as on an acquired window of vulnerability to the disease opened in the middle of the 20th century.
The article pointed out that during the rise in CHD mortality (1931-1935), the odds of finding hypertensive disease among cases of CHD was 5:1. In 1951-1955, the degree of atherosclerosis in males from all age categories was considerably greater, but the odds of finding hypertensive disease among cases had reversed to 1:2.5. Since there is no reason for assuming that the incidence of hypertensive disease had significantly decreased over this period, the authors felt justified in concluding that these findings indicate a considerable increase in CHD that is independent of hypertension as a factor in its pathogenesis. During the 20th century, then, the profile of the CHD cases varied from the pre-epidemic period (until the 1920s and 1930s) to the height of the epidemic period (1950s and 1960s), and again during the decline in CHD mortality (1980s to date). Cases described during the pre- and post-epidemic periods were mostly associated with "inflammation" and an individual phenotype suggestive of insulin-resistance (obesity, diabetes), hypertension, and/or smoking. During the epidemic period, hypercholesterolemia became the hallmark of CHD cases. The authors wondered how these trends should be interpreted.
Azambuja and Levins conceive CHD as encompassing different diseases associated with vulnerabilities and triggers with varying distributions over time and space. Therefore, they suggest that changes in CHD features accompanying the changes in CHD occurrence resulted from expansions and retractions of sub-populations of CHD cases over time. According to them, the steep rise in CHD mortality seen after the 1920s resulted from a huge expansion of a particular subpopulation of cases, characterized by high cholesterol levels and high case fatality.
While individual vulnerability is routinely considered in modeling infectious diseases, it is frequently ignored with respect to chronic diseases. Vulnerability to chronic "degenerative" diseases is usually conceived as a genetic attribute and, as such, not subject to short-term variation. Over the past years, different pathways have been postulated that could change individuals phenotypically and favor vulnerability to chronic diseases and CHD, including autoimmunity upon infection, metabolic reprogramming upon infection, and metabolic reprogramming associated with nongenomic mechanisms of inheritance. An alternative explanation of the huge expansion of a specific subpopulation of CHD cases occurring from the 1920s to the 1960s could depend not as much on changes in exposure to CHD risk factors as on an acquired window of vulnerability to the disease opened in the middle of the 20th century.
The article postulates that both hypercholesterolemia and coronary thrombosis reported frequently among the CHD cases registered from the 1920s to the 1960s were secondary to an autoimmune response to influenza (re)infection developed among a specific subgroup of vulnerable individuals (those 15 to 45 years old in 1918) marked by the 1918 influenza pandemic virus. This vulnerability may be due to autoimmune disruption of low-density lipoprotein-receptor interactions.
One subgroup of CHD cases, however, has grown since the 1980s: that associated with inflammation and insulin resistance. The growth of this subtype of CHD cases does not seem to be merely relative or secondary to the impressive fall in the number of hypercholesterolemic cases. We need to ask what caused the emergence of the vulnerable (insulin-resistant) phenotype underlying the rising rates of obesity, diabetes, and their associated pool of CHD cases in the population. An important contribution may come from Barker\'s hypothesis and from other theories of nongenetic inheritance of vulnerability across generations. Evidence suggests that the interaction of genes and the pre- and postnatal environments, against a heterogeneous background of vulnerability, could operate to produce metabolic programming effects across generations and result in obesity, diabetes, and cardiovascular diseases later in life.
Comments: This article proposes an alternative causation for the emergence and decline of the CHD "epidemic" experienced by many developed countries during the 20th century. The authors of the article did not address the emergence of CHD currently observed in most developing countries, although a consistent explanation with their argument would be that many populations of developing countries have had high prevalence of infectious diseases and malnutrition which has created a vulnerability to CHD when these people later in their lives are exposed to tobacco smoking and other risky behaviors.
Another issue not addressed in the article is the implications of the proposed theory of CVD causation on the prevention of CHD. The cornerstone of CHD prevention and control is the reduction of traditional risk factors such as blood cholesterol and hypertension. These prevention strategies have proved to be very effective to prevent or delay the onset of CVD outcomes in diverse populations of the world and many studies have indicated that the reduction of CHD mortality rates observed in many countries was associated to the reduction of mean cholesterol levels, fat consumption and other risk factors of populations. It would be interesting that Azambuja and Levins discuss these issues to reconcile their theory with the large evidence regarding effective CHD prevention.
The article postulates that both hypercholesterolemia and coronary thrombosis reported frequently among the CHD cases registered from the 1920s to the 1960s were secondary to an autoimmune response to influenza (re)infection developed among a specific subgroup of vulnerable individuals (those 15 to 45 years old in 1918) marked by the 1918 influenza pandemic virus. This vulnerability may be due to autoimmune disruption of low-density lipoprotein-receptor interactions.
One subgroup of CHD cases, however, has grown since the 1980s: that associated with inflammation and insulin resistance. The growth of this subtype of CHD cases does not seem to be merely relative or secondary to the impressive fall in the number of hypercholesterolemic cases. We need to ask what caused the emergence of the vulnerable (insulin-resistant) phenotype underlying the rising rates of obesity, diabetes, and their associated pool of CHD cases in the population. An important contribution may come from Barker's hypothesis and from other theories of nongenetic inheritance of vulnerability across generations. Evidence suggests that the interaction of genes and the pre- and postnatal environments, against a heterogeneous background of vulnerability, could operate to produce metabolic programming effects across generations and result in obesity, diabetes, and cardiovascular diseases later in life.
Comments: This article proposes an alternative causation for the emergence and decline of the CHD "epidemic" experienced by many developed countries during the 20th century. The authors of the article did not address the emergence of CHD currently observed in most developing countries, although a consistent explanation with their argument would be that many populations of developing countries have had high prevalence of infectious diseases and malnutrition which has created a vulnerability to CHD when these people later in their lives are exposed to tobacco smoking and other risky behaviors.
Another issue not addressed in the article is the implications of the proposed theory of CVD causation on the prevention of CHD. The cornerstone of CHD prevention and control is the reduction of traditional risk factors such as blood cholesterol and hypertension. These prevention strategies have proved to be very effective to prevent or delay the onset of CVD outcomes in diverse populations of the world and many studies have indicated that the reduction of CHD mortality rates observed in many countries was associated to the reduction of mean cholesterol levels, fat consumption and other risk factors of populations. It would be interesting that Azambuja and Levins discuss these issues to reconcile their theory with the large evidence regarding effective CHD prevention
Tuesday, May 1, 2007
Beta-blockers for hypertension. Cochrane Database of Systematic Reviews
Review
Beta-blockers for hypertension
CS Wiysonge, H Bradley, BM Mayosi, R Maroney, A Mbewu, LH Opie, J Volmink
Cochrane Database of Systematic Reviews 2007 Issue 2Copyright © 2007
The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.DOI: 10.1002/14651858.CD002003.pub2
This version first published online: 24 January 2007 in Issue 1, 2007
Date of Most Recent Substantive Amendment: 25 October 2006
This record should be cited as: Wiysonge CS, Bradley H, Mayosi BM, Maroney R, Mbewu A, Opie LH, Volmink J. Beta-blockers for hypertension.
Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD002003. DOI: 10.1002/14651858.CD002003.pub2.
Abstract
Background
Two recent systematic reviews found first-line beta-blockers to be less effective in reducing the incidence of stroke and the combined endpoint of stroke, myocardial infarction, and death compared to all other antihypertensive drugs taken together. However, beta-blockers might be better or worse than a specific class of drugs for a particular outcome measure so that comparing beta-blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta-blockers relative to other antihypertensive medications. We thus undertook this review to re-assess the place of beta-blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs.
Objectives
To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension.
Search strategy
We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts.
Selection criteria
We selected randomised controlled trials which assessed the effectiveness of beta-blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for hypertension, on mortality and morbidity endpoints in men and non-pregnant women aged 18 years or older.
Data collection and analysis
At least two authors independently applied study selection criteria, assessed study quality, and extracted data; with differences resolved by consensus. We expressed study results as relative risks (RR) with 95% confidence intervals (CI) and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity between studies (p>0.1), we performed meta-analysis using a fixed effects method. Otherwise, we used the random effects method and investigated the cause of heterogeneity by stratified analysis. In addition, we used the Higgins statistic (I2) to quantify the amount of between-study variability in effect attributable to true heterogeneity rather than chance.
Main results
Thirteen randomised controlled trials (N=91,561 participants), which met our inclusion criteria, compared beta-blockers to placebo or no treatment (4 trials with 23,613 participants), diuretics (5 trials with 18,241 participants), calcium-channel blockers (CCBs: 4 trials with 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 trials with 10,828 participants). The risk of all-cause mortality was not different between first-line beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11, I2=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14, I2=2.2%; ARI=0.5%, NNH=200). The risk of total cardiovascular disease (CVD) was lower for first-line beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97, I2=21.4%, ARR=0.7%, NNT=140). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I2=0%; ARR=0.5%, NNT=200); coronary heart disease (CHD) risk was not significantly different between beta-blockers and placebo. The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08 to 1.29, I2=0%; ARI=1.3%, NNH=80), but was not significantly different from that of diuretics or RAS inhibitors. Increased total CVD was due to an increase in stroke compared to CCBs (RR 1.24, 95%CI 1.11 to 1.40, I2=0%; ARI=0.6%, NNH=180).There was also an increase in stroke with beta-blockers as compared to RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53, I2=29.1%; ARI=1.5%, NNH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In addition, patients on beta-blockers were more likely to discontinue treatment due to side effects than those on diuretics (RR 1.86, 95%CI 1.39 to 2.50, I2=78.2%, ARI=6.4% NNH=16) and RAS inhibitors (RR 1.41, 95%CI 1.29 to 1.54, I2=12.1%; ARI=5.5%, NNH=18), but there was no significant difference with CCBs.
Authors' conclusions
The available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta-blockers to reduce stroke and the absence of an effect on coronary heart disease when compared to placebo or no treatment. More importantly, it is based on the trend towards worse outcomes in comparison with calcium-channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials where atenolol was the beta-blocker used (75% of beta-blocker participants in this review). However, it is not known at present whether beta-blockers have differential effects on younger and elderly patients or whether there are differences between the different sub-types of beta-blockers.
Plain language summary
At the present time members of the class of drugs called beta-blockers are commonly used as first-line treatment for elevated blood pressure. We asked whether this class of drugs was as good as other classes in preventing death, stroke and heart attacks associated with elevated blood pressure. The available scientific literature was searched to find all the randomised controlled trial (RCT) evidence to assess this question. Thirteen RCTs were found and these trials suggested that first-line beta-blockers for elevated blood pressure were not as good at decreasing mortality and morbidity as other classes of drugs: thiazides, calcium channel blockers, and renin angiotensin system inhibitors.
Beta-blockers for hypertension
CS Wiysonge, H Bradley, BM Mayosi, R Maroney, A Mbewu, LH Opie, J Volmink
Cochrane Database of Systematic Reviews 2007 Issue 2Copyright © 2007
The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.DOI: 10.1002/14651858.CD002003.pub2
This version first published online: 24 January 2007 in Issue 1, 2007
Date of Most Recent Substantive Amendment: 25 October 2006
This record should be cited as: Wiysonge CS, Bradley H, Mayosi BM, Maroney R, Mbewu A, Opie LH, Volmink J. Beta-blockers for hypertension.
Cochrane Database of Systematic Reviews 2007, Issue 1. Art. No.: CD002003. DOI: 10.1002/14651858.CD002003.pub2.
Abstract
Background
Two recent systematic reviews found first-line beta-blockers to be less effective in reducing the incidence of stroke and the combined endpoint of stroke, myocardial infarction, and death compared to all other antihypertensive drugs taken together. However, beta-blockers might be better or worse than a specific class of drugs for a particular outcome measure so that comparing beta-blockers with all other classes taken together could be misleading. In addition, these systematic reviews did not assess the tolerability of beta-blockers relative to other antihypertensive medications. We thus undertook this review to re-assess the place of beta-blockade as first-line therapy for hypertension relative to each of the other major classes of antihypertensive drugs.
Objectives
To quantify the effectiveness and safety of beta-blockers on morbidity and mortality endpoints in adults with hypertension.
Search strategy
We searched eligible studies up to June 2006 in the Cochrane Controlled Trials Register, Medline, Embase, and reference lists of previous reviews, and by contacting hypertension experts.
Selection criteria
We selected randomised controlled trials which assessed the effectiveness of beta-blockers compared to placebo, no therapy or other drug classes, as monotherapy or first-line therapy for hypertension, on mortality and morbidity endpoints in men and non-pregnant women aged 18 years or older.
Data collection and analysis
At least two authors independently applied study selection criteria, assessed study quality, and extracted data; with differences resolved by consensus. We expressed study results as relative risks (RR) with 95% confidence intervals (CI) and conducted quantitative analyses with trial participants in groups to which they were randomly allocated, regardless of which or how much treatment they actually received. In the absence of significant heterogeneity between studies (p>0.1), we performed meta-analysis using a fixed effects method. Otherwise, we used the random effects method and investigated the cause of heterogeneity by stratified analysis. In addition, we used the Higgins statistic (I2) to quantify the amount of between-study variability in effect attributable to true heterogeneity rather than chance.
Main results
Thirteen randomised controlled trials (N=91,561 participants), which met our inclusion criteria, compared beta-blockers to placebo or no treatment (4 trials with 23,613 participants), diuretics (5 trials with 18,241 participants), calcium-channel blockers (CCBs: 4 trials with 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 trials with 10,828 participants). The risk of all-cause mortality was not different between first-line beta-blockers and placebo (RR 0.99, 95%CI 0.88 to 1.11, I2=0%), diuretics or RAS inhibitors, but was higher for beta-blockers compared to CCBs (RR 1.07, 95%CI 1.00 to 1.14, I2=2.2%; ARI=0.5%, NNH=200). The risk of total cardiovascular disease (CVD) was lower for first-line beta-blockers compared to placebo (RR 0.88, 95%CI 0.79 to 0.97, I2=21.4%, ARR=0.7%, NNT=140). This is primarily a reflection of the significant decrease in stroke (RR 0.80, 95%CI 0.66 to 0.96; I2=0%; ARR=0.5%, NNT=200); coronary heart disease (CHD) risk was not significantly different between beta-blockers and placebo. The effect of beta-blockers on CVD was significantly worse than that of CCBs (RR 1.18, 95%CI 1.08 to 1.29, I2=0%; ARI=1.3%, NNH=80), but was not significantly different from that of diuretics or RAS inhibitors. Increased total CVD was due to an increase in stroke compared to CCBs (RR 1.24, 95%CI 1.11 to 1.40, I2=0%; ARI=0.6%, NNH=180).There was also an increase in stroke with beta-blockers as compared to RAS inhibitors (RR 1.30, 95%CI 1.11 to 1.53, I2=29.1%; ARI=1.5%, NNH=65). CHD was not significantly different between beta-blockers and diuretics or CCBs or RAS inhibitors. In addition, patients on beta-blockers were more likely to discontinue treatment due to side effects than those on diuretics (RR 1.86, 95%CI 1.39 to 2.50, I2=78.2%, ARI=6.4% NNH=16) and RAS inhibitors (RR 1.41, 95%CI 1.29 to 1.54, I2=12.1%; ARI=5.5%, NNH=18), but there was no significant difference with CCBs.
Authors' conclusions
The available evidence does not support the use of beta-blockers as first-line drugs in the treatment of hypertension. This conclusion is based on the relatively weak effect of beta-blockers to reduce stroke and the absence of an effect on coronary heart disease when compared to placebo or no treatment. More importantly, it is based on the trend towards worse outcomes in comparison with calcium-channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics. Most of the evidence for these conclusions comes from trials where atenolol was the beta-blocker used (75% of beta-blocker participants in this review). However, it is not known at present whether beta-blockers have differential effects on younger and elderly patients or whether there are differences between the different sub-types of beta-blockers.
Plain language summary
At the present time members of the class of drugs called beta-blockers are commonly used as first-line treatment for elevated blood pressure. We asked whether this class of drugs was as good as other classes in preventing death, stroke and heart attacks associated with elevated blood pressure. The available scientific literature was searched to find all the randomised controlled trial (RCT) evidence to assess this question. Thirteen RCTs were found and these trials suggested that first-line beta-blockers for elevated blood pressure were not as good at decreasing mortality and morbidity as other classes of drugs: thiazides, calcium channel blockers, and renin angiotensin system inhibitors.
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