Immunotherapy 'benefits large proportion of heart failure patients'
By Cher Thornhill
18 January 2008
Lancet 2008; 371: 228-236
MedWire News: Immunomodulation therapy (IMT) appears to prolong life and delay readmission for a large proportion of heart failure patients, a large, placebo-controlled trial suggests.
Guillermo Torre-Amione (Methodist Hospital, Houston, Texas, USA) and co-workers found that heart failure patients with no history of myocardial infarction and those within New York Heart Association (NYHA) class II who receive IMT have around 25% and 40% reductions in a composite of time to death and hospitalization for cardiac reasons.
But editorialists Karen Sliwa (University of Witwatersrand, Johannesburg, South Africa) and Aftab Ansari (Emory University School of Medicine, Atlanta, Georgia, USA) caution that the therapy could raise patients' susceptibility to infections and cancer, or trigger autoimmune disease.
Torre-Amione and team studied 2426 patients with NYHA functional class II-IV chronic heart failure, left ventricular systolic dysfunction, and who had been hospitalized for heart failure or intravenous drug therapy within the past year.
Patients in the treatment arm received IMT on days 1, 2, and 14 and then every 28 days for at least 22 weeks.
For IMT, anticoagulated blood taken from the patients was exposed to ozone and ultraviolet light and then re-injected.
During a mean follow-up of 10.2 months, the incidence of primary events was statistically comparable in the treatment and placebo groups (339 vs 429, HR=0.92).
Torre-Amione et al say the null result "was disappointing in view of increasing evidence that inflammation plays a part in the progression of heart failure."
However, IMT was associated with a 26% reduction in the primary events in patients with no history of myocardial infarction (n=919) and a 39% reduction among patients with NYHA class II heart failure (n=689).
The researchers note that, compared with the entire population, these subgroups consisted of younger patients with baseline variables consistent with less severe disease.
Thus, IMT may only be effective when started early, before permanent cellular damage, they suggest.
In their editorial, Sliwa and Ansari said there are several "potential problems" with the approach taken by Torre-Amione's team.
Susceptibility to opportunistic infections may increase and elimination of potentially malignant cells may decrease. While neither was reported, the effects may be slow to emerge, they commented.
They added: "The study was too short to detect new onset of autoimmune diseases.
"Long-term follow-up of patients receiving this type of therapy should be mandatory."
Journal
Saturday, January 19, 2008
Wednesday, January 16, 2008
Calcium Supplements in Older Women Possibly Linked to More Cardiovascular Events
Blog observations about this study:
Calcium supplementation may adversely affect cardiovascular health in older women.
New Zealand researchers randomized nearly 1500 postmenopausal women to either 1 g of calcium or placebo daily; they then measured cardiovascular events over the ensuing 5 years
Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial
Mark J Bolland, research fellow1, P Alan Barber, senior lecturer1, Robert N Doughty, associate professor1, Barbara Mason, research officer1, Anne Horne, research fellow1, Ruth Ames, research officer1, Gregory D Gamble, research fellow1, Andrew Grey, associate professor1, Ian R Reid, professor1
Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
Correspondence to: I R Reid i.reid@auckland.ac.nz
Abstract
Objective
To determine the effect of calcium supplementation on myocardial infarction, stroke, and sudden death in healthy postmenopausal women.
Design
Randomised, placebo controlled trial.
Setting
Academic medical centre in an urban setting in New Zealand.
Participants
1471 postmenopausal women (mean age 74): 732 were randomised to calcium supplementation and 739 to placebo.
Main outcome measures
Adverse cardiovascular events over five years: death, sudden death, myocardial infarction, angina, other chest pain, stroke, transient ischaemic attack, and a composite end point of myocardial infarction, stroke, or sudden death.
Results
Myocardial infarction was more commonly reported in the calcium group than in the placebo group (45 events in 31 women v 19 events in 14 women, P=0.01). The composite end point of myocardial infarction, stroke, or sudden death was also more common in the calcium group (101 events in 69 women v 54 events in 42 women, P=0.008). After adjudication myocardial infarction remained more common in the calcium group (24 events in 21 women v 10 events in 10 women, relative risk 2.12, 95% confidence interval 1.01 to 4.47). For the composite end point 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group (relative risk 1.47, 0.97 to 2.23). When unreported events were added from the national database of hospital admissions in New Zealand the relative risk of myocardial infarction was 1.49 (0.86 to 2.57) and that of the composite end point was 1.21 (0.84 to 1.74). The respective rate ratios were 1.67 (95% confidence intervals 0.98 to 2.87) and 1.43 (1.01 to 2.04); event rates: placebo 16.3/1000 person years, calcium 23.3/1000 person years. For stroke (including unreported events) the relative risk was 1.37 (0.83 to 2.28) and the rate ratio was 1.45 (0.88 to 2.49).
Conclusion
Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates. This potentially detrimental effect should be balanced against the likely benefits of calcium on bone.
Calcium supplementation may adversely affect cardiovascular health in older women.
New Zealand researchers randomized nearly 1500 postmenopausal women to either 1 g of calcium or placebo daily; they then measured cardiovascular events over the ensuing 5 years
Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial
Mark J Bolland, research fellow1, P Alan Barber, senior lecturer1, Robert N Doughty, associate professor1, Barbara Mason, research officer1, Anne Horne, research fellow1, Ruth Ames, research officer1, Gregory D Gamble, research fellow1, Andrew Grey, associate professor1, Ian R Reid, professor1
Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand
Correspondence to: I R Reid i.reid@auckland.ac.nz
Abstract
Objective
To determine the effect of calcium supplementation on myocardial infarction, stroke, and sudden death in healthy postmenopausal women.
Design
Randomised, placebo controlled trial.
Setting
Academic medical centre in an urban setting in New Zealand.
Participants
1471 postmenopausal women (mean age 74): 732 were randomised to calcium supplementation and 739 to placebo.
Main outcome measures
Adverse cardiovascular events over five years: death, sudden death, myocardial infarction, angina, other chest pain, stroke, transient ischaemic attack, and a composite end point of myocardial infarction, stroke, or sudden death.
Results
Myocardial infarction was more commonly reported in the calcium group than in the placebo group (45 events in 31 women v 19 events in 14 women, P=0.01). The composite end point of myocardial infarction, stroke, or sudden death was also more common in the calcium group (101 events in 69 women v 54 events in 42 women, P=0.008). After adjudication myocardial infarction remained more common in the calcium group (24 events in 21 women v 10 events in 10 women, relative risk 2.12, 95% confidence interval 1.01 to 4.47). For the composite end point 61 events were verified in 51 women in the calcium group and 36 events in 35 women in the placebo group (relative risk 1.47, 0.97 to 2.23). When unreported events were added from the national database of hospital admissions in New Zealand the relative risk of myocardial infarction was 1.49 (0.86 to 2.57) and that of the composite end point was 1.21 (0.84 to 1.74). The respective rate ratios were 1.67 (95% confidence intervals 0.98 to 2.87) and 1.43 (1.01 to 2.04); event rates: placebo 16.3/1000 person years, calcium 23.3/1000 person years. For stroke (including unreported events) the relative risk was 1.37 (0.83 to 2.28) and the rate ratio was 1.45 (0.88 to 2.49).
Conclusion
Calcium supplementation in healthy postmenopausal women is associated with upward trends in cardiovascular event rates. This potentially detrimental effect should be balanced against the likely benefits of calcium on bone.
Monday, January 14, 2008
ENHANCE - Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone
Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE)
Trial Summary
Title:
Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE)
Trial Sponsor: Merck/Schering-PloughYear
Presented: 2008
Description
The following information was derived from a Merck/Schering-Plough press release from January 14, 2008; full data are to be presented at the 2008 ACC Scientific Session.
Hypothesis
The goal of this trial was to compare the mean change in the intima-media thickness (IMT) measured at three sites in the carotid arteries between patients with Heterozygous Familial Hypercholesterolemia (HeFH) treated with ezetimibe/simvastatin 10/80 mg versus patients treated with high-dose simvastatin 80 mg alone over a two-year period.
Principal Findings
A total of 720 patients with HeFH were randomized in this multinational, randomized, double-blind, active comparator trial: 357 to the ezetimibe/simvastatin arm and 363 to the high-dose simvastatin arm. Images were obtained from the right and left carotid arteries at three sites at baseline, 6, 12, 18, and 24 months. The baseline low-density lipoprotein (LDL) cholesterol levels between the two arms were comparable (319 vs. 318 mg/dl; p=non-significant [NS]). Approximately 80% of patients enrolled in the trial had been on statins previously. The baseline mean carotid IMT measurements were similar between the two arms.
There was no statistically significant difference between the two arms with respect to the primary endpoint, the mean change in carotid IMT. The change from baseline for the ezetimibe/simvastatin arm was 0.0111 mm, compared with 0.0058 mm for the high-dose simvastatin arm (p=0.29).There was no difference in the incidence of cardiovascular clinical events: cardiovascular deaths (0.6 vs. 0.3%), non-fatal myocardial infarction (0.8% vs. 0.6%), non-fatal stroke (0.3% vs. 0.3%), and need for revascularization (1.7% vs. 1.4%) [p=NS for all].
There was, however, a significant reduction in LDL lowering noted in the ezetimibe/simvastatin arm compared with the simvastatin arm (58% vs. 41%; p<0.01).The overall incidence of treatment-related adverse events was similar between the two groups: consecutive elevations of serum transaminases ≥ 3X ULN (2.8% vs. 2.2%), elevated CPK ≥ 10 X ULN (1.1% vs. 2.2%), and elevated CPK ≥ 10X ULN with muscle symptoms (0.6% vs. 0.3%) [p=NS for all]. There were no cases of rhabdomyolysis reported in either arm.
Interpretation
The results of the multicenter, randomized ENHANCE trial seem to suggest that in patients with very high baseline LDL levels, such as those with heterozygous familial hypercholesterolemia, the combination of ezetimibe/simvastatin 10/80 mg does not result in significant changes in the mean carotid IMT at 2 years when compared with high-dose simvastatin 80 mg alone. There was also no difference in the incidence of cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, or need for revascularization, although this study was not powered to study clinical outcomes. The LDL-lowering effect of ezetimibe/simvastatin was greater than that achieved with high-dose simvastatin alone.
Although this was a negative study, it will be interesting to see if larger ongoing trials will be able to demonstrate any relative superiority of the combination of ezetimibe/simvastatin in improving cardiovascular outcomes in high-risk patients as compared with simvastatin alone.
Study DesignRandomized. Blinded. Parallel.
Patients Enrolled: 720
Mean Follow-Up: 24 months
Trial Summary
Title:
Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE)
Trial Sponsor: Merck/Schering-PloughYear
Presented: 2008
Description
The following information was derived from a Merck/Schering-Plough press release from January 14, 2008; full data are to be presented at the 2008 ACC Scientific Session.
Hypothesis
The goal of this trial was to compare the mean change in the intima-media thickness (IMT) measured at three sites in the carotid arteries between patients with Heterozygous Familial Hypercholesterolemia (HeFH) treated with ezetimibe/simvastatin 10/80 mg versus patients treated with high-dose simvastatin 80 mg alone over a two-year period.
Principal Findings
A total of 720 patients with HeFH were randomized in this multinational, randomized, double-blind, active comparator trial: 357 to the ezetimibe/simvastatin arm and 363 to the high-dose simvastatin arm. Images were obtained from the right and left carotid arteries at three sites at baseline, 6, 12, 18, and 24 months. The baseline low-density lipoprotein (LDL) cholesterol levels between the two arms were comparable (319 vs. 318 mg/dl; p=non-significant [NS]). Approximately 80% of patients enrolled in the trial had been on statins previously. The baseline mean carotid IMT measurements were similar between the two arms.
There was no statistically significant difference between the two arms with respect to the primary endpoint, the mean change in carotid IMT. The change from baseline for the ezetimibe/simvastatin arm was 0.0111 mm, compared with 0.0058 mm for the high-dose simvastatin arm (p=0.29).There was no difference in the incidence of cardiovascular clinical events: cardiovascular deaths (0.6 vs. 0.3%), non-fatal myocardial infarction (0.8% vs. 0.6%), non-fatal stroke (0.3% vs. 0.3%), and need for revascularization (1.7% vs. 1.4%) [p=NS for all].
There was, however, a significant reduction in LDL lowering noted in the ezetimibe/simvastatin arm compared with the simvastatin arm (58% vs. 41%; p<0.01).The overall incidence of treatment-related adverse events was similar between the two groups: consecutive elevations of serum transaminases ≥ 3X ULN (2.8% vs. 2.2%), elevated CPK ≥ 10 X ULN (1.1% vs. 2.2%), and elevated CPK ≥ 10X ULN with muscle symptoms (0.6% vs. 0.3%) [p=NS for all]. There were no cases of rhabdomyolysis reported in either arm.
Interpretation
The results of the multicenter, randomized ENHANCE trial seem to suggest that in patients with very high baseline LDL levels, such as those with heterozygous familial hypercholesterolemia, the combination of ezetimibe/simvastatin 10/80 mg does not result in significant changes in the mean carotid IMT at 2 years when compared with high-dose simvastatin 80 mg alone. There was also no difference in the incidence of cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, or need for revascularization, although this study was not powered to study clinical outcomes. The LDL-lowering effect of ezetimibe/simvastatin was greater than that achieved with high-dose simvastatin alone.
Although this was a negative study, it will be interesting to see if larger ongoing trials will be able to demonstrate any relative superiority of the combination of ezetimibe/simvastatin in improving cardiovascular outcomes in high-risk patients as compared with simvastatin alone.
Study DesignRandomized. Blinded. Parallel.
Patients Enrolled: 720
Mean Follow-Up: 24 months
Sunday, January 13, 2008
Commentary:
Physicians and patients shoul boicott Zetia an Vytorin
Is Vytorin about to be renamed Whytorin?
Link:
http://pharmagossip.blogspot.com/2007/11/is-vytorin-about-to-be-renamed-whytorin.html
Matt Herper writes:
Every day millions of people swallow Zetia and Vytorin in the hopes of reducing their risk of heart attacks and strokes, generating $5 billion a year in sales for Merck and Schering-Plough, which produce them.
Do they work?
Despite millions of prescriptions, no study has ever shown that these $3-a-day pills prevent heart attacks, strokes or deaths any better than just taking older drugs like Pfizer's Lipitor or Merck's off-patent Zocor, even though they're proven cholesterol fighters. That's why a two-year delay in a 720-person study aimed at clarifying the issue has cardiologists expressing skepticism and spinning conspiracy theories. If the news were good, the companies would rush it out, the thinking goes. Delay doesn't bode well. "It starts to raise suspicion," says Allen J. Taylor, head of cardiology at Walter Reed Army Medical Center. "The more time it takes, the more you start to naturally wonder what is wrong."
Related:
http://blogs.wsj.com/health/
Physicians and patients shoul boicott Zetia an Vytorin
Is Vytorin about to be renamed Whytorin?
Link:
http://pharmagossip.blogspot.com/2007/11/is-vytorin-about-to-be-renamed-whytorin.html
Matt Herper writes:
Every day millions of people swallow Zetia and Vytorin in the hopes of reducing their risk of heart attacks and strokes, generating $5 billion a year in sales for Merck and Schering-Plough, which produce them.
Do they work?
Despite millions of prescriptions, no study has ever shown that these $3-a-day pills prevent heart attacks, strokes or deaths any better than just taking older drugs like Pfizer's Lipitor or Merck's off-patent Zocor, even though they're proven cholesterol fighters. That's why a two-year delay in a 720-person study aimed at clarifying the issue has cardiologists expressing skepticism and spinning conspiracy theories. If the news were good, the companies would rush it out, the thinking goes. Delay doesn't bode well. "It starts to raise suspicion," says Allen J. Taylor, head of cardiology at Walter Reed Army Medical Center. "The more time it takes, the more you start to naturally wonder what is wrong."
Related:
http://blogs.wsj.com/health/
Risk Of Cardiovascular Mortality Secondary To Androgen Deprivation Therapy For Localized Prostate Cancer
Commentary:
The use of ADT appears to be associated with an increased risk of death from cardiovascular causes in patients undergoing radical prostatectomy for localized prostate cancer.
Risk Of Cardiovascular Mortality Secondary To Androgen Deprivation Therapy For Localized Prostate Cancer
October 17, 2007 issue of the Journal of the National Cancer Institute
13 Jan 2008
UroToday.com - Androgen deprivation therapy (ADT) is associated with metabolic syndrome, which includes the development of type II diabetes mellitus and coronary artery disease. In the October 17, 2007 issue of the Journal of the National Cancer Institute evaluated whether ADT induced metabolic changes result in an increased risk of cardiovascular (CV) death.
The longitudinal, observational prostate cancer registry CaPSURE was used to study a cohort of 4,892 men. Of these, 1,015 patients were treated with ADT with local therapy and 3,977 men were not treated with ADT. ADT was used in 266 patients who had RP and in 749 men who received nonsurgical treatment. The primary endpoint of the study was death due to CV causes.
This was defined as myocardial infarction, sudden cardiac arrest, coronary artery disease, cardiac ischemia, arrhythmia, pulmonary embolism, or stroke.
Median patient age was 64 years and median followup was 3.8 years. Patients receiving radiotherapy, cryotherapy or brachytherapy as primary treatment in combination with ADT were older than men who had RP. The overall median duration of ADT therapy was 4.1 months. The proportion of patients with baseline hypertension and heart disease were similar among those who did and did not receive ADT. The proportion of patients with baseline diabetes was statistically higher in patients using ADT than in patients not using ADT. Analysis of patients treated with RP, both ADT and older age were associated with significantly increased risks of death from CV causes, but the presence of baseline heart disease or diabetes was not. This risk of CV death was evident in patients younger and older than 65 years. The cumulative incidence of death from CV causes among the younger patients using ADT was 3.6%, as compared to 1.2% in those not using ADT. Among patients treated with radiotherapy, brachytherapy or cryotherapy, only older age was associated with an increased risk of death from CV disease. Patients older than age 65 years who were treated with RP and ADT also had higher 5-year estimates of death from CV causes. In multivariable analysis among patients treated with RP, ADT use was associated with increased risk of death from any cause.
Older age, Gleason score greater than 8 and presence of baseline diabetes were also associated with an increased risk of death from any cause. Among those who did not undergo RP, a shorter time to all-cause mortality was not associated with ADT use, but was associated with advancing age.
To access the latest urology news releases from UroToday, go to: http://www.urotoday.com/
Saturday, January 12, 2008
Meta-Analysis of Effect of Statin Treatment on Risk of Sudden Death
Meta-Analysis of Effect of Statin Treatment on Risk of Sudden Death
Title: Meta-Analysis of Effect of Statin Treatment on Risk of Sudden Death
Topic: Arrhythmias
Date Posted: 1/11/2008
Author(s): Levatesi G, Scarano M, Marfisi R, et al.
Citation: Am J Cardiol. 2007;100:1644-1650.
Study Question: Do statins prevent sudden death (SD)?
Methods: This was a meta-analysis of 10 randomized, controlled trials in which a statin was compared with placebo or no therapy. There were a total of 22,275 patients, with 11,136 randomly assigned to receive a statin. The mean age was 60 years, 81% were male, and 69% had a history of myocardial infarction. The mean duration of follow-up was 4.4 years.
Results: The incidence of SD was significantly lower in the statin group (3.0%) than in the control group (3.8%). The 19% reduction in relative risk of SD in the statin group was independent of the extent to which the plasma cholesterol level decreased.
Conclusions: Stains reduce the relative risk of SD by approximately 20% over 4 years of follow-up.
Perspective: A reduction in SD by statins is consistent with the results of implantable cardioverter defibrillator trials that have demonstrated a reduction in the risk of appropriate shocks in patients treated with a statin. There are several possible mechanisms by which statins might reduce the risk of malignant ventricular arrhythmias, including prevention of ischemia and indirect channel effects mediated by alterations in the lipid content of cell membranes. Fred Morady, M.D., F.A.C.C.
Alcohol and long-term prognosis after a first acute myocardial infarction: the SHEEP study
Alcohol and long-term prognosis after a first acute myocardial infarction: the SHEEP study
Eur Heart J 2008 29: 45-53.
Context: Few studies have investigated the relation between alcohol consumption, former drinking, and prognosis after an acute myocardial infarction (AMI), particularly for non-fatal outcomes.
Objective: To investigate the prognostic importance of drinking habits among patients surviving a first AMI.
Design, settings, and patients: A total of 1346 consecutive patients between 45–70 years with a first non-fatal AMI underwent a standardized clinical examination and were followed for over 8 years.
Main outcome measures: Total and cardiac mortality and hospitalization for non-fatal cardiovascular disease in relation to individual alcoholic beverage consumption at the time of AMI and 5 years before inclusion, assessed by a standardized questionnaire administered during hospitalization.
Results: We recorded 267 deaths, and 145 deaths from cardiac causes, during the follow-up period. After adjustment for several potential confounders, hazard ratios for total and cardiac mortality were 0.77 (0.51–1.15) and 0.61 (0.36–1.02) for those drinking >0–<5 g per day, 0.77 (0.50–1.18) and 0.62 (0.36–1.07) for those drinking 5–20 g per day, and 0.89 (0.56–1.40) and 0.69 (0.38–1.25) for those drinking over 20 g per day. Risk of hospitalization for recurrent non-fatal AMI, stroke, or heart failure generally showed a similar pattern to that of total and cardiac mortality. Recent quitters at the time of AMI had a hazard ratio of 4.55 (2.03–10.20) for total mortality. Measures of insulin sensitivity appeared to be the strongest mediators of this association.
Conclusions: Moderate alcohol drinking might have beneficial effects on several aspects of long-term prognosis after an AMI. Our findings also highlight that former drinkers should be examined separately from long-term abstainers. The potential mechanisms that underlie this association still need to be elucidated.
Eur Heart J 2008 29: 45-53.
Context: Few studies have investigated the relation between alcohol consumption, former drinking, and prognosis after an acute myocardial infarction (AMI), particularly for non-fatal outcomes.
Objective: To investigate the prognostic importance of drinking habits among patients surviving a first AMI.
Design, settings, and patients: A total of 1346 consecutive patients between 45–70 years with a first non-fatal AMI underwent a standardized clinical examination and were followed for over 8 years.
Main outcome measures: Total and cardiac mortality and hospitalization for non-fatal cardiovascular disease in relation to individual alcoholic beverage consumption at the time of AMI and 5 years before inclusion, assessed by a standardized questionnaire administered during hospitalization.
Results: We recorded 267 deaths, and 145 deaths from cardiac causes, during the follow-up period. After adjustment for several potential confounders, hazard ratios for total and cardiac mortality were 0.77 (0.51–1.15) and 0.61 (0.36–1.02) for those drinking >0–<5 g per day, 0.77 (0.50–1.18) and 0.62 (0.36–1.07) for those drinking 5–20 g per day, and 0.89 (0.56–1.40) and 0.69 (0.38–1.25) for those drinking over 20 g per day. Risk of hospitalization for recurrent non-fatal AMI, stroke, or heart failure generally showed a similar pattern to that of total and cardiac mortality. Recent quitters at the time of AMI had a hazard ratio of 4.55 (2.03–10.20) for total mortality. Measures of insulin sensitivity appeared to be the strongest mediators of this association.
Conclusions: Moderate alcohol drinking might have beneficial effects on several aspects of long-term prognosis after an AMI. Our findings also highlight that former drinkers should be examined separately from long-term abstainers. The potential mechanisms that underlie this association still need to be elucidated.
Statin therapy in diabetics supported
Statin therapy in diabetics supported
By Caroline Price
11 January 2008
Lancet 2008; 371: 117-125
MedWire News: Meta-analysis findings demonstrate that statin therapy should be considered in all individuals with diabetes if they are deemed at "sufficiently high" risk for vascular events, conclude the Cholesterol Treatment Trialists' (CTT) Collaborators in The Lancet.
An earlier CTT meta-analysis of 14 randomized trials of statin therapy showed that lowering low-density lipoprotein (LDL) cholesterol by 1 mmol/l reduces the risk of vascular events (myocardial infarction or coronary death, stroke, or coronary revascularization) by around one-fifth in a broad range of high-risk individuals, largely irrespective of baseline lipid levels and conditions, including diabetes.
For the current study, the CTT investigators conducted pre-specified analyses of the same 14 trials to determine whether individuals with diabetes derive the same benefits from statins as those without.
Uncertainties remain over the effects of statins in diabetic individuals on major coronary events, stroke, and the need for revascularization, and whether their benefits are worthwhile in those without a history of occlusive vascular disease, the team explains.
The researchers report that there were 3247 major vascular events over a mean follow-up of 4.3 years among the 18,686 participants who had diabetes.
These participants had a 9% reduction in all-cause mortality per mmol/l decrease in LDL cholesterol (relative risk [RR]=0.91, p=0.02). This reduction was similar in magnitude to the 13% RR reduction per mmol/l decrease in LDL cholesterol RR=0.87, p<0.0001) in the remaining 71,370 patients without diabetes, the researchers say.
The reduction in all-cause mortality reflected significant reductions in vascular mortality (0.87, p=0.008) and death due to coronary heart disease (0.88, p=0.03) per mmol/l reduction in LDL cholesterol in the diabetic individuals, with no significant effect on vascular mortality (RR=0.97).
There was a significant 21% reduction in major vascular events per mmol/l decrease in LDL cholesterol in both participants with and without diabetes.
Statin therapy was also associated with significant reductions in MI or coronary death, coronary revascularization, and stroke among the diabetic participants.
Finally, the proportional risk reductions for major vascular events among diabetic individuals were similar irrespective of history of vascular disease, gender, age, treated hypertension, body mass index, systolic or diastolic blood pressure, smoking history, and renal function.
The authors comment that the consistency of the reduction in major vascular events suggests that the benefit is likely to hold true in other populations with diabetes.
"Consequently, the absolute benefits in any specific population of patients may be best estimated by application of a reduction of about a fifth per mmol/l LDL cholesterol reduction to the relevant age-specific and sex-specific rates for that population," they write.
Journal
By Caroline Price
11 January 2008
Lancet 2008; 371: 117-125
MedWire News: Meta-analysis findings demonstrate that statin therapy should be considered in all individuals with diabetes if they are deemed at "sufficiently high" risk for vascular events, conclude the Cholesterol Treatment Trialists' (CTT) Collaborators in The Lancet.
An earlier CTT meta-analysis of 14 randomized trials of statin therapy showed that lowering low-density lipoprotein (LDL) cholesterol by 1 mmol/l reduces the risk of vascular events (myocardial infarction or coronary death, stroke, or coronary revascularization) by around one-fifth in a broad range of high-risk individuals, largely irrespective of baseline lipid levels and conditions, including diabetes.
For the current study, the CTT investigators conducted pre-specified analyses of the same 14 trials to determine whether individuals with diabetes derive the same benefits from statins as those without.
Uncertainties remain over the effects of statins in diabetic individuals on major coronary events, stroke, and the need for revascularization, and whether their benefits are worthwhile in those without a history of occlusive vascular disease, the team explains.
The researchers report that there were 3247 major vascular events over a mean follow-up of 4.3 years among the 18,686 participants who had diabetes.
These participants had a 9% reduction in all-cause mortality per mmol/l decrease in LDL cholesterol (relative risk [RR]=0.91, p=0.02). This reduction was similar in magnitude to the 13% RR reduction per mmol/l decrease in LDL cholesterol RR=0.87, p<0.0001) in the remaining 71,370 patients without diabetes, the researchers say.
The reduction in all-cause mortality reflected significant reductions in vascular mortality (0.87, p=0.008) and death due to coronary heart disease (0.88, p=0.03) per mmol/l reduction in LDL cholesterol in the diabetic individuals, with no significant effect on vascular mortality (RR=0.97).
There was a significant 21% reduction in major vascular events per mmol/l decrease in LDL cholesterol in both participants with and without diabetes.
Statin therapy was also associated with significant reductions in MI or coronary death, coronary revascularization, and stroke among the diabetic participants.
Finally, the proportional risk reductions for major vascular events among diabetic individuals were similar irrespective of history of vascular disease, gender, age, treated hypertension, body mass index, systolic or diastolic blood pressure, smoking history, and renal function.
The authors comment that the consistency of the reduction in major vascular events suggests that the benefit is likely to hold true in other populations with diabetes.
"Consequently, the absolute benefits in any specific population of patients may be best estimated by application of a reduction of about a fifth per mmol/l LDL cholesterol reduction to the relevant age-specific and sex-specific rates for that population," they write.
Journal
Thursday, January 10, 2008
Diagnosis of left-ventricular non-compaction in patients with left-ventricular systolic dysfunction
Diagnosis of left-ventricular non-compaction in patients with left-ventricular systolic dysfunction: time for a reappraisal of diagnostic criteria?
European Heart Journal - January 1, 2008
Kohli SK, Pantazis AA, Shah JS, Adeyemi B, Jackson G, McKenna WJ, Sharma S, Elliott PM.
The Heart Hospital, University College, 16-18 Westmoreland Street, W1G 8PH London, UK.
Aims
Left-ventricular non-compaction (LVNC) is characterized by excessive and prominent left-ventricular (LV) trabeculations and may be associated with systolic dysfunction in advanced disease. We sought to determine the proportion of patients fulfilling LVNC criteria in an adult population referred to a heart failure clinic using current diagnostic criteria.
Methods and results
One hundred and ninety-nine patients [age 63.5 +/- 15.9 years, 124 (62.3%) males] with LV systolic impairment were studied. All underwent clinical examination, electrocardiography, and 2-D echocardiography. The number of patients fulfilling diagnostic criteria for LVNC was retrospectively determined using three published definitions. Results were compared with 60 prospectively evaluated normal controls (age 35.7 +/- 13.5 years; 31 males, 30 blacks). Forty-seven patients (23.6%) fulfilled one or more echocardiographic definitions for LVNC. Patients fulfilling LVNC criteria were younger (P = 0.002), had larger LV end-diastolic dimension (P < 0.001), and smaller left atrial size (P = 0.01). LVNC was more common in black individuals (35.5 vs. 16.2%, P = 0.003). Five controls (four blacks) fulfilled one or more LVNC criteria.
Conclusions
This study demonstrates an unexpectedly high percentage of patients with heart failure fulfilling current echocardiographic criteria for LVNC. This might be explained by a hitherto underestimated cause of heart failure, but the comparison with controls suggests that current diagnostic criteria are too sensitive, particularly in black individuals.
European Heart Journal - January 1, 2008
Kohli SK, Pantazis AA, Shah JS, Adeyemi B, Jackson G, McKenna WJ, Sharma S, Elliott PM.
The Heart Hospital, University College, 16-18 Westmoreland Street, W1G 8PH London, UK.
Aims
Left-ventricular non-compaction (LVNC) is characterized by excessive and prominent left-ventricular (LV) trabeculations and may be associated with systolic dysfunction in advanced disease. We sought to determine the proportion of patients fulfilling LVNC criteria in an adult population referred to a heart failure clinic using current diagnostic criteria.
Methods and results
One hundred and ninety-nine patients [age 63.5 +/- 15.9 years, 124 (62.3%) males] with LV systolic impairment were studied. All underwent clinical examination, electrocardiography, and 2-D echocardiography. The number of patients fulfilling diagnostic criteria for LVNC was retrospectively determined using three published definitions. Results were compared with 60 prospectively evaluated normal controls (age 35.7 +/- 13.5 years; 31 males, 30 blacks). Forty-seven patients (23.6%) fulfilled one or more echocardiographic definitions for LVNC. Patients fulfilling LVNC criteria were younger (P = 0.002), had larger LV end-diastolic dimension (P < 0.001), and smaller left atrial size (P = 0.01). LVNC was more common in black individuals (35.5 vs. 16.2%, P = 0.003). Five controls (four blacks) fulfilled one or more LVNC criteria.
Conclusions
This study demonstrates an unexpectedly high percentage of patients with heart failure fulfilling current echocardiographic criteria for LVNC. This might be explained by a hitherto underestimated cause of heart failure, but the comparison with controls suggests that current diagnostic criteria are too sensitive, particularly in black individuals.
Vitamin-mineral supplement fails to reduce BP
Vitamin-mineral supplement fails to reduce BP
By Caroline Price
09 January 2008
J Hum Hypertens 2008; 121: 43-49
MedWire News: Study findings have failed to find any effect of consuming milk supplemented with additional potassium, calcium, magnesium, selenium, and vitamins C and E on blood pressure (BP).
The results "confirm the discrepancy between dietary intervention studies showing reasonable BP lowering effects and intervention studies with a combination of minerals or vitamins showing no effect," say the authors.
This highlights the need to explore potential BP lowering effects of vitamins and minerals consumed in "natural matrices" in the diet rather than as supplements, they add.
In a research letter to the Journal of Human Hypertension, P de Leeuw (University Hospital Maastricht, The Netherlands) and colleagues explain that dietary intervention studies have shown impressive reductions in BP, probably due in part to the mineral and vitamin components of such diets. Yet interventions with combinations of either minerals or vitamins have provided mixed results.
In the current study, the researchers tested the BP lowering effect of a combination of minerals and vitamins. They randomly assigned 124 adults with untreated mild hypertension to take a supplemented skimmed milk drink or a placebo drink daily for 8 weeks.
The milk was supplemented with 446 mg calcium, 100 mg magnesium, 40 µg selenium, 180 mg vitamin C, 30 mg vitamin E and tocopherol equivalents, and either 1500 mg (high-K) or 750 mg (low-K) potassium per serving.
At the end of the study, office systolic BP had decreased by 4.6, 4.5, and 5.1 mmHg from baseline in the low-K supplement, high-K supplement, and placebo groups, respectively. The differences in BP reduction among groups were nonsignificant.
Reductions in office diastolic BP, pulse pressure, 24-hour systolic BP, 24-hour diastolic BP, and heart rate over the 8 weeks did not differ among the three groups either.
The results "are in contrast with many studies addressing interventions with the individual components," the authors write. They note that the doses of the individual minerals and vitamins may have been too low, and that combinations of vitamins and minerals may counter the effects of the individual components.
Meanwhile, the contrast with findings of dietary interventions may reflect the reduction of components with negative effects by diet replacement, the increased presence of as-yet unidentified components in dietary interventions, or altered bioavailability of nutrients when provided in a dairy matrix.
"Future studies should focus on assessing the effect of subsets of combinations of minerals and vitamins in natural matrices to get a better understanding of the possible antagonistic action between some of these ingredients," de Leeuw and co-authors conclude.
Journal
By Caroline Price
09 January 2008
J Hum Hypertens 2008; 121: 43-49
MedWire News: Study findings have failed to find any effect of consuming milk supplemented with additional potassium, calcium, magnesium, selenium, and vitamins C and E on blood pressure (BP).
The results "confirm the discrepancy between dietary intervention studies showing reasonable BP lowering effects and intervention studies with a combination of minerals or vitamins showing no effect," say the authors.
This highlights the need to explore potential BP lowering effects of vitamins and minerals consumed in "natural matrices" in the diet rather than as supplements, they add.
In a research letter to the Journal of Human Hypertension, P de Leeuw (University Hospital Maastricht, The Netherlands) and colleagues explain that dietary intervention studies have shown impressive reductions in BP, probably due in part to the mineral and vitamin components of such diets. Yet interventions with combinations of either minerals or vitamins have provided mixed results.
In the current study, the researchers tested the BP lowering effect of a combination of minerals and vitamins. They randomly assigned 124 adults with untreated mild hypertension to take a supplemented skimmed milk drink or a placebo drink daily for 8 weeks.
The milk was supplemented with 446 mg calcium, 100 mg magnesium, 40 µg selenium, 180 mg vitamin C, 30 mg vitamin E and tocopherol equivalents, and either 1500 mg (high-K) or 750 mg (low-K) potassium per serving.
At the end of the study, office systolic BP had decreased by 4.6, 4.5, and 5.1 mmHg from baseline in the low-K supplement, high-K supplement, and placebo groups, respectively. The differences in BP reduction among groups were nonsignificant.
Reductions in office diastolic BP, pulse pressure, 24-hour systolic BP, 24-hour diastolic BP, and heart rate over the 8 weeks did not differ among the three groups either.
The results "are in contrast with many studies addressing interventions with the individual components," the authors write. They note that the doses of the individual minerals and vitamins may have been too low, and that combinations of vitamins and minerals may counter the effects of the individual components.
Meanwhile, the contrast with findings of dietary interventions may reflect the reduction of components with negative effects by diet replacement, the increased presence of as-yet unidentified components in dietary interventions, or altered bioavailability of nutrients when provided in a dairy matrix.
"Future studies should focus on assessing the effect of subsets of combinations of minerals and vitamins in natural matrices to get a better understanding of the possible antagonistic action between some of these ingredients," de Leeuw and co-authors conclude.
Journal
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