Is it smoking or related lifestyle variables that increase metabolic syndrome risk?

Metabolic syndrome is considered as mainly caused by a deleterious lifestyle (sedentarity and diet). That smoking contributes to metabolic syndrome had been suggested by several small studies and a meta-analysis. The interesting study by Slagter et al. published in BMC Medicine is the first very large study confirming this association in both genders, in all classes of body mass index, and in a dose-related manner. Surprisingly, smoking is even associated with increased abdominal fat. Rather than a direct causal effect of smoking, the reason for these associations is most probably the frequent presence of other lifestyle components in smokers. For example, physical inactivity and alcohol drinking are known to be more often present in smokers and could completely explain the observations of the Slagter et al. study. Unfortunately, these factors, already not properly checked in the first studies, were not assessed at all in the present one. However, as it is still on-going, we hope that other lifestyle factors will be included in future publications. Please see related research: http://www.biomedcentral.com/1741-7015/11/195

Beyond confusion and controversy, can we evaluate the real efficacy and safety of cholesterol-lowering with statins?

A strong controversy has emerged about the reality of safety and efficacy of statins as stated by company-sponsored reports. However, physicians need credible data to make medical decisions, in particular about the benefit/harm balance of any prescription. This study aimed to test the validity of data on the company-sponsored statin trial by comparing them over time and then comparing statins with each other. Around the years 2005/2006, new stricter Regulations were introduced in the conduct and publication of randomized controlled trials (RCTs). This would imply that RCTs were less reliable before 2006 than they were later on. To evaluate this, we first reviewed RCTs testing the efficacy of statins versus placebo in preventing cardiovascular complications and published after 2006. Our systematic review thereby identified four major RCTs, all testingrosuvastatin. They unambiguously showed that rosuvastatin is not effective in secondary prevention, while the results are highly debatable in primary prevention. Because of the striking clinical heterogeneity and the inconsistency of the published data in certain RCTs, meta-analysis was not feasible. We then examined the most recent RCTs comparing statins to each other: all showed that no statin is more effective than any other, including rosuvastatin. Furthermore, recent RCTs clearly indicate that intense cholesterol-lowering (including those with statins) does not protect high-risk patients any better than less-intense statin regimens. As for specific patient subgroups, statins appear ineffective in chronic heart failure and chronic kidney failure patients. We also conducted a MEDLINE search to identify all the RCTs testing a statin against a placebo in diabetic patients, and we found that once secondary analyses and subgroup analyses are excluded, statins do not appear to protect diabetics. As for the safety of statin treatment – a major issue for medical doctors – it is quite worrisome to realize that it took 30 years to bring to light the triggering effect of statins on new-onset diabetes, manifestly reflecting a high level of bias in reporting harmful outcomes in commercial trials, as has been admitted by the recent confession of prominent experts in statin treatment. In conclusion, this review strongly suggests that statins are not effective for cardiovascular prevention. The studies published before 2005/2006 were probably flawed, and this concerned in particular the safety issue. A complete reassessment is mandatory. Until then, physicians should be aware that the present claims about the efficacy and safety of statins are not evidence based

Recent flaws in Evidence Based Medicine: statin effects in primary prevention and consequences of suspending the treatment.

Statin therapy is presented as a protection against ischemic heart disease (IHD) complications. As IHD is often a fatal disease, statins are thereby supposed to decrease cardiovascular mortality and increase life expectancy. However, these benefits are increasingly challenged in the medical community, the controversy being particularly intense when discussing the effects of statins in primary prevention and the consequences of statin discontinuation. Both primary prevention and treatment discontinuation have been recently used by investigators linked to the pharmaceutical industry to justify and boost prescription and consumption of statins and other cholesterol-lowering medications. We herein review some recent commercial data related to primary prevention with rosuvastatin and statin discontinuation and their respective effects on IHD and overall mortality rate. We conclude that (1) despite the recent hype raised by HOPE-3, the cholesterol-lowering rosuvastatin is likely not beneficial in intermediate-risk individuals without cardiovascular disease (primary prevention). This trial may even represent a typical example of how evidence-based medicine has been flawed in commercial studies. (2) Statin discontinuation does not lead to increased IHD and overall mortality, at least in the months following interruption of treatment. On the contrary, one might even conclude that statin discontinuation could save lives. One possible explanation of this apparently paradoxical finding is that statin discontinuers, in the same time they stop statin therapy, likely try to adopt a healthy lifestyle. Further studies are needed to confirm the real effects of statin discontinuation in various clinical conditions. In the meantime, it is not evidence based to claim that statin discontinuation increases mortality or saves lives

Is the use of cholesterol-lowering drugs for the prevention of cardiovascular complications in type 2 diabetics evidence-based? A systematic review.

International audienceCholesterol-lowering drugs are often prescribed to patients with type 2 diabetes mellitus despite uncertainty about the benefits of this treatment in the prevention of cardiovascular complications. We here systematically review (PRISMA guidelines) the results of high-quality double blind trials testing whether cholesterol-lowering drugs (statins and fibrates) reduce mortality and cardiovascular complications specifically in type 2 diabetics. Trials with premature termination without pertinent medical justification or using nonrandomized subgroups of diabetics were excluded from the review. Only four trials met our predefined inclusion criteria. Among the 3 statin trials, CARDS was discontinued 2 years before the anticipated end and in the absence of significant effect on both overall and cardiovascular mortality, suggesting that the trial should not have been prematurely stopped. The two other statin trials showed no significant effect on the primary endpoint (relative risk 0.92, 95% CI 0.77 to 1.10 in 4D and 0.90, 95% CI 0.73 to 1.12 in ASPEN) and on both cardiovascular and overall mortality. Finally, the fibrate trial (FIELD) showed no significant benefit on the primary endpoint (relative risk 0.89, 95% CI 0.75 to 1.05) and mortality (relative risk 1.11, 95% CI 0.95 to 1.29). Because of a huge medical heterogeneity between patients in the selected trials, it was consensually decided to stop the analysis at this stage. This review does not support the use of cholesterol-lowering drugs (such as statin and fibrate) to reduce mortality and cardiovascular complications in type 2 diabetics. Official guidelines should be re-examined and reformulated by experts independent from the pharmaceutical industry

Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy: a critical reappraisal.

International audienceBACKGROUND: Among the recently reported cholesterol-lowering drug trials, the JUPITER (Justification for the Use of Statins in Primary Prevention) trial is unique: it reports a substantial decrease in the risk of cardiovascular diseases among patients without coronary heart disease and with normal or low cholesterol levels. METHODS: Careful review of both results and methods used in the trial and comparison with expected data. RESULTS: The trial was flawed. It was discontinued (according to prespecified rules) after fewer than 2 years of follow-up, with no differences between the 2 groups on the most objective criteria. Clinical data showed a major discrepancy between significant reduction of nonfatal stroke and myocardial infarction but no effect on mortality from stroke and myocardial infarction. Cardiovascular mortality was surprisingly low compared with total mortality-between 5% and 18%-whereas the expected rate would have been close to 40%. Finally, there was a very low case-fatality rate of myocardial infarction, far from the expected number of close to 50%. The possibility that bias entered the trial is particularly concerning because of the strong commercial interest in the study. CONCLUSION: The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors

Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions: do statins inhibit omega-3?

<p>Abstract</p> <p>Early randomized controlled trials (RCTs) demonstrated the health benefits of omega-3 fatty acids (n-3), whereas recent RCTs were negative. We now address the issue, focusing on the temporal changes having occurred: most patients in recent RCTs are no longer n-3 deficient and the vast majority are now treated with statins. Recent RCTs testing n-3 against arrhythmias suggest that n-3 reduce the risk only in patients not taking a statin. Other recent RCTs in secondary prevention were negative although, in a <it>post-hoc </it>analysis separating statin users and non-users, non-significant protection of n-3 was observed among statin non-users whereas statin users had no effect. Recent RCTs testing statins - after the implementation of the New Clinical Trial Regulation in 2007 - are negative (or flawed) suggesting that the lack of effect of n-3 cannot be attributed to a parallel protection by statins. Finally, statins favor the metabolism of omega-6 fatty acids (n-6), which in turn inhibits n-3 and, contrary to n-3, they increase insulin resistance and the risk of diabetes. Thus, n-3 and statins are counteractive at several levels and statins appear to inhibit n-3.</p