LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature

ABSTRACT

Introduction: For half a century, a high level of total cholesterol (TC) or low-density lipoprotein cholesterol (LDL-C) has been considered to be the major cause of atherosclerosis and cardiovascular disease (CVD), and statin treatment has been widely promoted for cardiovascular prevention. However, there is an increasing understanding that the mechanisms are more complicated and that statin treatment, in particular when used as primary prevention, is of doubtful benefit.

Areas covered: The authors of three large reviews recently published by statin advocates have attempted to validate the current dogma. This article delineates the serious errors in these three reviews as well as other obvious falsifications of the cholesterol hypothesis.

Expert commentary: Our search for falsifications of the cholesterol hypothesis confirms that it is unable to satisfy any of the Bradford Hill criteria for causality and that the conclusions of the authors of the three reviews are based on misleading statistics, exclusion of unsuccessful trials and by ignoring numerous contradictory observations.     

Baseline,delta, and achieved low-density lipoprotein cholesterol levels and cardiovascular risk in patients on statin therapy: A post-hoc resampling mediation analysis of treating new targets [TNT] trial

Clinical guidelines for monitoring low-density lipoprotein cholesterol (LDL-C) after statin therapy do not clearly define the clinical roles of baseline LDL-C, ΔLDL-C, and achieved LDL-C according to statin intensity. We performed post-hoc analysis of the Treating to New Target (TNT) study to evaluate individual LDL-C parameters after statin therapy. Primary outcome was the risk for total major adverse cardiovascular events (MACE). We use resampling multilevel mediation analysis to analyze complex relationships among LDL-C parameters based on similar statin intensities. Tertiles for resample A (matched baseline LDL-C; distinct achieved LDL), resample B (matched ΔLDL-C; distinct baseline LDL-C), and resample C (matched achieved LDL-C; distinct ΔLDL-C) were analyzed using Cox proportional hazard ratios. In original data analysis, the incidence of MACE was reduced in those with lower achieved LDL-C in total, low, and high intensity statin users (hazard ratios [HRs] = 0.990, 0.992, 0.992; respectively; all P-values < .001). In mediation analysis, resample A showed consistently high incidence for MACE in the middle tertile (HR = 1.237; 95% confidential interval [CI] = 1.008-1.517; P-value = .041) and highest tertile (HR = 1.275; 95% CI = 1.021-1.592; P-value = .032) compared to the lowest tertile. However, resamples B and C did not show consistent differences. Similarly, no consistent statistical difference in MACE according to statin intensity. Lower achieved LDL-C decreased MACE in participants with a similar baseline LDL-C after statin therapy. However, the change in absolute values of ΔLDL-C and achieved LDL-C should be interpreted in an individualized manner due to their complex collinearity, and statin intensity should also be taken into consideration.     

Statins and the risk of Parkinson disease: an update on the controversy

Background: Parkinson disease (PD) is the second most common neuro- degenerative disease and the number of affected patients is growing. Until now, information on either risk factors (genetic or environmental) or neuro- protective agents is still scarce. Recently, hydroxymethylglutary-coenzyme A reductase inhibitors have been related to protective as well as to potential harmful effects with regard to the development of a PD diagnosis. Objective: To give an overview and comment on the data available so far on this topic. Methods: Relevant literature was identified using a PubMed search of articles published up to October 2008. Search terms included: ‘Parkinson disease’, ‘statins’, and ‘epidemiology’. Original articles were reviewed and relevant citations from these articles were also considered. Results/conclusion: Results of the available observational studies were inconsistent with most studies reporting a protective effect of statins on the risk of PD. Others found no altered risk of PD in statin users compared to non-users or even an increased risk. Studies largely varied in size and analysis methods. Thus, comparison of the results is difficult. Until now, no definite conclusion on this topic can be made.