Abstract 858: Increase in High-Density Lipoprotein Cholesterol is Not Related With Higher Non-Cardiovascular Mortality; Systematic Review and Meta-Regression Analysis
Introduction: Many observational prospective studies have confirmed the inverse relationship between HDL cholesterol and coronary heart disease. However, although various clinical trials have tried to improve cardiovascular prognosis by increasing HDL concentration using different approaches, the results of these trials have been mostly unsuccessful. The explanation of this discrepancy between observational and intervention studies is unknown. The recent ILLUMINATE study, in which HDL cholesterol levels rose to 72% using the cholesteryl ester transfer protein inhibitor Torcetrapib, was suspended because of a substantial increase in the non-cardiovascular mortality in the treatment group, raising the possibility that some interventions associated with increased HDL cholesterol could have deleterious effects.
Hypothesis: A great increase in HDL cholesterol raised with any type of intervention could be associated with higher non-cardiovascular mortality.
Review Methods: This is a systematic review and meta-regression analysis of randomised controlled trials. Four reviewers identified 538 randomised trials in Medline database prior to December 2008. We excluded 494 trials because they did not meet inclusion criteria. Finally, we included 44 trials in which HDL cholesterol increase in the treatment group was higher than 4% compared to control group, both groups reported separately non-cardiovascular mortality and the duration of the study was at least one year. Data of HDL cholesterol concentrations and deaths were collected as they appeared in the original studies. If needed, reviewers calculated data from trial information.
Results: Meta-regression analysis included 44 articles corresponding to 107773 participants. Analysis did not show an association between HDL cholesterol increase and non-cardiovascular mortality (Q=0.0649, p-value=0.7987) neither a statistical difference between the type of treatment and HDL cholesterol increase.
Conclusions: Meta-regression results suggest that increase in HDL cholesterol is not associated with higher non-cardiovascular death. The increase in adverse events observed in some trials in which HDL cholesterol was raised in higher proportions could be related with the drug mechanisms.