High-density lipoprotein cholesterol increase and non-cardiovascular mortality: a meta-analysis

Context Many observational prospective studies have confirmed the inverse relationship between high-density lipoprotein (HDL) cholesterol and coronary heart disease. However, the potential benefit of the pharmacological increase in HDL cholesterol has not been clearly demonstrated. Moreover, in some interventions an increase in total mortality has been reported.

Objective The objective of this meta-analysis was to determine the relationship between HDL cholesterol increase and non-cardiovascular mortality in randomised trials.

Data sources Authors searched Medline up to December 2008.

Study selection Four reviewers identified randomised trials in which, through different types of interventions, HDL cholesterol increase in the treatment group was >4% compared to control group, both groups reported separately non-cardiovascular mortality and the duration of the study was, at least, one year.

Data extraction Data of HDL cholesterol concentrations and deaths were collected as they appeared in the original studies. If necessary, reviewers calculated data by using trial information.

Results Meta-regression analysis included 44 articles corresponding to 107 773 participants. Analysis showed an association between HDL cholesterol increase and non-cardiovascular mortality (p=0.023), however, the correlation disappeared when we excluded the ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerosis Events) trial from the analysis (p=0.972).

Conclusions Meta-regression analysis results suggest that increases in HDL cholesterol up to 40% are not associated with higher non-cardiovascular death. The increase in adverse events observed in some trials where HDL cholesterol was raised in large amounts could be related with the drug mechanisms more than the HDL cholesterol increase itself.