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


METHODS
Authors searched Medline up to December 2008.


METHODS
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.


METHODS
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.
Burillo
Elena
E
Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Zaragoza, Spain. eburilloi.iacs@aragon.es
Andres
Eva Maria
EM
Mateo-Gallego
Rocio
R
Fiddyment
Sarah
S
Jarauta
Estibaliz
E
Cenarro
Ana
A
Civeira
Fernando
F
D002318:Cardiovascular Diseases / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D009026:Mortality; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents