Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: Systematic review and meta-regression analysis

Department of Clinical Epidemiology and Biostatistics, McMaster University, 1200 Main Street West, Hamilton, ON, Canada.
BMJ (online) (Impact Factor: 17.45). 02/2009; 338(feb16 1):b92. DOI: 10.1136/bmj.b92
Source: PubMed


To investigate the association between treatment induced change in high density lipoprotein cholesterol and total death, coronary heart disease death, and coronary heart disease events (coronary heart disease death and non-fatal myocardial infarction) adjusted for changes in low density lipoprotein cholesterol and drug class in randomised trials of lipid modifying interventions.
Systematic review and meta-regression analysis of randomised controlled trials.
Medline, Embase, Central, CINAHL, and AMED to October 2006 supplemented by contact with experts in the field.
In teams of two, reviewers independently determined eligibility of randomised trials that tested lipid modifying interventions to reduce cardiovascular risk, reported high density lipoprotein cholesterol and mortality or myocardial infarctions separately for treatment groups, and treated and followed participants for at least six months.
Using standardised, pre-piloted forms, reviewers independently extracted relevant information from each article. The change in lipid concentrations for each trial and the weighted risk ratios for clinical outcomes were calculated.
The meta-regression analysis included 108 randomised trials involving 299 310 participants at risk of cardiovascular events. All analyses that adjusted for changes in low density lipoprotein cholesterol showed no association between treatment induced change in high density lipoprotein cholesterol and risk ratios for coronary heart disease deaths, coronary heart disease events, or total deaths. With all trials included, change in high density lipoprotein cholesterol explained almost no variability (<1%) in any of the outcomes. The change in the quotient of low density lipoprotein cholesterol and high density lipoprotein cholesterol did not explain more of the variability in any of the outcomes than did the change in low density lipoprotein cholesterol alone. For a 10 mg/dl (0.26 mmol/l) reduction in low density lipoprotein cholesterol, the relative risk reduction was 7.2% (95% confidence interval 3.1% to 11%; P=0.001) for coronary heart disease deaths, 7.1% (4.5% to 9.8%; P<0.001) for coronary heart disease events, and 4.4% (1.6% to 7.2%; P=0.002) for total deaths, when adjusted for change in high density lipoprotein cholesterol and drug class.
Available data suggest that simply increasing the amount of circulating high density lipoprotein cholesterol does not reduce the risk of coronary heart disease events, coronary heart disease deaths, or total deaths. The results support reduction in low density lipoprotein cholesterol as the primary goal for lipid modifying interventions.

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    • "Meta-analyses designed to ascertain the impact of HDL-C raising on hard CV endpoints are decidedly mixed. One meta-analysis conducted by Briel and colleagues included 108 randomized clinical trials (including statins, fibrates, niacin, and combinations of lipid modifying drugs) that enrolled nearly 300,000 men and women [54]. After adjustment for changes in LDL-C, no association was found between HDL-C elevation and risk of nonfatal MI, CHD mortality, or all-cause mortality. "
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