Meta-Analysis: Statin Therapy Does Not Alter the Association Between Low Levels of High-Density Lipoprotein Cholesterol and Increased Cardiovascular Risk

Study Questions:

Does treatment with statins alter the association of low levels of high-density lipoprotein cholesterol (HDL-C) and increased risk for cardiovascular events (CVEs)?


A meta-analysis of large randomized controlled trials (RCTs) of statins was conducted to determine whether statins alter the relationship between high-density lipoprotein cholesterol (HDL-C) level and myocardial infarction (MI).


Twenty eligible RCTs were identified (543,210 person-years of follow-up and 7,838 MIs). After adjustment for on-treatment low-density lipoprotein cholesterol levels, age, hypertension, diabetes, and tobacco use, there was a significant inverse association between HDL-C levels and risk for MI in statin-treated patients and control participants. In Poisson meta-regressions, every 10 mg/dl decrease in HDL-C was associated with 7.1 (95% confidence interval [CI], 6.8-7.3) and 8.3 (95% CI, 8.1-8.5) more MIs per 1,000 person-years in statin-treated patients and control participants, respectively. The inverse association between HDL-C levels and MI did not differ between statin-treated patients and control participants (p = 0.57).


Statins do not alter the relationship between HDL-C level and cardiovascular risk, such that low levels of HDL-C remain significantly and independently associated with increased risk despite statin treatment. The remaining risk seen in statin-treated patients may be partly explained by low HDL-C levels or other factors associated with low levels of HDL-C.


The outcome of two placebo-controlled niacin + statin trials will be available within the next few years. Until then, considering the safety and efficacy data on niacin alone and niacin + statins in atherosclerosis and coronary disease, when statins are indicated, combining niacin with statins makes good clinical sense in men with an HDL-C <40 mg/dl and women <50 mg/dl.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Hypertension

Keywords: Lipoproteins, LDL, Cholesterol, Myocardial Infarction, Follow-Up Studies, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Cardiovascular Diseases, Coronary Disease, Cholesterol, HDL, Lipoproteins, HDL, Hypertension, Diabetes Mellitus

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