Meta-analysis: statin therapy does not alter the association between low levels of high-density lipoprotein cholesterol and increased cardiovascular risk.

BACKGROUND: Low levels of high-density lipoprotein cholesterol (HDL-C) are associated with an increased risk for myocardial infarction (MI). Although statins reduce the risk for MI, most cardiovascular events still occur despite statin treatment.

PURPOSE: Using meta-analysis of large randomized, controlled trials (RCTs) of statins to determine whether statins alter the relationship between HDL-C level and MI.

DATA SOURCES: MEDLINE search to February 2010, ClinicalTrials.gov, and reference lists from eligible studies.

STUDY SELECTION: English-language RCTs of statin-treated patients versus control participants with 1000 or more person-years of follow-up and reported HDL-C levels and MI.

DATA EXTRACTION: Two independent investigators extracted data from eligible RCTs.

DATA SYNTHESIS: Twenty eligible RCTs were identified (543,210 person-years of follow-up and 7838 MIs). After adjustment for on-treatment LDL-C 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 0.26-mmol/L (10-mg/dL) decrease in HDL-C was associated with 7.1 (95% CI, 6.8 to 7.3) and 8.3 (CI, 8.1 to 8.5) more MIs per 1000 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).

LIMITATION: The observed associations may be explained by unmeasured confounding and do not imply causality in the relationship between HDL-C level and cardiovascular risk.

CONCLUSION: 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.

PRIMARY FUNDING SOURCE: None.