title: Meta-analysis: statin therapy does not alter the association between low levels of high-density lipoprotein cholesterol and increased cardiovascular risk.
abstract: 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.
  
  
  OBJECTIVE
  Using meta-analysis of large randomized, controlled trials (RCTs) of statins to determine whether statins alter the relationship between HDL-C level and MI.
  
  
  METHODS
  MEDLINE search to February 2010, ClinicalTrials.gov, and reference lists from eligible studies.
  
  
  METHODS
  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.
  
  
  METHODS
  Two independent investigators extracted data from eligible RCTs.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  The observed associations may be explained by unmeasured confounding and do not imply causality in the relationship between HDL-C level and cardiovascular risk.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  None.
authors.affiliation: Molecular Cardiology Research Institute, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, and Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
authors.forename: Haseeb
authors.initials: H
authors.lastname: Jafri
authors.forename: Alawi A
authors.initials: AA
authors.lastname: Alsheikh-Ali
authors.forename: Richard H
authors.initials: RH
authors.lastname: Karas
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology*; D012307:Risk Factors
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors