Baseline and on-treatment high-density lipoprotein cholesterol and the risk of cancer in randomized controlled trials of lipid-altering therapy

J Am Coll Cardiol. 2010 Jun 22;55(25):2846-54. doi: 10.1016/j.jacc.2009.12.069.

Abstract

Objectives: We sought to examine the relationship between high-density lipoprotein cholesterol (HDL-C) levels and the risk of the development of cancer in large randomized controlled trials (RCTs) of lipid-altering interventions.

Background: Epidemiologic data demonstrate an inverse relationship between serum total cholesterol levels and incident cancer. We recently reported that lower levels of low-density lipoprotein cholesterol are associated with a significantly higher risk of incident cancer in a meta-analysis of large RCTs of statin therapy. However, little is known about the relationship between HDL-C levels and cancer risk.

Methods: A systematic MEDLINE search identified lipid intervention RCTs with >or=1,000 person-years of follow-up, providing baseline HDL-C levels and rates of incident cancer. Using random-effects meta-regressions, we evaluated the relationship between baseline HDL-C and incident cancer in each RCT arm.

Results: A total of 24 eligible RCTs were identified (28 pharmacologic intervention arms and 23 control arms), with 625,477 person-years of follow-up and 8,185 incident cancers. There was a significant inverse association between baseline HDL-C levels and the rate of incident cancer (p = 0.018). The inverse association persisted after adjusting for baseline low-density lipoprotein cholesterol, age, body mass index (BMI), diabetes, sex, and smoking status, such that for every 10-mg/dl increment in HDL-C, there was a 36% (95% confidence interval: 24% to 47%) relatively lower rate of the development of cancer (p < 0.001).

Conclusions: There is a significant inverse association between HDL-C and the risk of incident cancer that is independent of LDL-C, age, BMI, diabetes, sex, and smoking.

Publication types

  • Review

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Cholesterol, HDL / blood*
  • Cholesterol, HDL / drug effects
  • Cholesterol, LDL / blood
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / diagnosis
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / epidemiology*
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Incidence
  • Male
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / epidemiology*
  • Neoplasms / physiopathology
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Sex Distribution
  • Survival Analysis

Substances

  • Cholesterol, HDL
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents