Baseline and On-Treatment High-Density Lipoprotein Cholesterol and the Risk of Cancer in Randomized Controlled Trials of Lipid-Altering Therapy

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 betwe...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2010-06, Vol.55 (25), p.2846-2854
Main Authors: Jafri, Haseeb, MD, Alsheikh-Ali, Alawi A., MD, MS, Karas, Richard H., MD, PhD
Format: Article
Language:English
Subjects:
Adult
Age Distribution
Aged
Biological and medical sciences
Body mass index
Cancer
Cardiology
Cardiology. Vascular system
Cardiovascular
Cardiovascular disease
Cholesterol
Cholesterol, HDL - blood
Cholesterol, HDL - drug effects
Cholesterol, LDL - blood
Clinical trials
Diabetes
Disease prevention
Female
Follow-Up Studies
Heart
high-density lipoprotein cholesterol
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
Internal Medicine
Lipids
Lipoproteins
Male
Medical sciences
Middle Aged
Neoplasms - blood
Neoplasms - epidemiology
Neoplasms - physiopathology
randomized controlled trials
Randomized Controlled Trials as Topic
Risk Assessment
Sex Distribution
Statistical methods
Studies
Survival Analysis
Variables
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Summary: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 ≥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.
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2009.12.069