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

Haseeb Jafri, MD^_*, Alawi A. Alsheikh-Ali, MD, MS^,and Richard H. Karas, MD, PhD^_*,_*

^_* Molecular Cardiology Research Institute, Department of Medicine, Tufts Medical Center and Tufts University School of Medicine, Boston, Boston, Massachusetts
 Institute for Clinical Research and Health Policy Studies, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts
 Institute of Cardiac Sciences, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates

Manuscript received October 1, 2009; revised manuscript received December 14, 2009, accepted December 17, 2009.

^_* Reprint requests and correspondence: Dr. Richard H. Karas, Molecular Cardiology Research Institute, Box # 80, Tufts Medical Center, 750 Washington Street, Boston, Massachusetts 02111 (Email:rkaras@tuftsmedicalcenter.org).

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-alteringinterventions.

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 a36% (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.

Key Words: cancer • high-density lipoprotein cholesterol • lipids • randomized controlled trials