HDL as independent risk factor for heart disease

Nutrition Research Newsletter, April, 2006

Coronary heart disease (CHD) is the leading cause of death in the United States. Risk factors for CHD include age, sex, family history, smoking, diabetes, hypertension, elevated total cholesterol, elevated low-density lipoprotein cholesterol (LDL-C), and reduced high-density lipoprotein cholesterol (HDL-C). Randomized controlled trials of bile acid sequestrants and HMG-CoA reductase inhibitors (statins) have demonstrated conclusively that lowering LDL-C results in the primary and secondary prevention of CHD.

The National Cholesterol Education Program Adult Treatment Panel III guidelines released in 2001 continued to emphasize lowering of LDL-C as a primary goal of cardiovascular risk reduction. However, the guidelines also stated that lowering non-HDL-C (total cholesterol minus HDL-C) should be a secondary goal in persons with elevated triglyceride levels, based on the assumption that all plasma cholesterol 1 other than HDL-C is atherogenic. However, several large trials of drugs to Iower triglycerides (the main component of non-HDL-C besides LDL-C) were either negative or raised doubts concerning long-term safety.

Epidemiologic studies have shown a correlation between low levels of HDL-C and risk of adverse coronary events. Separating the effects of raising HDL-C from lowering LDL-C is difficult as drugs effective at lowering LDL-C can also increase HDL-C.

A recent study used data from one of the largest, most enduring clinical data repositories to assess the independent effect in everyday clinical practice of HDL-C and its change over time on the incidence of major adverse coronary events among patients receiving care in a large urban academic primary care, general internal medicine practice. The study cohort included 6928 patients, treated by the outpatient primary care and specialty services of Indiana University Medical Group-Primary Care (IUMG-PC).

All IUMG-PC data are stored in the Regenstrief Medical Record System (RMRS) and include all laboratory data from every outpatient, inpatient, and emergency/urgent patient encounter. Investigators identified a retrospective cohort of subjects that included all IUMG-PC patients who had lipids measured between January 1, 1985 and December 31, 1997.

To assess the effect of change in lipid values on coronary events, analysis was limited to patients who had two or more lipid measurements.

From each patient's RMRS record, demographic, important cardiovascular risk factors, and prior evidence of CHD was extracted. In addition to CHD, a variable indicating patients who had a prior MI was included. The outcome variable was the first evidence of an acute coronary event occurring after a patient's inception date. The primary independent (predictor) variables were the first recorded lipid values and the change in each of these values between the first and second recorded measurements.

The time between the first and second lipid measurements averaged 2.6 years. During a mean of 5.1 [ or -] 3.2 years of observation after their second lipid measurements, 2167 (31%) patients had an acute coronary event. Patients having events were significantly older, more often white, male, and smokers and more often had antecedent diabetes, hypertension, coronary heart disease, and myocardial infarctions. Adjusting for covariates, a 10-mg/dL higher initial HDL-C was associated with an 11% (95% CI; 7% to 14%) lower risk of coronary events. A 10-mg/dL increase in HDLC between lipid measurements was associated with a 7% (95% CI; 3% to 10%) lower risk of events. Neither initial or change in triglycerides nor LDL-C predicted subsequent coronary events.

HDL-C initial measurements and change in HDL-C predicted major adverse coronary events in this large, urban practice. This supports intervention targeting HDL-C for cardiovascular risk reduction.

C. Koro, S. Bowlin, T. Stump, et al. The independent correlation between high-density lipoprotein cholesterol and subsequent major adverse coronary events. Am Heart J; 151:755.el-755.e6 (March, 2006) [Correspondence: William M. Tierney, MD, Room M200-OPW, Wishard Memorial Hospital, 1001 West Tenth Street, Indianapolis, IN 46202. E-mail: wtierney@iupui.edu]