Combined Effects of HDL Cholesterol, Triglyceride, and Total Cholesterol Concentrations on 18-Year Risk of Atherosclerotic Disease

Abstract

Background Whether the combination of a low level of HDL cholesterol (HDL-C) and high level of triglyceride (TG) confers increased risk of cardiovascular disease and whether risk varies across levels of total cholesterol (TC) are not well established. Combined effects of HDL-C, TG, and TC on the incidence of atherosclerotic disease were examined prospectively in Japanese-American men from the Honolulu Heart Program. Methods and Results Among 1646 men aged 51 to 72 years who were free of coronary heart disease (CHD), stroke, and cancer and were not taking lipid-lowering medication, 318 developed atherosclerotic events (angina, coronary insufficiency, aortic aneurysm, definite CHD, or thromboembolic stroke) and 170 developed definite CHD between 1970 and 1988. Subjects were stratified by TC level (desirable, <200 mg/dL; borderline high, 200 to 239 mg/dL; high, ≥240 mg/dL), HDL-C level (<35 and ≥35 mg/dL), and TG level (<200 and ≥200 mg/dL). With Cox regression with high HDL-C and low TG as reference, age-adjusted relative risks (RR) of atherosclerotic events were significantly elevated in men with low HDL-C and high TG at borderline-high (RR, 2.46; 95% CI, 1.48 to 4.09) and high (RR, 2.21; 95% CI, 1.34 to 3.66) TC levels but not in men with desirable TC levels (RR, 0.89; 95% CI, 0.38 to 2.09). Elevated risks were independent of blood pressure, obesity, fat distribution, diabetes, smoking, and alcohol. Results were not materially altered by exclusion of subjects with angina alone and were similar but somewhat weaker for CHD. Conclusions Risk of atherosclerotic disease appears elevated in subjects with low HDL-C and high TG levels when TC is borderline high or high, independent of other cardiovascular risk factors. These findings support recent cholesterol screening recommendations and suggest that joint effects of HDL-C and TG may be important to consider.