Large-scale clinical trials have shown that long-term treatment with lipid-lowering therapy results in a significant reduction in the occurrence of heart failure among patients with coronary artery disease without previous evidence of congestive heart failure, suggesting dyslipidemia may have an adverse effect on left ventricular performance. To examine whether dyslipidemia has a detrimental effect on left ventricular systolic function and whether this effect is dependent on the corresponding severity of coronary atherosclerosis, 114 consecutive patients with stable angina and a positive exercise thallium-201 myocardial perfusion single-photon emission computed tomography were studied. All patients underwent measurement of serum lipid profiles, right-sided heart catheterization, left ventriculography, and selective coronary arteriography. Mean serum levels of total cholesterol and triglycerides were 4.5 and 1.4 mmol/l, respectively. In univariate analysis, a significant positive correlation between serum high-density lipoprotein (HDL) cholesterol and left ventricular ejection fraction (LVEF) (r = 0.49, P<0.0001) was found. Patients in the lower tertile of serum HDL cholesterol had a significantly lower mean LVEF than those in the upper tertile (55.9+/-15.2 vs. 72.8+/-6.8%, P<0.0001). Stepwise multiple linear regression analysis revealed that LVEF significantly correlated with HDL cholesterol (P<0.0001), the Gensini score (P = 0.008), and diabetes mellitus (P = 0.08) (r = 0.55, P<0.0001). In subgroup analysis of patients with angiographically normal coronary arteries, serum HDL cholesterol was still significantly associated with LVEF. The present study demonstrated an independent association between low HDL cholesterol and subclinical left ventricular systolic dysfunction in Chinese patients with stable angina whose serum levels of total cholesterol and triglycerides were relatively low. Moreover, this correlation remained significant even in patients with normal coronary angiograms, suggesting HDL cholesterol might influence left ventricular systolic performance through extra-atherosclerotic mechanisms.