FREE-CHOLESTEROL CONCENTRATIONS IN THE HIGH-DENSITY-LIPOPROTEIN SUBFRACTION-3 AS A RISK INDICATOR IN PATIENTS WITH ANGIOGRAPHICALLY DOCUMENTED CORONARY-ARTERY DISEASE

Background: The pathophysiology of plasma lipoprotein metabolism has l ong been linked to coronary artery disease (CAD). The present study ev aluated the association between plasma lipoprotein lipid and apolipopr otein (ape) components and CAD in a group of 80 consecutive Caucasian patients undergoing coronary angiography. Methods: Coronary cineangiog raphy was carried out using the Judkins technique and the lesions quan tified by calculating a coronary artery lesion score (CALS). Very low- and low-density lipoproteins (VLDL and LDL) were separated by ultrace ntrifugation, and high-density lipoprotein (HDL) and HDL subfraction-3 (HDL(3)) isolated by a differential precipitation procedure. Apo A-I, A-II, and B were assayed by endpoint laser nephelometry using specifi c antibodies. Total cholesterol, free cholesterol, and fatty acid conc entrations were measured by gas-liquid chromatography, and lecithin: c holesterol acyltransferase (LCAT) activity by the decrease in the conc entration of free cholesterol. Results: On the basis of the presence o f CAD, the 80 patients were divided into two groups: 52 (65%) with CAD (mean CALS = 7.8) and 28 (35%) without CAD (zero CALS). The lipoprote in fraction that most clearly differentiated the groups was HDL choles terol concentration, with a mean rf:SEM value of 36.5 +/- 1.5 mg/dl fo r those with CAD and 45.1 +/- 2.1 mg/dl for those without (P < 0.01). The mean HDL(3) cholesterol concentration was 29.9 +/- 1.2 mg/dl for p atients with CAD and 37.4 +/- 1.8 mg/dl for those without (P < 0.001). These differences in HDL cholesterol and HDL(3) cholesterol were main ly caused by differences in the free cholesterol component, with a mea n HDL free cholesterol level of 10.8 +/- 1.1 and 16.1 +/- 1.4 mg/dl (P < 0.01), and a mean HDL(3) free cholesterol level of 7.6 +/- 0.6 and 11.9 +/- 0.8 mg/dl (P < 0.001) in patients with and without CAD, respe ctively. Plasma LCAT activity was decreased in patients with CAD (P < 0.05), as were the ape A-I and A-II concentrations in both the HDL (P < 0.001) and HDL(3) (P < 0.001) fractions. No significant association was found between CAD and HDL(2) cholesterol or plasma total cholester ol, LDL cholesterol, or VLDL cholesterol concentrations. A stepwise di scriminant analysis revealed that HDL(3) free cholesterol was the only variable selected. Using HDL(3) free cholesterol as a screening varia ble for CAD (cutoff 10.55 mg/dl), the sensitivity for CAD was 87% and the specificity for non-CAD 67%. The positive and negative predictive values of HDL(3) free cholesterol were 82 and 75%, respectively. Concl usion: We have shown that the concentrations of HDL cholesterol and HD L(3) most clearly differentiated between patients with and without CAD .