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 long been linked to coronary artery disease (CAD). The present study evaluated the association between plasma lipoprotein lipid and apolipoprotein (apo) components and CAD in a group of 80 consecutive Caucasian patients undergoing coronary angiography.


METHODS
Coronary cineangiography was carried out using the Judkins technique and the lesions quantified by calculating a coronary artery lesion score (CALS). Very low- and low-density lipoproteins (VLDL and LDL) were separated by ultracentrifugation, and high-density lipoprotein (HDL) and HDL subfraction-3 (HDL3) isolated by a differential precipitation procedure. Apo A-I, A-II, and B were assayed by endpoint laser nephelometry using specific antibodies. Total cholesterol, free cholesterol, and fatty acid concentrations were measured by gas-liquid chromatography, and lecithin: cholesterol acyltransferase (LCAT) activity by the decrease in the concentration of free cholesterol.


RESULTS
On the basis of the presence of 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 lipoprotein fraction that most clearly differentiated the groups was HDL cholesterol concentration, with a mean +/- SEM value of 36.5 +/- 1.5 mg/dl for those with CAD and 45.1 +/- 2.1 mg/dl for those without (P < 0.01). The mean HDL3 cholesterol concentration was 29.9 +/- 1.2 mg/dl for patients with CAD and 37.4 +/- 1.8 mg/dl for those without (P < 0.001). These differences in HDL cholesterol and HDL3 cholesterol were mainly caused by differences in the free cholesterol component, with a mean HDL free cholesterol level of 10.8 +/- 1.1 and 16.1 +/- 1.4 mg/dl (P < 0.01), and a mean HDL3 free cholesterol level of 7.6 +/- 0.6 and 11.9 +/- 0.8 mg/dl (P < 0.001) in patients with and without CAD, respectively. Plasma LCAT activity was decreased in patients with CAD (P < 0.05), as were the apo A-I and A-II concentrations in both the HDL (P < 0.001) and HDL3 (P < 0.001) fractions. No significant association was found between CAD and HDL2 cholesterol or plasma total cholesterol, LDL cholesterol, or VLDL cholesterol concentrations. A stepwise discriminant analysis revealed that HDL3 free cholesterol was the only variable selected. Using HDL3 free cholesterol as a screening variable 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 HDL3 free cholesterol were 82 and 75%, respectively.


CONCLUSIONS
We have shown that the concentrations of HDL cholesterol and HDL3 most clearly differentiated between patients with and without CAD.
Smuts
C M
CM
National Research Programme for Nutritional Intervention, South Africa Medical Research Council, Tygerberg.
Weich
H F
HF
Weight
M J
MJ
Faber
M
M
Kruger
M
M
Lombard
C J
CJ
Benadé
A J
AJ
D000328:Adult; D001053:Apolipoproteins / Q000032:analysis*; D015415:Biomarkers / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000000981:diagnostic imaging; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012680:Sensitivity and Specificity
D001053:Apolipoproteins; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D008075:Lipoproteins, HDL