Related Experiment Videos
Free cholesterol concentrations in the high-density lipoprotein subfraction-3 as a risk indicator in patients with
C M Smuts1, H F Weich, M J Weight
1National Research Programme for Nutritional Intervention, South Africa Medical Research Council, Tygerberg.
Insights
Low high-density lipoprotein (HDL) cholesterol and HDL3 cholesterol levels, particularly free cholesterol, are strong indicators of coronary artery disease (CAD). HDL3 free cholesterol can effectively screen for CAD.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Biochemistry
Background:
- Plasma lipoprotein metabolism is intrinsically linked to the pathophysiology of coronary artery disease (CAD).
- This study investigates the relationship between lipoprotein components and CAD in Caucasian patients.
Purpose of the Study:
- To evaluate the association between plasma lipoprotein lipid and apolipoprotein (apo) components and CAD.
- To identify specific lipoprotein markers that differentiate patients with and without CAD.
Main Methods:
- Coronary cineangiography and coronary artery lesion score (CALS) calculation.
- Isolation of VLDL, LDL, HDL, and HDL3 fractions; assay of apo A-I, A-II, B, and cholesterol components.
- Measurement of lecithin: cholesterol acyltransferase (LCAT) activity.
Main Results:
- HDL cholesterol and HDL3 cholesterol concentrations were significantly lower in patients with CAD.
- Differences were primarily driven by free cholesterol levels in HDL and HDL3 fractions.
- Decreased plasma LCAT activity and lower apo A-I and A-II concentrations in HDL/HDL3 were observed in CAD patients.
- HDL3 free cholesterol demonstrated high sensitivity (87%) and specificity (67%) for CAD screening.
Conclusions:
- HDL cholesterol and HDL3 concentrations are key differentiators between patients with and without CAD.
- HDL3 free cholesterol emerges as a significant and effective screening variable for CAD.
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.
Conclusion:
We have shown that the concentrations of HDL cholesterol and HDL3 most clearly differentiated between patients with and without CAD.