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High-density lipoprotein: relations to metabolic parameters and severity of coronary artery disease
P Tornvall1, F Karpe, A Proudler
1Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institute, Stockholm, Sweden.
Insights
High-density lipoprotein (HDL) cholesterol levels are influenced by various metabolic factors in patients with coronary artery disease. These factors, including very-low-density lipoprotein (VLDL) cholesterol and hepatic lipase (HL) activity, explain HDL variability and its link to coronary stenosis.
Area of Science:
- Cardiovascular Medicine
- Metabolic Research
- Lipidology
Background:
- Plasma high-density lipoprotein (HDL) cholesterol plays a crucial role in cardiovascular health.
- Understanding the determinants of HDL cholesterol is vital for managing coronary artery disease (CAD).
- Previous studies suggest a link between HDL cholesterol and coronary stenosis severity.
Purpose of the Study:
- To investigate the regulation of plasma HDL cholesterol by various metabolic factors in young postinfarction patients and healthy controls.
- To analyze the association between HDL cholesterol, HDL subclasses, and coronary stenosis severity.
- To identify key determinants of HDL cholesterol variability and their impact on CAD.
Main Methods:
- Investigated plasma lipoprotein lipids, lipoprotein lipase (LPL), hepatic lipase (HL), cholesteryl ester transfer protein (CETP), oral glucose tolerance, and insulin/proinsulin levels.
- Measured HDL subclasses using gradient gel electrophoresis.
- Employed multiple stepwise regression analysis to determine predictors of HDL cholesterol and its relationship with coronary stenosis score.
Main Results:
- In patients, VLDL cholesterol, LDL triglyceride, and postheparin HL activity significantly predicted HDL cholesterol variability (42%).
- In controls, VLDL cholesterol and postheparin HL activity predicted HDL cholesterol variability (35%).
- HDL cholesterol and subclass relationships with coronary stenosis score disappeared when metabolic parameters were controlled, indicating their mediating role.
Conclusions:
- Metabolic parameters, particularly VLDL cholesterol and HL activity, are key determinants of HDL cholesterol levels in both patients and controls.
- The association between HDL cholesterol and coronary artery disease severity is mediated by these metabolic factors.
- Considering triglyceride-rich lipoproteins and lipolytic enzymes is essential for understanding the HDL-CAD relationship.
Abstract:
The regulation of plasma high-density lipoprotein (HDL) cholesterol level by the joint influence of plasma lipoprotein lipids, lipoprotein lipase (LPL), hepatic lipase (HL), cholesteryl ester transfer protein (CETP), oral glucose tolerance, and postload plasma insulin and proinsulin levels was investigated in young postinfarction patients and healthy population-based control subjects. In addition, the association between HDL cholesterol and the number and severity of coronary stenoses previously reported in this cohort of young postinfarction patients was further investigated by analyzing the determinants and angiographic relations of HDL subclasses measured by gradient gel electrophoresis. The following parameters showed significant univariate relations with HDL cholesterol level in the patient group: very-low-density lipoprotein (VLDL) cholesterol and triglyceride, low-density lipoprotein (LDL) triglyceride, and postload plasma insulin concentrations, preheparin plasma LPL mass, and postheparin plasma HL activity. In the control group, significant correlations with HDL cholesterol concentration in addition to those noted among the patients were found for body mass index (BMI), LDL cholesterol level, postload plasma intact proinsulin concentration, and LPL activity in postheparin plasma. In contrast to the patients, no significant relations were noted for postload plasma insulin level and preheparin plasma LPL mass. Multiple stepwise regression analysis showed that 42% of the variability of HDL cholesterol in the patients could be accounted for by VLDL cholesterol concentration (29%), LDL triglyceride level (7%), and postheparin plasma HL activity (8%), whereas the corresponding figure in controls was 35% (VLDL cholesterol concentration [9%] and postheparin plasma HL activity [26%]. The strength of the relationships of HDL cholesterol and HDL subclasses to the coronary stenosis score was similar and statistically significant (r = .25 to .36). When the metabolic parameters that correlated with HDL cholesterol and HDL subclass concentrations in univariate analysis were used as covariates, all relations to the coronary stenosis score disappeared. This clearly indicates that the influence of triglyceride-rich lipoproteins and lipolytic enzymes needs to be considered when assessing the association between HDL cholesterol and coronary artery disease (CAD).