Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis

Study Questions:

Does cholesterol efflux capacity from macrophages predict atherosclerosis burden independently of high-density lipoprotein (HDL) levels?

Methods:

Cholesterol efflux capacity was measured in 203 healthy volunteers who underwent assessment of carotid artery intima-media thickness (CIMT), 442 patients with angiographically confirmed coronary artery disease (CAD), and 351 patients without such angiographically confirmed disease.

Results:

Levels of HDL cholesterol and apolipoprotein (apo) A-I were significant determinants of cholesterol efflux capacity, but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and CIMT both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of CAD status (adjusted odds ratio for CAD per 1-standard deviation [SD] increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59-0.83; p < 0.001). This relationship remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63-0.90; p = 0.002) or apo A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61-0.89; p = 0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins.

Conclusions:

The authors concluded that cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both CIMT and the likelihood of angiographic CAD, independently of the HDL cholesterol level.

Perspective:

Although HDL levels are inversely associated with CAD risk, it remains unclear whether raising HDL with drugs will lead to the cardiovascular benefits expected based on epidemiological studies. This suggests that the relationship between HDL levels and CAD may be more complex than initially thought. Additional understanding of the mechanism(s) by which HDL may confer cardiovascular benefits is needed. A means by which to measure the different properties of HDL and then to correlate them with cardiovascular risk will facilitate progress in this field. The current study quantified cholesterol efflux capacity by incubating macrophages with serum from the study participants depleted of apo B. Because this property of HDL was largely independent of HDL cholesterol levels and independently predicted presence of atherosclerosis (in this cross-sectional study), these results confirm that methods to analyze HDL function are needed and will be helpful in the evaluation and design of therapeutic strategies affecting HDL.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Coronary Artery Disease, Atherosclerosis, Macrophages, Biological Markers, Coronary Angiography, Cardiovascular Diseases, Cholesterol, HDL, Hypercholesterolemia, Lipoproteins, HDL, Thiazolidinediones


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