High-Density Lipoprotein (HDL) Phospholipid Content and Cholesterol Efflux Capacity Are Reduced in Patients With Very High HDL Cholesterol and Coronary Disease

Abstract

Objective Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with coronary artery disease (CAD), and high HDL-C is generally associated with reduced risk of CAD. Extremely high HDL-C with CAD is an unusual phenotype, and we hypothesized that the HDL in such individuals may have an altered composition and reduced function when compared to controls with similarly high HDL-C and no CAD. Approach 55 subjects with very high HDL-C (mean 86 mg/dL) and onset of CAD around age 60 with no known risk factors for CAD (‘cases’) were identified through systematic recruitment. 120 control subjects without CAD, matched for race, gender, and HDL-C level (‘controls’), were identified. In all subjects, HDL composition was analyzed and HDL cholesterol efflux capacity was assessed. Results HDL phospholipid composition was significantly lower in cases (92 ± 37 mg/dL) than in controls (109 ± 43 mg/dL, p= 0.0095). HDL cholesterol efflux capacity was significantly lower in cases (1.96 ± 0.39) compared with controls (2.11 ± 0.43, p= 0.04). Conclusions In persons with very high HDL-C, reduced HDL phospholipid content and cholesterol efflux capacity is associated with the paradoxical development of CAD.

Theobromine Does Not Affect Fasting and Postprandial HDL Cholesterol Efflux Capacity, While It Decreases Fasting miR‐92a Levels in Humans

“…However, this effect was not changed by theobromine consumption. As the phospholipid content of HDL is a significant predictor of cholesterol efflux capacity, the intake of a high‐fat meal may lead to the production of more functional HDL particles, via an enrichment in phospholipids. In addition, preβ‐HDL concentrations have been shown to increase in the postprandial state in overweight and obese subjects .…”

Association Between Cholesterol Efflux Capacity and Atherosclerotic Cardiovascular Disease in Patients With Familial Hypercholesterolemia

“…In addition, HDL phospholipid composition has been positively associated with cholesterol efflux capacity. 7,35,36 Therefore, identification of ApoAI modification and HDL phospholipid composition in patients with FH would provide important information for predicting ASCVD risks.…”

The Changing Face of HDL and the Best Way to Measure It

“…In an analysis comparing patients with incident CHD vs healthy controls, CEC was significantly and inversely associated with incident CHD events (70 ). HDL CEC is also significantly lower in patients with both coronary disease and increased HDL-C compared with healthy controls (71 ), suggesting that HDL may be dysfunctional in some patients with markedly increased HDL-C concentrations. These studies underscore the importance of continuing research into better understanding the role of HDL-C efflux and for standardizing the CEC assay.…”