High-density lipoprotein (HDL) functionality and its relevance to atherosclerotic cardiovascular disease

Abstract

Several prospective epidemiological studies have shown that there is a clear inverse relationship between serum high-density lipoprotein-cholesterol (HDL-C) concentrations and risk for coronary heart disease (CHD), even at low-density lipoprotein-cholesterol (LDL-C) levels below 70 mg/dL. However, more recent evidence from genetic studies and clinical research has come to challenge the long-standing notion that higher HDL-C levels are always beneficial, while lower HDL-C levels are always detrimental. Thus, it becomes apparent that HDL functionality plays a much more important role in atheroprotection than circulating HDL-C levels. HDL cholesterol efflux capacity (CEC) from macrophages is a key metric of HDL functionality and exhibits a strong inverse association with both carotid intima-media thickness and the likelihood of angiographic coronary artery disease (CAD), independent of the HDL-C level. Thus, extensive research is being conducted to identify new agents with a favorable side effect profile, which would be able to enhance CEC, improve HDL functionality and potentially decrease cardiovascular risk. This review aims to present and discuss the current clinical and scientific evidence pertaining to the significance of HDL functionality over the actual HDL-C concentration in mediating the favorable effects on the cardiovascular system. Thus, we conducted a PubMed search until December 2017 through the English literature using the search terms ‘HDL function/functionality’, ‘HDL properties’, ‘cardiovascular risk’ and ‘cholesterol efflux capacity’. We also included references from the articles identified and publications available in the authors’ libraries.

Serum Level of Interleukin-33, C-Reactive Protein, and Troponin in Iraqi Coronary Artery Disease Patients

“…Troponin concentration in CAD patients in the present study was within the normal range, and this disagrees with the previously reported association with increased CVD risk, which may be due small sample size or medications intake [28]. The lipid profile analysis showed only a significant association between HDL and CAD There is a clear inverse relationship between serum high-density lipoproteincholesterol (HDL-C) concentrations and the risk for coronary heart disease (CHD), even at lowdensity lipoprotein-cholesterol (LDL-C) levels below 70 mg/dL [29]. High HDL-C, reduced HDL phospholipid content, and cholesterol efflux capacity are associated with the paradoxical development of CAD [30].…”

Dysfunctional high-density lipoprotein and atherogenesis

“…HDL is synthesized in the intestine and the liver and consists of a heterogeneous group of particles, which differ in density, size, electrophoretic mobility, and apolipoprotein content [5,9] . Furthermore, the HDL particles present marked structural, physiochemical, compositional and functional heterogeneity and have significant differences in their biological properties [5,10,11] .…”

“…On the other hand, there is ample clinical evidence showing that HDL functionality, more than HDL-C concentration per se, plays a crucial role in atheroprotection [5,6] . HDL functionality is assessed by the cholesterol efflux capacity (CEC), which determines the ability of HDL to accept cholesterol from macrophages for excretion into the liver.…”

HDL Cholesterol Efflux Capacity and Concentration in Patients With Rheumatoid Arthritis: a Systematic Review and Meta-Analysis

“…Macrophages cholesterol e ux as the rst critical step of RCT which is considered a key atheroprotective property [16]. The impaired HDL cholesterol e ux capacity (CEC) has been proven to increase the risk of CVD, which is independent of the plasma HDL-C levels [17,18]. However, the epidemiological data that have been performed to explore the association between CEC and RA was less convincing.…”