HDL cholesterol: reappraisal of its clinical relevance

Abstract

BackgroundWhile several lines of evidence prove that elevated concentrations of low-density lipoproteins (LDL) causally contribute to the development of atherosclerosis and its clinical consequences, high-density lipoproteins are still widely believed to exert atheroprotective effects. Hence, HDL cholesterol (HDL-C) is in general still considered as “good cholesterol”. Recent research, however, suggests that this might not always be the case and that a fundamental reassessment of the clinical significance of HDL-C is warranted.MethodThis review article is based on a selective literature review.ResultsIn individuals without a history of cardiovascular events, low concentrations of HDL-C are inversely associated with the risk of future cardiovascular events. This relationship may, however, not apply to patients with metabolic disorders or manifest cardiovascular disease. The classical function of HDL is to mobilise cholesterol from extrahepatic tissues for delivery to the liver for excretion. These roles in cholesterol metabolism as well as many other biological functions of HDL particles are dependent on the number as well as protein and lipid composition of HDL particles. They are poorly reflected by the HDL-C concentration. HDL can even exert negative vascular effects, if its composition is pathologically altered. High serum HDL-C is therefore no longer regarded protective. In line with this, recent pharmacological approaches to raise HDL-C concentration have not been able to show reductions of cardiovascular outcomes.ConclusionIn contrast to LDL cholesterol (LDL-C), HDL-C correlates with cardiovascular risk only in healthy individuals. The calculation of the ratio of LDL-C to HDL-C is not useful for all patients. Low HDL-C should prompt examination of additional metabolic and inflammatory pathologies. An increase in HDL-C through lifestyle change (smoking cessation, physical exercise) has positive effects and is recommended. However, HDL-C is currently not a valid target for drug therapy.

Physical Activity in the Prevention and Treatment of Coronary Artery Disease

“…As reviewed extensively by März et al, HDL confers protection from damage, necrosis, and the apoptosis of endothelial cells 62. However, HDL from patients with CAD, hypertension, diabetes mellitus, chronic kidney dysfunction, and obesity (independent of its concentration) turns dysfunctional and shows diminished cholesterol efflux capacity and blunted capability of eNOS activation 62, 63…”

Enzymatic Production, Bioactivity, and Bitterness of Chickpea (Cicer arietinum) Peptides

“…Cholesterol is transferred to the liver from peripheral tissues by high‐density lipoproteins (HDL). While the elevation of blood serum HDL levels have historically been seen as a positive health outcome, this might only apply to individuals without cardiovascular disease (März et al., ; Tietge, ). Consumption of legumes, such as chickpeas, has been associated with a lower incidence of cardiovascular disease (Afshin, Micha, Khatibzadeh, & Mozaffarian, ; Marventano et al., ).…”

Structure-function relationships of HDL in diabetes and coronary heart disease

“…Low plasma levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased risks of coronary heart disease (CHD) and diabetes mellitus type 2 (T2DM) (1,2). HDL particles exert diverse potentially antiatherogenic and antidiabetic effects (3,4).…”

“…Furthermore, atherosclerosis or hyperglycemia could be decreased or even reverted in several animal models by transgenic overexpression or exogenous application of apolipoprotein A-I (apoA-I), the most abundant protein of HDL (3,4). However, in humans, drugs increasing HDL-C such as fibrates, niacin, and inhibitors of cholesteryl ester transfer protein (CETP) have failed to prevent fatal or nonfatal cardiovascular endpoints (2,5). Moreover, in several inborn errors of human HDL metabolism and genetic mouse models with altered HDL metabolism, low or high HDL-C levels were not associated with any differences in cardiovascular risk and atherosclerotic plaque load, respectively (2,3).…”