Cholesterol Efflux Capacity and Cardiovascular Disease: The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.

Andreas Ritsch,Guenther Silbernagel,Tatjana Stojakovic,Marcus E Kleber,Monika Hunjadi,Winfried März,Hubert Scharnagl,Patrick Kahler,Angela Duerr

doi:10.3390/biomedicines8110524

Abstract

(1) Background and Aims: Efforts to reduce coronary artery disease (CAD) by raising high-density lipoprotein (HDL) cholesterol (HDL-C) have not been uniformly successful. A more important factor than HDL-C may be cellular cholesterol efflux mediated by HDL, which has been shown to be associated with CAD. In this report, we analyzed the influence of cardiovascular biomarkers and risk factors on cholesterol efflux in a prospective observational study of patients referred to coronary angiography. (2) Methods: HDL-mediated efflux capacity was determined for 2468 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study who were referred to coronary angiography at baseline between 1997 and 2000. Median follow-up time was 9.9 years. Primary and secondary endpoints were cardiovascular and all-cause mortality, respectively. (3) Results: Cholesterol efflux strongly correlated with HDL-related markers including HDL cholesterol, HDL phospholipids, and apolipoproteins AI and AII, as well as HDL particle concentration, which was not seen for low density lipoprotein (LDL) markers including LDL cholesterol and apoB. Cholesterol efflux was associated negatively with C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), and serum amyloid A. Cardiovascular mortality was higher in patients in the lowest cholesterol efflux quartile. This association was weakened, but not fully abolished, after adjustment for HDL cholesterol. (4) Conclusions: We demonstrate that cholesterol efflux was associated with HDL-composition as well as inflammatory burden in patients referred for coronary angiography, and that this inversely predicts cardiovascular mortality independently of HDL cholesterol.

Highlights

Low levels of high-density lipoprotein cholesterol (HDL-C) have been shown to represent an independent risk marker for atherosclerotic cardiovascular disease in the general population [1].there is a growing body of evidence that raising HDL cholesterol levels may not consistently protect from atherosclerosis
To obtain further insight into the regulation of cholesterol efflux we investigated the associations of cholesterol efflux capacity with cardiovascular mortality and a number of typical cardiovascular biomarkers and risk factors
We found that biologically effective HDL cholesterol (HDL-Cl) calculated using a recently developed formula based on measurements of HDL-C and serum amyloid A was positively associated with cholesterol efflux capacity (Figure 2) [11]

Summary

Introduction

Low levels of high-density lipoprotein cholesterol (HDL-C) have been shown to represent an independent risk marker for atherosclerotic cardiovascular disease in the general population [1].there is a growing body of evidence that raising HDL cholesterol levels may not consistently protect from atherosclerosis. Low levels of high-density lipoprotein cholesterol (HDL-C) have been shown to represent an independent risk marker for atherosclerotic cardiovascular disease in the general population [1]. Patients with genetically elevated apoA-I and HDL-C are not at reduced risk for cardiovascular disease [6], this was not evident in another study from the same research group [7,8]. Inhibitors or niacin (on top of statins) have not provided evidence that the increased HDL levels were protective [2]. These observations point towards the presence of other actions of HDL that are not readily reflected by HDL-C. To obtain further insight into the regulation of cholesterol efflux we investigated the associations of cholesterol efflux capacity with cardiovascular mortality and a number of typical cardiovascular biomarkers and risk factors

Objectives

Methods

Conclusion