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

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.

High Density Lipoprotein Cholesterol Efflux Capacity and Atherosclerosis in Cardiovascular Disease: Pathophysiological Aspects and Pharmacological Perspectives

“…Concerning the relationship between CEC and mortality, in the prospective observational study including 468 participants of the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, HDL CEC displayed an inverse relationship with CV mortality, with a reduction of about 27% in the higher CEC quartile both in patients with and without verified CAD, and after adjustment for traditional risk factors [ 219 ].…”

HDL in Atherosclerotic Cardiovascular Disease: In Search of a Role

“…Fibrates are believed to increase HDL-C mainly by increasing apoA-I and apoA-II gene transcription [28]. Some data have suggested that fibrates can reduce the risk of cardiovascular events, mainly in patients who have high TG (>200 mg/dL) and low HDL-C (<35 mg/dL) levels at baseline [29].…”

“…The ability of HDL particles to receive free cholesterol from cells has emerged as the culprit mechanism to explain HDL-related atheroprotective effects [103,104]; the cholesterol efflux capacity (CEC) has been shown to be inversely associated with CAD, independently of HDL-C concentrations [7,17,28,105], and with markers of preclinical atherosclerosis [29]. We must highlight the importance of taking into account all the different cholesterol-driving cellular pathways that may contribute to a specific condition.…”

Subpopulations of High-Density Lipoprotein: Friends or Foes in Cardiovascular Disease Risk in Chronic Kidney Disease?

“…Interestingly, it was reported that HDL concentration, composition, and function were not independent predictors for CVD outcome in CKD patients not receiving dialysis treatment [ 87 ]. However, an inverse association between cholesterol efflux capacity and CVD mortality has been reported for subjects without CKD [ 88 , 89 ]. According to Bauer et al [ 90 ], HDL cholesterol efflux capacity is not a prognostic marker of CVD risk in CKD patients.…”