Introduction: Previous studies have shown that high density lipoprotein (HDL) cholesterol is protective against coronary artery disease. However, recent studies suggested that the quality or function of HDL was more important than levels of HDL cholesterol. Recently, we have developed a brand-new assay to detect serum modified HDL, which is thought to be a non-functional or atherogenic form of HDL.
Purpose: The relationship between modified HDL and coronary artery calcification (CAC) was examined in apparently healthy Japanese individuals who participated in a cohort study for examination of subclinical atherosclerosis of community dwellers. Participants were randomly selected from one city in the west part of Japan.
Method: Study population consists of 1,009 Japanese men aged 40–79 years without clinical cardiovascular diseases, of which mean age was 64 (Standard Deviation, SD: 10.1). CAC was measured by electron-beam computed tomography (EBCT) or multi-detector-row computed tomography (MDCT). LOX-1 (lectin-like oxidized LDL receptor) is the receptor that mediates modified LDL (low density lipoprotein) activity in vascular endothelial cells; however, some lipoproteins with apolipoprotein A1 (Apo A-1) are also bonded to LOX-1. In the present study, serum LOX-1 ligand containing Apo A-1 was defined as modified HDL. Modified HDL levels were measured by enzyme-linked immunosorbent assays (ELISAs) with recombinant LOX-1 and anti-Apo A-1 antibody. Associations of modified HDL with CAC (>10 Agatston score) were examined using logistic regression with adjustment for confounding factors, including HDL cholesterol.
Results: Mean HDL cholesterol level was 58.5 mg/dl (SD: 16.8) and mean modified HDL cholesterol level was 204 ng/ml (SD: 89.7). Serum modified HDL levels were significantly associated with CAC; age-adjusted OR (odd ratio) for the presence of CAC was 1.29 (95% confidence interval: 95% CI: 1.12–1.48). After further adjustment for hypertension, diabetes, smoking, body mass index, HDL cholesterol, non-HDL cholesterol and lipid lowering medication, the significant association was still observed, of which OR was 1.22 (95% CI: 1.05–1.42). Additional adjustment for high sensitivity C-reactive protein (CRP) also did not alter the results.
Conclusions: Serum modified HDL, i.e., LOX-1 ligand containing Apo A-1, might be a novel biomarker for subclinical atherosclerosis in apparently healthy individuals.