Circulating Oxidized LDL Is Associated With Subclinical Atherosclerosis Development and Inflammatory Cytokines (AIR Study)

TLDR

Ox‑LDL is known to be linked to clinical atherosclerosis, yet its relationship with subclinical disease had not been examined. The study aimed to determine whether ultrasound‑detected carotid and femoral atherosclerosis correlates with Ox‑LDL and whether Ox‑LDL associates with CRP, IL‑6, and TNF‑α. In 391 healthy 58‑year‑old men, Ox‑LDL was measured with the monoclonal antibody mAb‑4E6 while carotid and femoral intima‑media thickness and plaque were assessed by ultrasound. Ox‑LDL independently predicted carotid/femoral plaque and intima‑media thickness and correlated with TNF‑α and CRP, whereas LDL cholesterol was also an independent plaque predictor; no association was found with blood pressure or smoking.

Abstract

Objective— Circulating oxidized LDL (Ox-LDL) is associated with clinical manifestations of atherosclerosis. However, no previous study has examined the relationship between subclinical atherosclerosis and Ox-LDL. The aims of the present study were to investigate the relationship between clinically silent ultrasound-assessed atherosclerotic changes in the carotid and femoral arteries and Ox-LDL and to explore the relationship between Ox-LDL, C-reactive protein, and the inflammatory cytokines interleukin-6 and tumor necrosis factor-α. Methods and Results— The study group (n=391) consisted of clinically healthy, 58-year-old men recruited from the general population. Ox-LDL was measured by using a specific monoclonal antibody, mAb-4E6. The results showed that Ox-LDL was related to intima-media thickness and plaque occurrence in the carotid and femoral arteries. In addition, Ox-LDL was associated with tumor necrosis factor-α and C-reactive protein. Circulating Ox-LDL was also associated with LDL cholesterol but not with blood pressure or smoking. When adjusting for other risk factors, both LDL cholesterol and Ox-LDL seemed to be independent predictors of plaque occurrence in the carotid and femoral arteries (odds ratios for quintile 5 versus quintile 1 were 2.17, P =0.049 and 2.25, P =0.050, for LDL cholesterol and Ox-LDL, respectively). Conclusions— Ox-LDL was associated with both subclinical atherosclerosis and inflammatory variables, supporting the concept that oxidatively modified LDL may play a major role in atherosclerosis development, although no causality can be shown in this cross-sectional study.