Association of endothelial and oxidative stress with metabolic syndrome and subclinical atherosclerosis: multi-ethnic study of atherosclerosis.

BACKGROUND/OBJECTIVES: A cluster of metabolic abnormalities termed metabolic syndrome (MetS) is associated with vascular endothelial dysfunction and oxidative internal milieu. We examined whether the association of MetS with subclinical atherosclerosis is explained by biomarkers of endothelial damage and oxidative stress. SUBJECTS/METHODS: Multi-Ethnic Study of Atherosclerosis (MESA) is a population-based study of 45- to 84-year-old individuals of four US ethnicities without clinical cardiovascular disease. A random sample of 997 MESA participants had data on the following biomarkers: von Willebrand factor, soluble intercellular adhesion molecule-1 (sICAM-1), CD40 ligand (CD40L), soluble thrombomodulin, E-selectin and oxidized LDL (oxLDL). We examined whether the associations of MetS with B-mode ultrasound-defined common and internal carotid intimal-medial thickness (IMT) and coronary artery calcium (CAC) measured using computerized tomography were explained by the biomarkers using multiple regression methods. RESULTS: MetS was associated with higher levels of each of the biomarkers (P<0.001, CD40L-suggestive association P=0.004), with greater IMT (P<0.001), and with greater extent of CAC in those in whom CAC was detectable (P=0.01). The association of MetS with measures of subclinical atherosclerosis remained unchanged after adjustment for the biomarkers. After adjusting for MetS, oxLDL was suggestively associated with greater prevalence of detectable CAC (P=0.005) and thicker internal carotid IMT (P=0.002), whereas sICAM-1 was significantly associated with greater prevalence of detectable CAC (P=0.001). CONCLUSIONS: The association of MetS with subclinical atherosclerosis was independent of its association with biomarkers of endothelial damage and oxidative stress, suggesting that metabolic abnormalities and oxidative endothelial damage may lead to atherosclerotic disease through distinct mechanisms.