Low-grade inflammation, but not endothelial dysfunction, is associated with greater carotid stiffness in the elderly

Abstract

Biomarkers of low-grade inflammation and endothelial dysfunction are associated with cardiovascular disease. Arterial stiffening may be a mechanism through which low-grade inflammation and (or) endothelial dysfunction lead to cardiovascular disease. Therefore, we investigated whether low-grade inflammation and endothelial dysfunction were associated with greater carotid stiffness in a population-based cohort of elderly individuals. We determined biomarkers of low-grade inflammation (C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumour necrosis factor α and soluble intercellular adhesion molecule 1), and of endothelial dysfunction (von Willebrand factor, soluble vascular cell adhesion molecule 1, soluble endothelial selectin, soluble thrombomodulin, soluble intercellular adhesion molecule 1 and flow-mediated dilation), and combined these into mean z-scores (n = 572; women = 286; age 67.5 ± 6.6 years). Additionally, we determined by ultrasonography carotid diameter, distension, pulse pressure and intima-media thickness. Carotid stiffness indices were determined by calculation of the distensibility and compliance coefficient, Young's elastic modulus and β stiffness index. The study population was characterized by a high prevalence of cardiovascular disease (46%), hypertension (66%) and the use of lipid-lowering (16%) and antihypertensive (34%) medication. After adjustment for the above in addition to sex, age, glucose tolerance status and current smoking, the low-grade inflammation z-score was positively associated with Young's elastic modulus [β (95% confidence interval) 0.080 (0.021-0.139), P = 0.008]. This association was primarily driven through greater diameter. After adjustment for the variables above, the endothelial dysfunction z-score was not associated with carotid stiffness. These data suggest that low-grade inflammation, in the elderly, plays an important role in carotid artery remodelling and stiffening.