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

OBJECTIVE:: 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. METHODS:: We determined biomarkers of low-grade inflammation (C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumour necrosis factor alpha 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 beta stiffness index. RESULTS:: 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 [beta (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. CONCLUSION:: These data suggest that low-grade inflammation, in the elderly, plays an important role in carotid artery remodelling and stiffening.