Circulating Markers of Inflammation and Endothelial Dysfunction Associated With Increased Progression of Internal Carotid Intima‐Media Thickness in the Population‐Based Framingham Heart Study

Background Circulating markers of inflammation may be associated with carotid artery intima‐media thickness (CIMT), a marker of subclinical atherosclerosis associated with cardiovascular and cerebrovascular disease, although the exact relationship between these circulating markers of inflammation and progression of CIMT is unclear. We hypothesize that markers of circulating inflammation and endothelial dysfunction are associated with progression of CIMT in the FHS (Framingham Heart Study) cohort. Methods Multivariable linear regression was used to assess the association between specific circulating markers of inflammation with cross‐sectional internal CIMT (ICIMT) measurement and ICIMT progression defined as rate of change of intima‐media thickness (mm/y) in the internal carotid artery. Our primary analyses adjusted for age, sex, hypertension, diabetes, APOE4 , body mass index, and smoking at the time of baseline CIMT measurement. Secondary analyses additionally adjusted for baseline CIMT measurements. Results We studied 2264 participants (mean age 57.2 years, 54% women). In our primary multivariable adjusted analysis, we observed that participants with higher baseline C‐reactive protein (β=0.057 [95% CI, 0.012–0.102]; P =0.013), lipoprotein‐associated phospholipase A activity (β=0.050 [95% CI, 0.006–0.094]; P =0.027), and isoprostanes (β=0.054 [95% CI, 0.013–0.101]; P =0.012) had significantly higher ICIMT progression, after adjusting for vascular risk factors and baseline CIMT. In a cross‐sectional analysis at follow‐up, we also observed that participants with higher levels of interleukin‐6, osteoprotegerin, and P‐selectin had significantly higher ICIMT. Conclusions Specific markers of inflammation and endothelial dysfunction were associated with increased ICIMT and carotid atherosclerosis progression.