title: Endothelial dysfunction and low-grade inflammation are associated with greater arterial stiffness over a 6-year period.
abstract: Endothelial dysfunction and low-grade inflammation are associated with cardiovascular disease. Arterial stiffening plays an important role in cardiovascular disease and, thus, may be a mechanism through which endothelial dysfunction and/or low-grade inflammation lead to cardiovascular disease. We investigated the associations between, on the one hand, biomarkers of endothelial dysfunction (soluble endothelial selectin, thrombomodulin, and both vascular and intercellular adhesion molecules 1 and von Willebrand factor) and of low-grade inflammation (C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumor necrosis factor-α and, soluble intercellular adhesion molecule 1) and, on the other hand, arterial stiffness over a 6-year period, in 293 healthy adults (155 women). Biomarkers were combined into mean z scores. Carotid, femoral, and brachial arterial stiffness and carotid-femoral pulse wave velocity were determined by ultrasonography. Measurements were obtained when individuals were 36 and 42 years of age. Associations were analyzed with generalized estimating equation and adjusted for sex, height, and mean arterial pressure. The endothelial dysfunction z score was inversely associated with femoral distensibility (β: -0.51 [95% CI: -0.95 to -0.06]) and compliance coefficients (β: -0.041 [95% CI: -0.076 to -0.006]) but not with carotid or brachial stiffness or carotid-femoral pulse wave velocity. The low-grade inflammation z score was inversely associated with femoral distensibility (β: -0.51 [95% CI: -0.95 to -0.07]) and compliance coefficients (β: -0.050 [95% CI: -0.084 to -0.016]) and with carotid distensibility coefficient (β: -0.910 [95% CI: -1.810 to -0.008]) but not with brachial stiffness or carotid-femoral pulse wave velocity. Biomarkers of endothelial dysfunction and low-grade inflammation are associated with greater arterial stiffness. This provides evidence that arterial stiffening may be a mechanism through which endothelial dysfunction and low-grade inflammation lead to cardiovascular disease.
authors.affiliation: Department of Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Bas C
authors.initials: BC
authors.lastname: van Bussel
authors.forename: Fleur
authors.initials: F
authors.lastname: Schouten
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Henry
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Michiel R
authors.initials: MR
authors.lastname: de Boer
authors.forename: Isabel
authors.initials: I
authors.lastname: Ferreira
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Jos W
authors.initials: JW
authors.lastname: Twisk
authors.forename: Coen D
authors.initials: CD
authors.lastname: Stehouwer
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity / Q000502:physiology; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016207:Cytokines / Q000097:blood; D019040:E-Selectin / Q000097:blood; D004548:Elasticity / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology*; D008137:Longitudinal Studies; D008297:Male; D012307:Risk Factors; D000685:Serum Amyloid A Protein / Q000378:metabolism; D018180:Thrombomodulin / Q000097:blood; D014463:Ultrasonography; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines; D019040:E-Selectin; D000685:Serum Amyloid A Protein; D018180:Thrombomodulin; D014841:von Willebrand Factor; D002097:C-Reactive Protein