Abstract
Background & AimsIron accumulation within the arterial wall has been hypothesized to promote atherosclerosis progression. Aim of this study was to evaluate whether the hormone hepcidin and iron stores are associated with arterial stiffness in subjects with essential hypertension.MethodsCirculating hepcidin, ferritin, and mutations in the hemochromatosis gene were compared between subjects included in the first vs. third tertile (n=284 each) of carotid-femoral pulse wave velocity (PWV) in an unselected cohort of patients with arterial hypertension.ResultsAt univariate logistic regression analysis, high PWV was associated with higher ferritin levels (p=0.010), but lower hepcidin (p=0.045), and hepcidin ferritin/ratio (p<0.001). Hemochromatosis mutations predisposing to iron overload were associated with high PWV (p=0.025). At multivariate logistic regression analysis, high aortic stiffness was associated with older age, male sex, lower BMI, higher systolic blood pressure and heart rate, hyperferritinemia (OR 2.05, 95% c.i. 1.11-3.17 per log ng/ml; p=0.022), and lower circulating hepcidin concentration (OR 0.29, 95% c.i. 0.16-0.51 per log ng/ml; p<0.001). In subgroup analyses, high PWV was associated with indices of target organ damage, including micro-albuminuria (n=125, p=0.038), lower ejection fraction (n=175, p=0.031), cardiac diastolic dysfunction (p=0.004), and lower S wave peak systolic velocity (p<0.001). Ferritin was associated with cardiac diastolic dysfunction, independently of confounders (p=0.006).ConclusionsIn conclusion, hyperferritinemia is associated with high aortic stiffness and cardiac diastolic dysfunction, while low circulating hepcidin with high aortic stiffness.
Highlights
Atherosclerosis, the leading cause of cardiovascular disease and mortality worldwide, is a chronic inflammatory disease characterized by the progressive formation of neo-intimal lesions and lumen narrowing of affected arteries
At multivariate logistic regression analysis, high aortic stiffness was associated with older age, male sex, lower body mass index (BMI), higher systolic blood pressure and heart rate, hyperferritinemia, and lower circulating hepcidin concentration
Hyperferritinemia is associated with high aortic stiffness and cardiac diastolic dysfunction, while low circulating hepcidin with high aortic stiffness
Summary
Atherosclerosis, the leading cause of cardiovascular disease and mortality worldwide, is a chronic inflammatory disease characterized by the progressive formation of neo-intimal lesions and lumen narrowing of affected arteries. Development of atherosclerotic lesions is caused by retention of low-density lipoprotein cholesterol within arterial intima, favored by activation of immune cells with induction of oxidative stress [1]. A physical phenotype of the vascular wall, can be estimated by measurement of aortic pulse wave velocity (PWV) [2]. Mechanisms linking arterial stiffness with cardiovascular risk are related to the effect on cardiac afterload increasing cardiac work, and the promotion of target organ damage by facilitation of the transmission of pulse waves to the microcirculation [5, 6]. Iron accumulation within the arterial wall has been hypothesized to promote atherosclerosis progression. Aim of this study was to evaluate whether the hormone hepcidin and iron stores are associated with arterial stiffness in subjects with essential hypertension
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