Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. Differentiating these closely coupled mechanisms is important to understanding vascular aging. MESA (Multi-Ethnic Study of Atherosclerosis) participants with B-mode carotid ultrasound and brachial blood pressure at exam 1 and exam 5 (year 10) were included in this study (n=2604). Peterson and Young elastic moduli were calculated to represent total stiffness. Structural stiffness was calculated by adjusting Peterson and Young elastic moduli to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Changes in carotid artery stiffness mechanisms over 10 years were compared by age groups with ANCOVA models adjusted for baseline cardiovascular disease risk factors. The 75- to 84-year age group had the greatest change in total, structural, and load-dependent stiffening compared with younger groups ( P <0.05). Only age and cessation of antihypertensive medication were predictive of structural stiffening, whereas age, race/ethnicity, education, blood pressure, cholesterol, and antihypertensive medication were predictive of increased load-dependent stiffening. On average, structural stiffening accounted for the vast majority of total stiffening, but 37% of participants had more load-dependent than structural stiffening. Rates of structural and load-dependent carotid artery stiffening increased with age. Structural stiffening was consistently observed, and load-dependent stiffening was highly variable. Heterogeneity in arterial stiffening mechanisms with aging may influence cardiovascular disease development.
Right ventricular (RV) failure, which occurs in the setting of pressure overload, is characterized by abnormalities in mechanical and energetic function. The effects of these cell- and tissue-level changes on organ-level RV function are unknown. The primary aim of this study was to investigate the effects of myofiber mechanics and mitochondrial energetics on organ-level RV function in the context of pressure overload using a multiscale model of the cardiovascular system. The model integrates the mitochondria-generated metabolite concentrations that drive intracellular actin-myosin cross-bridging and extracellular myocardial tissue mechanics in a biventricular heart model coupled with simple lumped parameter circulations. Three types of pressure overload were simulated and compared to experimental results. The computational model was able to capture a wide range of cardiovascular physiology and pathophysiology from mild RV dysfunction to RV failure. Our results confirm that, in response to pressure overload alone, the RV is able to maintain cardiac output (CO) and predict that alterations in either RV active myofiber mechanics or RV metabolite concentrations are necessary to decrease CO.
Background: Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. It is unknown how these different mechanisms contribute to incident cardiovascular disease (CVD) events. Methods: The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6814 men and women without CVD at enrollment, from 6 communities in the United States. MESA participants with B-mode carotid ultrasound and brachial blood pressure at baseline Exam in (2000–2002) and CVD surveillance (mean follow-up 14.3 years through 2018) were included (n=5873). Peterson’s elastic modulus was calculated to represent total arterial stiffness. Structural stiffness was calculated by adjusting Peterson’s elastic modulus to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Results: In Cox models adjusted for traditional risk factors, load-dependent stiffness was significantly associated with higher incidence of CVD events (hazard ratio/100 mm Hg, 1.21 [95% CI, 1.09–1.34] P <0.001) events while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99–1.07] P =0.10). Analysis of participants who were normotensive (blood pressure <130/80, no antihypertensives) at baseline exam (n=2122) found higher load-dependent stiffness was also associated with significantly higher incidence of hypertension (hazard ratio, 1.53 [95% CI, 1.35–1.75] P <0.001) while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99–1.07] P =0.16). Conclusions: These results provide valuable new insights into mechanisms underlying the association between arterial stiffness and CVD. Load-dependent stiffness was significantly associated with CVD events but structural stiffness was not.
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