The relation between sex, age and vascular function in the Framingham Heart Study
Leleiko, Rebecca Maya
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Endothelial dysfunction is a key modulator of the development of cardiovascular disease. Prior studies in selected samples have suggested that the association of age and vascular function may vary between men and women. To investigate the sex-specific patterns of this association, we utilized non-invasive vascular function testing in the Framingham Heart Study. We measured brachial artery flow-mediated vasodilation, a measure of conduit artery function, and hyperemic flow velocity, a measure of small vessel function, in 6790 participants (49±14 years, 53% women) in the Offspring and Third Generation cohorts. We found evidence of effect modification by sex on the relation of age and flow-mediated dilation (P=0.0001) and the relation of age and hyperemic flow velocity (P<0.0001). Using restricted cubic spine analysis, we observed that the relation of age and flow-mediated dilation was linear in men but nonlinear in women. To further characterize the patterns of vascular aging, we divided the cohort by the median age of 47 years old. In multivariable regression models adjusting for cardiovascular risk factors, there was a greater decline in flow-mediated dilation with increasing age in older as compared to younger women (β=-0.113 95% CI -0.129,-0.098 vs β=-0.046 95%CI -0.064,-0.029, p<0.0001 for difference). Whereas in men the association of age and flow-mediated dilation was similar in old and young men (β=-0.038 95%CI-0.054,-0.021 vs β=-0.038 95%CI-0.061,-0.023, p=0.199 for difference). For reactive hyperemia, we found a greater decline in older participants for both men and women (for young men, β=-0.087 95%CI-0.200,0.027 compared to older men β=-0.776 95%CI-0.883,-0.669 p<0.0001 for difference, for young women β=0.141 95%CI 0.033,0.249 compared to older women, β=-1.054 95%CI-1.156,-0.952, p<0.0001 for difference). In a large, community-based cohort the patterns of association between age and conduit vessel vasodilation differed in men and women with an accelerated decline in women after age 47. Small vessel function declined more rapidly in older participants in both men and women, however the decline was more pronounced in women. Our findings suggest that the process of vascular aging differs based on sex and between conduit vessels and the microcirculation. Further studies are needed to evaluate the longitudinal patterns of vascular aging in men and women.
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