Vasculature of older females shows heterogeneity in the association between cardiovascular risk and vascular function.

Although affecting both sexes, loss of sex hormones and consequently increased risk for cardiovascular disease (CVD) render particular features to vascular aging in females. More importantly, although the female's vasculature is more sensitive to CVD risk factors, CVD is often underdiagnosed in women. In the present study, we investigated vascular function in the arm and leg skeletal muscle microvasculature and conduit artery in young and older females. We also applied a mixed-effect regression analysis to examine the relationship between vascular function and CVD risk factors in women. We showed that the detrimental effects of age in conduit artery vascular function, as assessed by flow-mediated dilation (%FMD), were more evident in the lower limb (older, 2.6 ± 0.5 vs. young, 7.2 ± 0.9%; P = 0.0116) compared with the upper limb (older, 5.3 ± 0.5 vs. young, 7.3 ± 0.4%; P = 0.175). In addition, we demonstrate that CVD risk factors, mainly plasma lipid levels [very low-density lipoprotein cholesterol (VLDL-c): r² = 0.415, P = 0.007; high-density lipoprotein cholesterol (HDL-c): r² = 0.313, P = 0.024; triglycerides: r² = 0.422, P = 0.006] and insulin sensitivity index [homeostasis model assessment of insulin resistance (HOMA-IR): r² = 0.635, P < 0.001; QUICKI: r² = 0.792, P < 0.001], were exclusively associated with upper limb skeletal muscle microvascular function in older females. In aggregate, our findings provide novel evidence that impairments in conduit artery function in older females are more pronounced in the lower limb vasculature compared with the upper limb. Also, we demonstrate that older women's upper limb microvasculature function may be more susceptible to the impact of CVD risk factors than lower limb microvasculature function and both limb's conduit arteries.NEW & NOTEWORTHY Even though the vasculature of older females has been suggested to be more sensitive to the detrimental effects of traditional cardiovascular risk factors, cardiovascular disease in women is often underdiagnosed. We show that aging-associated vascular dysfunction is more evident in the lower limb conduit arteries compared with the upper limb in older women. More importantly, we demonstrate that traditional cardiovascular risk factors were exclusively associated with upper limb skeletal muscle microvascular function in older females.