This study aimed to elucidate the effects of change in estrogen during the menstrual cycle and menopause on shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebrovascular endothelial function. Shear-mediated dilation of the ICA and serum estradiol were measured in 11 premenopausal (Pre-M, 21±1yrs), 13 perimenopausal (Peri-M, 49±2yrs), and 10 postmenopausal (Post-M, 65±7yrs) women. Measurements were made twice within the Pre-M group at their early follicular (EF, lower estradiol) and late follicular (LF, higher estradiol) phases. Shear-mediated dilation was induced by 3min of hypercapnia (target PETCO2 +10mmHg from individual baseline) and was calculated as the percent rise in peak diameter relative to baseline diameter. ICA diameter and blood velocity were simultaneously measured by Doppler ultrasound. In Pre-M, shear-mediated dilation was higher during the LF phase than during the EF phase (P<0.01). Comparing all groups, shear-mediated dilation was reduced across the menopausal transition (P<0.01), and Pre-M during the LF phase showed the highest value (8.9±1.4%) compared with other groups (Pre-M in EF, 6.4±1.1%; Peri-M, 5.5±1.3%; Post-M, 5.2±1.9%, P<0.05 for all). Shear-mediated dilation was positively correlated with serum estradiol even after adjustment of age (P<0.01, r=0.55, age-adjusted; P=0.02, r=0.35). Collectively, these data indicate that controlling the menstrual cycle phase is necessary for the cross-sectional assessments of shear-mediated dilation of the ICA in premenopausal women. Moreover, current findings suggest that a decline in cerebrovascular endothelial function may be partly related to the reduced circulating estrogen levels in peri- and postmenopausal women.

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Funding Acknowledgements Type of funding sources: None. Introduction Sarcopenia is associated with poor functional status and clinical outcomes in heart failure (HF) patients. Although recent observational studies showed the relationship between lower serum vitamin D levels and the development of poor physical function in community-dwelling older adults, involvement of vitamin D status in the development of sarcopenia in HF patients remain unclear. This study aimed to investigate the impact of serum vitamin D concentrations on sarcopenia in patients with HF. Methods We retrospectively enrolled 269 consecutive patients [median age of 73 years (interquartile range 63-82 years); 35% female] admitted to our institute for diagnosis and management of HF, and received the dual-energy X-ray absorptiometry (DEXA) method during the period from 1 September 2018 to 30 September 2021. The 25-hydroxyvitamin D [25(OH)D] was detected by a chemiluminescence immunoassay (CLIA) technology. The diagnosis of sarcopenia was made according to the criteria of Asia Working Group for Sarcopenia incorporating reduced skeletal muscle mass (appendicular skeletal muscle index [ASMI], &lt;7.00 kg/m2 in males and &lt;5.40 kg/m2 in females), and lower muscle strength (handgrip strength, &lt;28 kg in males and &lt;18 kg in females) and/or poor physical performance (gait speed, &lt;1.0 m/s; chair stand test time, ≥12 s; short physical performance battery, ≤9 points). Results Of 269 patients, 116 (43%) patients had sarcopenia. An adjusted logistic regression model with a restricted cubic spline function showed that the odds ratio (OR) for sarcopenia increased as the serum 25(OH)D levels decreased. When the value that corresponded to an upper limit of 95% confidence interval (CI) for an OR of 1.0 was defined as the cut-off value of 25(OH)D levels for predicting sarcopenia, it was 18 ng/mL (Figure 1A). A multivariate logistic regression model was fit to calculate the propensity score (PS) for the 25(OH)D levels being &lt;18 ng/mL based on covariates such as age, sex, and N-terminal pro B-type natriuretic peptide. (C-statistics 0.761). The inverse probability of treatment weighting (IPTW) was computed using PS to minimize differences in potential confounding factors between patients with a low serum 25(OH)D levels (&lt;18 ng/mL) and those with a high serum 25(OH)D levels (≥18 ng/mL, Figure 1B). Results of the multivariate logistic regression analysis in the IPTW-weighted patients showed that a low serum 25(OH)D was independently associated with presence of sarcopenia (adjusted OR 2.03, 95% CI 1.31-3.16, p&lt;0.01). In addition, patients with a low serum 25(OH)D had a significantly lower muscle strength and poor physical performance, but not ASMI, than those with a high serum 25(OH)D (Figure 2). Conclusion Decreased serum 25(OH)D levels are associated with decline in muscle strength and physical performance in HF patients. Serum 25(OH)D levels of &lt;18 ng/mL may be a novel risk factor of sarcopenia in HF patients.

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