Late peri- and postmenopausal women display impaired vascular endothelial function at systolic blood pressures below the hypertensive threshold

High systolic blood pressure (SBP) is a major risk factor for cardiovascular disease (CVD), related in part to vascular endothelial dysfunction. In women, the increase in CVD risk begins at lower thresholds of SBP (≥100 mmHg) compared to men (≥130 mmHg). Whether women also display endothelial dysfunction at these lower thresholds of SBP (i.e., 100-129 mmHg) is unknown. Additionally, as the menopause transition, particularly the late peri- to postmenopausal period, promotes endothelial dysfunction, it is critical that investigations characterizing the impact of these lower thresholds of SBP on endothelial function in women do so across the stages of menopause. We aimed to determine if endothelial function differs across SBP ranges below the hypertensive threshold in pre- and early perimenopausal (PRE-EP) and late peri- and postmenopausal women (LP-POST). We hypothesized that endothelial function would be impaired across these lower thresholds of SBP in LP-POST, but not PRE-EP. Methods: We completed a retrospective analysis of endothelial function (assessed via brachial artery flow-mediated dilation, FMD) measured in healthy PRE-EP ( n =72) and LP-POST ( n =86) women stratified by clinic SBP level (<100, 100-109, 110-119, and 120-129 mmHg). Seated SBP was measured in triplicate following 10-minute rest and averaged. Values are mean ± standard deviation. Baseline characteristics were compared between menopause groups using unpaired t tests. One-way ANOVAs were used to compare endothelial function between SBP categories within each menopause group. Tukey post hoc tests were used to examine within-group differences. Results: LP-POST were older (LP-POST vs PRE-EP: 56±6 vs 38±10 yrs, P < 0.001), had higher SBP (113±10 vs 108±9 mmHg, P < 0.01), and lower FMD (5.6±2.0 vs 10.0±3.1%, P < 0.001) compared to PRE-EP. Among PRE-EP, there was no effect of SBP on FMD ( P = 0.10). In contrast, FMD was reduced with increasing categories of SBP in LP-POST ( P < 0.001) such that FMD was lower in LP-POST with a SBP between 120-129 mmHg (4.3±1.3%) compared to those with a SBP between 100-109 mmHg (6.4±2.0%; P <0.001) or 110-119 mmHg (6.1±2.0%; P <0.01). Conclusion: LP-POST, but not PRE-EP, display impaired endothelial function at SBPs below the hypertensive threshold. These findings suggest that the vascular endothelium in PRE-EP is protected against the damaging effects of higher SBPs, and that this protection is lost in LP-POST. As endothelial dysfunction precedes and contributes to the development of CVD, these findings provide insight into the vascular mechanisms underlying increased CVD risk at SBPs below the hypertensive threshold in women. NIH T32DK007135, R01AG027678, R56HL114073, K01AG020683, U54AG062319; CCTSI UM1 TR004399; Colorado NORC P30 DK048520; Ludeman Family Center for Women’s Health Research This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.