Cardiovascular disease (CVD) risk increases with age in males and females [1]. In females, menopause causes a rapid increase in CVD risk [1], partly due to the loss of estradiol. For example, reductions in estradiol from menopause are associated with vascular endothelial dysfunction [2] – an independent predictor of CVD risk [3]. Menopause is associated with a higher prevalence of obesity and excess visceral adipose tissue (VAT) [3], which is also associated with vascular endothelial dysfunction [4]. Specifically, VAT produces proinflammatory compounds, increases oxidative stress, and generates endothelin-1 – a potent vasoconstictor [5, 6]. Notably, these obesity-related factors contribute to vascular endothelial dysfunction, partly due to reduced nitric oxide (NO·) bioavailability [6]. Past work suggests no difference in brachial artery flow-mediated dilation (FMD; primarily NO·-mediated assessment of vascular endothelial function) across body mass index (BMI) categories [7]. However, FMD was not assessed in the lower limb in this past work. This is notable because aging impairs lower limb vascular function before upper limb vascular function [8], whereas it is unclear whether obesity is associated with lower limb vascular dysfunction. Additionally, this past work did not statistically adjust for potentially confounding factors like physical activity. Therefore, to fill this knowledge gap Fischer et al. [9] examined whether obesity is associated with upper and/or lower limb vascular dysfunction in females post-menopause.

Fischer et al. [9] studied 39 females post-menopause, comparing blood pressure (BP) and vascular function between those with lean, overweight, or obesity. Vascular function assessments included FMD and exercise-induced vasodilation (EIV) using sonography with continuous measurement of arterial diameter and blood flow velocity. Using the gold-standard methodology, the FMD protocol included distal upper or lower limb arterial occlusion for five minutes with FMD calculated as the percent change in peak arterial diameter after occlusion ended relative to the pre-occlusion baseline. The EIV protocol included dynamic forearm or plantar flexor exercise at 5%, 15%, and 30% of maximum strength in two-minute stages. The inclusion of vascular assessments in the upper (brachial artery) and lower (superficial femoral artery) limb is a novel feature of this research. Finally, the authors performed dual X-ray absorptiometry (DXA) to assess body composition.

By design, BMI differed between females with lean, overweight, and obesity ( ~ 23 vs. ~27 vs. ~33 kg/m2). As expected, the groups also differed in waist circumference, DXA-based body fat percentage, and DXA-based VAT. Importantly, age, time since menopause, BP, vasoactive medication use, and hormone replacement therapy (HRT) status did not differ between groups.

Agreeing with past work [7], the authors found no difference in brachial artery FMD between groups. Additionally, brachial blood flow, brachial vascular conductance, and BP responses during forearm exercise did not differ between groups. However, superficial femoral artery FMD was lower in adults with obesity (2.59 ± 0.38%) compared with the other two groups (lean: 4.25 ± 0.22%; overweight: 4.23 ± 0.42%) after adjusting for baseline superficial femoral artery diameter, physical activity, and shear rate under the curve (the endothelial cell-mediated stimulus for FMD). Additionally, for every 1% higher superficial femoral artery FMD value, there was a 46 mL/min (8% of group mean) higher superficial femoral artery blood flow at rest.

Superficial femoral blood flow and vascular conductance, but not BP, responses during plantar flexor exercise were reduced at the highest workload (i.e., 30% of maximum strength) in adults with obesity. Further, superficial femoral blood flow and vascular conductance had a moderate negative correlation with BMI and a weak negative correlation with VAT. Similarly, superficial femoral vascular conductance responses during plantar flexor exercise were negatively correlated with VAT and waist circumference, as well as positively correlated with physical activity.

The key findings from Fischer et al. [9] were that obesity was associated with vascular endothelial dysfunction in the lower, but not upper, limb. Similarly, obesity was associated with reduced blood flow and vascular conductance responses during plantar flexor, but not forearm, exercise. Together, these findings suggest that obesity is associated with lower limb vascular dysfunction in females who were, on average, one decade after menopause. These new results provide unique insights into the interplay between menopause, obesity, and vascular function.

With these new results in mind [9], it remains unclear whether obesity would be associated with reduced upper limb vascular dysfunction later in life (e.g., 20 years after menopause). Additionally, research is warranted on the effects of HRT timing relative to the onset of menopause. This could help to better understand the role of hormones on vascular endothelial function and CVD risk. Of note, such studies should carefully consider how HRT affects other components of physiology that impact both longevity and quality of life. For context, only 15% of the present cohort reported the use of HRT. Thus, future work could look at the interactions of HRT and obesity on vascular health. This could include examining the time of initiation of HRT relative to menopause, independent of chronological age, on vascular health to isolate the effects of HRT.

Additionally, lifestyle factors (e.g., physical activity, sedentary time, etc.) can affect vascular function. For example, reduced physical activity with extended periods of sedentary behavior is correlated with lower vascular function [10]. Notably, the current study did show differences in physical activity between groups [9]. This led the authors to statistically control for physical activity when concluding on the group differences in vascular function, which is a strength of the present work. Future work could further extend this idea to also integrate sedentary time and structured exercise habits on vascular function in females post-menopause with obesity. In addition to lifestyle changes (e.g., weight loss, nutrition, exercise), new pharmacological treatments, such as glucagon-like peptide 1 (GLP-1) agonizts, may help to restore or improve vascular function.

To summarize, menopausal changes contribute to higher CVD risk, at least partly related to vascular dysfunction. The present research highlights that the presence of obesity in females post-menopause is associated with lower, but not upper, limb vascular dysfunction. This work should evoke new studies to better understand and mitigate the effects of menopause and obesity on vascular health.