Sex differences in macro- and microvascular reactivity – a systematic review and meta-analysis

Q: What are the key findings of this study?

Females under the age of 40 showed significantly greater unadjusted flow-mediated dilation than males, but this difference was no longer significant after adjusting for age and BMI.

Q: What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Healthy young adults (n=2426). Intervention: Female sex vs. Male sex. Primary outcome: Flow-mediated dilation (FMD) adjusted for age and BMI (MD 0.009, 95% CI -0.019 to 0.020, p=0.110).

Q: What does this research mean for the field?

Females under the age of 40 have greater unadjusted flow-mediated dilation than males, but this sex difference is no longer significant after adjusting for age and BMI. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Ádám Fekete; Patrik Kreuter; Petrana Martineková; Eszter Ágnes Szalai; Gergely Agócs; Péter Sótonyi; Gábor Varga; Péter Hegyi; Beáta Kerémi; János Vág

doi:10.1016/j.ajpc.2025.101335

October 25, 2025American Journal of Preventive CardiologyOpen Access

Sex differences in macro- and microvascular reactivity – a systematic review and meta-analysis

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Key result

Young female advantage in flow-mediated dilation disappears after adjusting for age and BMI.

MD 0.009
95% CI -0.019 to 0.020
P=0.110
n=2,426

Why the study?

Sex differences in cardiovascular disease are well recognized, but underlying vascular mechanisms remain unclear.

Does female sex improve macro- and microvascular reactivity compared to male sex in healthy young adults?

Study Design

Type

Meta-Analysis (n=2,426)

Structured PICO

Does female sex improve macro- and microvascular reactivity compared to male sex in healthy young adults?

P

Population

2,426 healthy, non-smoking, non-obese adults with a mean age under 40 years were included in a meta-analysis to evaluate sex differences in vascular reactivity.

E

Exposure

Female sex (observational exposure assessing macro- and microvascular reactivity)

C

Comparator

Male sex

O

Outcome

Macro- and microvascular reactivity measured via flow-mediated dilation (FMD), baseline artery diameter (BAD), wall shear rate (WSR), relative change in blood flow on the brachial artery (ΔBF) and microcirculation (microΔBF), and time-to-peak (TTP)surrogate

Main Result

Mean Difference: 0.009 (95% CI -0.019–0.02)

p-value: p=0.110

In healthy young adults, previously observed sex differences in flow-mediated dilation appear to be driven by age and BMI rather than sex itself, though females maintain higher wall shear rates.

Limitations

Relied on means and standard deviations of studies rather than individual-level data for age and BMI
Exact laboratory parameters were not always provided to control their effect
Insufficient studies with upper arm occlusion in the multivariate analysis for FMD
Lack of racial or ethnic data
Risk of bias tool failed to identify confounding factors such as menopausal status, BMI, and the use of contraception
Evidence of possible publication bias for mean BAD, mean FMD, and mean WSR
Limited number of available studies for multivariate linear regression analysis of microΔBF

Implication

Supports sex-specific vascular phenotyping in research; leaves open whether reactivity differences influence clinical outcomes.

Abstract

Introduction: Sex differences in cardiovascular disease are well recognized, but underlying vascular mechanisms remain unclear. This meta-analysis investigates whether young adult healthy males and females differ in macro- and microvascular reactivity, via flow-mediated dilation (FMD) and post-occlusive reactive hyperemia (PORH). Methods: A systematic search of MEDLINE, Embase, and Central identified eligible studies meeting the criteria: FMD or PORH test assessment; Ultrasound or Laser Doppler was used on the brachial artery or the skin; including both sexes under the mean age of <40 years and a mean BMI of <30. We performed a quantitative analysis for baseline artery diameter (BAD), FMD, wall shear rate (WSR), relative change in blood flow on the brachial artery (ΔBF) and microcirculation (microΔBF), and time-to-peak (TTP). Random-effects model was used for synthesis with sex as a predictor and age and BMI as moderators. Results: A total of 51 eligible articles comprising 2426 subjects were included. Without adjustment for age and BMI (studies: 48), females had smaller BAD and TTP but higher FMD and WSR compared with males. No significant differences were found for ΔBF or microΔBF. After adjustment for age and BMI and inclusion of studies using forearm occlusion (studies: 23), FMD differences between sexes were no longer significant. Conclusion: While WSR was consistently higher in young females than in males, there was no clear evidence that females exhibit higher FMD after forearm occlusion. Likewise, greater vascular reactivity in microcirculation could not be statistically confirmed.

Discussion

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Published by American Journal of Preventive Cardiology · CC BY

Cite This Study

Fekete et al. (2025) conducted a meta-analysis in Healthy young adults (n=2,426). Female sex vs. Male sex was evaluated on Flow-mediated dilation (FMD) adjusted for age and BMI (MD 0.009, 95% CI -0.019 to 0.020, p=0.110). Females under the age of 40 showed significantly greater unadjusted flow-mediated dilation than males, but this difference was no longer significant after adjusting for age and BMI.

synapsesocial.com/papers/6a82e25bd88fdfcf4fa0cffa https://doi.org/10.1016/j.ajpc.2025.101335

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Sex differences in macro- and microvascular reactivity – a systematic review and meta-analysis

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Figures from the paper

Cite This Study

Sex differences in macro- and microvascular reactivity – a systematic review and meta-analysis

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Figures from the paper

Cite This Study

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