Sex-specific differences in vascular function in heart failure: a systematic review
S Younas, N Okwose, A Fuller, R J Stefanetti, S Chaman, F Bano, M Dobric, P M Seferovic, D Jakovljevic, P BanerjeeAbstract
Background
Biological sex is a fundamental determinant of heart failure (HF) pathophysiology and clinical outcomes. Heart failure with preserved ejection fraction (HFpEF) is more prevalent in women, whereas heart failure with reduced ejection fraction (HFrEF) predominates in men. Despite these well-established epidemiological differences, sex-specific alterations in vascular function in HF remain poorly characterised. Arterial stiffness, a key determinant of ventricular–vascular coupling, may contribute to cardiac dysfunction and adverse outcomes in HF.
Purpose
This study aimed to examine sex-related differences in vascular function in patients with HF.
Methods
This systematic review was prospectively registered with PROSPERO. PubMed, MEDLINE, and CINAHL were searched from inception to November 2024. Studies reporting sex-stratified measures of arterial stiffness (i.e., carotid–femoral pulse wave velocity, cardio-ankle vascular index, augmentation index, augmentation pressure, aortic pulse pressure, effective arterial elastance, aortic characteristic impedance, proximal aortic compliance, and systemic arterial compliance) among patients with HF were identified. Screening was performed using Rayyan, and the systematic review was conducted in accordance with PRISMA guidelines. Risk of bias was assessed using Cochrane tool for randomised trials and an adapted domain-based checklist for observational studies.
Results
Of 20,339 records identified, 9 studies met the inclusion criteria, comprising a total of 2,820 patients (1,390 men, 1,430 women, mean age 67 years). Across included studies, 78% evaluated HFpEF, 11% evaluated HFrEF, and 11% evaluated mixed-phenotype HF. Women exhibited higher pulsatile arterial load and lower arterial compliance than men. Augmentation index (28.9 ± 13.7% vs 21.7 ± 11.9%, p<0.001) and augmentation pressure (19.1 ± 12.4 vs 13.7 ± 10.1 mmHg, p=0.003) were higher in women, and effective arterial elastance was greater in women (2.4 [1.9–2.9] vs 1.8 [1.5–2.3] mmHg/mL, p<0.001), indicating increased arterial load and reduced compliance. Body mass index (BMI) showed variable relationships with arterial stiffness indices, including positive associations with pulse wave velocity (r=0.239, p<0.01), central pulse pressure (r=0.332, p<0.001), and augmentation index (r=0.234, p=0.01), but a negative correlation with the cardio-ankle vascular index (r= −0.204, p<0.001). Importantly, sex differences in HFpEF remained significant after adjustment for BMI.
Conclusion
Women with HF, particularly HFpEF, exhibit higher pulsatile arterial load and reduced arterial compliance compared with men. These sex differences persist after adjustment for BMI, despite variable associations between adiposity and arterial stiffness indices. The findings suggest that sex-specific vascular dysfunction contributes to HF pathophysiology and support the need for sex-informed assessment and management strategies, especially in HFpEF.