Sex differences in vascular function among individuals with heart failure: a systematic review

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 heart failure (HF) remain poorly characterised. This systematic review, using a narrative synthesis approach, evaluated sex-related differences in vascular function in individuals with HF. The review was prospectively registered with PROSPERO (CRD42024617745). MEDLINE and CINAHL were searched from inception to 26th November 2024 for studies reporting sex-stratified measures of arterial stiffness among individuals with HF. Nine studies met the eligibility criteria for inclusion (n = 2820; men: n = 1390, women: n = 1430). Of the included studies, 78% were characterised as HFpEF. Compared with men, women exhibited a higher pulsatile arterial load and lower arterial compliance. Representative findings from individual studies showed that women exhibited a higher 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). Body mass index (BMI) showed variable relationships with arterial stiffness indices, including positive associations with pulse wave velocity (r = 0.24, p < 0.01), central pulse pressure (r = 0.33, p < 0.001), and augmentation index (r = 0.23, p = 0.01), but an inverse relationship was found with cardio-ankle vascular index (r = -0.204, p < 0.001). Importantly, sex differences in HFpEF remained significant after adjustment for BMI. Women with HF exhibit higher pulsatile arterial load and reduced arterial compliance compared with men, which remain after adjustment for BMI. Sex-specific vascular dysfunction contributes to HF pathophysiology and supports the need for sex-informed assessment.