Hypertension and mortality risk in heart failure: a gender-specific analysis of HF subtypes

Introduction Heart failure (HF) risk factors differ by gender, yet their impact on mortality outcomes in women remains underexplored. Hypertension (HTN), a common modifiable comorbidity, may have distinct prognostic effects in men and women. This study investigated gender-specific mortality outcomes associated with HTN in HF patients. Purpose To evaluate the impact of HTN on mortality risk in men and women with HF, with a focus on HF subtypes. Methods A retrospective cohort study was conducted on HF patients treated between 2009 and 2024 at a tertiary center. Kaplan-Meier survival analysis and Cox proportional hazards models were used to assess mortality risk. Interaction analyses evaluated the combined effect of HTN and gender. Sensitivity analyses were performed based on HF subtype. Ethical approval was obtained from the Institutional Review Board. Results The cohort included 32,902 patients (median age: 72 years [IQR 64–82]), with 22,044 (67%) diagnosed with HTN and 15,135 (46%) female. Over a median follow-up of 5 years (IQR 1–7), 18,558 (56%) patients died. HTN was significantly associated with increased all-cause mortality in women (HR 1.17, 95% CI 1.07–1.29, p < 0.01) but not in men (HR 0.98, 95% CI 0.91–1.06, p = 0.64, p-interaction = 0.015). In HF with preserved ejection fraction (HFpEF), HTN was associated with higher mortality in women (HR 1.28, 95% CI 1.15–1.41, p < 0.01) compared to men (HR 1.01, 95% CI 0.91–1.11, p = 0.45, p-interaction < 0.01). This trend was not observed among patients with HF with reduced ejection fraction (HFrEF), as women with HTN had similar outcomes (HR 1.00, 95% CI 0.81- 1.2, p = 0.92) compared to men with HTN (HR 1.00, 95% CI 0.87-1.12, p = 0.93, p-interaction = 0.78). Once analysed by age, mortality was also sex specific with women with HTN under the age of 80 having worse outcomes (HR 1.17, 95% CI 1.04 - 1.32, p < 0.01) compared to men with HTN (HR 1.00 , 95% CI 0.89 - 1.07, p= 0.71, p-interaction <0.01 ). Conclusion(s) HTN is associated with increased mortality risk in women with HF, particularly in those with HFpEF. These findings highlight the need for gender-specific management strategies in HF patients with HTN.