Background: Research into pulmonary hypertension (PH) reveals significant sex-based disparities in long-term survival rates. Notably, women, despite being more susceptible to PH, often experience better survival outcomes than men—a phenomenon possibly linked to the "estrogen paradox." This study leverages the comprehensive UK Biobank to examine the role of sex in influencing these outcomes. By exploring differences in PH incidence and survival rates across genders, our research aims to provide a deeper understanding of the mechanisms at play and inform more effective, gender-specific analysis. Methods: This prospective cohort study utilized data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until November 30, 2023, for England and Scotland, and May 31, 2022, for Wales. Through diagnostic codes, medical records, and imaging studies, 3,296 PH cases and 497,580 cases without PH were identified . We followed them for the mortality rates over a period of 10 years. Survival analysis was conducted using Kaplan-Meier curves and Cox proportional hazards models to assess sex-specific survival differences, adjusting for confounders like age, BMI, ethnic, menopause, smoking status, and comorbidities. Results: During 7,978,349 person-years of follow-up, of 502,173 participants in this prospective cohort, 3,296 were diagnosed with PH, while 497,580 did not receive the PH diagnosis. The prevalence of PH in the male cohort and the female cohort were 0.76% (1743 of 228,991 men) and 0.57% (1553 of 273,182 women), respectively, with significant difference between the two groups (p<0.001). In the PH cohort, the mortality rates of patients were 47.06%. In the male patients with PH, the mortality rate was significantly higher than the female PH patients (51.78% vs. 41.53%, p<0.001). After stratifying women into menopause and no-menopause group, Kaplan-Meier curves showed that even the age of male group was significantly younger than the menopause group (p<0.001), the male still had worse survival situation. Conclusion: To conclude, the prevalence of PH in the male participants was significantly higher than the female participants. While the mortality rate in the male participants was also significantly higher than the female participants.
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