Heart Failure Phenotypes and Trajectory by Gender Identity in a National Veteran Cohort

BACKGROUND: Differences in heart failure (HF) phenotypes and trajectories among transgender and gender diverse (TGD) populations may provide insight into mechanisms of HF risk. OBJECTIVES: The objective of the study was to evaluate associations between gender identity, incident HF, and trajectories between HF phenotypes. METHODS: We conducted a retrospective cohort study of 1,103,923 veterans in the Veterans Health Administration (October 1, 2010-September 30, 2019; median follow-up 9.4 years). TGD status (n = 42,157; 3.8%) was identified using natural language processing. Gender identity was categorized as cisgender men, cisgender women, transmasculine, transfeminine, or unclassified TGD. Incident HF was defined using administrative codes and classified by ejection fraction (EF) as HF with reduced EF (<40%), HF with preserved EF (HFpEF) (>50%), HFpEF with EF decline, and HF with improved EF. Multivariable Cox regression estimated associations. RESULTS: The mean age of TGD veterans was 46 years. 107,766 incident HF events occurred, including 3,078 among TGD veterans. Incident HF rates ranged from 6.22 to 8.89 per 1,000 person-years across TGD identities vs 3.87 in cisgender women and 13.05 in cisgender men. TGD status was associated with higher HF risk than cisgender women (HR: 1.53; 95% CI: 1.46 to 1.60), but lower than cisgender men (HR: 0.90; 95% CI: 0.86-0.93). HF with reduced EF rates were intermediate between cisgender men and women; associations with HFpEF were inconsistent after adjustment. Rates of HFpEF with EF decline and HF with improved EF varied (130.0-163.3 and 161.3-262.6 per 1,000 person-years, respectively). CONCLUSIONS: Gender identity is associated with differences in HF incidence and trajectory among veterans. HF epidemiology may be incompletely characterized without inclusion of TGD populations.