Cardiovascular health and disease progression by multi-state transitions across atrial fibrillation, heart failure, and all-cause mortality

Abstract Background Atrial fibrillation (AF) and heart failure (HF) frequently coexist, reflecting shared pathophysiological pathways and overlapping risk profiles. However, the dynamic changes between these disease states, including their development, progression, and temporal sequences, as well as the favorable impact of cardiovascular health across these transitions, remain insufficiently understood. Sex-specific differences have been observed both in AF and HF, but inconsistencies across studies underscore the need for further investigation. Purpose To investigate the association between cardiovascular health (CVH) scores and transitions across AF, HF, combined AF and HF (AF&HF), and all-cause mortality, with a focus on sex-specific differences. Methods The study was conducted in the prospective population-based Study. The CVH score was defined based on the AHA seven metrics. The health outcome diagnoses were obtained during follow-up examinations at the research center, hospital discharge diagnoses data from the nationwide medical registry, outpatient clinics, and medical files of general practitioners. A multi-state model estimated competing risks for disease transitions, and Cox proportional hazards models assessed associations between CVH scores and transition risks. Results We included 7,360 participants (mean age: 65.4 years, 58.9% women) with complete CVH and health outcome data. During a median follow-up of 13.0 years, 15.1% of participants developed AF, 13.6% developed HF, and 29.8% died. Primary transitions included incident AF (12.1%), HF (9.5%), and AF&HF (1.1%). Secondary transitions showed that AF was more likely to progress to HF (24.9%) than vice versa (20.8%), and mortality was highest among HF patients (61.0%). Higher CVH scores were associated with lower risks of incident AF (HR: 0.93, 95% CI: 0.90–0.97), HF (HR: 0.89, 95% CI: 0.85–0.93), AF&HF (HR: 0.88, 95% CI: 0.79–1.00), and mortality (HR: 0.92, 95% CI: 0.90–0.95). Protective effects were observed in transitions from AF to AF&HF (HR: 0.89, 95% CI: 0.82–0.95) and AF&HF to mortality (HR: 0.84, 95% CI: 0.78–0.90). Women benefited more from healthier CVH score in AF-related transitions, while men showed reduced HF risk. Conclusions One in four individuals with AF subsequently develops HF, while about one in five individuals with HF later develops AF. Higher CVH scores are associated with reduced risks of AF, HF, and mortality, with women deriving greater benefits. Individuals with relatively low CVH score levels can achieve substantial benefits from modest lifestyle modifications for the prevention of adverse outcomes.Transition plotFor image description, please refer to the figure legend and surrounding text. Cox results for transitionsFor image description, please refer to the figure legend and surrounding text.