Abstract
Background: Cardiorespiratory fitness plays a crucial role in cardiovascular health; however, its effects on adverse cardiovascular outcomes across different diseases remain poorly defined. Specifically, the differential impact of cardiorespiratory fitness on patients with and without atrial fibrillation (AF) is yet to be fully understood. This study aimed to explore the relationships between resting heart rate (RHR), maximal heart rate (HRmax), and maximal oxygen uptake (VO₂max) in relation to adverse cardiovascular outcomes, providing valuable insights to inform exercise prescriptions and cardiac rehabilitation practices. Methods: Participants were classified into two groups: those with AF diagnosed prior to baseline (AF group) and those without AF at baseline (non-AF group). In the AF group, outcomes included heart failure (HF), stroke, and all-cause mortality; in the non-AF group, incident AF, stroke, HF, and mortality were assessed. Associations between cardiorespiratory indices-RHR, HRmax, and VO₂max-and adverse cardiovascular events were evaluated using Cox proportional hazards models. Dose-response relationships were examined via restricted cubic spline (RCS) models with three knots. Results: In the non-AF population, higher resting heart rate was significantly associated with an increased risk of adverse cardiovascular outcomes, including heart failure (HF: HR = 1.008, 95% CI 1.001-1.014, P = 0.0182), stroke (HR = 1.010, 95% CI 1.004-1.016, P = 0.0018), atrial fibrillation (AF: HR = 1.011, 95% CI 1.007-1.015, P < 0.0001), and all-cause mortality (HR = 1.016, 95% CI 1.010-1.022, P < 0.0001). In contrast, higher HRmax was inversely associated with these outcomes (HF: HR = 0.993, 95% CI 0.991-0.995, P < 0.0001; stroke: HR = 0.993, 95% CI 0.990-0.995, P < 0.0001; AF: HR = 0.993, 95% CI 0.991-0.994, P < 0.0001; cardiovascular death: HR = 0.994, 95% CI 0.990-0.997, P < 0.0001). Similarly, higher cardiorespiratory fitness, measured by VO₂max, was consistently associated with reduced risks of adverse outcomes (HR range: 0.930-0.961, P < 0.001). In the AF population, higher RHR was associated with elevated risks of HF (HR = 1.007, 95% CI 1.002-1.012, P = 0.0047) and all-cause mortality (HR = 1.009, 95% CI 1.004-1.014, P < 0.0001). Conversely, greater VO₂max was linked to reduced risks of adverse outcomes, including HF (HR = 0.934, 95% CI 0.899-0.972, P < 0.0001), stroke (HR = 0.943, 95% CI 0.891-0.999, P = 0.0446), and all-cause mortality (HR = 0.957, 95% CI 0.918-0.998, P = 0.038). Conclusion: In individuals without AF, higher resting heart rate was significantly associated with increased risks of incident AF, HF, stroke, and all-cause mortality, with the lowest risks of AF and HF observed at an RHR of 61 beats per minute. Among patients with AF, elevated RHR was significantly linked to higher risks of HF and all-cause mortality. Conversely, higher VO₂max was consistently associated with reduced risks of adverse outcomes across both populations. Furthermore, VO₂max showed strong predictive value for adverse cardiovascular prognostic risks in individuals with and without AF.