Whether resting heart rate (RHR) predicts mortality independent of fitness is not well established, particularly among women. We analyzed data from 56,634 subjects (49% women) without known coronary artery disease or atrial fibrillation who underwent a clinically indicated exercise stress test. Baseline RHR was divided into 5 groups with <60 beats/min as reference. The Social Security Death Index was used to ascertain vital status. Cox hazard models were performed to determine the association of RHR with all-cause mortality, major adverse cardiovascular events, myocardial infarction, or revascularization after sequential adjustment for demographics, cardiovascular disease risk factors, medications, and fitness (metabolic equivalents). The mean age was 53 ± 12 years and mean RHR was 73 ± 12 beats/min. More than half of the participants were referred for chest pain; 81% completed an adequate stress test and mean metabolic equivalents achieved was 9.2 ± 3. There were 6,255 deaths over 11.0-year mean follow-up. There was an increased risk of all-cause mortality with increasing RHR (p trend <0.001). Compared with the lowest RHR group, participants with an RHR ≥90 beats/min had a significantly increased risk of mortality even after adjustment for fitness (hazard ratio 1.22, 95% confidence interval 1.10 to 1.35). This relationship remained significant for men, but not significant for women after adjustment for fitness (p interaction <0.001). No significant associations were seen for men or women with major adverse cardiovascular events, myocardial infarction, or revascularization after accounting for fitness. In conclusion, after adjustment for fitness, elevated RHR was an independent risk factor for all-cause mortality in men but not women, suggesting gender differences in the utility of RHR for risk stratification.
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