Abstract
Background: Cardiorespiratory fitness (CRF) and chronotropic incompetence (CI) have both been associated with increased all - cause mortality. We tested the hypothesis that the association of CI with all - cause mortality is modified by a CRF level above and below 10 metabolic equivalents of task (METs). Methods: We included 43,402 patients who completed a clinical exercise stress test between 1991 and 2009. Patients on AV nodal blocking agents, antiarrhythmics and with known coronary artery disease/heart failure were excluded. Patients were followed-up for a mean duration of 11.5±5.2 years for all-cause mortality ascertained by a search of the social security death index in April 2013. CRF was estimated in metabolic equivalents of task (METs). Cox proportional hazards regression models were used to assess the risk of all - cause mortality associated with CI with adjustments for confounders. Results: Compared to no CI, patients with CI were older (51±12 vs. 54±13 years), less often white (68% vs. 58%), dyslipidemic (41% vs. 37%) and more likely to be hypertensive (46% vs. 60%), diabetic (15% vs. 22%), and smoke (40% vs. 51%). On average, patients with CI had lower CRF (9.8±2.8 vs. 7.4±3.0, p <.001). In adjusted Cox regression model, CI was associated with higher risk of mortality [Hazard ratio (HR), 2.12; 95% confidence interval (2.00 -2.27); p<.001)]. The association of CI and mortality was attenuated when METs was included as a covariate in the regression model [HR, 1.49; 95% confidence interval (1.39-1.61); p<.001]. There was a significant interaction of CRF ≥ 10 METs with the association of CI and mortality (p interaction 0.004) which is shown in Figure 1. This was a subaditive and multiplicative interaction of CRF with CI. Conclusions: This study demonstrates that CRF attenuates the mortality risk associated with CI. In addition, patients with CI in the presence of CRF ≥ 10 METs have a much lower risk than patients with CI and lower CRF.
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