Impaired Heart Rate Response to Graded Exercise: Prognostic Implications of Chronotropic Incompetence in the Framingham Heart Study

Abstract

Background Previous reports have suggested that an attenuated exercise heart rate response may be associated with coronary heart disease risk and with mortality. These observations may parallel the association between reduced heart rate variability during normal activities and adverse outcome. This investigation was designed to look at the prognostic implications of exercise heart rate response in a population-based sample. Methods and Results In this prospective cohort investigation, 1575 male participants (mean age, 43 years) in the Framingham Offspring Study who were free of coronary heart disease, who were not taking β-blockers, and who underwent submaximal treadmill exercise testing (Bruce protocol) were studied. Heart rate response was assessed in three ways: (1) failure to achieve 85% of the age-predicted maximum heart rate, which has been the traditional definition of chronotropic incompetence; (2) the actual increase in heart rate from rest to peak exercise; and (3) the ratio of heart rate to metabolic reserve used by stage 2 of exercise (“chronotropic response index”). Proportional hazards analyses were used to evaluate the associations of heart rate responses with all-cause mortality and with coronary heart disease incidence during 7.7 years of follow-up. Failure to achieve target heart rate occurred in 327 (21%) subjects. During follow-up there were 55 deaths (14 caused by coronary heart disease) and 95 cases of incident coronary heart disease. Failure to achieve target heart rate, a smaller increase in heart rate with exercise, and the chronotropic response index were predictive of total mortality and incident coronary heart disease ( P <.01). Failure to achieve target heart rate remained predictive of incident coronary heart disease even after adjusting for age, ST-segment response, physical activity, and traditional coronary disease risk factors (adjusted hazard ratio, 1.75; 95% confidence interval, 1.11 to 2.74; P =.02). After adjusting for the same factors, the increase in exercise heart rate remained inversely predictive of total mortality ( P =.04) and coronary heart disease incidence ( P =.0003). The chronotropic response index also was predictive of total mortality ( P =.05) and incident coronary heart disease ( P =.001) after adjusting for age and other risk factors. Conclusions An attenuated heart rate response to exercise, a manifestation of chronotropic incompetence, is predictive of increased mortality and coronary heart disease incidence.