Association of Cigarette Smoking With Chronotropic Incompetence and Prognosis in the Framingham Heart Study

BACKGROUND: In this study, we sought to determine whether cigarette smoking is associated with chronotropic incompetence and to explore prognostic implications of this association. METHODS AND RESULTS: Members of the Framingham Offspring Study (1468 men and 1642 women) underwent graded exercise. Chronotropic incompetence was assessed in two ways: (1) failure to achieve an age-predicted target heart rate and (2) a low chronotropic index, a heart rate response measure that accounts for effects of age, resting heart rate, and physical fitness. Smokers were more likely to fail to reach target heart rate than were nonsmokers (men, 25% versus 15%, odds ratio OR, 1.97; 95% confidence interval CI, 1.51 to 2.56; women, 32% versus 18%; OR, 2.10; 95% CI, 1.63 to 2.61) and were more likely to have a low chronotropic index (men, 17% versus 12%; OR, 1.50; 95% CI, 1.12 to 2.03; women, 17% versus 8%; OR, 2.28; 95% CI, 1.68 to 3.09). These associations persisted after adjustment for age, cardiovascular risk factors, pulmonary function, and ST-segment response to graded exercise. During 8 years of follow-up, there were 48 deaths and 90 incident coronary heart disease events among the men. After adjustment for the same confounders, men who were smokers and failed to achieve target heart rate were at particularly high risk for death (adjusted relative risk RR, 2.45; 95% CI, 1.14 to 5.24) and for coronary heart disease (adjusted RR, 4.92; 95% CI, 2.84 to 8.53). There were too few end points in women for analysis. CONCLUSIONS: In this population-based cohort, cigarette smoking was predictive of chronotropic incompetence. Male smokers who manifested chronotropic incompetence were at particularly high risk for death and coronary heart disease events.