Association of smoking with abnormal exercise heart rate responses and long-term prognosis in a healthy, population-based cohort

BACKGROUND: Cigarette smoking is associated with chronotropic incompetence, defined as an attenuated heart rate response to exercise. The long-term prognostic implications of this association have not been well explored. SUBJECTS AND METHODS: Adults enrolled in the Lipid Research Clinics’ Prevalence Study who had no history of cardiovascular disease and who were not taking beta-blockers were observed for 12 years. Chronotropic incompetence was assessed as the failure to achieve 90% of an age-predicted target heart rate during an exercise test or as a low chronotropic index, a measure of exercise heart rate response adjusted for age, resting heart rate, and physical fitness. RESULTS: Of the 5,354 eligible participants (mean [± SD] age of 44 ± 10 years; 61% male), 1,931 (36%) smoked cigarettes. Smokers were more likely to have a low chronotropic index (26% versus 16%, odds ratio = 1.8, 95% confidence interval [CI] 1.6 to 2.1) and fail to achieve an age-predicted target heart rate (32% versus 22%, odds ratio = 1.7, 95% CI 1.5 to 2.0). Adjustment for standard cardiac risk factors and physical fitness did not affect these associations. During follow-up, there were 327 deaths. Among subjects without chronotropic incompetence, the relative risk of mortality associated with smoking was moderately increased (hazard ratio = 1.8, 95% CI 1.3 to 2.3); among smokers with chronotropic incompetence, the relative risk of mortality was markedly increased (hazard ratio = 2.7, 95% CI 2.0 to 3.7, P for interaction = 0.02). CONCLUSIONS: In this large, middle-aged population-based cohort, smoking was associated with chronotropic incompetence, which in turn identified smokers with a particularly high mortality rate.