Markers of Autonomic Function and Cancer Mortality Risk in Healthy Adults

Abstract

Background Dysfunction of the autonomic nervous system increases cardiovascular risk, but its contribution to cancer outcomes is less well-characterized. Objectives The aim of this study was to evaluate associations between physiological measures reflective of autonomic function and all-site and site-specific cancer mortality in healthy adults. Methods The study included 75,308 participants (26.8% women) in the Cooper Center Longitudinal Study who completed a preventive medicine examination with a treadmill test between 1971 and 2018. Gompertz mortality models estimated associations between autonomic markers—resting heart rate, heart rate reserve, systolic blood pressure response to exercise, and heart rate recovery—and cancer mortality through 2019. Analyses were sex-stratified when significant interactions were present. Models adjusted for age, clinical and lifestyle factors, and cardiorespiratory fitness. Results Over a median follow-up of 21.9 years, 3,855 cancer deaths occurred. Lower heart rate reserve (HR per 10% lower: 1.05; 95% CI: 1.02-1.07) and heart rate recovery at 5 minutes (HR per 10 beats/min lower: 1.06; 95% CI: 1.03-1.09) were associated with higher all-site cancer mortality. Sex-specific associations were observed for certain markers: A higher resting heart rate was related to higher cancer mortality in men (HR per 10 beats/min: 1.04; 95% CI: 1.01-1.08), but not in women, whereas systolic blood pressure response associations were stronger in women. Associations with site-specific cancer mortality were particularly pronounced for lung cancer. Conclusions In apparently healthy adults, multiple noninvasive markers of autonomic function were associated with cancer mortality, independent of cardiorespiratory fitness.