Markers of Autonomic Function and Cancer Mortality Risk in Healthy Adults

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.