In 75,308 apparently healthy adults followed for a median of 21.9 years, four noninvasive autonomic nervous system markers — resting heart rate, heart rate reserve, systolic blood pressure response to exercise, and heart rate recovery — each predicted cancer mortality independently of cardiorespiratory fitness. Every 10% lower heart rate reserve raised all-site cancer mortality risk by 5% (HR 1.05; 95% CI 1.02–1.07), while each 10 beats/min lower heart rate recovery at 5 minutes raised risk by 6% (HR 1.06; 95% CI 1.03–1.09). Sex differences emerged: elevated resting heart rate carried greater mortality risk in men, while blood pressure response to exercise was more predictive in women. Associations were strongest for lung cancer.
This finding is meaningful because these markers are already collected during routine exercise stress tests — no additional cost or procedure required. The autonomic-cancer link likely reflects chronic sympathetic overdrive suppressing immune surveillance and promoting a pro-inflammatory tumour microenvironment, a mechanistic pathway gaining traction but not yet firmly established. Crucially, the association held after adjusting for fitness, suggesting autonomic function conveys information beyond VO2 max alone. Limitations are notable: the cohort skews male, predominantly white, and health-seeking (Cooper Institute clients), limiting generalisability. Observational design precludes causality — poor autonomic tone may merely co-vary with undetected early cancer. Still, for clinicians, these markers deserve attention as low-cost, actionable screening signals, particularly given that aerobic training demonstrably improves heart rate recovery and reserve.