Uncoupling Between Heart Rate Variability and Heart Rate During Exercise and Recovery as a Predictor of Cardiovascular Events

Heart rate (HR) variability (HRV) is a non-invasive cardiac autonomic marker, which, in normal conditions, is inversely associated with the underlying HR. This study investigates the hypothesis that uncoupling between HRV and HR during exercise and recovery may indicate increased cardiovascular risk. UK Biobank participants without underlying cardiovascular disease (n =48,671, 46.3% male 56.3±8.2 years old) underwent an ECG exercise stress test. Uncoupling between HR and HRV was measured as v = 1 - rHR,HRV, where r indicates the Spearman's correlation coefficients between the HR profile and the instantaneous HRV power. Cox regressions were used to assess the association between the uncoupling index, v, and major adverse cardiovascular events (MACE). Models were adjusted for age, sex, body mass index, blood pressure, resting HR, HR increase and decrease during exercise and recovery, respectively. During a median follow-up of 10 years, incidence of MACE was 2.9%. In the adjusted model, 1 standard deviation increase in log-transformed v was associated with MACE, with hazard ratio (95% confidence interval) = 1.09 (1.03, 1.15), p=0.004. In conclusion, in middle-aged man and women without underlying cardiovascular disease, the uncoupling between HR and HRV during exercise and recovery was associated with MACE.