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

Michele Orini1, Stefan van Duijvenboden2, Julia Ramirez3, Andrew Tinker3, Patricia Munroe3, Pier Lambiase4
1University College London, Department of Mechanical Engineering, 2UCL institute of cardiovascular science, 3Queen Mary University of London, 4University College London


Heart rate variability (HRV) is a non-invasive marker of the cardiac autonomic nervous system modulation. In normal conditions, HRV is inversely associated with the underlying heart rate. 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 diseases underwent an ECG exercise stress test on a static bicycle, consisting of 15 sec rest, 6 min cycling at increasing workload and 1 min recovery. The HR profile was measured by low-pass filtering the beat-to-beat HR time series. The instantaneous power of HRV during exercise and recovery was estimated using multi-taper spectrogram time-frequency distributions. Uncoupling between HR and HRV was measured as υ=1-r_(HR,HRV), where r indicates the Spearman’s correlation coefficients between HR profile and instantaneous HRV power with frequency band 0.04 – 0.50 Hz. Cox regressions were used to assess the association between υ and major adverse cardiovascular events (MACE). Models were adjusted for age, sex, body mass index, blood pressure, resting heart rate, heart rate increase and decrease during exercise and recovery, respectively.

At baseline, 48,671 participants (46.3% male 56.3±8.2 years old) underwent the exercise stress test. During a median follow-up of 10 years, incidence of MACE was 2.9%. In an adjusted model, increased uncoupling between HRV and HR was associated with MACE (hazard ratio (95% confidence interval) = 1.09 (1.03, 1.15), p=0.004 for 1 SD increase in log-transformed υ).

In conclusion, in middle aged man and women without underlying cardiovascular disease, the uncoupling between the profile of HR and HRV during exercise and recovery was significantly associated with long-term risk of MACE. Future studies are needed to assess whether it may help identifying subclinical autonomic dysfunction.