Cardiovascular autonomic dysfunction precedes cardiovascular disease and all-cause mortality: 11-year follow-up of the ADDITION-PRO study
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Background
Cardiovascular autonomic dysfunction remains a silent complication in people at high risk of diabetes. We aim to determine the impact of week-long heart rate variability (HRV) on the risk of cardiovascular events and mortality in this population.
Methods
Week-long HRV and mean heart rate (mHR) were measured in 1,627 participants from the ADDITION-PRO study between 2009-2011. As measurement for HRV, we calculated a proxy for standard deviation of normal heartbeat (SDNN) both weekly, daily and hourly. Data on cardiovascular events (CVD) and all-cause mortality were obtained from Danish patient registers until 2021. We fitted poisson regression to determine incidence rate ratios (IRR) for major adverse cardiovascular events (MACE) (myocardial infarction, stroke, cardiovascular death), heart failure, and all-cause mortality.
Results
Mean (SD) age was 66 years (7), and 47 % were women. The population had a mean (SD) week-long SDNN of 139.0 (32.3) ms. Week-long HRV index SDNN showed an IRR of 0.82 (CI: 0.69; 0.97), 0.76 (CI: 0.58; 0.99), and 0.79 (CI: 0.66; 0.94) per SD for MACE, heart failure, and all-cause mortality, respectively. The risk for MACE, heart failure, and all-cause mortality was higher at SDNN values below 120ms. SDNN measurements taken from 6:00-7:00 AM showed the strongest association with the risk of MACE. Lower SDNN was consistently associated with higher all-cause mortality risk across all hours of the day. Adjustment for concurrent physical acceleration and heart rate did not materially change the magnitude of these associations. Night-time heart rate was associated with a higher risk of MACE, heart failure and all-cause mortality.
Conclusion
Cardiovascular autonomic dysfunction, measured by week-long HRV, is associated with higher risk of CVD, heart failure and all-cause mortality. Certain time frames of the day for HRV and heart rate under free-living conditions showed higher risk of CVD. Hence, long-term HRV and the diurnal response are linked with CVD risk among people with high risk of diabetes. Studies exploring the benefit of HRV modifications in CVD prevention are warranted.
