Circadian heart rate fluctuations predict cardiovascular and all-cause mortality in type 2 and type 1 diabetes: a 21-year retrospective longitudinal study

Aims Circadian heart rate (HR) fluctuations are associated with cardiovascular health. We examined their relationship with microvascular disease and long-term survival in patients with diabetes. Methods and results In this secondary analysis from the CHAMP1ON cohort of 497 adults with metabolic disease, 349 participants who had type 1 or type 2 diabetes, baseline 24-h ambulatory blood pressure and HR monitoring (ABPM), and survival data over a 21-year observational follow-up were included. Clinical features, microvascular complications, and mortality rates were examined in participants with low circadian HR fluctuations [24-h HR standard deviation (SD) below the median of 30.4] and blunted nocturnal HR dip (<10%). Low 24-h HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and 12-23% higher prevalence of cardiac autonomic neuropathy and nephropathy. After 6251 person-year follow-up [21.0 (14.0-21.0) years], a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. The low 24-h HR SD group had a higher risk for both cardiovascular [adjusted hazard ratio (aHR) 2.00, 95% confidence interval (CI) 1.30-3.08, P = 0.002] and all-cause mortality (aHR 1.61, 95% CI 1.13-2.29, P = 0.009), compared with high 24-h HR SD. Similarly, patients with blunted nocturnal HR dip had a higher risk for cardiovascular (aHR 1.63, 95% CI 1.08-2.46, P = 0.019) and all-cause mortality (aHR 1.69, 95% CI 1.20-2.38, P = 0.003), compared with those with preserved nocturnal HR dip. Conclusion Impaired circadian HR fluctuations are associated with microvascular disease and long-term cardiovascular and all-cause mortality in diabetes. The ABPM-derived HR measures may provide a widely available and inexpensive risk stratification tool in this high-risk population.