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

Background: 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: 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 24h 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 (24h-HR SD below the median of 30.4) and blunted nocturnal HR dip (<10%). Results: Low 24h-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 6,251 person-years 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 24h-HR SD group had a higher risk for both cardiovascular (adjusted hazard ratio [aHR] 2.00, 95%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 24h-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. Conclusions: Impaired circadian HR fluctuations are associated with microvascular disease and long-term cardiovascular and all-cause mortality in diabetes. ABPM-derived HR measures may provide a widely available and inexpensive risk stratification tool in this high-risk population.