Circadian heart rate fluctuations predict 21-year cardiovascular and all-cause mortality in type 2 and type 1 diabetes

Abstract Background Alterations in circadian heart rate (HR) fluctuations have been associated with cardiovascular events in the general population. This study aimed at defining their long-term prognostic value for cardiovascular and all-cause mortality in patients with diabetes. Methods We examined a cohort of 349 patients with type 2 or type 1 diabetes (52% women, age 57.1±11.9 years, BMI 29.4±5.9 kg/m2, HbA1c 8.6±2.1%, 81% type 2 diabetes) who underwent 24h ambulatory blood pressure and HR monitoring (ABPM) and assessment of diabetic microvascular complications. The median standard deviation (SD) value of ABPM-derived HR measurements was used to define patients with low daily HR fluctuations (low 24h-HR SD), while a <10% decline in average night-time vs day-time HR identified patients with blunted nocturnal HR dip (n=107, 31%). The clinical features and time-dependent prognostic impact of these conditions were evaluated over a 21-year observational follow-up. Results Low 24h-HR SD and blunted nocturnal HR dip were associated with an adverse cardiometabolic risk profile and high prevalence of cardiac autonomic neuropathy and nephropathy. After 6,251 person-years of follow-up (21.0 [14.0-21.0] years), a total of 136 (39%) deaths occurred, of which 100 (68%) of cardiovascular cause. After adjustment for potential confounders, the low 24h-HR SD group had a higher risk for both cardiovascular (hazard ratio 1.99, 95% CI 1.29–3.06, p=0.002) and all-cause mortality (hazard ratio 1.50, 95% CI 1.03–2.18, p=0.033), compared with high 24h-HR SD. Consistently, patients with blunted nocturnal HR dip had a higher adjusted risk for cardiovascular (1.61, 95% CI 1.07–2.43, p=0.023) and all-cause mortality (1.61, 95% CI 1.11–2.34, p=0.012), compared with those with preserved nocturnal HR dip. Conclusions Impaired circadian HR fluctuations are frequent in patients with long-standing diabetes and are associated with microvascular disease and increased long-term cardiovascular and all-cause mortality. Identifying these conditions via 24h-ABPM may provide a cost-effective risk stratification tool in this high-risk population.Kaplan-Meier curves