Diabetic cardiac autonomic dysfunction predicts adverse vascular function and clinical heart failure: counter-physiological dissociation of resting heart rate with PR interval

Abstract

Background: Clinical Implications of chronic hyperglycemia-related cardiac autonomic disruption were unclear. We investigated relations of resting heart rate (HR) and PR interval, an indicator of cardiac vagal tone, with chronic hyperglycemia, and effects on vascular function and new-onset heart failure (HF). Methods: We prospectively studied 550 patients with coronary disease, ischemic stroke and/or type 2 diabetes. Carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were performed. Heart rate-PR interval dissociation was defined as counter-physiological co-occurrence of increased PR interval (>median 173.3ms) and increased resting HR (>median 64.4 BPM). Results: Over 63±11 months, 6.7% patients developed new-onset HF. Resting HR was associated with increased carotid IMT (R=0.20, P<0.001) and PWV (R=0.30, P<0.001), and new-onset HF (P<0.001). C-statistic for HF prediction by resting HR was 0.68 (Figure 1, P<0.001). Adjusted for potential confounders, resting HR>75bpm was independently predictive of HF (HR=3.35, 95% CI: 1.2–9.1, P=0.017). Furthermore, resting HR was associated with HbA1c (R=0.11, P=0.012). Adjusted for potential confounders, HbA1c remained independently associated with increased resting HR>75 bpm (OR=1.18, 95% CI 1.0–1.4, P=0.046). Normal inverse relation between PR interval and resting HR was lost (R=−0.03, P=0.46). Moreover, heart rate-PR interval dissociation was associated with HbA1c>7 (P=0.006). Conclusion: Chronic hyperglycemia is associated with resting tachycardia and counter-physiological dissociation of resting HR and PR interval, and that such resting tachycardia is an important predictor of new-onset HF in cardiovascular/ diabetic patients, supporting a pathophysiological mechanistic role of autonomic dysfunction in hyperglycemia.