Cardiac autonomic dysfunction and risk of incident stroke among adults with type 2 diabetes

Abstract

Introduction: There is a dearth of data on the association between cardiac autonomic neuropathy (CAN) with incident stroke among individuals with diabetes mellitus. We evaluated this association in a large sample of adults with type 2 diabetes.

Patients and methods: Participants with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study without atherosclerotic cardiovascular disease at baseline were included. CAN was assessed at baseline by heart rate variability (HRV) indices and QT index (QTI) calculated from 10-s resting electrocardiograms. HRV was assessed using standard deviation of all normal-to-normal R-Rs intervals (SDNN) and root mean square of successive differences between normal-to-normal R-R intervals (rMSSD). CAN was defined based on several composite measures of SDNN, QTI, resting heart rate and peripheral neuropathy. We used Cox proportional hazards regression to generate hazard ratios (HR) and 95% confidence intervals (CI) for incident stroke in relation to CAN.

Results: A total of 3493 participants (mean age 62.2 years, 44.5% women, 62.9% White) were included. Over a median follow-up of 5.0 years, 50 stroke cases occurred (incidence rate 3.0/1000 person-years [95% CI 2.2-3.9]). After adjusting for confounders, low HRV was associated with a higher risk of stroke (HR of 2.20 [95% CI 1.23-3.93] and 1.88 [95% CI 1.04-3.41] for low SDNN and rMSSD, respectively). Participants with CAN (defined as lowest quartile of SDNN and highest quartiles of QTI and heart rate) had a 5.7-fold greater risk of stroke (HR 5.70, 95% CI 2.49-13.08).

Discussion and conclusion: CAN was independently associated with an increased risk of incident stroke in a large cohort of adults with type 2 diabetes.

Keywords: Cardiac autonomic neuropathy; heart rate variability; risk; stroke; type 2 diabetes.

Graphical abstract

Figure 1.

Cumulative Incidence of Stroke by cardiac autonomic dysfunction (CAN) status among individuals with type 2 diabetes. Panel A includes the link between CAN1 and stroke, Panel B includes the link between CAN2 and stroke, Panel C includes the link between CAN3 and stroke, and Panel D includes the link between CAN 4 and stroke. CAN1 was defined as SDNN < 8.2 ms and rMSSD < 8.0 ms; CAN2 as SDNN < 7.815 ms and QTI > 104.32%; CAN3 as SDNN < 7.815 ms, QTI > 104.32% and resting heart rate >77 bpm; CAN4 as SDNN < 7.815 ms, QTI > 104.32%, resting heart rate >77 bpm and MNSI score >2. CAN: cardiac autonomic neuropathy; MNSI: Michigan Neuropathy Screening Instrument; QTI: QT index; rMSSD: root mean square of successive differences between normal-to-normal R-R intervals; SDNN: standard deviation of all normal-to-normal R-R intervals. P value for log–rank test.