Abstract

BackgroundThe mechanisms linking cardiovascular autonomic neuropathy, diabetic kidney disease and cardiovascular mortality in type 2 diabetes are widely unknown. We investigated the relationship between baseline cardiovascular autonomic function and changes in kidney and myocardial function over six years in patients with type 2 diabetes and healthy controls.Methods Post-hoc analysis of a cohort study in 24 patients with type 2 diabetes and 18 healthy controls. Baseline determinants were cardiovascular autonomic reflex tests (heart rate response to: standing (30:15); deep breathing (E:I); and the Valsalva test) and time- and frequency-domain heart rate variability indices. Outcomes were changes in estimated glomerular filtration rate (eGFR), albuminuria, myocardial flow reserve (MFR) measured by cardiac 82Rb Positron emission tomography computed tomography (PET/CT), and coronary artery calcium score (CACS).ResultsMean age at inclusion was 61 ± 10 years and 36% were female. Mean follow up time was 6 ± 0 years. A lower response in heart rate to the Valsalva test (corresponding to weaker autonomic function) was associated with a larger decline in eGFR (p=0.04), but not significantly after adjustment for sex, baseline age, smoking status, systolic blood pressure, heart rate, HbA1c, body mass index and baseline eGFR (p=0.12). A higher baseline response in heart rate to standing (30:15) was associated with a larger decline in myocardial flow reserve in the unadjusted analysis (p=0.02) and after adjustment (p=0.02). A higher response in heart rate to the Valsalva maneuver was associated with a larger increase in CACS (p = 0.02), but the association became insignificant after adjustment (p = 0.16).ConclusionA lower response in heart rate to the Valsalva test was associated with a larger decline in kidney function, indicating that autonomic dysfunction may predict future loss of kidney function. However, we did not find any association between lower values in cardiovascular autonomic function at baseline and a worsening in albuminuria, myocardial function, or atherosclerotic burden.

Highlights

  • Cardiovascular autonomic neuropathy (CAN) is an overlooked and frequent diabetic complication seen in up to 65% of persons with type 2 diabetes [1]

  • We observed that a lower response in heart rate to the Valsalva test was associated with a larger decline in kidney function over six years

  • We did not evaluate the cardiovascular autonomic function at follow up with the Vagus device as in the baseline examination and are not able to relate changes in cardiovascular autonomic function to the outcomes. With this post hoc analysis we are the first to investigate the longitudinal associations between cardiovascular autonomic function at baseline and changes in kidney function, myocardial function, and atherosclerotic burden over six years of follow up

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Summary

Introduction

Cardiovascular autonomic neuropathy (CAN) is an overlooked and frequent diabetic complication seen in up to 65% of persons with type 2 diabetes [1]. CAN has been suggested to promote the progression of diabetic kidney disease and is an independent risk factor for cardiovascular mortality [1,2,3]. The mechanisms linking CAN, diabetic kidney disease and cardiovascular mortality are widely unknown. We could not find studies investigating the association between cardiovascular autonomic function and longitudinal changes in myocardial flow reserve in type 2 diabetes. Another cardiovascular measure associated with CAN in diabetes is the coronary artery calcium score, an established marker of coronary atherosclerosis [8,9,10,11]. The mechanisms linking cardiovascular autonomic neuropathy, diabetic kidney disease and cardiovascular mortality in type 2 diabetes are widely unknown. We investigated the relationship between baseline cardiovascular autonomic function and changes in kidney and myocardial function over six years in patients with type 2 diabetes and healthy controls

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