Microalbuminuria and Cardiovascular Autonomic Dysfunction Are Independently Associated With Cardiovascular Mortality: Evidence for Distinct Pathways

Abstract

OBJECTIVEMicroalbuminuria is associated with cardiovascular mortality, particularly among individuals with type 2 diabetes, but the mechanisms underlying this association are not completely understood. Microalbuminuria is known to be associated with cardiovascular autonomic dysfunction (C-AD), and C-AD in turn is associated with cardiovascular mortality. The purpose of this study, therefore, was to investigate whether C-AD can explain the relationship between microalbuminuria and cardiovascular mortality.RESEARCH DESIGN AND METHODSWe studied 490 individuals from a population-based cohort of individuals aged 50–75 years who were followed for a median period of 13.6 years. Microalbuminuria was defined as an albumin-to-creatinine ratio ≥2.0 mg/mmol in an early-morning spot-urine sample. Ten parameters reflecting different aspects of cardiovascular autonomic function were measured and compiled into a total score of C-AD (mean of separate z scores). The association between C-AD and microalbuminuria was estimated by multiple linear regression, and relative risks (RRs) for cardiovascular mortality were estimated by Cox proportional hazards analyses.RESULTSAfter adjustments for age, sex, glucose tolerance status, and other risk factors, C-AD was associated with microalbuminuria (β = 0.16 [95% CI 0.01–0.33]), and both microalbuminuria (RR 2.09 [1.07–4.08]) and C-AD (1.74 [1.04–2.89]) were associated with cardiovascular mortality. These associations did not change after further mutual adjustment for C-AD (2.13 [1.09–4.17]) or microalbuminuria (1.76 [1.05–2.94]), respectively.CONCLUSIONSBoth microalbuminuria and C-AD are independently associated with cardiovascular mortality, and the excess mortality attributable to microalbuminuria cannot be explained by C-AD.

Orthostatic hypotension in diabetic patients—10-year follow-up study

“…Negative association of non-dipping AH with progression of diabetic nephropathy was previously observed in DM2 (Bendzala, Kruzliak, Gaspar, et al, 2015), whereas non-dipping has been linked to OH (Spallone, Ziegler, Freeman, Toronto Consensus Panel on Diabetic Neuropathy, et al, 2011). Effect of CAN in pathogenesis of diabetic nephropathy consists of changing hemodynamic in the kidney glomeruli mainly by endothelial dysfunction, albuminuria and erythropoietin insufficiency induced anemia (Beijers, Ferreira, Bravenboer, et al, 2009).…”

Cardiovascular disease in chronic kidney disease: untying the Gordian knot

“…Autonomic dysfunction affecting the cardiovascular system (ADC) has been implicated in the link between microalbuminuria and CVD (59) and mortality (60,61). Various pathophysiological pathways for this link have been proposed, including impaired heart rate variability, resting tachycardia, exercise intolerance, abnormal blood pressure regulation and orthostatic hypotension (62).…”

Dysfunction of Autonomic Nervous System in Childhood Obesity: A Cross-Sectional Study

“…Childhood obesity is associated with a number of metabolic, cardiovascular and other disturbances, which include lipid abnormalities, altered glucose metabolism and type 2 diabetes, pulmonary disorders including obstructive sleep apnoea and reactive airway disease, a pro-inflammatory state and coagulation abnormalities [3]. Because dysfunction of the autonomic nervous system (ANS) may contribute to development or stabilization of obesity and is associated with cardiovascular mortality [4], the study of ANS function in obesity is of considerable clinical interest. Most previous studies of ANS function in obese children have been limited to investigations of cardiac autonomic function through analysis of heart rate variability.…”