Cardiovascular Autonomic Neuropathy, HDL Cholesterol, and Smoking Correlate With Arterial Stiffness Markers Determined 18 Years Later in Type 1 Diabetes

Abstract

OBJECTIVETo examine the relationship between cardiovascular autonomic neuropathy and pulse waveform analysis (PWA) measures of arterial stiffness in a childhood-onset type 1 diabetes population.RESEARCH DESIGN AND METHODSCardiac autonomic nerve function was measured in the baseline examination of the Pittsburgh Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes by heart rate variability (R-R interval) during deep breathing and expressed as expiration-to-inspiration (E/I) ratio. Other cardiovascular and diabetes factors were also assessed. PWA was performed using SphgymoCor Px on 144 participants at the 18-year follow-up examination. Univariate and multivariate analyses for associations between baseline nerve function and other cardiovascular and diabetes-related factors were performed for augmentation index (AIx), augmentation pressure (AP), and subendocardial viability ratio (SEVR), a surrogate marker of myocardial perfusion.RESULTSE/I ratio correlated negatively with both AIx (r = −0.18, P = 0.03) and AP (r = −0.32, P < 0.001) and positively with SEVR (r = 0.47, P < 0.001) univariately. Lower baseline E/I ratio, HDL cholesterol, and a history of smoking were associated with higher follow-up (18 years later) AIx and AP and lower SEVR in multivariate analyses. Higher baseline HbA1 was also associated with higher AP and lower SEVR multivariately.CONCLUSIONSCardiovascular autonomic neuropathy is associated with increased arterial stiffness measures and decreased estimated myocardial perfusion in those with type 1 diabetes some 18 years later. This association persists after adjustment for potential confounders as well as for baseline HbA1, HDL cholesterol, and smoking history, which were also associated with these PWA measures.

The prevalence of dyslipidemia and associated factors in children and adolescents with type 1 diabetes

“…A study from Brazil investigating poor metabolic control and endothelial dysfunction in patients with T1DM determined a positive relationship between age, smoking and dyslipidemia and hypertension [44]. Smoking and dyslipidemia are major risk factors for chronic complications of T1DM [44][45][46][47][48][49]. Another study emphasizes that smoking is one of the most influential factors for atherosclerosis [50].…”

Cardiovascular Disease Risk Factors in Youth With Diabetes Mellitus

“…136 These early changes in neurological function have implications for future CVD because autonomic dysfunction measured in childhood predicts increased arterial stiffness 18 years later. 137 Retinopathy is a microvascular complication of longstanding diabetes mellitus 138 that is associated with cognitive decline in adults. 139 Estimates of the incidence of retinopathy in youth with T1DM vary from 9% 140 to ≈15% per 100 personyears.…”

Haemodynamic changes during a squat test, pulsatile stress and indices of cardiovascular autonomic neuropathy in patients with long-duration type 1 diabetes

“…Despite the fact that only a slight (non-significant) difference could be detected in recent HbA 1c levels between the two T1DM subgroups with low and high RR E/I ratios, the quality of chronic glycaemic control most probably plays a role in the development of CAN [32][33][34]. There may also be links between PP and CAN [24], between aortic stiffness and CAN [13,14], and between arterial stiffness, cardiovagal baroreflex sensitivity and postural BP changes [35]. Increased SBP was identified as a factor associated with an increased risk of developing CAN in the cohort of T1DM patients in the EURODIAB Prospective Complications Study [16].…”

“…Both CAN [10] and increased PP [11,12] are considered to be independent risk factors of cardiovascular disease and total mortality in T1DM patients. Furthermore, CAN may be linked to aortic stiffness [13,14], endothelial dysfunction [15] and increased SBP [16] or PP [17] in T1DMpatients. Moreover, CAN is known to be associated with a greater risk of orthostatic hypotension [18,19].…”