Catherine T. Prince

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

OBJECTIVE To 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 METHODS Cardiac 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. RESULTS E/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. CONCLUSIONS Cardiovascular 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.

Augmentation pressure and subendocardial viability ratio are associated with microalbuminuria and with poor renal function in type 1 diabetes

In this report we explore the hypothesis that arterial stiffness indices, which predict cardiovascular disease, might also correlate with microalbuminuria (MA) in type 1 diabetes (T1D), and thus have potential for risk assessment. Three pulse wave analysis (PWA) indices, measured using the SphygmoCor device, were evaluated on 144 participants with childhood-onset T1D. These variables, augmentation index (AIx), augmentation pressure (AP) and subendocardial viability ratio (SEVR, an estimate of myocardial perfusion) (an estimate of myocardial perfusion), were each analysed cross-sectionally in relation to both prevalent MA (defined as albuminuria excretion rate (AER) = 20—199 μg/min) and renal function (assessed by both eGFR and serum cystatin C). AP and SEVR were each univariately associated with AER, estimated glomerular filtration rate (eGFR) and cystatin C. Lower SEVR was also independently related to the presence of MA and degree of albuminuria within normo- and microalbuminuric participants. SEVR, not AP, was independently and negatively associated with both measures of renal function. SEVR is a better predictor of AER than brachial blood pressure measures in those without clinical proteinuria, indicating a potential use for PWA in the early detection of individuals at risk for cardiovascular and renal complications of T1D.

Retinal Vessel Diameter and the Incidence of Coronary Artery Disease in Type 1 Diabetes

PURPOSE To examine the relationship between retinal vessel diameter and coronary artery disease (CAD) incidence in type 1 diabetes (T1D) using data from the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. DESIGN Prospective cohort study of childhood-onset T1D. METHODS Data are from 448 participants who had retinal photographs taken at baseline examination (May 1986 to November 1988) and no history of laser photocoagulation. Computer-assisted grading was used to measure retinal arteriolar and venular caliber. CAD incidence (CAD death, myocardial infarction, revascularization/stenosis > or =50%, ischemic electrocardiogram, or physician-diagnosed angina) was ascertained over a median follow-up time of 18 years (range, 2 months to 20.5 years). RESULTS Mean baseline arteriolar and venular caliber were 180.0 microm (standard deviation [SD], 15.2 microm) and 273.3 microm (SD, 28.0 microm), respectively; 80 (17.9%) CAD events occurred during follow-up. After covariate adjustment for T1D duration, gender, hypertension, serum lipids, and smoking status, smaller arteriolar caliber was significantly associated with CAD (hazard ratio [HR], 1.42; P = .03), but larger venular caliber was not. A vessel diameter-gender interaction term was significant for arteriolar caliber (P = .006). Stratified by gender, smaller arteriolar caliber was significantly associated with the incidence of CAD in women (HR, 1.92; P = .004), but not men. Venular caliber was not associated with CAD in either gender. CONCLUSION Smaller arteriolar caliber may indicate an increased risk of CAD in women, but not men, with T1D. Additional studies are needed to further examine the role of microvascular disease in the pathogenesis of CAD in women with T1D.

Pulse wave analysis and prevalent cardiovascular disease in type 1 diabetes

OBJECTIVE Type 1 diabetes (T1D) is associated with a high risk for and mortality from premature coronary artery disease (CAD), including coronary artery calcification (CAC), a subclinical marker, and lower extremity arterial disease (LEAD). Pulse wave analysis (PWA) arterial stiffness indices have been associated with cardiovascular disease (CVD) risk factors and outcomes in various populations, but little is known regarding these relationships in T1D. METHODS PWA was performed using the SphygmoCor Px device on 144 participants in the Pittsburgh EDC Study of childhood-onset T1D. The cross-sectional associations between arterial stiffness indices, augmentation index (AIx) and augmentation pressure (AP), and subendocardial viability ratio (SEVR), an estimate of myocardial perfusion, with prevalent CAD, electron beam computed tomography-measured CAC and low (<0.90) ankle-brachial index (ABI) were examined. RESULTS Higher AP (but not AIx) and lower SEVR were univariately associated with prevalent CAD, high CAC score, and low ABI. AP and SEVRs association with CAD and CAC did not, however, remain significant after adjustment for age. In individuals not using nitrates, which profoundly affect PWA measures, AP was significantly higher in those with CAD events and explained more of the variance than either age or brachial blood pressure measures. SEVR was associated with low ABI in multivariable models. CONCLUSIONS Greater augmentation pressure is independently associated with prevalent CAD and estimated myocardial perfusion with low ABI in type 1 diabetes. These measures may thus help to better characterize CVD risk in type 1 diabetes and need to be examined prospectively.

Predictors of and survival after incident stroke in type 1 diabetes

Few studies have examined stroke risk in type 1 diabetes mellitus (T1DM). Stroke incidence, predictors, and survival were thus explored in this study. Pittsburgh Epidemiology of Diabetes Complications (EDC) Study participants (n = 658) with childhood-onset T1DM were followed biennially for 18 years. Baseline (1986–1988) mean age and diabetes duration were 28 and 19 years respectively. Stroke incidence and type was determined via survey or physician interview and, when possible, confirmed with medical or autopsy records. During follow-up, 31 (4.7%) strokes occurred (21 ischaemic, 8 haemorrhagic, 2 unclassified) in participants of mean age = 40.2 years (range 23–60). In exploratory multivariable Cox modelling, diabetes duration, systolic blood pressure (SBP), non-high density lipoprotein cholesterol (non-HDLc), white blood cells (WBC), and pulse significantly predicted ischaemic stroke. Adding overt nephropathy (ON) (hazard ratio = 4.4, 95% CI, 1.5–12.4) to the model replaced SBP. Participant survival after stroke was 80.6%, 45.2%, and 9.6% at 1, 5, and 10 years, respectively, and significantly worse after haemorrhagic stroke (p = 0.03). These risk factors merit careful evaluation and management to prevent stroke in T1DM, which occurs at least 20 years earlier than in the general population.

Pulse wave analysis and cardiac autonomic neuropathy in type 1 diabetes: a report from the Pittsburgh Epidemiology of Diabetes Complications Study.

BACKGROUND The cross-sectional associations of cardiac autonomic neuropathy (CAN) with pulse wave analysis (PWA) measures (both arterial stiffness and myocardial perfusion) have not been explored in type 1 diabetes, despite recognition of an association of CAN with coronary artery disease. METHODS Both CAN and PWA measures were obtained from 144 participants of the Pittsburgh Epidemiology of Diabetes Complications Study of childhood-onset type 1 diabetes at the 18-year follow-up examination. CAN was measured as variability in the R-R interval during deep breathing, and PWA was performed using SphgymoCor Px (AtCor Medical, Sydney, Australia). Other clinical and demographic factors were also assessed. Univariate and multivariable analyses for associations with CAN were performed for arterial stiffness measures (augmentation index [AIx] and augmentation pressure [AP]) and a myocardial perfusion measure (subendocardial viability ratio [SEVR]). RESULTS Presence of CAN was univariately associated with all three PWA measures: AIx (odds ratio [OR]=1.5, P=0.03), AP (OR=2.1, P=0.001), and SEVR (OR=0.4, P<0.001). These relationships persisted after adjustment for potential PWA confounders. Adjusting for age and diabetes-related factors (glycosylated hemoglobin, systolic blood pressure, and overt nephropathy), CAN only remained significantly associated with SEVR (OR=0.3, P=0.005). CONCLUSIONS CAN is cross-sectionally associated with measures of both increased arterial stiffness and decreased myocardial perfusion in type 1 diabetes; however, only the association with decreased estimated myocardial perfusion persisted in fully adjusted models. These results provide potential insight into the CAN association with coronary artery disease.

Modeling Chronic Glycemic Exposure Variables as Correlates and Predictors of Microvascular Complications of Diabetes: Response to Dyck et al.

We read with interest the article by Dyck et al. (1), in which the authors described a chronic glycemic exposure variable (GEi) in the Rochester Study. They examined GEi and its individual components (A1C, duration, and age at onset) in terms of prediction/correlation with complications and concluded that GEi is generally predicted better than its individual components (see Table 3 of ref. 1). Dyck et al. compared their results with our previously published analyses (2) using a different chronic glycemic exposure variable, A1 months, noting …