؊1 cut-points, diagnostic efficiencies of cystatin C (89% and 92%) were better than those of the other variables (79%-82% and 85%-86%, respectively; P ‫؍‬ 0.01).

Aims/hypothesis Endothelium-derived factors are thought to be physiological modulators of large artery stiffness. The aim of the study was to investigate whether endothelial function could be a determinant of arterial stiffness in essential hypertensive patients, in relation with the concomitant presence of type 2 diabetes mellitus. Methods The study included 341 participants (84 hypertensive patients with and 175 without type 2 diabetes mellitus, 82 matched controls). Brachial artery endotheliumdependent flow-mediated dilation (FMD) was determined by high-resolution ultrasound and computerised edge detection system. Applanation tonometry was used to measure carotid-femoral pulse wave velocity (PWV). Results Hypertensive patients with diabetes had higher PWV (10.1±2.3 m/s vs 8.6±1.4 m/s, p<0.001) and lower FMD (3.51±2.07 vs 5.16±2.96%, p<0.001) than non-diabetic hypertensive patients, who showed impaired vascular function when compared with healthy participants (7.9±1.6 m/s and 6.68 ± 3.67%). FMD was significantly and negatively correlated to PWV only in hypertensive diabetic patients (r0−0.456, p<0.001), but not in hypertensive normoglycaemic patients (r0−0.088, p00.248) or in healthy participants (r 00.008, p 00.946). Multivariate analysis demonstrated that, in the diabetic group, FMD remained an independent predictor of PWV after adjustment for confounders (r 2 00.083, p 00.003). Subgroup analysis performed in non-diabetic hypertensive patients revealed that neither obesity nor the metabolic syndrome affected the relationship between FMD and PWV. Conclusions/interpretation Endothelial dysfunction is a determinant of aortic stiffness in hypertensive diabetic patients but not in hypertensive patients without diabetes. These results suggest that type 2 diabetes mellitus on top of hypertension might worsen arterial compliance by endothelium-related mechanisms.

BackgroundMicrovascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes.MethodsWe recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis.ResultsOut of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59–7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65–15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42–94.57], p < 0.0001). After adjustments, HRs were: 1 MC 2.05 (95% CI 0.88–4.76), 2 MC 1.98 (95% CI 0.75–5.21), 3 MC 7.02 (95% CI 2.44–20.20, p = 0.002). Forty-nine subjects (6.7%) had at least one cardiovascular event, and cumulative incidence went from no-MC 2.2% (Ref) to 1 MC 5.0%; (HR 2.27 [95% CI 0.96–5.38]), 2 MC 26.8% (HR 12.88 [95% CI 5.82–28.50]) and 3 MC 40.9% (HR 29.34 [95% CI 11.59–74.25], p < 0.0001). Upon adjustments, HRs were: 1 MC 1.59 (95% CI 0.65–3.88), 2 MC 4.33 (95% CI 1.75–10.74), 3 MC 9.31 (95% CI 3.18–27.25, p < 0.0001). Thirty-five individuals (4.8%) had at least one coronary event, which cumulative incidence increased with MC burden (p < 0.0001).ConclusionsIn type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.

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