Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction

Abstract

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.

Might hypovitaminosis D aggravate endothelial dysfunction-related increases in arterial stiffness seen in patients with hypertension and type 2 diabetes? Reply to Boucher BJ [letter]

“…All these observations seem to fit well with the hypothesis brought up by Boucher [9]. She suggests, indeed, that hypovitaminosis D could be responsible for the incremental detriment in endothelial function that we have documented [10] in hypertensive patients with diabetes compared with those with normal glucose tolerance. Although intriguing, this explanation remains highly speculative and cannot be demonstrated in our study population as, unfortunately, we did not provide for vitamin D serum levels to be measured at the time of study planning.…”

Increased plasma serotonin metabolite 5-hydroxyindole acetic acid concentrations are associated with impaired systolic and late diastolic forward flows during cardiac cycle and elevated resistive index at popliteal artery and renal insufficiency in type 2 diabetic patients with microalbuminuria

“…In case of decreased aortic elasticity, less blood can be stored in the aorta, resulting in reduced late diastolic forward flow into the lower-leg arteries [13]. Glycation of extracellular matrix [27], endothelial dysfunction [28], increased intima-media thickness [29], and arterial calcification in the vessel wall [30] are responsible for the pathogenesis of aortic stiffness in diabetic patients. The small-caliber arteries and arterioles act as resistance vessels that regulate blood flow to the capillaries, arterial blood pressure, and cardiac output [13].…”

Comparison of benazepril and losartan on endothelial function and vascular stiffness in patients with Type 2 diabetes mellitus and hypertension: A randomized controlled trial

“…29 Three recent meta-analyses with hypertensive patients show that both ACEi and ARB improve FMD, when compared to placebo or no treatment, but there is no difference among them. [13][14][15] Eight trials compare ACEi to ARB, but only one shows a higher FMD response with ACEi.…”