Effects of Vitamin D3 on asymmetric- and symmetric dimethylarginine in arterial hypertension.

BACKGROUND AND AIMS: Accumulating evidence has proposed a correlation between vitamin D (25(OH)D) insufficiency and cardiovascular (CV) disease. Vitamin D associated effects on endothelial function have been suggested to be a possible culprit. The present study investigated the association of vitamin D3 treatment on markers of endothelial dysfunction in patients with arterial hypertension. METHODS AND RESULTS: The Styrian Vitamin D Hypertension Trial is a double-blind, placebo-controlled, single-centre study conducted at the Medical University of Graz, Austria. A total of 200 study participants with arterial hypertension and 25(OH)D levels below 30ng/mL were enrolled. The study participants were randomized to receive 2800 IU of vitamin D3 per day as oily drops (n=100) or placebo (n=100) for a duration of eight weeks. The present study uses an analysis of covariance (ANCOVA) to investigate the effect of vitamin D3 treatment on symmetric (SDMA) and asymmetric dimethylarginine (ADMA). A total of 187 participants (mean [SD] age 60.0 [11.3] years; 47% women; 25(OH)D 21.2 [5.6]ng/mL; mean systolic blood pressure of 131.4 [8.9] mmHg on a median of 2 antihypertensive drugs) completed the trial. Mean treatment effect was -0.004 (95%CI [-0.03 to 0.04]; P=0.819) on ADMA and 0.001 (95%CI [-0.05 to 0.05]; P=0.850) on SDMA. In the subgroup analysis patients with a 25(OH)D concentration <20ng/mL had a significant increase in their log l-arginine/ADMA ratio (mean treatment effect 18.4 95%CI [1.84-34.9]µmol/L/µmol/L; P=0.030). ClinicalTrials.gov Identifier: NCT02136771 EudraCT number: 2009-018125-70 CONCLUSIONS: Vitamin D3 supplementation in hypertensive patients with low 25-hydroxyvitamin D has no significant effect on ADMA and SDMA.

Carotid artery stiffness is related to hyperinsulinemia and insulin-resistance in middle-aged, non-diabetic hypertensive patients.

BACKGROUND AND AIMS: Glycometabolic abnormalities are frequently found in hypertension and could affect the mechanical properties of carotid arteries. The aim of the study was to investigate the relationship of glucose tolerance, plasma insulin, and insulin sensitivity with carotid distensibility in middle-aged, non-diabetic hypertensive patients free of cardiac and vascular complications. METHOD AND RESULTS: In 93 patients with grade 1-2, uncomplicated, primary hypertension and 68 matched normotensive controls we measured plasma glucose and insulin at fast and after an oral glucose load (OGTT), calculated the HOMA-index as a marker of insulin sensitivity, and assessed distensibility of common carotid arteries by B-mode ultrasonography. Hypertensive patients were hyperinsulinemic and insulin-resistant as compared to normotensive controls. Hypertensive patients with impaired fasting glucose and/or impaired glucose tolerance had comparable distensibility of carotid arteries. Patients with decreased carotid distensibility were older and had higher body mass, fasting and post-OGTT plasma insulin, HOMA-index, and carotid IMT than the remaining patients, but no differences in glycated hemoglobin, and fasting or post-OGTT plasma glucose. Carotid coefficient of distensibility was inversely related and ß-stiffness directly related with fasting and post-OGTT plasma insulin, and HOMA-index. Multivariate logistic regression showed that age and post-OGTT plasma insulin levels predicted carotid artery stiffening independent of body mass index, sex, blood pressure, and plasma glucose levels. CONCLUSIONS: The study demonstrates that decreased insulin sensitivity and the related hyperinsulinemia but not hyperglycemia could contribute to carotid artery stiffening in middle-aged, non-diabetic hypertensive patients free of cardiovascular complications.