Association of endothelial dysfunction with cardiovascular risk factors and new-onset diabetes mellitus in patients with hypertension.

Asymmetric dimethylarginine (ADMA), which is the main endogenous inhibitor of nitric oxide synthase, plays a critical role in the process of endothelial dysfunction. The authors evaluated the association between high plasma ADMA levels in patients with hypertension and the presence of cardiovascular risk factors and the development of type 2 diabetes mellitus (DM) and cardiovascular outcomes, including death. The authors evaluated 191 patients with hypertension who were stratified into two groups according to the median value of basal ADMA: those with high levels of plasma ADMA (>0.55 µmol/L) and low levels of plasma ADMA (≤0.55 µmol/L) who were prospectively evaluated over 5.8 years. High ADMA levels were seen in patients with higher weight, body mass index, waist circumference, triglycerides, uric acid, and high-sensitivity C-reactive protein, and lower levels of high-density lipoprotein cholesterol and in patients with type 2 DM. There was an association between high plasma ADMA levels and the occurrence of cardiovascular death. In a subgroup of patients with hypertension free from metabolic syndrome and DM at baseline, there was an association between high ADMA levels and the development of type 2 DM. This study confirms the association of high plasma ADMA levels and the presence of cardiovascular risk factors in patients with hypertension and suggests a positive predictive value of high plasma ADMA levels for cardiovascular death in patients with hypertension and also for the development of type 2 DM in a subgroup of patients with hypertension free from metabolic abnormalities.

Relation of asymmetrical dimethylarginine levels with renal outcomes in hypertensive patients with and without type 2 diabetes mellitus.

AIM: The aim of the study was to evaluate the association between high plasma ADMA levels, a biomarker of endothelial dysfunction, with the progression of albuminuria and chronic kidney disease (CKD) in hypertensive patients, with and without type 2 diabetes mellitus. METHODS: We successfully contacted 213 of 644 patients who had been evaluated between 2004 and 2005 and for whom basal data were available. After the exclusion of 51 patients, 162 hypertensive patients who were free from albuminuria were stratified into the following 4 groups according to the presence of diabetes and plasma ADMA percentiles: general hypertensive patients with high levels of plasma ADMA (>P4 or ADMA > 0.61 µmol/L), general hypertensive patients with low levels of plasma ADMA (≤P4), diabetic hypertensive patients with high levels of plasma ADMA (>P4), and diabetic hypertensive patients with low levels of plasma ADMA (≤P4). RESULTS: The patients were prospectively evaluated over 5.8 years. High ADMA levels were associated with the progression of albuminuria in hypertensive patients, with and without type 2 diabetes. Major increases in the ADMA value during follow-up were associated with the progression of CKD, and direct correlations between ADMA changes and GFR changes were observed in the whole group and in the subgroup of diabetic patients. CONCLUSIONS: We suggest that high plasma ADMA levels might be a biomarker of renal disease progression and might even be an early predictor of albuminuria and its progression to the late stages of renal disease in hypertensive and diabetic hypertensive patients.