Increased levels of symmetric dimethyl-arginine are associated with all-cause mortality in patients with symptomatic peripheral arterial disease

Staniszewska, A., Rajagopalan, S., Al-Shaheen, A., Thies, F. and Brittenden, J. (2015) Increased levels of symmetric dimethyl-arginine are associated with all-cause mortality in patients with symptomatic peripheral arterial disease. Journal of Vascular Surgery, 61(5), pp. 1292-1298. (doi: 10.1016/j.jvs.2015.01.002) (PMID:25776186)

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Abstract

Objective: Recent interest has focused on the role of the methyl-arginines, endogenous inhibitors of nitric oxide, as adverse prognostic indicators. To date, few studies have assessed the role of symmetric dimethyl-arginine (SDMA) in patients with peripheral arterial disease. We aimed to determine the relationship, if any, of SDMA to all-cause mortality and disease severity as assessed by the ankle-brachial index (ABI) in patients with symptomatic peripheral arterial disease (PAD). Methods: In 238 patients with symptomatic PAD and an ABI of <0.8, l-arginine, asymmetric dimethyl-arginine (ADMA) and SDMA levels were measured by hydrophilic-interaction liquid chromatography-electrospray tandem mass spectrometry. Results: The median follow-up was 6 years 11 months (interquartile range [IQR], 4 years 5 months-7 years 10 months). SDMA and ADMA levels were higher in those who died compared with those who survived (0.51 [IQR, 0.44-0.66] μmol/L vs 0.46 [IQR, 0.39-0.55] μmol/L, P ≤ .001; and 0.48 [IQR, 0.41-0.55] μmol/L vs 0.45 [IQR, 0.39-0.50] μmol/L, P = .007, respectively). l-arginine levels were similar in the two groups. On multivariate analysis, SDMA and ADMA as continuous variable were significantly associated with mortality (P = .001). For SDMA and ADMA, the highest compared with the lowest quartile levels were significantly associated with mortality (SDMA: hazard ratio, 3.855; 95% confidence interval, 1.625-9.143; P = .002; ADMA: hazard ratio, 2.277; 95% confidence interval, 1.114-4.654; P = .024). ADMA and SDMA showed a negative correlation with severity of PAD as assessed by ABI (r = −0.236, N = 216, P < .001; r = −0.209, N = 208, P = .002, respectively). Conclusions: The novel finding of this study is that SDMA levels were predictive of all cause-mortality and correlated with disease severity. Further studies should assess the role of nitric oxide donors in patients with high levels of SDMA.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brittenden, Professor Julie
Authors: Staniszewska, A., Rajagopalan, S., Al-Shaheen, A., Thies, F., and Brittenden, J.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Journal of Vascular Surgery
Publisher:Elsevier
ISSN:0741-5214
ISSN (Online):1097-6809
Published Online:13 March 2015

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