Asymmetric and symmetric dimethylarginine as risk markers for total mortality and cardiovascular outcomes: A systematic review and meta-analysis of prospective studies

Schlesinger, Sabrina; Sonntag, Svenja Rebecca; Lieb, Wolfgang; Maas, Renke

doi:10.1016/j.atherosclerosis.2017.06.434

Cited by 10 publications

(13 citation statements)

References 43 publications

(68 reference statements)

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“…We found, in a well‐characterized hypertension population, that individuals above the median value of ADMA concentration were at higher risk for cardiovascular death. Similarly, a recent systematic review described ADMA as an independent risk marker for all‐cause mortality (relative risk, 1.52; 95% confidence interval, 1.37–1.68) and cardiovascular disease (relative risk, 1.33; 95% confidence interval, 1.22–1.45) comparing high vs low ADMA concentrations . Zobel and colleagues also demonstrated in a population of patients with type 2 DM with microalbuminuria and without symptoms of coronary artery disease the association of ADMA with all‐cause mortality.…”

Section: Discussionmentioning

confidence: 90%

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

Triches

Mayer

Quinto

et al. 2018

J of Clinical Hypertension

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Section: Discussionmentioning

confidence: 90%

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

Triches

Mayer

Quinto

et al. 2018

J of Clinical Hypertension

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“…Ornithine may be considered a marker of low arginine bioavailability as a substrate of NOS . However, our finding that SDMA was inversely associated with HOMA‐IR is surprising given the established role of SDMA in inhibiting NOS and its positive association with CVD . Since low SDMA concentration is a validated marker of high glomerular filtration rate, significant inverse associations of SDMA with T2D may be a marker for hyperfiltration characteristic of prediabetes …”

Section: Discussionmentioning

confidence: 75%

“…17 However, our finding that SDMA was inversely associated with HOMA-IR is surprising given the established role of SDMA in inhibiting NOS and its positive association with CVD. 18 Since low SDMA concentration is a validated marker of high glomerular filtration rate, 19 significant inverse associations of SDMA with T2D may be a marker for hyperfiltration characteristic of prediabetes. 20 Lastly, we found a significant modification effect by the Mediterranean diet intervention on the relationship between 1-year changes in NMMA and T2D, suggesting that harmful changes in plasma NMMA may be offset by consuming a Mediterranean diet.…”

Section: Discussionmentioning

confidence: 99%

Changes in arginine are inversely associated with type 2 diabetes: A case‐cohort study in the PREDIMED trial

Ruíz-Canela

Razquín

et al. 2018

Diabetes Obesity Metabolism

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The associations between arginine-based metabolites and incident type 2 diabetes (T2D) are unknown. We employed a case-cohort design, nested within the PREDIMED trial, to examine six plasma metabolites (arginine, citrulline, ornithine, asymmetric dimethylarginine [ADMA], symmetric dimethylarginine [SDMA] and N-monomethyl-l-arginine [NMMA]) among 892 individuals (251 cases) for associations with incident T2D and insulin resistance. Weighted Cox models with robust variance were used. The 1-year changes in arginine (adjusted hazard ratio [HR] per SD 0.68, 95% confidence interval [CI] 0.49, 0.95; Q4 vs. Q1 0.46, 95% CI 0.21, 1.04; P trend = 0.02) and arginine/ADMA ratio (adjusted HR per SD 0.73, 95% CI 0.51, 1.04; Q4 vs. Q1 0.52, 95% CI 0.22, 1.25; P trend = 0.04) were associated with a lower risk of T2D. Positive changes of citrulline and ornithine, and negative changes in SDMA and arginine/(ornithine + citrulline) were associated with concurrent 1-year changes in homeostatic model assessment of insulin resistance. Individuals in the low-fat-diet group had a higher risk of T2D for 1-year changes in NMMA than individuals in Mediterranean-diet groups (P interaction = 0.02). We conclude that arginine bioavailability is important in T2D pathophysiology.

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“…The best known process is the role of NO as a signaling molecule in the regulation of blood flow, but NO is crucial for invoking an inflammatory response; it has also been demonstrated to affect various phenomena in the nervous system like membrane function, synaptic plasticity and memory formation (Forstermann & Sessa, ). Abnormalities in NO synthesis and metabolism underline many pathologies; some of them are cardiovascular disease (Au Yeung, Lin, Lam, & Schooling, ; Prokopowicz et al, ; Schlesinger, Sonntag, Lieb, & Maas, ), diabetes mellitus (Carmann et al, ; Celik, Cerrah, Arabul, & Akalin, ; Cieślak, Wojtczak, & Cieślak, ; Huemer et al, ; Pitocco et al, ) and chronic kidney disease (Boelaert et al, ; El‐Sadek et al, ; Fleck, Schweitzer, Karge, Busch, & Stein, ; Takahashi & Harris, ).…”

Section: Introductionmentioning

confidence: 99%

A novel mass spectrometry‐based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l‐arginine and l‐citrulline optimized for LC‐MS‐TOF and LC‐MS/MS

Wiśniewski

Fleszar

Piechowicz

et al. 2017

Biomedical Chromatography

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Nitric oxide (NO) is a regulatory molecule involved in many biological processes. NO is produced by nitric oxide synthase by conversion of l-arginine to l-citrulline. l-Arginine methylated derivatives, asymmetric and symmetric dimethylarginines (asymmetric dimethylarginine, ADMA, and symmetric dimethylarginine, SDMA), regulate l-arginine availability and the activity of nitric oxide synthase. As such, they have been frequently investigated as potential biomarkers in pathologies associated with dysfunctions in NO synthesis. Here, we present a new multistep analytical methodology based on liquid chromatography combined with mass spectrometry for the accurate identification of l-arginine, l-citrulline, ADMA and SDMA. Compounds are measured as stable 2,3,4,5,6-pentafluorobenzoyl chloride derivatives, which allows for simultaneous analysis of all compounds through chromatographic separation of ADMA and SDMA using a reverse-phase column. Serum aliquots (100 μL) were spiked with isotope-labeled internal standards and sodium carbonate buffer. The derivatization process was carried out at 25°C for 10 minu using pentafluorobenzoyl chloride as derivatization reagent. Calibration demonstrated good linearity (R = 0.9966-0.9986) for all derivatized compounds. Good accuracy (94.67-99.91%) and precision (1.92-11.8%) were observed for the quality control samples. The applicability of the method was evaluated in a cohort of angiological patients and healthy volunteers. The method discerned significantly lower l-arginine and l-citrulline in angiologic patients. This robust and fast LC-ESI-MS method may be a useful tool in quantitative analysis of l-arginine, ADMA, SDMA and l-citrulline.

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Asymmetric and symmetric dimethylarginine as risk markers for total mortality and cardiovascular outcomes: A systematic review and meta-analysis of prospective studies

Abstract: Background

Cited by 10 publications

References 43 publications

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

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

Changes in arginine are inversely associated with type 2 diabetes: A case‐cohort study in the PREDIMED trial

A novel mass spectrometry‐based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l‐arginine and l‐citrulline optimized for LC‐MS‐TOF and LC‐MS/MS

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