Synergistic effects of asymmetrical dimethyl-L-arginine accumulation and endothelial progenitor cell deficiency on renal function decline during a 2-year follow-up in stable angina

Surdacki, Andrzej; Marewicz, Ewa; Wieczorek-Surdacka, Ewa; Rakowski, Tomasz; Szastak, Grzegorz; Pryjma, J; Dudek, Dariusz; Dubiel, Jacek S.

doi:10.1093/ndt/gfp439

Cited by 13 publications

(14 citation statements)

References 55 publications

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“…In this study, elevated plasma ADMA levels were also observed in patients with macroalbuminuria. Finally, ADMA has been shown to inhibit mobilization, differentiation, and function of endothelial progenitor cells (32), and recently, both ADMA accumulation and epithelial progenitor cell deficiency have been found to synergistically accelerate the deterioration of renal function in patients with stable angina (33). In summary, it may be hypothesized that in patients with mild to moderate CKD, the association between ADMA and long-term adverse events may be attributed to the reducing NO bioavailability/impaired endothelial dysfunction and/or increased oxidative stress and/or suppressed function of endothelial progenitor cells via inhibition of NO synthase and its association with proteinuria.…”

Section: Discussionmentioning

confidence: 99%

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

Chung²,

Lin

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Elevated plasma level of asymmetric dimethylarginine (ADMA) have been reported to be associated with endothelial dysfunction and atherosclerosis risk factors, and may predict cardiovascular events in patients with ESRD. In this study, we aimed to assess the association between plasma ADMA and long-term outcome in a cohort of patients with stage 3 to 4 chronic kidney disease (CKD).Design, setting, participants, & measurements From July 2006 to June 2009, 298 consecutive patients with stage 3 to 4 CKD scheduled to undergo coronary angiography were recruited. Plasma ADMA levels were determined using HPLC. ResultsThe mean age was 73 Ϯ 10 years. Approximately half of the patients had diabetes and 88 patients had proteinuria. The baseline estimated GFR (eGFR) was 44 Ϯ 13 ml/min per 1.73 m 2 . The plasma ADMA levels of the patients with proteinuria were significantly higher than those without. The plasma ADMA levels correlated significantly with eGFR. During the median follow-up period of 2.7 years, we observed 26 all-cause deaths, 12 nonfatal myocardial infarctions, and 2 strokes. Multivariate Cox analysis revealed that an increase of 0.1 mol/L in plasma ADMA level was associated with a 37% increased risk of the composite outcomes of all-cause deaths, nonfatal myocardial infarctions, and strokes. ConclusionsIn this elder and high-risk population with stage 3 to 4 CKD, high plasma ADMA level was associated with low eGFR and macroalbuminuria. Furthermore, high plasma ADMA level appeared to be an independent predictor of long-term outcome.

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Section: Discussionmentioning

confidence: 99%

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

Chung²,

Lin

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…We studied the previously characterized group of 80 non-diabetic men with stable angina who underwent successful elective complex coronary angioplasty with implantation of ≥1 bare-metal stent in our tertiary care center due to the presence of a diameter stenosis of ≥70% of ≥1 major epicardial artery segment [24,25]. Prior to the hospitalization, the patients were on low-dose aspirin, angiotensin-converting enzyme inhibitors (ACEI) and statins for ≥3 months and this medication was maintained after discharge and supplemented by clopidogrel following current practice guidelines (Tables 1 and 2).…”

Section: Methodsmentioning

confidence: 99%

Asymmetric dimethylarginine predicts decline of glucose tolerance in men with stable coronary artery disease: a 4.5-year follow-up study

Surdacki

Kruszelnicka

Rakowski

et al. 2013

Cardiovasc Diabetol

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BackgroundEndothelial dysfunction, largely dependent on impaired nitric oxide bioavailability, has been reportedly associated with incident type 2 diabetes. Our aim was to test the hypothesis that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide formation, might be linked to future deterioration in glucose tolerance in stable coronary artery disease (CAD).MethodsWe studied 80 non-diabetic men (mean age 55 ± 11 years) with stable angina who underwent successful elective complex coronary angioplasty and were receiving a standard medication according to practice guidelines. Plasma ADMA and its structural isomer symmetric dimethylarginine (SDMA) were measured prior to coronary angiography. An estimate of insulin resistance by homeostasis model assessment (HOMA-IR index) was calculated from fasting insulin and glucose. Deterioration in glucose tolerance was defined as development of type 2 diabetes or progression from a normal glucose tolerance to impaired fasting glucose.ResultsOver a median follow-up of 55 months 11 subjects developed type 2 diabetes and 13 progressed to impaired fasting glucose. Incident deterioration of glucose tolerance was associated with ADMA (hazard ratio [HR] per 1-SD increment 1.64 [95% CI: 1.14–2.35]; P = 0.007), log (HOMA-IR index) (HR = 1.60 [1.16–2.20]; P = 0.004) and body-mass index (HR = 1.44 [0.95–2.17]; P = 0.08) by univariate Cox regression. ADMA (HR = 1.65 [1.14–2.38]; p = 0.008) and log (HOMA-IR index) (HR = 1.55 [1.10–2.17]; P = 0.01) were multivariate predictors of a decline in glucose tolerance. ADMA and SDMA were unrelated to body-mass index, HOMA-IR index, insulin or glucose.ConclusionsADMA predicts future deterioration of glucose tolerance independently of baseline insulin resistance in men with stable CAD. Whether this association reflects a contribution of endothelial dysfunction to accelerated decline of insulin sensitivity, or represents only an epiphenomenon accompanying pre-diabetes, remains to be elucidated. The observed relationship might contribute to the well-recognized ability of ADMA to predict cardiovascular outcome.

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“…The study subjects were being treated with low-dose aspirin, statins and angiotensinconverting enzyme inhibitors (ACEI) for ≥3 months prior to admission to limit the heterogeneity of the patients in terms of the use of drugs known to improve CV outcome in CAD, as described previously (Surdacki et al 2010). The study population was divided into 2 groups according to metformin use for at least 1 year before index hospitalization.…”

Section: Patientsmentioning

confidence: 99%

“…Exclusion criteria included overt heart failure, congenital heart disease, significant valvular heart disease, arterial hypertension uncontrolled adequately by drugs, major surgery during past 6 months, any infections within preceding 2 months, estimated glomerular filtration rate (eGFR) below 45 mL/min per 1.73 m 2 of body surface area according to the Chronic Kidney Disease Epidemiology Collaboration formula, endocrine disorders other than diabetes, abnormal liver function, coexistent inflammatory or malignant diseases, relevant laboratory abnormalities in the routine blood and urine analysis, and any chronic non-CV or non-diabetic medication (Surdacki et al 2010).…”

Section: Patientsmentioning

confidence: 99%

Differential associations of circulating asymmetric dimethylarginine and cell adhesion molecules with metformin use in patients with type 2 diabetes mellitus and stable coronary artery disease

et al. 2015

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Metformin, the drug of first choice in type 2 diabetes mellitus (T2DM), reduces cardiovascular (CV) morbidity and mortality in part independently of improved glycemic control and changes in traditional risk factors. However, there are discordant reports on the effects of metformin on endothelial function in T2DM. Our aim was to compare biochemical endothelial markers in patients with stable coronary artery disease (CAD) and T2DM stratified by metformin use. We studied 70 patients (29 women, age 68 ± 9 years) with established T2DM referred for elective coronary angiography owing to stable angina who were receiving a standard CV medication and metformin or other oral antidiabetic drugs. Exclusion criteria included heart failure and other relevant coexistent disorders. Biochemical indices of endothelial dysfunction and activation at admission were compared according to metformin use for at least 1 year prior to index hospitalization. Clinical characteristics were similar in patients receiving metformin (n = 40) vs. those on other oral antidiabetic agents (n = 30). Plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) was lower (553 ± 148 vs. 668 ± 170 µg/L, P = 0.004) and asymmetric dimethylarginine (ADMA) higher (0.53 ± 0.09 vs. 0.48 ± 0.08 µM, P = 0.01) in subjects on metformin, which was maintained in multivariate analysis. Symmetric dimethylarginine, intercellular adhesion molecule-1, monocyte chemotactic protein-1 and E-selectin did not differ across the groups. The results were substantially unchanged after exclusion of insulin users. Thus, metformin use appears differentially associated with sVCAM-1 and ADMA in patients with T2DM and stable CAD. Whether this observation may reflect different prognostic effects of these endothelial markers in diabetes remains to be studied.

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Synergistic effects of asymmetrical dimethyl-L-arginine accumulation and endothelial progenitor cell deficiency on renal function decline during a 2-year follow-up in stable angina

Abstract: Elevated ADMA and EPC deficiency may synergistically contribute to accelerated renal function decline in stable angina. This could result from the impairment of the EPC-dependent endothelial renewal in the kidney, an NO-dependent process.

Cited by 13 publications

References 55 publications

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

Asymmetric dimethylarginine predicts decline of glucose tolerance in men with stable coronary artery disease: a 4.5-year follow-up study

Differential associations of circulating asymmetric dimethylarginine and cell adhesion molecules with metformin use in patients with type 2 diabetes mellitus and stable coronary artery disease

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