Omega-3 Status and the Relationship between Plasma Asymmetric Dimethylarginine and Risk of Myocardial Infarction in Patients with Suspected Coronary Artery Disease

Borgeraas, Heidi; Strand, Elin; Pedersen, Eva Kristine Ringdal; Dierkes, Jutta; Ueland, Per Magne; Seifert, Reinhard; Wilberg, E.R.; Bohov, Pavol; Berge, Rolf K.; Nilsen, Dennis W.T.; Nygård, Ottar

doi:10.1155/2012/201742

Cited by 13 publications

(16 citation statements)

References 36 publications

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“…Nevertheless, they also observed no relationship between ADMA and the presence of 3-vessel CAD [14], in accordance with our data. Finally, as Schnabel et al [7] did not list any measure of angiographic CAD among covariates associated with ADMA in 1,874 CAD patients from the Athero Gene study, it can possibly be suspected that those correlations were statistically insignificant.…”

Section: Discussionsupporting

confidence: 92%

Differential associations of angiographic extent and severity of coronary artery disease with asymmetric dimethylarginine but not insulin resistance in non-diabetic men with stable angina: a cross-sectional study

Kruszelnicka

Surdacki

Golay³

2013

Cardiovasc Diabetol

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BackgroundAsymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthesis inhibitor, and insulin resistance (IR) have been implicated in atherogenesis. Our aim was to estimate relations between ADMA, the magnitude of IR and angiographic indices of extent and severity of coronary atherosclerosis in non-diabetic men with stable coronary artery disease (CAD).MethodsWe studied 151 non-diabetic men (mean age 57 ± 11 years) with stable angina, obstructive CAD (at least 1 luminal diameter stenosis of ≥70% in major coronary segments) and without heart failure, and 34 age-matched controls free of ≥50% coronary narrowings. The following CAD indices were computed: the number of major epicardial vessels with ≥70% stenosis, Sullivan extent score representing a proportion of the visible coronary tree with vessel wall irregularities, and Gensini score which reflects both CAD severity and extent, yet assigning a heavier weight to proximal segments and to the more severe narrowings by a non-linear point system. An estimate of IR was derived by homeostasis model assessment (HOMA-IR) from fasting insulin and glucose.ResultsAmong the CAD patients, the proportions of subjects with 1-vessel, 2- vessel and 3-vessel CAD were 26%, 25% and 49%, respectively. ADMA levels were higher in patients with obstructive CAD compared to the controls (0.51 ± 0.10 vs. 0.46 ± 0.09 μmol/L [SD], P = 0.01), whereas HOMA-IR was similar (median, 3.2 [interquartile range: 2.4–4.9] vs. 2.9 [2.3–4.7], P = 0.2). Within the CAD group, ADMA increased across ascending quartiles of Sullivan score (Spearman’s rho = 0.23, P = 0.004), but not with Gensini score (rho = 0.12, P = 0.15) or the number of vessels involved (rho = 0.08, P = 0.3). ADMA correlated to log-transformed Sullivan score (Pearson's r = 0.21, P = 0.008), which was only slightly attenuated upon multivariate adjustment (β = 0.19 ± 0.08 [SEM], P = 0.015). HOMA-IR did not differ according to any measure of angiographic CAD (P ≥ 0.2). ADMA and log (HOMA-IR) were mutually unrelated (r = 0.07, P = 0.4).ConclusionsADMA is associated with diffuse but not focal coronary atherosclerosis in non-diabetic men with stable CAD irrespectively of the degree of IR. The independent relationship between ADMA and coronary atherosclerotic burden may contribute to the well-recognized prognostic effect of ADMA in CAD.

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Section: Discussionsupporting

confidence: 92%

Differential associations of angiographic extent and severity of coronary artery disease with asymmetric dimethylarginine but not insulin resistance in non-diabetic men with stable angina: a cross-sectional study

Kruszelnicka

Surdacki

Golay³

2013

Cardiovasc Diabetol

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“…(5) PRMT may be downregulated (reducing ADMA production) by reducing cholesterol concentration. (7) DDAH may be modified by reducing inhibitory influences (proton pump inhibitors,(37) smoking(5)), statins (38) or via upregulation by PPAR-γ (peroxisome proliferator-activated receptor γ) ligands (such as pioglitazone), (39) omega-3 fatty acids(40), and erythropoietin. (41) Interestingly, angiotensin-converting enzyme inhibitors may increase ADMA concentrations in hemodialysis patients via bradykinin signaling and may need discontinuation in select patients.…”

Section: Discussionmentioning

confidence: 99%

Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients

Shafi

Hostetter

Meyer

et al. 2017

American Journal of Kidney Diseases

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Background Asymmetric and symmetric dimethylarginines (ADMA and SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients. Study Design Post hoc analysis of the Hemodialysis (HEMO) Study. Setting & Participants 1,276 prevalent hemodialysis patients with available samples 3–6 months after randomization. Predictor ADMA and SDMA measured in stored specimens. Outcomes Cardiac death, sudden cardiac death, first cardiovascular event, and any-cause death. Association with predictors analyzed using Cox regression adjusted for potential confounders (including demographics, clinical characteristics, comorbidities, albumin, and residual kidney function). Results Mean age of patients was 57 ±14 (SD) years, 63% were Black and 57% were female. Mean ADMA (0.9 ± 0.2 µM) and SDMA (4.3 ± 1.4 µM) were moderately correlated (r=0.418). Higher dialysis dose or longer session length were not associated with lower predialysis concentrations of ADMA or SDMA. In fully adjusted models, each doubling of ADMA was associated with higher risk (HR per 2-fold higher concentration; 95% CI) of cardiac death (1.83; 1.29–2.58), sudden cardiac death (1.79; 1.19–2.69), first cardiovascular event (1.50; 1.20–1.87), and any-cause death (1.44; 1.13–1.83). Compared to the lowest ADMA quintile (≤0.745 µM), the highest ADMA quintile (≥1.07 µM) was associated with higher risk (HR; 95% CI) of cardiac death (2.10; 1.44–3.05), sudden cardiac death (2.06; 1.46–2.90), first cardiovascular event (1.75; 1.35–2.27), and any-cause death (1.56; 1.21–2.00). SDMA was associated with higher risk of cardiac death (1.40; 1.03–1.92) but this was no longer statistically significant after adjusting for ADMA (1.20; 0.86–1.68). Limitations Single time-point measurement of ADMA and SDMA. Conclusions ADMA and, to a lesser extent SDMA are associated with cardiovascular outcomes in hemodialysis patients.

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“…[12] With respect to SDMA, initial studies did not find an association with adverse outcomes,[7, 13, 14] but some more recent studies reported positive associations with all-cause mortality or CVD. [11, 15, 16] Overall, prior studies on ADMA/SDMA and CVD or all-cause mortality were derived from many different study populations (general population,[15, 17, 18] patients with CVD,[9, 11, 19, 20] renal diseases,[7, 13, 21–24] diabetes,[25, 26] or critically ill patients from intensive care unit,[27–29] respectively), differed in their methodological approaches (e.g. using types of samples (plasma vs. serum) or methods to determine the biomarker levels (HPLC vs. tandem mass spectroscopy vs. ELISA), or considered different confounders in their analysis.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies

et al. 2016

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BackgroundA growing number of studies linked elevated concentrations of circulating asymmetric (ADMA) and symmetric (SDMA) dimethylarginine to mortality and cardiovascular disease (CVD) events. To summarize the evidence, we conducted a systematic review and quantified associations of ADMA and SDMA with the risks of all-cause mortality and incident CVD in meta-analyses accounting for different populations and methodological approaches of the studies.MethodsRelevant studies were identified in PubMed until February 2015. We used random effect models to obtain summary relative risks (RR) and 95% confidence intervals (95%CIs), comparing top versus bottom tertiles. Dose-response relations were assessed by restricted cubic spline regression models and potential non-linearity was evaluated using a likelihood ratio test. Heterogeneity between subgroups was assessed by meta-regression analysis.ResultsFor ADMA, 34 studies (total n = 32,428) investigating associations with all-cause mortality (events = 5,035) and 30 studies (total n = 30,624) investigating the association with incident CVD (events = 3,396) were included. The summary RRs (95%CI) for all-cause mortality were 1.52 (1.37–1.68) and for CVD 1.33 (1.22–1.45), comparing high versus low ADMA concentrations. Slight differences were observed across study populations and methodological approaches, with the strongest association of ADMA being reported with all-cause mortality in critically ill patients. For SDMA, 17 studies (total n = 18,163) were included for all-cause mortality (events = 2,903), and 13 studies (total n = 16,807) for CVD (events = 1,534). High vs. low levels of SDMA, were associated with increased risk of all-cause mortality [summary RR (95%CI): 1.31 (1.18–1.46)] and CVD [summary RR (95%CI): 1.36 (1.10–1.68) Strongest associations were observed in general population samples.ConclusionsThe dimethylarginines ADMA and SDMA are independent risk markers for all-cause mortality and CVD across different populations and methodological approaches.

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Omega-3 Status and the Relationship between Plasma Asymmetric Dimethylarginine and Risk of Myocardial Infarction in Patients with Suspected Coronary Artery Disease

Cited by 13 publications

References 36 publications

Differential associations of angiographic extent and severity of coronary artery disease with asymmetric dimethylarginine but not insulin resistance in non-diabetic men with stable angina: a cross-sectional study

Differential associations of angiographic extent and severity of coronary artery disease with asymmetric dimethylarginine but not insulin resistance in non-diabetic men with stable angina: a cross-sectional study

Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients

Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies

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