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The prognostic value of asymmetric dimethylarginine in patients with cardiac syndrome X.

ABSTRACT: The pathophysiology of cardiac syndrome X is multifactorial and endothelial dysfunction has been implicated as important contributing factor. Asymmetric dimethylarginine (ADMA), characterized as a circulating endogenous inhibitor of nitric oxide synthase, may have been implicated as an important contributing factor for the development of endothelial dysfunction. In this study, we aim to assess the predictive power of ADMA for long-term prognosis in patients with cardiac syndrome X.We enrolled 239 consecutive patients with cardiac syndrome X diagnosed by coronary angiography. The mean age was 58.7±10.1 years. The patients were grouped into tertiles according to the plasma ADMA levels: <0.38 ?mol/l (tertile I), 0.38-0.44 ?mol/l (tertile II), and >0.44 ?mol/l (tertile III). All patients were followed up for a mean period of 6.5±1.5 years (median: 6.3 years, inter-quartile range: 5.7-8.0 years). During the follow-up period, major adverse events (MAE) were observed in 15 patients (6.3%), including 13 deaths. The plasma ADMA levels in patients who developed MAE were significantly higher than those who did not (0.48±0.06 ?mol/l vs. 0.42±0.08 ?mol/l, p = 0.005). In multivariate Cox regression analysis adjusted for age, eGFR and LVEF, ADMA tertile I and II were identify to be associated with a significantly lower risk of MAE compared to ADMA tertile III (p = 0.017). By considering the plasma ADMA level as a continuous variable, the plasma ADMA level remained a significant independent predictor for outcomes of MAE, and the relative risk of MACE increased by 50% when plasma ADMA level increased by 1 SD of value (p = 0.018).In patients with cardiac syndrome X, elevated plasma ADMA levels appeared to be an independent predictor of long-term adverse clinical outcomes.

SUBMITTER: Lu TM

PROVIDER: S-EPMC5716529 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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The prognostic value of asymmetric dimethylarginine in patients with cardiac syndrome X.

Lu Tse-Min TM Lee Tzong-Shyuan TS Lin Shing-Jong SJ Chan Wan-Leong WL Hsu Chiao-Po CP

PloS one 20171205 12

<h4>Background</h4>The pathophysiology of cardiac syndrome X is multifactorial and endothelial dysfunction has been implicated as important contributing factor. Asymmetric dimethylarginine (ADMA), characterized as a circulating endogenous inhibitor of nitric oxide synthase, may have been implicated as an important contributing factor for the development of endothelial dysfunction. In this study, we aim to assess the predictive power of ADMA for long-term prognosis in patients with cardiac syndro ...[more]

PMID: 29206850

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Project description:Background and objectivesLevels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, are elevated in kidney disease and associated with mortality in white European hemodialysis populations. Nitric oxide production and degradation are partially genetically determined and differ by racial background. No studies have measured asymmetric dimethylarginine in African Americans on dialysis and assessed whether differences exist in its association with mortality by race.Design, setting, participants, & measurementsAsymmetric dimethylarginine was measured in 259 patients on maintenance hemodialysis assembled from 2004 to 2012 in Boston area outpatient centers. Cox proportional hazards models were used to determine the association between asymmetric dimethylarginine and all-cause mortality, and an interaction with race was tested.ResultsMean (SD) age was 63 (17) years, 46% were women, and 22% were African American. Mean asymmetric dimethylarginine in non-African Americans was 0.79 µmol/L (0.16) versus 0.70 µmol/L (0.11) in African Americans (P<0.001); 130 patients died over a median follow-up of 2.3 years. African Americans had lower mortality risk than non-African Americans (hazard ratio, 0.27; 95% confidence interval, 0.15 to 0.50) that was robust to adjustment for age, comorbidity, and asymmetric dimethylarginine (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.69). An interaction was noted between race and asymmetric dimethylarginine (P=0.03), such that asymmetric dimethylarginine was associated with higher mortality in non-African Americans (adjusted hazard ratio, 1.29; 95% confidence interval, 1.06 to 1.57 per 1 SD higher asymmetric dimethylarginine) but not in African Americans (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28 to 1.18). Additional adjustment for fibroblast growth factor 23 partially attenuated the association for non-African Americans (adjusted hazard ratio, 1.22; 95% confidence interval, 0.98 to 1.50).ConclusionsAfrican Americans have lower asymmetric dimethylarginine levels and lower hazard for mortality compared with non-African Americans. Levels of asymmetric dimethylarginine did not explain lower hazard for mortality in non-African American patients. High asymmetric dimethylarginine was a risk factor for mortality exclusively in non-African Americans. Mechanisms explaining these relationships need to be evaluated.

Project description:Asymmetric (ADMA) and symmetric dimethylarginine (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.Post hoc analysis of the Hemodialysis (HEMO) Study.1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization.ADMA and SDMA measured in stored specimens.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, comorbid conditions, albumin level, and residual kidney function).Mean age of patients was 57±14 (SD) years, 63% were black, and 57% were women. Mean ADMA (0.9±0.2?mol/L) and SDMA levels (4.3±1.4?mol/L) were moderately correlated (r=0.418). Higher dialysis dose or longer session length were not associated with lower predialysis ADMA or SDMA concentrations. In fully adjusted models, each doubling of ADMA level 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 ?mol/L), the highest ADMA quintile (?1.07?mol/L) 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 level was associated with higher risk for cardiac death (HR, 1.40; 95% CI, 1.03-1.92), but this was no longer statistically significant after adjusting for ADMA level (HR, 1.20; 95% CI, 0.86-1.68).Single time-point measurement of ADMA and SDMA.ADMA and, to a lesser extent, SDMA levels are associated with cardiovascular outcomes in hemodialysis patients.

Dataset Information

The prognostic value of asymmetric dimethylarginine in patients with cardiac syndrome X.

Publications

The prognostic value of asymmetric dimethylarginine in patients with cardiac syndrome X.

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