233: Symmetric dimethylarginine serum level as a new marker of left ventricular ejection fraction in patients with acute myocardial infarction

Asymmetric dimethylarginine (ADMA) is a by-product of protein methylation implicated in the prognosis after acute myocardial infarction (MI) and heart failure through Nitric Oxide Synthase (NOS) inhibition. We aimed to investigate whether SDMA - the endogenous symmetrical stereoisomer of ADMA - that has insignificant inhibitory effects on NOS might be a marker of left ventricular function in acute MI.MethodsBlood samples from 468 consecutive patients hospitalized <24 hours after acute MI were taken on admission. Serum levels of ADMA and SDMA were determined using high-performance liquid chromatography. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at 2±1 d after admission.ResultsAmong the study population, mean age was 66±14 y, most were male (77%), hypertensive (54%), with prior CAD (20%) or diabetes (20%). On admission, half had ST segment elevation MI (STEMI) (55%), and ¼ suffered from heart failure, as assessed by killip>1 (23%). Mean LVEF was 52±13%. Mean ADMA and SDMA levels were at 0.81±0.42 and 0.61±0.44, respectively. Spearman analysis showed that LVEF was correlated negatively with SDMA (r=-0.135, p=0.006), but neither with ADMA (r=-0.001, p=0.99). SDMA was strongly associated with age (r=+0.354, p<0.001), creatinine clearance (r=-0.416, p<0.001), CRP (r=+0.134, p=0.004) and homocysteine (r=+0.413, p<0.001). By univariate linear regression analysis, age, homocysteine, hypertension, diabetes, prior CAD, admission heart rate, creatinine clearance, anterior wall location, STEMI, CK peak, and acute statin treatment, in addition to SDMA, were significantly associated with LVEF (p<0.05). Backward multivariate analysis including these covariates showed that SDMA remains an independent predictor of LVEF (B=-3.422; SE=1.687, p=0.043), beyond classical determinants of LVEF including age, homocysteine and renal function.ConclusionOur large prospective study showed for the first time that SDMA, but ADMA, may be linked to left ventricular function in patients with acute MI, and suggests that such dimethylarginines may probably exert biological activity by other pathways than NOS activity inhibition and beyond renal function

Etude de la relation entre l'intensité du stress oxydatif et les teneurs plasmatiques en diméthylarginine asymétrique (ADMA) (approches clinique et expérimentale)

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Increase in Levels of BDNF is Associated with Inflammation and Oxidative Stress during Cardiopulmonary Bypass

International audiencecardiopulmonary bypass (cPb) is thought to generate reactive oxygen species associated with a systemic inflammation and neurotrophins seem to be involved in cardiovascular inflammatory reactions. The aim of this study was to determine the impact of cPb on plasma neurotrophins levels and to appreciate the links existing between inflammation, oxidative stress and neurotrophins. Blood samples were taken from 27 patients undergoing cardiac surgery: before CPB, during ischemia and at reperfusion under CPB. Oxidative stress was evaluated using an Electron Spin Resonance technique by superoxide detection, and antioxidant defences by measurement of Endogenous Peroxidase Activity (EPA). The evolution of two neurotrophins: brain Derived Neurotrophic Factor (bDNF) and Nerve Growth Factor (NGF) was assessed with an ELIsA method. An inflammatory index was determined by a multiplex flow cytometry method. The inflammatory index showed that MCP-1, P-selectin, t-PA and interleukins 6, 8 and 10 levels increased during CPB (p<0.05). Superoxide production and EPA were higher during ischemia and reperfusion than before CPB (p<0.05). bDNF plasma levels were higher at reperfusion (p<0.05). NGF levels did not change. Our study shows an increase of BDNF levels, associated with an inflammatory phenomenon and a redox modification, in the plasma of patients undergoing cardiac surgery under CPB. The role played by this neurotrophin in this complex situation still needs to be elucidated, in particular its cellular origin. It is also necessary to understand whether BDNF has a beneficial or deleterious effect during CPB

High Levels of Asymmetric Dimethylarginine Are Strongly Associated with Low HDL in Patients with Acute Myocardial Infarction

International audienceObjectives: Low levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of acute myocardial infarction possibly through impaired endothelial atheroprotection and decreased nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA) mediates endothelial function by inhibiting nitric oxide synthase activity. In patients with acute myocardial infarction, we investigated the relationship between serum levels of HDL and ADMA. Approach and Results: Blood samples from 612 consecutive patients hospitalized for acute MI ,24 hours after symptom onset were taken on admission. Serum levels of ADMA, its stereoisomer, symmetric dimethylarginine (SDMA) and L-arginine were determined using high-performance liquid chromatography. Patients with low HDL (,40 mg/dL for men and ,50 mg/dL for women) were compared with patients with higher HDL. Most patients (59%) had low HDL levels. Median ADMA levels were markedly higher in the low HDL group (0.69 vs. 0.50 mmole/L, p,0.001). In contrast, SDMA and L-arginine levels were similar for the two groups (p = 0.120 and p = 0.064). Notably, ADMA, but not SDMA or L-arginine, was inversely correlated with HDL (r = 20.311, p,0.001). In stratified analysis, this relationship was only found for low HDL levels (r = 20.265, p,0.001), but not when HDL levels were higher (r = 20.077, p = 0.225). By multivariate logistic regression analysis, ADMA level was strongly associated with low HDL levels (OR(95%CI):6.06(3.48-10.53), p,0.001), beyond traditional confounding factors. Conclusions: Our large population-based study showed for the first time a strong inverse relationship between HDL and ADMA in myocardial infarction patients, suggesting a functional interaction between HDL and endothelium, beyond metabolic conditions associated with low HDL levels

Anti-hypertensive effects of Rosuvastatin are associated with decreased inflammation and oxidative stress markers in hypertensive rats

International audienc

Impact of Asymmetric Dimethylarginine on Mortality After Acute Myocardial Infarction

International audienceObjective-Asymmetrical dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthases. From a prospective cohort of patients with acute myocardial infarction (MI), we aimed to analyze the predictive value of circulating ADMA concentrations on prognosis. Methods and Results-Blood samples from 249 consecutive patients hospitalized for acute MI Ͻ24 hours were taken on admission. Serum levels of ADMA and its stereoisomer, symmetrical dimethylarginine (SDMA), were determined using high-performance liquid chromatography. The independent predictors of ADMA were glomerular filtration rate, female sex, and SDMA (R 2 ϭ0. 25). Baseline ADMA levels were higher in patients who had died than in patients who were alive at 1 year follow-up (1.23 [0.98 to 1.56] versus 0.95 [0.77 to 1.20] mol/L, PϽ0.001). By Cox multivariate analysis, the higher tertile of ADMA (median [interquartile range]: 1.45 [1.24 to 1.70] mol/L) was a predictor for mortality (Hazard Ratio [95% CI], 4.83 [1.59 to 14.71]), when compared to lower tertiles, even when adjusted for potential confounders, such as acute therapy, biological, and clinical factors. Conclusion-Our study suggests that the baseline ADMA level has a strong prognostic value for mortality after MI, beyond traditional risk factors and biomarkers

L-arginine and dimethylarginines concentrations in patients according to their HDL levels.

<p>The horizontal line is the median, box is the IQR (interquartile range) and whiskers are the 95% range. P values are from Mann-Whitney tests.</p

Correlations between dimethylarginines, L-arginine and biological data (N = 612).

<p>ADMA: Asymmetric dimethylarginine; CRP: C-reactive protein; HbA1c: glycated hemoglobin; HDL-C: high-density lipoprotein; LDL-C: low-density lipoprotein; SDMA: Symmetric dimethylarginine.</p

Correlations between dimethylarginines, and Larginine in the high and low HDL groups.

<p>Low HDL was defined as <40 mg/dL in men and <50 mg/dL in women.</p><p>ADMA: Asymmetric dimethylarginine; HDL-C: high-density lipoprotein; SDMA: Symmetric dimethylarginine.</p

Correlations between ADMA and HDL circulating levels (r = −0.311, p<0.001).

<p>Correlations between ADMA and HDL circulating levels (r = −0.311, p<0.001).</p