Abstract

ObjectivesWe aimed to investigate whether SDMA- symmetric dimethylarginine -the symmetrical stereoisomer of ADMA- might be a marker of left ventricular function in AMI.BackgroundAsymmetric dimethylarginine (ADMA) has been implicated in the prognosis after acute myocardial infarction (AMI) and heart failure (HF).MethodsCross sectional prospective study from 487 consecutive patients hospitalized <24 hours after AMI. Patients with HF on admission were excluded. Serum levels of ADMA, SDMA and L-arginine were determined using HPLC. Glomerular filtration rate (eGFR) was estimated based on creatinine levels. Outcomes were in-hospital severe HF, as defined by Killip class >2, and death.ResultsPatients were analysed based on SDMA tertiles. Sex, diabetes, dyslipidemia, and prior MI were similar for all tertiles. In contrast, age and hypertension increased across the tertiles (p<0.001). From the first to the last tertile, GRACE risk score was elevated while LVEF and eGFR was reduced. The rate of severe HF and death were gradually increased across the SDMA tertiles (from 0.6% to 7.4%, p = 0.006 and from 0.6% to 5.0%, p = 0.034, respectively). Backward logistic multivariate analysis showed that SDMA was an independent estimate of developing severe HF, even when adjusted for confounding (OR(95%CI): 8.2(3.0–22.5), p<0.001). Further, SDMA was associated with mortality, even after adjustment for GRACE risk score (OR(95%CI): 4.56(1.34–15.52), p = 0.015).ConclusionsOur study showed for the first time that SDMA is associated with hospital outcomes, through altered LVEF and may have biological activity beyond renal function.

Highlights

  • Coronary artery disease (CAD) including acute myocardial infarction (MI) is the most frequent cause of altered Left Ventricular Ejection Fraction (LVEF) and Heart Failure (HF)

  • We aimed to investigate whether SDMA- symmetric dimethylarginine -the symmetrical stereoisomer of Asymmetric dimethylarginine (ADMA)- might be a marker of left ventricular function in acute myocardial infarction (AMI)

  • Our study showed for the first time that SDMA is associated with hospital outcomes, through altered LVEF and may have biological activity beyond renal function

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Summary

Introduction

Coronary artery disease (CAD) including acute myocardial infarction (MI) is the most frequent cause of altered Left Ventricular Ejection Fraction (LVEF) and Heart Failure (HF). HF is a frequent complication of acute MI and significantly worsens the prognosis of patients with CAD. Impaired nitric oxide (NO) bioavailability is involved in the pathogenesis and progression of CAD. In patients with chronic HF, accumulation of methylated arginine metabolites has been associated with disease progression [1]. Asymmetric dimethylarginine (ADMA), as a methylated product of L-arginine, may compete with L-arginine as the substrate for the nitric oxide synthases (NOS) or inhibit NOS phosphorylation and decrease NO production [2]. Asymmetric dimethylarginine (ADMA) has been implicated in the prognosis after acute myocardial infarction (AMI) and heart failure (HF)

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