title: Circulating levels of dimethylarginines, chronic kidney disease and long-term clinical outcome in non-ST-elevation myocardial infarction.
abstract: BACKGROUND
  Mechanisms linking chronic kidney disease (CKD) and adverse outcomes in acute coronary syndromes (ACS) are not fully understood. Among potential key players, reduced nitric oxide (NO) synthesis due to its endogenous inhibitors, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine could be involved. We measured plasma concentration of arginine, ADMA and SDMA and investigated their relationship with CKD and long-term outcome in non-ST-elevation myocardial infarction (NSTEMI).
  
  
  RESULTS
  We prospectively measured arginine, ADMA, and SDMA at hospital admission in 104 NSTEMI patients. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2). We considered a primary end point of combined cardiac death and re-infarction at a median follow-up of 21 months. In CKD (n = 33) and no-CKD (n = 71) patients, arginine and ADMA were similar, whereas SDMA was significantly higher in CKD patients (0.65±0.23 vs. 0.42±0.12 µmol/L; P<0.0001). Twenty-four (23%) patients had an adverse cardiac event during follow-up: 12 (36%) were CKD and 12 (17%) no-CKD patients (P = 0.02). When study population was stratified according to arginine, ADMA and SDMA median values, only SDMA (median 0.46 µmol/L) was associated with the primary end-point (P = 0.0016). In models adjusted for age, hemoglobin and left ventricular ejection fraction, the hazard ratio (HR) for CKD and SDMA were high (HR 2.93, interquartile range [IQR] 1.15-7.53; P = 0.02 and HR 6.80, IQR 2.09-22.2; P = 0.001, respectively) but, after mutual adjustment, only SDMA remained significantly associated with the primary end point (HR 5.73, IQR 1.55-21.2; P = 0.009).
  
  
  CONCLUSIONS
  In NSTEMI patients, elevated SDMA plasma levels are associated with CKD and worse long-term prognosis.
authors.affiliation: Centro Cardiologico Monzino, I.R.C.C.S, Milan, Italy. viviana.cavalca@unimi.it
authors.forename: Viviana
authors.initials: V
authors.lastname: Cavalca
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Veglia
authors.forename: Isabella
authors.initials: I
authors.lastname: Squellerio
authors.forename: Monica
authors.initials: M
authors.lastname: De Metrio
authors.forename: Mara
authors.initials: M
authors.lastname: Rubino
authors.forename: Benedetta
authors.initials: B
authors.lastname: Porro
authors.forename: Marco
authors.initials: M
authors.lastname: Moltrasio
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Marenzi
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D023381:Endpoint Determination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology; D009569:Nitric Oxide / Q000096:biosynthesis; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000000981:diagnostic imaging* / Q000503:physiopathology; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: C487735:dimethylarginine; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; D001120:Arginine