title: Asymmetric dimethylarginine and coronary artery calcium scores are increased in patients infected with human immunodeficiency virus.
abstract: OBJECTIVE
  Patients infected with human immunodeficiency virus (HIV) have an increased risk for cardiovascular events and mortality. Elevated concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are associated with increased subclinical atherosclerosis and cardiovascular events. The objective of this study was to determine whether plasma ADMA levels are increased in patients infected with HIV and whether this is associated with cardiovascular risk factors, inflammatory/thrombotic biomarkers, and elevated coronary artery calcium scores (CACS).
  
  
  METHODS
  HIV-infected patients and control patients were recruited in a case-control study. Medical history and laboratory measurements including plasma ADMA and biomarkers for inflammation and thrombosis such as C-reactive protein (CRP), fibrinogen, and homocysteine were obtained in both cohorts. Using multidetector computed tomography, CACS were measured in Agatston Units (AU). Bivariate differences between HIV-infected and control patients were analyzed.
  
  
  RESULTS
  HIV-infected patients (n=37, male=27, age=45 years) had significantly higher concentrations of ADMA (0.40±0.10 μmol/l) compared to a similarly matched cohort of non-HIV-infected patients (n=43, male=27, age=45 years), (0.35±0.07 μmol/l, p=0.03). There were no significant differences in CRP, homocysteine, and fibrinogen between the two cohorts. However, HIV-infected patients had a higher CACS distribution compared to control patients [0.0 (8.5) vs. 0.0 (0.0) AU, p=0.01]. In a multivariable regression analysis HIV-infected patients with a relative CACS of 75-90% for age and gender had the highest ADMA concentrations (0.48±0.09 μmol/l, p=0.04) among all CACS subgroups.
  
  
  CONCLUSIONS
  HIV-infected patients have significantly higher ADMA concentrations compared to control patients. In addition, increased CACS was associated with elevated ADMA concentrations. Thus, increased ADMA levels appear to be associated with the presence of subclinical atherosclerosis in HIV-infected patients.
authors.affiliation: Division of Cardiology, San Jose Medical Center, Kaiser Permanente, San Jose, CA, United States. james.j.jang@kp.org
authors.forename: James J
authors.initials: JJ
authors.lastname: Jang
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Berkheimer
authors.forename: Maqdooda
authors.initials: M
authors.lastname: Merchant
authors.forename: Ashok
authors.initials: A
authors.lastname: Krishnaswami
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000821:virology*; D002140:California; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000821:virology*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications / Q000821:virology*; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D012367:RNA, Viral; C018524:N,N-dimethylarginine; D001120:Arginine