title: Novel Biomarkers of Cardiac Stress, Cardiovascular Dysfunction, and Outcomes in HIV-Infected Individuals.
abstract: OBJECTIVE
  This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality.
  
  
  BACKGROUND
  HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information.
  
  
  METHODS
  Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction <50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure ≥35 mm Hg. Mortality data were obtained from the National Death Index.
  
  
  RESULTS
  Patients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy.
  
  
  CONCLUSIONS
  Among HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death.
authors.affiliation: Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Secemsky
authors.affiliation: Department of Medicine, Veteran's Affairs Medical Center, San Francisco, University of California-San Francisco, San Francisco, California.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Scherzer
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California-San Francisco, San Francisco, California.
authors.forename: Elaine
authors.initials: E
authors.lastname: Nitta
authors.affiliation: Laboratory Medicine, San Francisco General Hospital, University of California-San Francisco, San Francisco, California.
authors.forename: Alan H B
authors.initials: AH
authors.lastname: Wu
authors.affiliation: Division of Cardiology, Department of Medicine, Cedars-Sinai Hospital, Los Angeles, California.
authors.forename: David C
authors.initials: DC
authors.lastname: Lange
authors.affiliation: San Francisco General Hospital HIV/AIDS Division, Department of Medicine, University of California-San Francisco, San Francisco, California.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.affiliation: Department of Epidemiology and Biostatistics, University of California-San Francisco and San Francisco General Hospital HIV/AIDS Division, San Francisco, California.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Martin
authors.affiliation: Critical Diagnostics, San Diego, California.
authors.forename: James
authors.initials: J
authors.lastname: Snider
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California-San Francisco, San Francisco, California.
authors.forename: Peter
authors.initials: P
authors.lastname: Ganz
authors.affiliation: Division of Cardiology, Department of Medicine, San Francisco General Hospital, University of California-San Francisco, San Francisco, California. Electronic address: phsue@medsfgh.ucsf.edu.
authors.forename: Priscilla Y
authors.initials: PY
authors.lastname: Hsue
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D004452:Echocardiography; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis*; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis*; D054144:Heart Failure, Diastolic / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000175:diagnosis*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D017063:Outcome Assessment, Health Care; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011956:Receptors, Cell Surface / Q000097:blood*; D012016:Reference Values; D015996:Survival Rate
chemical_list: D015415:Biomarkers; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: HIV; biomarkers; cardiovascular dysfunction; death; mortality