title: Biomarkers of chronic cardiac injury and hemodynamic stress identify a malignant phenotype of left ventricular hypertrophy in the general population.
abstract: OBJECTIVE
  The goal of this study was to determine if biomarkers of subclinical myocardial injury and hemodynamic stress identify asymptomatic individuals with left ventricular hypertrophy (LVH) at higher risk for heart failure (HF) and death.
  
  
  BACKGROUND
  The interaction between LVH, low but detectable cardiac troponin T (cTnT), and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) on cardiovascular (CV) outcomes in the general population is unknown.
  
  
  METHODS
  Participants in the Dallas Heart Study without clinical HF, LV dysfunction, or chronic kidney disease underwent measurement of LV mass by magnetic resonance imaging (MRI), cTnT by highly sensitive assay, and NT-proBNP analysis (n = 2,413). Subjects were stratified according to LVH and by detectable cTnT (≥3 pg/ml) and increased NT-proBNP (>75th age- and sex-specific percentile) levels. For each analysis, participants were categorized into groups based on the presence (+) or absence (-) of LVH and biomarker levels above (+) or below (-) the predefined threshold.
  
  
  RESULTS
  Nine percent of participants were LVH+, 25% cTnT+, and 24% NT-proBNP+. Those LVH+ and cTnT+ and/or NT-proBNP+ (n = 144) were older and more likely to be male, with a greater risk factor burden and more severe LVH compared with those who were LVH+ biomarker- (p < 0.01 for each). The cumulative incidence of HF or CV death over 8 years among LVH+ cTnT+ was 21% versus 1% (LVH- cTnT-), 4% (LVH- cTnT+), and 6% (LVH+ cTnT-) (p < 0.0001). The interactions between LVH and cTnT (p(interaction) = 0.0005) and LVH and NT-proBNP (p(interaction) = 0.014) were highly significant. Individuals who were LVH+ and either cTnT+ or NT-proBNP+ remained at >4-fold higher risk for HF or CV death after multivariable adjustment for CV risk factors, renal function, and LV mass compared with those who were LVH- biomarker-.
  
  
  CONCLUSIONS
  Minimal elevations in biomarkers of subclinical cardiac injury and hemodynamic stress modify the association of LVH with adverse outcomes, identifying a malignant subphenotype of LVH with high risk for progression to HF and CV death.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Neeland
authors.forename: Mark H
authors.initials: MH
authors.lastname: Drazner
authors.forename: Jarett D
authors.initials: JD
authors.lastname: Berry
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.forename: Christopher
authors.initials: C
authors.lastname: deFilippi
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Seliger
authors.forename: Vijay
authors.initials: V
authors.lastname: Nambi
authors.forename: Darren K
authors.initials: DK
authors.lastname: McGuire
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Omland
authors.forename: James A
authors.initials: JA
authors.lastname: de Lemos
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D003643:Death; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis*; D006335:Heart Injuries / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood*; D015994:Incidence; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D010641:Phenotype; D015995:Prevalence; D012307:Risk Factors; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain