title: Association of novel biomarkers of cardiovascular stress with left ventricular hypertrophy and dysfunction: implications for screening.
abstract: BACKGROUND
  Currently available screening tools for left ventricular (LV) hypertrophy (LVH) and systolic dysfunction (LVSD) are either expensive (echocardiography) or perform suboptimally (B-type natriuretic peptide [BNP]). It is unknown whether newer biomarkers are associated with LVH and LVSD and can serve as screening tools.
  
  
  RESULTS
  We studied 2460 Framingham Study participants (mean age 58 years, 57% women) with measurements of biomarkers mirroring cardiac biomechanical stress (soluble ST-2 [ST2], growth differentiation factor-15 [GDF-15] and high-sensitivity troponin I [hsTnI]) and BNP. We defined LVH as LV mass/height(2) ≥the sex-specific 80th percentile and LVSD as mild/greater impairment of LV ejection fraction (LVEF) or a fractional shortening <0.29. Adjusting for standard risk factors in logistic models, BNP, GDF-15, and hsTnI were associated with the composite echocardiographic outcome (LVH or LVSD), odds ratios (OR) per SD increment in log-biomarker 1.29, 1.14, and 1.18 (95% CI: 1.15 to 1.44, 1.004 to 1.28, and 1.06 to 1.31), respectively. The C-statistic for the composite outcome increased from 0.765 with risk factors to 0.770 adding BNP, to 0.774 adding novel biomarkers. The continuous Net Reclassification Improvement was 0.212 (95% CI: 0.119 to 0.305, P<0.0001) after adding the novel biomarkers to risk factors plus BNP. BNP was associated with LVH and LVSD in multivariable models, whereas GDF-15 was associated with LVSD (OR 1.41, 95% CI: 1.16 to 1.70), and hsTnI with LVH (OR 1.22, 95% CI: 1.09 to 1.36). ST2 was not significantly associated with any outcome.
  
  
  CONCLUSIONS
  Our community-based investigation suggests that cardiac stress biomarkers are associated with LVH and LVSD but may have limited clinical utility as screening tools.
authors.affiliation: Framingham Heart Study, Framingham, MA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Xanthakis
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Kai C
authors.initials: KC
authors.lastname: Wollert
authors.forename: Jayashri
authors.initials: J
authors.lastname: Aragam
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ho
authors.forename: Erin
authors.initials: E
authors.lastname: Coglianese
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Colucci
authors.forename: G
authors.initials: G
authors.lastname: Michael Felker
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015150:Echocardiography, Doppler; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016015:Logistic Models; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood; D016017:Odds Ratio; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000097:blood; D012307:Risk Factors; D013312:Stress, Physiological; D013318:Stroke Volume; D019210:Troponin I / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D011956:Receptors, Cell Surface; D019210:Troponin I; D020097:Natriuretic Peptide, Brain
keywords: biomarkers; echocardiography; heart failure; hypertrophy; screening