Association of novel biomarkers of cardiovascular stress with left ventricular hypertrophy and dysfunction: implications for screening

J Am Heart Assoc. 2013 Nov 7;2(6):e000399. doi: 10.1161/JAHA.113.000399.

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.

Methods and 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.

Keywords: biomarkers; echocardiography; heart failure; hypertrophy; screening.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Echocardiography, Doppler
  • Female
  • Growth Differentiation Factor 15 / blood
  • Humans
  • Hypertrophy, Left Ventricular / blood
  • Hypertrophy, Left Ventricular / diagnosis*
  • Hypertrophy, Left Ventricular / epidemiology
  • Hypertrophy, Left Ventricular / physiopathology
  • Interleukin-1 Receptor-Like 1 Protein
  • Logistic Models
  • Male
  • Massachusetts / epidemiology
  • Middle Aged
  • Multivariate Analysis
  • Natriuretic Peptide, Brain / blood
  • Odds Ratio
  • Predictive Value of Tests
  • Prevalence
  • Prognosis
  • Receptors, Cell Surface / blood
  • Risk Factors
  • Stress, Physiological*
  • Stroke Volume*
  • Troponin I / blood
  • Ventricular Dysfunction, Left / blood
  • Ventricular Dysfunction, Left / diagnosis*
  • Ventricular Dysfunction, Left / epidemiology
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left*

Substances

  • Biomarkers
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • IL1RL1 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Receptors, Cell Surface
  • Troponin I
  • Natriuretic Peptide, Brain