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

Xanthakis V, Larson MG, Wollert KC, Aragam J, Cheng S, Ho J, Coglianese E, Levy D, Colucci WS, Michael Felker G, Benjamin EJ, Januzzi JL, Wang TJ, Vasan RS
J Am Heart Assoc. 2013 2 (6): e000399

PMID: 24200688 · PMCID: PMC3886765 · DOI:10.1161/JAHA.113.000399

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.

MeSH Terms (25)

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

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