Key result
Cardiac stress biomarkers BNP, GDF-15, and hsTnI were associated with LVH or LVSD (ORs 1.29, 1.14, and 1.18 per SD increment), but adding them to risk factors yielded limited screening utility.
Why the study?
Does the addition of novel biomarkers (ST2, GDF-15, hsTnI) to standard risk factors and BNP improve screening for LVH and LVSD in a community-based cohort?
Cohort (n=2,460)
Does the addition of novel biomarkers (ST2, GDF-15, hsTnI) to standard risk factors and BNP improve screening for LVH and LVSD in a community-based cohort?
Effect estimate: OR 1.29 (BNP), 1.14 (GDF-15), 1.18 (hsTnI) (95% CI 1.15-1.44, 1.004-1.28, 1.06-1.31)
Although novel cardiac stress biomarkers (GDF-15, hsTnI) are associated with LVH and LVSD, they provide limited incremental value over standard risk factors and BNP for screening purposes.
Limited utility precludes routine biomarker addition for LVH/LVSD screening; leaves open targeted validation in prospective cohorts.
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.
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Xanthakis et al. (2013) conducted a cohort in Left ventricular hypertrophy and systolic dysfunction (n=2,460). Biomarkers (ST2, GDF-15, hsTnI, BNP) vs. Standard risk factors was evaluated on Composite echocardiographic outcome (LVH or LVSD) (OR 1.29 (BNP), 1.14 (GDF-15), 1.18 (hsTnI), 95% CI 1.15-1.44, 1.004-1.28, 1.06-1.31). Cardiac stress biomarkers BNP, GDF-15, and hsTnI were associated with LVH or LVSD (ORs 1.29, 1.14, and 1.18 per SD increment), but adding them to risk factors yielded limited screening utility.
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