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Association of novel biomarkers of cardiovascular stress with left ventricular hypertrophy and dysfunction:
Vanessa Xanthakis1, Martin G Larson, Kai C Wollert
1Framingham Heart Study, Framingham, MA.
Insights
Newer cardiac stress biomarkers, including growth differentiation factor-15 (GDF-15) and high-sensitivity troponin I (hsTnI), show associations with left ventricular hypertrophy (LVH) and systolic dysfunction (LVSD). However, their clinical utility as standalone screening tools remains limited.
Area of Science:
- Cardiology
- Biomarker Discovery
- Diagnostic Tools
Background:
- Current screening tools for left ventricular hypertrophy (LVH) and systolic dysfunction (LVSD) are either costly (echocardiography) or suboptimal (B-type natriuretic peptide [BNP]).
- The potential of newer biomarkers to identify LVH and LVSD is not well-established.
Purpose of the Study:
- To investigate the association of novel cardiac stress biomarkers (soluble ST-2 [ST2], growth differentiation factor-15 [GDF-15], and high-sensitivity troponin I [hsTnI]) with LVH and LVSD.
- To evaluate the potential of these biomarkers as screening tools for LVH and LVSD.
Main Methods:
- Analysis of 2460 participants from the Framingham Study.
- Measurement of biomarkers including ST2, GDF-15, hsTnI, and BNP.
- Definition of LVH and LVSD based on echocardiographic parameters.
- Logistic regression models adjusted for standard risk factors to assess biomarker associations.
Main Results:
- BNP, GDF-15, and hsTnI were significantly associated with the composite outcome of LVH or LVSD.
- Adding novel biomarkers to risk factors plus BNP improved the prediction of the composite outcome (Net Reclassification Improvement = 0.212).
- GDF-15 was specifically associated with LVSD, and hsTnI with LVH; ST2 showed no significant association.
Conclusions:
- Cardiac stress biomarkers are associated with LVH and LVSD in a community-based population.
- Despite associations, the clinical utility of these novel biomarkers as standalone screening tools for LVH and LVSD may be limited.
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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