Association of Novel Biomarkers of Cardiovascular Stress With Left Ventricular Hypertrophy and Dysfunction: Implications for Screening

Author:

Xanthakis Vanessa123,Larson Martin G.14,Wollert Kai C.5,Aragam Jayashri67,Cheng Susan17,Ho Jennifer18,Coglianese Erin9,Levy Daniel110,Colucci Wilson S.8,Michael Felker G.11,Benjamin Emelia J.11238,Januzzi James L.13,Wang Thomas J.14,Vasan Ramachandran S.138

Affiliation:

1. Framingham Heart Study, Framingham, MA

2. Department of Biostatistics, Boston University School of Public Health, Boston, MA

3. Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA

4. Department of Mathematics and Statistics, Boston University, Boston, MA

5. Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany

6. Veterans Administration Hospital, West Roxbury, MA

7. Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA

8. Section of Cardiology, Boston University School of Medicine, Boston, MA

9. Division of Cardiology, Loyola University, Chicago, IL

10. Center for Population Studies, National Heart, Lung, & Blood Institute, Bethesda, MD

11. Division of Cardiology, Duke University School of Medicine, Durham, NC

12. Department of Epidemiology, Boston University School of Public Health, Boston, MA

13. Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA

14. Division of Cardiovascular Medicine, Division of Medicine, Vanderbilt University, Nashville, TN

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 F ramingham Study participants (mean age 58 years, 57% women) with measurements of biomarkers mirroring cardiac biomechanical stress (soluble ST ‐2 [ ST 2], 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). ST 2 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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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