Author + information
- Received October 24, 2014
- Revision received December 3, 2014
- Accepted December 10, 2014
- Published online June 1, 2015.
- Stephen L. Seliger, MD, MS∗∗ (, )
- James de Lemos, MD†,
- Ian J. Neeland, MD†,
- Robert Christenson, PhD∗,
- John Gottdiener, MD∗,
- Mark H. Drazner, MD, MSc†,
- Jarett Berry, MD†,
- John Sorkin, MD, PhD∗ and
- Christopher deFilippi, MD∗
- ∗University of Maryland School of Medicine, Baltimore, Maryland
- †University of Texas Southwestern Medical Center, Dallas, Texas
- ↵∗Reprint requests and correspondence:
Dr. Stephen Seliger, University of Maryland School of Medicine, 22 South Greene Street, N3W143, Baltimore, Maryland 21201.
Objectives This study hypothesized that biomarkers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) and hemodynamic stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) would differentiate heart failure (HF) risk among older adults with left ventricular hypertrophy (LVH).
Background The natural history of LVH, an important risk factor for HF, is heterogeneous.
Methods NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years in older adults without prior HF or myocardial infarction in the CHS (Cardiovascular Health Study). LVH and left ventricular ejection fraction were determined by echocardiography. HF events were adjudicated over a median of 13.1 years and classified as preserved or reduced left ventricular ejection fraction (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction [HFrEF]). Adjusted risk of HF by LVH and biomarker tertiles, and by LVH and longitudinal increase in each biomarker was estimated using Cox regression.
Results Prevalence of LVH was 12.5% among 2,347 participants with complete measures. Adjusted risk of HF (N = 643 events) was approximately 3.8-fold higher among participants with LVH and in the highest biomarker tertile, compared with those with low biomarker levels without LVH (NT-proBNP, hazard ratio [HR]: 3.78; 95% confidence interval [CI]: 2.78 to 5.15 and hs-cTnT, HR: 3.86; 95% CI: 2.84 to 5.26). The adjusted risk of HFrEF was 7.8 times higher among those with the highest tertile of hs-cTnT and LVH (HR: 7.83; 95% CI: 4.43 to 13.83). Those with LVH and longitudinal increases in hs-cTnT or NT-proBNP were approximately 3-fold more likely to develop HF, primarily HFrEF, compared with those without LVH and with stable biomarkers.
Conclusions The combination of LVH with greater hs-cTnT or NT-proBNP levels, and their longitudinal increase, identifies older adults at highest risk for symptomatic HF, especially HFrEF. These biomarkers may characterize sub-phenotypes in the transition from LVH to HF and suggest modifiable targets for prevention.
This work was supported by Contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086, and Grant HL080295 from the National Heart, Lung, and Blood Institute, with additional contribution from the National Institute of Neurological Disorders and Stroke. Additional support was provided by AG023629 from the National Institute on Aging. A full list of principal Cardiovascular Health Study investigators and institutions can be found at CHS-NHLBI.org. Funding for measurement of NT-proBNP and hs-cTnT was provided by investigator-initiated grants from Roche Diagnostics Corporation. Dr. Seliger has received grant support from Singulex, Inc. Drs. Seliger, Christenson, and deFilippi have received grant support from Roche Diagnostics. Drs. Seliger, de Lemos, Christenson, and deFilippi have a patent pending relating to combined left ventricular hypertrophy and cardiac biomarkers for heart failure risk stratification. Dr. de Lemos has received grant support and consulting income from Roche Diagnostics and Abbott Diagnostics. Dr. Sorkin is funded by National Institute of Diabetes and Digestive and Kidney Diseases P30 DK072488, National Institute on Aging P30 AG028747, and the Baltimore Veterans Affairs Geriatric Research Education Clinical Center. Dr. deFilippi is a consultant to Siemens Healthcare Diagnostics; receives honorarium from Radiometer; and receives investigator-initiated research funding from Critical Diagnostics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 24, 2014.
- Revision received December 3, 2014.
- Accepted December 10, 2014.
- 2015 American College of Cardiology Foundation