期刊
BIOMARKERS
卷 25, 期 7, 页码 556-565出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/1354750X.2020.1810319
关键词
Tenascin-C; interstitial fibrosis; biomarkers; heart failure with preserved ejection fraction; inflammation; prognosis
资金
- National Institute for Health Research (NIHR) Leicester Cardiovascular Biomedical Research Centre [IRS_BRU_0211_20033]
- John and Lucille Van Geest Foundation
- British Heart Foundation [FS/15/10/31223]
- NIHR Research Fellowships [PDF-2011-0451, CDF 2014-07-045]
Introduction Tenascin-C is a marker of interstitial fibrosis. We assessed whether plasma Tenascin-C differed between heart failure with preserved ejection fraction (HFpEF) and asymptomatic controls and related to clinical outcomes. Materials and Methods Prospective, observational study of 172 age- and sex-matched subjects (HFpEFn = 130; controlsn = 42, age 73 +/- 9, males 50%) who underwent phenotyping with 20 plasma biomarkers, echocardiography, cardiac MRI and 6-minute-walk-testing. The primary endpoint was the composite of all-cause death/HF hospitalisation. Results Tenascin-C was higher in HFpEF compared to controls (13.7 [10.8-17.3] vs (11.1 [8.9-12.9] ng/ml,p < 0.0001). Tenascin-C correlated positively with markers of clinical severity (NYHA, E/E', BNP) and plasma biomarkers reflecting interstitial fibrosis (ST-2, Galectin-3, GDF-15, TIMP-1, TIMP-4, MMP-2, MMP-3, MMP-7, MMP-8), cardiomyocyte stress (BNP, NTpro-ANP), inflammation (MPO, hs-CRP, TNFR-1, IL6) and renal dysfunction (urea, cystatin-C, NGAL);p < 0.05 for all. During follow-up (median 1428 days), there were 61 composite events (21 deaths, 40 HF hospitalizations). In multivariable Cox regression analysis, Tenascin-C (adjusted hazard ratio [HR] 1.755, 95% confidence interval [CI] 1.305-2.360;p < 0.0001) and indexed extracellular volume (HR 1.465, CI 1.019-2.106;p = 0.039) were independently associated with adverse outcomes. Conclusions In HFpEF, plasma Tenascin-C is higher compared to age- and sex-matched controls and a strong predictor of adverse outcomes.
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