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Abstract
Aims
To define plasma concentrations, determinants, and optimal prognostic cut‐offs of soluble suppression of tumorigenesis‐2 (sST2), high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) in women and men with chronic heart failure (HF).
Methods and results
Individual data of patients from the Biomarkers In Heart Failure Outpatient Study (BIOS) Consortium with sST2, hs‐cTnT, and NT‐proBNP measured were analysed. The primary endpoint was a composite of 1 year cardiovascular death and HF hospitalization. The secondary endpoints were 5 year cardiovascular and all‐cause death. The cohort included 4540 patients (age 67 ± 12 years, left ventricular ejection fraction 33 ± 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/mL, P < 0.001) and hs‐cTnT level (15 vs. 20 ng/L, P < 0.001), and similar concentrations of NT‐proBNP (1540 vs. 1505 ng/L, P = 0.408). Although the three biomarkers were confirmed as independent predictors of outcome in both sexes, the optimal prognostic cut‐off was lower in women for sST2 (28 vs. 31 ng/mL) and hs‐cTnT (22 vs. 25 ng/L), while NT‐proBNP cut‐off was higher in women (2339 ng/L vs. 2145 ng/L). The use of sex‐specific cut‐offs improved risk prediction compared with the use of previously standardized prognostic cut‐offs and allowed to reclassify the risk of many patients, to a greater extent in women than men, and for hs‐cTnT than sST2 or NT‐proBNP. Specifically, up to 18% men and up to 57% women were reclassified, by using the sex‐specific cut‐off of hs‐cTnT for the endpoint of 5 year cardiovascular death.
Conclusions
In patients with chronic HF, concentrations of sST2 and hs‐cTnT, but not of NT‐proBNP, are lower in women. Lower sST2 and hs‐cTnT and higher NT‐proBNP cut‐offs for risk stratification could be used in women.
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Details
1 Institute of Life Sciences, Scuola Superiore Sant'Anna and Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana Gabriele Monasterio, Pisa, Italy
2 Cardiology Division, Pisa University Hospital, Pisa, Italy
3 Massachusetts General Hospital and Baim Institute for Clinical Research, Boston, MA, USA
4 Department of Medicine, University of Otago, New Zealand & National University Heart Centre, National University of Singapore, Singapore
5 National Heart Centre Singapore and Duke‐National University of Singapore, Singapore
6 University Medical Centre Groningen, Groningen, The Netherlands
7 Istituto di Ricerche Farmacologiche – “Mario Negri” (IRCCS), Milan, Italy
8 University of Minnesota Medical Center, University of Minnesota, Minneapolis, MN, USA, VA Medical Centre, Minneapolis, MN, USA
9 University of Minnesota Medical Center, University of Minnesota, Minneapolis, MN, USA
10 Oslo University Hospital, Ullevål, Oslo, Norway, Oslo University Hospital, Rikshospitalet, Oslo, Norway, Institute of Clinical Medicine, University of Oslo, Oslo, Norway, K. G. Jebsen Thrombosis Research and Expertise Center, University of Tromsø, Tromsø, Norway
11 KG Jebsen Center for Cardiac Research, University of Oslo and Center for Heart Failure Research, Oslo University Hospital, Norway
12 Oslo University Hospital, Rikshospitalet, Oslo, Norway
13 Maastricht University Medical Centre, Maastricht, The Netherlands
14 Hospital Universitari Germans Trias i Pujol, Badalona (Barcelona) and CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain
15 First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan
16 Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
17 Heart Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
18 Department of Medical Sciences, Uppsala University, Uppsala, Sweden
19 Wilhelminenspital and Sigmund Freud University Medical School, Vienna, Austria
20 Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
21 Department of Cardiology, National University Heart Centre and National University of Singapore, Singapore
22 Changi General Hospital, Singapore
23 Tan Tock Seng Hospital, Singapore
24 Khoo Teck Puat Hospital, Singapore
25 Singapore General Hospital, Singapore
26 Gisborne Hospital, Gisborne, New Zealand
27 Middlemore Hospital, Auckland, New Zealand