Rudolf A de Boer1, Qi Cao2, Douwe Postmus2, Kevin Damman3, Adriaan A Voors3, Tiny Jaarsma4, Dirk J van Veldhuisen3, William D Arnold5, Hans L Hillege6, Herman H W Silljé3. 1. Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands. Electronic address: r.a.de.boer@umcg.nl. 2. Department of Epidemiology, University Medical Center Groningen, University of Groningen, the Netherlands. 3. Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands. 4. Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands; Department of Social and Welfare Studies, Faculty of Health Sciences, Linköping University, Norrköping, Sweden. 5. Alere San Diego, Inc., San Diego, California. 6. Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands; Department of Epidemiology, University Medical Center Groningen, University of Groningen, the Netherlands.
Abstract
OBJECTIVES: This study investigated clinical determinants and added prognostic value of HE4 as a biomarker not previously described in heart failure (HF). BACKGROUND: Identification of plasma biomarkers that help to risk stratify HF patients may help to improve treatment. METHODS: Plasma HE4 levels were determined in 567 participants of the COACH (Coordinating study evaluating outcomes of Advising and Counseling in Heart failure). Patients had been hospitalized for HF and were followed for 18 months. The primary endpoint of this study was a composite of all-cause mortality and HF hospitalization. RESULTS: HE4 showed a strong correlation with HF severity, according to New York Heart Association functional class and brain natriuretic peptide (BNP) levels (p < 0.001). HE4 also showed a positive correlation with GDF15 (p < 0.001) and, in addition, correlated with kidney function (estimated glomerular filtration rate [eGFR]; p < 0.001). Cox regression analysis revealed that a doubling of HE4 levels was associated with a hazard ratio (HR) of 1.73 (95% confidence interval [CI]: 1.53 to 1.95) for the primary outcome (p < 0.001). After correction for age, gender, BNP, and eGFR, the HR was 1.46 (95% CI: 1.23 to 1.72; p < 0.001), and after additional adjustment for GDF15, the HR lowered to 1.30 (95% CI: 1.07 to 1.59; p = 0.009). The area under the curve in the receiver-operating characteristic curve analysis increased from 0.727 to 0.752 when HE4 was included in the clinical evaluation (p = 0.051). The integrated discrimination improvement and net reclassification index for reclassification showed significant improvements when HE4 was added to the clinical model, and this remained significant after BNP inclusion in the model. CONCLUSIONS: HE4 plasma levels are correlated with markers of HF severity, show prognostic value, and can improve risk assessment in HF.
OBJECTIVES: This study investigated clinical determinants and added prognostic value of HE4 as a biomarker not previously described in heart failure (HF). BACKGROUND: Identification of plasma biomarkers that help to risk stratify HF patients may help to improve treatment. METHODS: Plasma HE4 levels were determined in 567 participants of the COACH (Coordinating study evaluating outcomes of Advising and Counseling in Heart failure). Patients had been hospitalized for HF and were followed for 18 months. The primary endpoint of this study was a composite of all-cause mortality and HF hospitalization. RESULTS:HE4 showed a strong correlation with HF severity, according to New York Heart Association functional class and brain natriuretic peptide (BNP) levels (p < 0.001). HE4 also showed a positive correlation with GDF15 (p < 0.001) and, in addition, correlated with kidney function (estimated glomerular filtration rate [eGFR]; p < 0.001). Cox regression analysis revealed that a doubling of HE4 levels was associated with a hazard ratio (HR) of 1.73 (95% confidence interval [CI]: 1.53 to 1.95) for the primary outcome (p < 0.001). After correction for age, gender, BNP, and eGFR, the HR was 1.46 (95% CI: 1.23 to 1.72; p < 0.001), and after additional adjustment for GDF15, the HR lowered to 1.30 (95% CI: 1.07 to 1.59; p = 0.009). The area under the curve in the receiver-operating characteristic curve analysis increased from 0.727 to 0.752 when HE4 was included in the clinical evaluation (p = 0.051). The integrated discrimination improvement and net reclassification index for reclassification showed significant improvements when HE4 was added to the clinical model, and this remained significant after BNP inclusion in the model. CONCLUSIONS:HE4 plasma levels are correlated with markers of HF severity, show prognostic value, and can improve risk assessment in HF.
Authors: Brian R Lindman; Marie-Annick Clavel; Rami Abu-Alhayja'a; Nancy Côté; François Dagenais; Eric Novak; Pierre Voisine; Anthony Poulin; Benoit J Arsenault; Philippe Desmeules; Abdellaziz Dahou; Lionel Taster; Khitam Aldahoun; Yohan Bossé; Patrick Mathieu; Philippe Pibarot Journal: JACC Cardiovasc Interv Date: 2018-11-12 Impact factor: 11.195
Authors: Gianluigi Savarese; Alicia Uijl; Wouter Ouwerkerk; Jasper Tromp; Stefan D Anker; Kenneth Dickstein; Camilla Hage; Carolyn S P Lam; Chim C Lang; Marco Metra; Leong L Ng; Nicola Orsini; Nilesh J Samani; Dirk J van Veldhuisen; John G F Cleland; Adriaan A Voors; Lars H Lund Journal: ESC Heart Fail Date: 2022-04-06
Authors: Thor Ueland; Lars Gullestad; Lei Kou; Pål Aukrust; Inderjit S Anand; Marianne Nordlund Broughton; John J McMurray; Dirk J van Veldhuisen; David J Warren; Nils Bolstad Journal: ESC Heart Fail Date: 2018-08-25
Authors: C Shi; H H van der Wal; H H W Silljé; M M Dokter; F van den Berg; L Huizinga; M Vriesema; J Post; S D Anker; J G Cleland; L L Ng; N J Samani; K Dickstein; F Zannad; C C Lang; P L van Haelst; J A Gietema; M Metra; P Ameri; M Canepa; D J van Veldhuisen; A A Voors; R A de Boer Journal: J Intern Med Date: 2020-05-05 Impact factor: 8.989