TY - JOUR
T1 - Tumor biomarkers
T2 - association with heart failure outcomes
AU - Shi, Canxia
AU - van der Wal, Haye H.
AU - Silljé , H. H. W.
AU - Dokter, Martin
AU - van den Berg, Freek
AU - Huizinga, Leon
AU - Vriesema, Michelle
AU - Post, Joliene
AU - Anker, Stefan D.
AU - Cleland, John G. F.
AU - Ng, Leong Loke
AU - Samani, Nilesh J.
AU - Dickstein, Kenneth
AU - Zannad, Faiez
AU - Lang, Chim
AU - van Haelst, Paul L.
AU - Gietema , Jourik A.
AU - Metra, Marco
AU - Ameri , Pietro
AU - Canepa , Marco
AU - van Veldhuisen, Dirk Jan
AU - Voors, Adriaan A.
AU - de Boer, Rudolf A.
N1 - We thank all BIOSTAT participants and investigators. Canxia Shi is supported with a scholarship from the China Scholarship Council [CSC number: 201806170057]. Dr de Boer is ¬¬furthermore supported by the Dutch Heart Foundation [CVON DOSIS, grant 2014-40, CVON SHE-PREDICTS-HF, grant 2017-21; CVON RED-CVD, grant 2017-11; and CVON PREDICT2, grant 2018-30]; and the Innovational Research Incentives Scheme program of the Netherlands Organization for Scientific Research [NWO VIDI, grant 917·13·350], and by a grant from the Leducq Foundation [Cure PhosphoLambaN induced Cardiomyopathy (Cure-PLaN)]. We would like to thank Roche Diagnostics for providing reagents to measure the tumor biomarkers (Dr. K van Lynden, Roche Diagnostics BV, The Netherlands).
PY - 2020/8/1
Y1 - 2020/8/1
N2 - Background: There is increasing recognition that heart failure (HF) and cancer are conditions with a number of shared characteristics.
Objectives: To explore the association between tumor biomarkers and HF outcomes.
Methods: In 2,079 patients of BIOSTAT-CHF cohort, we measured six established tumor biomarkers: CA125, CA15-3, CA19-9, CEA, CYFRA 21-1, and AFP.
Results: During a median follow-up of 21 months, 555 (27%) patients reached the primary endpoint of all-cause mortality. CA125, CYFRA 21-1, CEA, and CA19-9 levels were positively correlated with NT-proBNP quartiles (all P<0.001, P for trend <0.001), and were respectively associated with a hazard ratio of 1.17 (95% CI 1.12 – 1.23; P<0.0001), 1.45 (95% CI 1.30 – 1.61; P<0.0001), 1.19 (95% CI 1.09 – 1.30; P =0.006), and 1.10 (95% CI 1.05 – 1.16; P<0.001)for all-cause mortality after correction for BIOSTAT risk model (age, BUN, NT-proBNP, hemoglobin, and beta-blocker). All tumor biomarkers (except AFP) had significant associations with secondary endpoints (composite of all-cause mortality and HF hospitalization, HF hospitalization, cardiovascular (CV) mortality, and non-CV mortality). ROC curves showed the AUC of CYFRA 21-1 (0.64) had a non-inferior AUC compared to NT-proBNP (0.68) for all-cause mortality (P =0.08). A combination of CYFRA 21-1 and NT-proBNP (AUC =0.71) improved the predictive value of the model for all-cause mortality (P =0.0002 compared to NT-proBNP).
Conclusions: Several established tumor biomarkers showed independent associations with indices of severity of HF and independent prognostic value for HF outcomes. This demonstrates that pathophysiological pathways sensed by these tumor biomarkers are also dysregulated in HF.
AB - Background: There is increasing recognition that heart failure (HF) and cancer are conditions with a number of shared characteristics.
Objectives: To explore the association between tumor biomarkers and HF outcomes.
Methods: In 2,079 patients of BIOSTAT-CHF cohort, we measured six established tumor biomarkers: CA125, CA15-3, CA19-9, CEA, CYFRA 21-1, and AFP.
Results: During a median follow-up of 21 months, 555 (27%) patients reached the primary endpoint of all-cause mortality. CA125, CYFRA 21-1, CEA, and CA19-9 levels were positively correlated with NT-proBNP quartiles (all P<0.001, P for trend <0.001), and were respectively associated with a hazard ratio of 1.17 (95% CI 1.12 – 1.23; P<0.0001), 1.45 (95% CI 1.30 – 1.61; P<0.0001), 1.19 (95% CI 1.09 – 1.30; P =0.006), and 1.10 (95% CI 1.05 – 1.16; P<0.001)for all-cause mortality after correction for BIOSTAT risk model (age, BUN, NT-proBNP, hemoglobin, and beta-blocker). All tumor biomarkers (except AFP) had significant associations with secondary endpoints (composite of all-cause mortality and HF hospitalization, HF hospitalization, cardiovascular (CV) mortality, and non-CV mortality). ROC curves showed the AUC of CYFRA 21-1 (0.64) had a non-inferior AUC compared to NT-proBNP (0.68) for all-cause mortality (P =0.08). A combination of CYFRA 21-1 and NT-proBNP (AUC =0.71) improved the predictive value of the model for all-cause mortality (P =0.0002 compared to NT-proBNP).
Conclusions: Several established tumor biomarkers showed independent associations with indices of severity of HF and independent prognostic value for HF outcomes. This demonstrates that pathophysiological pathways sensed by these tumor biomarkers are also dysregulated in HF.
KW - Heart failure
KW - Neoplasms
KW - Biomarkers
KW - tumor
KW - Natriuretic peptides
U2 - 10.1111/joim.13053
DO - 10.1111/joim.13053
M3 - Article
C2 - 32372544
VL - 288
SP - 207
EP - 218
JO - Journal of Internal Medicine
JF - Journal of Internal Medicine
SN - 0954-6820
IS - 2
ER -