Tumour biomarkers: association with heart failure outcomes

Abstract

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 tumour biomarkers and HF outcomes. Methods. In 2,079 patients of BIOSTAT-CHF cohort, we measured six established tumour 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 end-point 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, haemoglobin and beta blocker). All tumour biomarkers (except AFP) had significant associations with secondary end-points (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 noninferior AUC compared with 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 with NT-proBNP). Conclusions. Several established tumour 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 tumour biomarkers are also dysregulated in HF.

Carbohydrate Antigen 125 Is a Biomarker of the Severity and Prognosis of Pulmonary Hypertension

“…Compared to those with CA 125 ≤ 5 U/ml, patients with CA 125 > 35 U/ml had higher serum levels of NT-proBNP and worse echocardiographic and haemodynamic parameters at baseline. In all 5 Cox models we constructed, CA125 > 35 U/ml was associated with an over 2-fold increased risk of 1-year clinical worsening, which was similar to the results seen in heart failure ( 32 , 33 ). Furthermore, ROC analysis showed that CA 125 provided additional predictive value in addition to the established PH biomarker NT-proBNP ( 18 ).…”

Common mechanistic pathways in cancer and heart failure. A scientific roadmap on behalf of the Translational Research Committee of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC)

“…Specific studies focusing on HF-cancer interactions would be needed to answer important unsolved questions such as defining the characteristics of patients who are more susceptible to present both conditions, identifying some early and specific predictive biomarkers, [130][131][132][133][134][135][136][137] adequately adjusting the management of those patients, and better understanding of shared mechanisms that could lead to target common regulators of HF and cancer. To answer these questions, dedicated registries and studies would need to reach three main requirements.…”

Cardiac Biomarkers in Patients with Cancer: Considerations, Clinical Implications, and Future Avenues

“…Meijers et al went a step further and showed that failing heart serves as a secreting organ that stimulates tumor growth [18•]. Recently, Shi et al also reported a correlation between several tumor biomarkers and heart failure, showing that tumor biomarkers have an independent prognostic value in heart failure patients [19]. This link also suggests a strong overlap and possible direct pathophysiological mechanism connecting CVD and cancer [6,7,20].…”