New cardiovascular biomarkers in patients with advanced cancer - A prospective study comparing MR-proADM, MR-proANP, copeptin, high-sensitivity troponin T and NT-proBNP

Abstract

Aims: Traditional cardiovascular (CV) biomarkers (high-sensitivity troponinT [hsTnT] and N-terminal pro-B-type natriuretic peptide [NT-proBNP]) are important to monitor cancer patients' cardiac function and to assess prognosis. Newer CV biomarkers (mid-regional pro-adrenomedullin [MR-proADM], C-terminal pro-arginine vasopressin [copeptin], and mid-regional pro-atrial natriuretic peptide [MR-proANP]) might outperform traditional biomarkers.

Methods and results: Overall, 442 hospitalized cancer patients without significant CV disease or current infection were enrolled (61 ± 15 years, 52% male, advanced cancer stage: 85%) and concentrations of CV biomarkers were analysed. Differences in echocardiographic, clinical, laboratory parameters were assessed. Patients were followed for up to 69 months for all-cause mortality. In univariable analyses, MR-proADM, hsTnT, copeptin, MR-proANP, and NT-proBNP predicted all-cause mortality. In multivariable analyses (adjusted for sex, age, Eastern Cooperative Oncology Group performance status, estimated glomerular filtration rate [eGFR], C-reactive protein, anti-cancer therapy, reason for hospitalization, cancer stage and type), only MR-proADM remained an independent predictor of mortality (MR-proADM per 1 ln: hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.47-3.50], p < 0.001). MR-proADM had the highest area under the curve (AUC) using receiver operating characteristic analysis (AUC [95% CI] 0.74 [0.69-0.79]; hsTnT: AUC 0.69; copeptin: AUC 0.66; MR-proANP: AUC 0.63; NT-proBNP: AUC 0.62). Optimal cut-point for mortality prediction with MR-proADM was 0.94 nmol/L (HR 2.43 [95% CI 1.92-3.06], p < 0.001). Patients with MR-proADM >0.94 nmol/L were older, more often had cancer stage IV, showed reduced performance status, eGFR, haemoglobin, diastolic left ventricular function, and elevated systolic pulmonary artery pressure.

Conclusion: MR-proADM is an independent predictor of mortality in advanced stage, hospitalized cancer patients without significant CV disease or current infection. The optimal MR-proADM cut-point for mortality prediction was 0.94 nmol/L with hazards for mortality being approximately 2.5 times higher. There was a continuous increase in mortality risk with stepwise increase of MR-proADM concentrations. Elevated concentrations of MR-proADM were also associated with reduced performance status and mildly reduced left ventricular diastolic function as well as higher age and more often cancer stage IV.

Keywords: Cardiovascular biomarkers; Cardio‐oncology; Diastolic dysfunction; MR‐proADM; Mortality.

Figure 1

(A) Univariable receiver operating characteristic (ROC) curves. (B) Time‐dependent area under the curve (AUC) from 0 to 69 months. CI, confidence interval; HR, hazard ratio; hsTnT, high‐sensitivity troponin T; MR‐proADM, mid‐regional pro‐adrenomedullin; MR‐proANP, mid‐regional pro‐atrial natriuretic peptide; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide.

Figure 2

(A) Kaplan–Meier curves for the cut‐point of mid‐regional pro‐adrenomedullin (MR‐proADM, 0.94 nmol/L). (B) Contour plot. Multivariable survival probability in relation to baseline levels of MR‐proADM (nmol/L), adjusted for sex, age, performance status, estimated glomerular filtration rate, C‐reactive protein, cancer stage (I‐IV), anti‐cancer therapy‐naïve (yes vs. no), reason for hospital admission (staging/diagnostics vs. anti‐cancer therapy vs. worsening of the clinical condition) and solid cancer vs. haematological cancer. CI, confidence interval.