Differential associations of cardiorenal-inflammatory markers with cardiac and cancer mortality in cancer survivors

AIMS: To examine the associations of cardiorenal-inflammatory biomarkers with cardiac vs. cancer mortality in cancer survivors. METHODS AND RESULTS: We conducted a prospective analysis of 1384 U.S. cancer survivors (mean age: 67.5 years; 52.1% women; aged ≥ 20 years) from the NHANES cohort (1999-2004), with follow-up through 2019. Using Cox proportional hazards models, we examined the associations of the following cardiorenal-inflammatory biomarkers with cardiac vs. cancer mortality: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin-T (hs-TnT), high-sensitivity troponin I (hs-TnI; measured using three assays), urinary albumin-to-creatinine ratio (UACR), fractional excretion of albumin (FEalb) and C-reactive protein (CRP). Analyses were biomarker-specific i.e. participants with missing values for a given biomarker were excluded from that analysis. During a median P25-P75 follow-up of 11.8 5.1-16.8 years, 199 cardiac deaths (14.4%) and 259 cancer deaths (18.7%) occurred. In multivariable models, all biomarkers except CRP were significantly associated with cardiac mortality, and all biomarkers except cardiac troponins were significantly associated with cancer mortality (P ≤ 0.001 for all). When formally compared, cardiac troponins and NT-proBNP displayed stronger associations with cardiac mortality than cancer mortality (Pdifference ≤ 0.006). By contrast, CRP displayed stronger associations with cancer mortality than cardiac mortality (Pdifference 0.7). CONCLUSION: In cancer survivors, increased cardiac stress was more strongly associated with cardiac mortality whereas systemic inflammation was more strongly associated with cancer mortality. Renal dysfunction was similarly associated with both cardiac and cancer mortality.