Effect Modification of Chronic Kidney Disease on the Association of Circulating and Imaging Cardiac Biomarkers With Outcomes

Abstract

BackgroundCardiac troponin T and brain natriuretic peptide (BNP) are elevated in >50% of dialysis patients and are associated with poor outcomes. Few data investigated these associations in earlier chronic kidney disease (CKD).Methods and ResultsWe studied whether CKD modified associations of elevated BNP, N‐terminal‐pro‐BNP, high‐sensitivity cardiac troponin T, coronary artery calcification, and left ventricular hypertrophy with all‐cause death and cardiovascular death/events in 3218 multiethnic individuals followed for 12.5 years, and whether biomarkers added prognostic information to traditional cardiovascular risk factors in CKD. Of the cohort, 279 (9%) had CKD. There were 296 deaths and 218 cardiovascular deaths/events. Of non‐CKD individuals, 7% died and 6% had cardiovascular death/event versus 32% and 30% of CKD participants, P<0.001 for both. The interaction between BNP and CKD on death was significant (P=0.01): the adjusted hazard ratio in CKD was 2.05, 95% CI (1.34, 3.14), but not significant in non‐CKD, 1.04 (0.76, 1.41). CKD modified the association of high‐sensitivity cardiac troponin T with cardiovascular death/event, adjusted hazard ratio 3.34 (1.56, 7.18) in CKD versus 1.65 (1.16, 2.35) in non‐CKD, interaction P=0.09. There was an interaction between N‐terminal‐pro‐BNP and CKD for death in those without prior cardiovascular disease. Addition of each biomarker to traditional risk factors improved risk prediction, except coronary artery calcification was not discriminatory for cardiovascular death/event in CKD.ConclusionsCardiac biomarkers, with the exception of coronary artery calcification, prognosticated outcomes in early‐stage CKD as well as, if not better than, in non‐CKD individuals, even after controlling for estimated glomerular filtration rate, and added to information obtained from traditional cardiovascular risk factors alone.

Assessment of functional capacity before major non-cardiac surgery: an international, prospective cohort study

“…More research is required to define optimal thresholds for these measures, and determine how they should be utilised in combination with other prognostically important information, including alternative preoperative biomarkers (e.g., high-sensitivity troponin). 47 These other biomarkers might also help address, in part, the limitations of NT pro-BNP as a prognostic biomarker in the presence of obesity, 48 chronic renal kidney, 49 or heart failure with preserved ejection fraction. 50 Our findings also indicate that CPET, specifically VO 2 peak, can be used to identify patients at elevated risk for postoperative complications.…”

Utility of Cardiac Biomarkers in the Setting of Kidney Disease

“…In contrast, Lamb et al [8] reported that cTnT concentration, but not cTnI, was independently associated with all-cause death. A multiethnic cohort study that followed 3,218 patients for 12.5 years reported that hs-cTnT was a valid indicator of all-cause death and cardiovascular events in CKD patients [12]. Increased levels of dp-ucMGP have been associated with increased mortality in dialysis patients CKD, chronic kidney disease; cTnT, cardiac troponin T; cTnI, cardiac troponin I; BNP, B-type natriuretic peptide; NT-proBNP, N-terminal proBNP; ST2, suppression of tumorigenicity 2; sST2, soluble ST2; GDF-15, growth and differentiation factor-15; MGP, matrix gla protein; ucMGP, undercarboxylated MGP; Dp-ucMGP, dephosphorylated undercarboxylated MGP.…”

“…In a multiethnic cohort study that followed 3,218 patients for 12.5 years, Gregg et al [12] reported that BNP, NT-proBNP, and hs-cTnT were valid indicators of all-cause death and cardiovascular events in CKD patients, and associations were equivalent if not stronger as compared to non-CKD individuals. The prognostic value persisted even after the adjustment for eGFR and traditional cardiovascular risk factors [12]. However, studies have failed to identify consistent thresholds for BNP and NT-proBNP in CKD patients with decompensated heart failure that can help clinicians differentiate cardiac vs. non-cardiac causes of shortness of breath or volume overload.…”

Novel Biomarkers in Patients with Chronic Kidney Disease: An Analysis of Patients Enrolled in the GCKD-Study

“…Furthermore, the clinical performance of biomarkers needs to be confirmed in large prospective endpoint trials. In this regard, recent trials investigated the plasma concentrations of NT-proBNP, troponin T, and IGF-BP2 in patients with CKD and reported a higher prognostic value of the investigated biomarkers in these patients [61,62]. However, it is always questionable whether such studies consistently correct their statistical models for kidney function.…”