Prognostic value of soluble ST2, high-sensitivity cardiac troponin, and NT-proBNP in type 2 diabetes: a 15-year retrospective study

Abstract

Background Patients with type 2 diabetes (T2DM) present an increased risk of cardiovascular (CV) disease and excess CV-related mortality. Beyond the established role of brain natriuretic peptide (BNP) and cardiac troponins (cTn), other non-cardiac-specific biomarkers are emerging as predictors of CV outcomes in T2DM. Methods Serum levels of soluble suppression of tumorigenesis 2 (sST2), high-sensitivity (hs)-cTnI, and N-terminal (NT)-proBNP were assessed in 568 patients with T2DM and 115 healthy controls (CTR). Their association with all-cause mortality and the development of diabetic complications was tested in T2DM patients over a median follow-up of 16.8 years using Cox models and logistic regressions. Results sST2 followed an increasing trend from CTR to uncomplicated T2DM patients (T2DM-NC) to patients with at least one complication (T2DM-C), while hs-cTnI was significantly higher in T2DM-C compared to CTR but not to T2DM-NC. A graded association was found between sST2 (HR 2.76 [95% CI 1.20–6.33] for ≥ 32.0 ng/mL and 2.00 [1.02–3.94] for 16.5–32.0 ng/mL compared to < 16.5 ng/mL, C-statistic = 0.729), NT-proBNP (HR 2.04 [1.90–4.55] for ≥ 337 ng/L and 1.48 [1.05–2.10] for 89–337 ng/L compared to < 89 ng/L, C-statistic = 0.741), and 15-year mortality in T2DM, whereas increased mortality was observed in patients with hs-cTnI ≥ 7.8 ng/L (HR 1.63 [1.01–2.62]). A ‘cardiac score’ based on the combination of sST2, hs-cTnI, and NT-proBNP was significantly associated with all-cause mortality (HR 1.35 [1.19–1.53], C-statistic = 0.739) and development of CV events. Conclusions sST2, hs-cTnI, and NT-proBNP are associated with 15-year mortality and onset of CV events in T2DM. The long-term prognostic value of sST2 and its ability to track variables related to insulin resistance and associated metabolic disorders support its implementation into routine clinical practice.

Diabetes mellitus status modifies the association between N-terminal B-type natriuretic peptide and all-cause mortality risk in ischemic heart failure: a prospective cohort study

“…NT-proBNP is strongly associated with adverse cardiovascular outcomes and mortality in HF populations [ 16 ] and plays an important role in the diagnosis and management of HF [ 17 , 18 ]. Beyond HF, NT-proBNP also has a good ability to predict death in general populations [ 10 ] and patients with DM [ 19 ]. Furthermore, a recent study from the Atherosclerosis Risk in Communities (ARIC) cohort showed that NT-proBNP discriminated mortality risk better than conventional risk factors only in subjects with DM instead of non-DM people after a median of 7.2 years of follow-up [ 11 ], which suggested that DM status may modify the relationship between NT-proBNP and risk of death.…”

Elevated Soluble Suppressor of Tumorigenicity 2 Predict Hospital Admissions Due to Major Adverse Cardiovascular Events (MACE)

“…The ADVANCE study [30] and the EMPA-REG OUTCOME trial [31] showed that type 2 diabetic patients receiving glucose-lowering agents reduced their risk of MACE by 10-14%. Importantly, more of the recent studies demonstrated the prognostic value of sST2 in patients with diabetes: sST2, Hs-cTnI, and NT-proBNP are independently associated with mortality and onset of MACE in patients with diabetes; specifically, higher levels of sST2 led to an almost three-fold increase in the risk of death in a 15 year follow-up [32]. Additionally, sST2 remained a predictor of MACEs and mortality in patients with coronary artery disease, both with and without diabetes [33], as well as in patients with acute coronary syndrome and diabetes [34].…”

Associations of Cardiac Biomarkers With Peripheral Artery Disease and Peripheral Neuropathy in US Adults Without Prevalent Cardiovascular Disease

“…[39][40][41] hs-troponin I is strongly associated with ischemic heart disease and other markers of end organ damage. 6,11,13 hs-troponin assays are the preferred biomarker by the American Heart Association for the detection of myocardial injury, 42 and both hs-troponin T and hs-troponin I are indicative of cardiomyocyte injury or necrosis. Prior studies have demonstrated that hs-troponin T and hs-troponin I are strongly associated with major adverse cardiovascular events, mortality, and rapid progression to symptomatic heart failure in asymptomatic adults.…”

“…4,5 NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T (hs-troponin T), and high-sensitivity cardiac troponin I (hs-troponin I) are increasingly being recommended for risk stratification for a variety of cardiovascular outcomes. [6][7][8][9][10][11][12][13] NT-proBNP is used in the evaluation of heart failure and is a cleavage product of proBNP that is secreted by cardiomyocytes during ventricular stretch. 14 High-sensitivity assays for cardiac troponin T and I are biomarkers of myocardial damage.…”