Prognostic value of sST2 in heart failure patients with diabetes

Abstract Background Soluble suppression of tumorigenesis-2 (sST2) is released in response to inflammation and vascular injury, and holds prognostic value in heart failure (HF). Type 2 diabetes (T2D) is characterized by a pro-inflammatory status and is highly prevalent among HF patients, with adverse impact on outcomes. The clinical value of sST2 in HF patients with T2D has never been characterized. Purpose We aimed to assess sST2 clinical correlates and prognostic value in HF patients with T2D. Methods Individual data of 3476 patients with stable chronic HF from 5 cohorts from the BIOS (Biomarkers In Heart Failure Outpatient Study) dataset were analysed, with available N-terminal fraction of pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and sST2 levels. Results Mean age was 65±12 years (75% males). T2D was present in 1386 patients (40%), who had higher body mass index (BMI, 27 [24–30] vs. 26 [23–29] kg/m2, p<0.001), lower estimated glomerular filtration rate (eGFR, 56±22 vs. 60±19 mL/min/1,73 m2, p<0.001), higher sST2 (33 [24–47] vs. 27 [20–40] ng/mL, p<0.001), NT-proBNP (1735 [742–3963] vs. 1450 [514–3299] ng/L, p<0.001), hs-TnT (28 [16.2–51.5] vs. 17 [9–31] ng/L, p<0.001) and high-sensitivity C-reactive protein (hs-CRP, 6 [2–11] vs. 4. [2–9] mg/L, p=0.003) (Figure). Differences between sST2 levels in patients with or without T2D were influenced by hs-CRP (p for interaction=0.010) and hs-TnT (p=0.031), but not by NT-proBNP and eGFR. At multivariate linear regression analysis, NT-proBNP, hs-TnT and hs-CRP were independently associated with sST2 levels in both T2D and non-T2D patients. Compared with patients without T2D, those with T2D showed higher 1-year all-cause mortality (12% vs. 10%, p=0.034), cardiovascular mortality (9% vs. 7%, p=0.011), and HF hospitalization rate (22% vs. 12%, p<0.001). In a prognostic model including age, sex, eGFR, ischemic vs- non-ischemic aetiology, left ventricular ejection fraction class, New York Heart Association class, NT-proBNP, hs-TnT, and hs-CRP, sST2 retained independent prognostic value in both patients with or without T2D for 1-year all-cause and cardiovascular mortality, and 1-year HF hospitalization, with higher optimal cut-offs for mortality prediction in T2D vs. non-T2D (39 and 45 vs. 29 and 29 ng/mL respectively for 1-year all-cause and cardiovascular mortality). Conclusions sST2 is higher in HF patients with T2D and likely linked to a pro-inflammatory status. sST2 maintains its prognostic value both in diabetic and non-diabetic HF patients, independently of NT-proBNP, hs-TnT and hs-CRP. Funding Acknowledgement Type of funding sources: None. Figure 1