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Combination of ST2 and B-type natriuretic peptide in diabetic patients with acute heart failure

relation with ventricular stiffness and outcome

Ruocco, Gaetanoa; Evangelista, Isabellaa; Franci, Beatricea; Lucani, Barbaraa; Martini, Simonab; Nuti, Ranuccioa; Palazzuoli, Albertoa

Journal of Cardiovascular Medicine: February 2019 - Volume 20 - Issue 2 - p 81–90
doi: 10.2459/JCM.0000000000000741
Research articles: Heart failure

Background Diabetes is a common disease in heart failure and its prevalence ranges from 10 to 30%. ST-2 is a novel biomarker of myocardial fibrosis and remodelling in heart failure and may be involved in the inflammatory process of diabetes mellitus. In this study, we sought: to evaluate levels of ST-2 and B-type natriuretic peptide (BNP) in groups with acute heart failure with and without diabetes; to analyse the prognostic impact of ST-2 over a 6-month follow-up period.

Methods We performed an echocardiographic examination and measured ST-2 and BNP within 24 h of hospital admission. Patients were classified as heart failure with reduced ejection fraction {HFrEF [left ventricular ejection fraction (LVEF) <50%]} or heart failure with preserved ejection fraction (HFpEF, LVEF ≥50%). We defined diastolic function according to recent guidelines, and we calculated left ventricular stiffness was assessed by the ratio between E/e’ (index of left ventricular filling pressure) and left ventricular diastolic diameter (LVEDD) (index of left ventricular volume). The sum of death and rehospitalization due to cardiovascular causes was considered in the composite outcome.

Results Of 121 patients enrolled, 58 experienced diabetes and 63 had normal glucose levels. Sixty patients showed HFrEF and 61 HFpEF. Among patients with diabetes, we observed significantly increased levels of serum ST-2 with respect to patients without diabetes [89 (29–147) 72 ± 42 vs. 48 (29–80) 59 ± 33 ng/ml; P = 0.04]. No differences were found between the two groups in terms of BNP levels, risk factors, renal function and echocardiographic measurements. Conversely, BNP was significantly higher in HFrEF with respect to HFpEF [786 (344–1390) vs. 423 (195–796) pg/ml; P = 0.004]. A significant correlation between ST-2 and BNP in diabetic patients (r = 0.50; P < 0.001) compared with nondiabetic patients (r = 0.40; P = 0.001) was found. ST-2 showed a numerically greater correlation with left ventricular stiffness in patients with diabetes (r = 0.56; P < 0.001) than patients without (r = 0.29; P = 0.04). Moreover, in all patients, ST-2 demonstrated a significant correlation with glycated glycosylated haemoglobin HbA1c (r = 0.40; P < 0.001). Univariate analysis demonstrated that both ST-2 more than 54 ng/ml and BNP more than 567 pg/ml were related to adverse events occurrence within 6 months [hazard ratio (HR): 3.64 (1.90–6.94), P < 0.001; HR: 2.21 (1.20–4.07), P = 0.01, respectively]. After adjustment for potential confounding factors, the multivariable analysis showed that only ST-2 levels greater than 54 ng/ml were associated with poor prognosis [HR: 3.56 (1.66–7.62); P = 0.001].

Conclusion ST-2 confirmed its prognostic power independently of diabetes and LVEF. Patients with diabetes showed higher levels of ST-2. However, the mechanism related to ST-2 increase needs to be better understood, although increased left ventricle stiffness and filling pressure seem to be the most important causative factors.

Clinical trial registration Diur-HF Trial (Trial ID: NCT01441245).

aCardiovascular Diseases Unit, Department of Internal Medicine, Le Scotte Hospital, University of Siena

bUO Chemical Laboratory, Le Scotte Hospital, Siena, Italy

Correspondence to Alberto Palazzuoli, MD, PhD, Department of Internal Medicine, Cardiovascular Diseases Unit, Le Scotte Hospital, Viale Bracci, Siena 53100, Italy. Tel: +39577585363- +39577585461; fax: +39577233480; e-mail:

Received 23 March, 2018

Accepted 11 November, 2018

© 2019 Italian Federation of Cardiology. All rights reserved.