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Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that increased in patients with established type 2 diabetes mellitus (DM). Diabetic cardiomyopathy (DC), defined as left ventricular diastolic dysfunction (LVDD) in patients with type 2 DM in the absence of arterial hypertension, heart disease, or other heart disease, was assessed by GDF-15 levels in type 2 DM patients with and without DC. A total of 213 DM outpatients had blood samples drawn and on the same day (basal) underwent echocardiography and treadmill exercise testing. Plasma GDF-15 concentrations were measured by an enzymelinked immunosorbent assay (ELISA) at baseline. DC was diagnosed in the presence of LVDD, defined when early mitral valve flow velocity (E) and early diastolic lengthening velocity (E') ratio was E/E' ⩾15. The prevalence of DC was 21.13%. GDF-15 levels were higher in patients with DC compared with those without DC (5,273 [8,708.4] vs 2,812.66 [7,662.1] pg/ml, respectively, p <0.001). We assessed predictors of DC using multivariate regression analysis. GDF-15 (odds ratio 9.9; 95% confidence interval [3.9 to 24.5], p <0.001) was the unique independent predictor of DC. The results of receiver operating characteristic curve show that the cut-off point of 3,812 pg/ml of GDF-15 was indicative for DC (AUC = 0.83, sensitivity = 82.2% and specificity = 70.2%, p <0.0001). In conclusion, GDF-15 represents a useful and novel tool to screen DC in patients with type 2 DM. [ABSTRACT FROM AUTHOR]

The development of left ventricular remodeling (LVR) after myocardial infarction is associated with a high risk of heart failure and death. LVR is difficult to predict, and limited information is available on the association of cardiac biomarkers and LVR. Growth-differentiation factor-15 (GDF-15) is induced during heart failure development and, in animals models, might influence the different processes involved in cardiac remodeling. The aim of the present investigation was to assess the association between the serum levels of GDF-15 within the first 24 hours of ST-segment elevation myocardial infarction and the development of subsequent LVR at 12 months of follow-up. This prospective study included 97 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Echocardiography was performed in all patients within the first 96 hours of admission and at 12 months of follow-up. LVR was defined as a >20% increase in the left ventricular end-diastolic volume at 12 months of follow-up compared to baseline. Blood samples for the determination of GDF-15 and brain natriuretic peptide were obtained within the first 24 hours after symptom onset. According to the pre-established criteria, 21 patients (22%) had LVR. Patients with LVR had greater levels of GDF-15 at study entry (median 3,439 pg/ml, interquartile range 2,391 to 6,168 vs median 1998 pg/ml, interquartile range 1,204 to 3,067, respectively; p <0.001). Multivariate analysis showed that GDF-15 (odds ratio 10.1, 95% confidence interval 2.5 to 40.1, p <0.001) and treatment with angiotensin-converting enzyme inhibitors (odds ratio 3.9, 95% confidence interval 1.2 to 12.3, p <0.01) were independents predictors of LVR. Receiving operating characteristics analysis showed an area under the curve of 0.77 for GDF-15 (95% confidence interval 0.67 to 0.84, p <0.001). In conclusion, the results of the present study have identified GDF-15 as an independent marker of LVR in patients with ST-segment elevation myocardial infarction. [Copyright &y& Elsevier]