Background: GLP-1 and GLP-2 (glucagon-like peptide-1/2) are incretin hormones that are co-secreted from intestinal L-cells in response to food intake. While GLP-1 is known to induce postprandial insulin secretion, GLP-2 has no direct insulinotropic effect. Functionally, GLP-2 enhances intestinal nutrient absorption and is clinically used for the treatment of patients with short bowel syndromee. Interestingly, GLP-2 has been found to provide cardioprotective effects in a rodent model of myocardial infarction. The aim of this study was to assess the predictive value of GLP-2 for cardiovascular outcome in patients with myocardial infarction.

Methods: Total GLP-2 levels, NT-proBNP concentrations and the Global Registry of Acute Coronary Events (GRACE) score were assessed at time of admission in 918 patients with myocardial infarction presenting with acute chest pain, among them 597 patients with NSTEMI and 321 with STEMI. The primary composite outcome of the study was the first occurrence of all-cause death, nonfatal myocardial infarction, or nonfatal stroke (3-P-MACE) with a median follow-up of 311 days. 

Results: Kaplan-Meier survival plots (separated by the median of GLP-2 with a cut-off value of 4.4 pM) and univariable cox regression analyses found GLP-2 values to be associated with adverse outcome (combined endpoint and all-cause mortality) (logarithmized GLP-2 values HR: 2.87; p<.0001). Further adjustment for age, sex, smoking, hypertension, hypercholesterinemia, previous cardiovascualar disease and diabetes mellitus did not affect the association of GLP-2 with adverse outcome (logarithmized GLP-2 values HR: 2.66; p=0.0055). Receiver operating characteristic curve (ROC) analyses illustrated that GLP-2 is a strong indicator for early events (area under the curve of the combined endpoint at 7 days: 0.74; 14 days: 0.76; 30 days: 0.76; 6 months: 0.72), which proved to be superior to Troponin T and hs-CRP. Adjustment of the GRACE risk estimate by GLP-2 increased the area under the receiver-operating characteristic curve (AUC) after 1 month from 0.85 to 0.87 in NSTEMI patients. Addition of GLP-2 to a model containing GRACE and NT-proBNP led to a further improvement in model performance (increase in AUC from 0.88 for GRACE + NT-proBNP to 0.90 for GRACE + NT-proBNP + GLP-2). 

Conclusion: The gut-derived incretin hormone GLP-2 may be a novel biomarker of cardiovascular risk and adverse outcomes in patients with acute myocardial infarction and improves the predictive value of the GRACE score in patients with NSTEMI.