The gut hormone GLP-2 predicts cardiovascular risk in patients with acute myocardial infarction

Abstract

Background GLP-1 and GLP-2 (glucagon-like peptide-1/2) are gut derived 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 enhances intestinal nutrient absorption and is clinically used for the treatment of patients with short bowel syndrome. The relevance of the GLP-2 system for cardiovascular disease is unknown. Purpose The aim of this study was to assess the predictive capacity of GLP-2 for cardiovascular prognosis 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, among them 597 patients with NSTEMI and 321 with STEMI. The primary composite outcome of the study was the first occurrence of cardiovascular 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 ng/mL) and univariable cox regression analyses found GLP-2 values to be associated with adverse outcome (logarithmized GLP-2 values HR: 2.87; 95% CI: 1.75–4.68; p<0.0001). Further adjustment for age, sex, smoking, hypertension, hypercholesterolemia, diabetes mellitus, family history of cardiovascular disease, hs-Troponin T, NT-proBNP and hs-CRP levels did not affect the association of GLP-2 with poor prognosis (logarithmized GLP-2 values HR: 2.96; 95% CI: 1.38–6.34; p=0.0053). Receiver operating characteristic curve (ROC) analyses illustrated that GLP-2 is a strong indicator for cardiovascular events and proved to be comparable to other established risk markers (area under the curve of the combined endpoint at 6 months; GLP-2: 0.72; hs-Troponin: 0.56; NT-proBNP: 0.70; hs-CRP: 0.62). Adjustment of the GRACE risk estimate by GLP-2 increased the area under the receiver-operating characteristic curve for the combined triple endpoint after 6 months from 0.70 (GRACE) to 0.75 (GRACE + GLP-2) 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 0.72 for GRACE + NT-proBNP to 0.77 for GRACE + NT-proBNP + GLP-2). Conclusions In patients admitted with acute myocardial infarction, GLP-2 levels are associated with adverse cardiovascular prognosis. This demonstrates a strong yet not appreciated crosstalk between the heart and the gut with relevance for cardiovascular outcome. Future studies are needed to further explore this crosstalk with the possibility of new treatment avenues for cardiovascular disease. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): German Society of Cardiology (DGK), German Research Foundation (DFG)

Heart–gut microbiota communication determines the severity of cardiac injury after myocardial ischaemia/reperfusion

“… 20 , 21 Circulating level of GLP-2 was recently found to be increased in patients with AMI. 22 Therefore, we determined to investigate whether GLP-2 could protect the gut barrier, restore intestinal microbiota dysbiosis, and thus alleviate gut microbial translocation under myocardial I/R injury. We first induced myocardial I/R injury in mice, 600 μg/kg degradation-resistant GLP-2 analogue dissolved in saline was injected subcutaneously immediately after reperfusion and continuously delivered twice daily for 3 days.…”

Peptide YY (PYY) Is Associated with Cardiovascular Risk in Patients with Acute Myocardial Infarction

“…The same cell population produces GLP-1 in response to nutritional but also inflammatory stimuli, leading to elevated GLP-1 levels in patients with acute myocardial infarction or sepsis [4,31]. Importantly, GLP-1 was found to be an excellent and independent predictor for future cardiovascular events or mortality in both groups of patients, demonstrating a relevant interaction between the cardiovascular system and the gut [5,32]. Similar predictive power was not detected for PYY as an additional gut-derived peptide in this study.…”

“…Recent studies have identified gastrointestinal hormones as modulators of cardiovascular risk. The gut-derived peptide GLP-1 was found to be secreted in response to acute myocardial infarction and to independently predict adverse outcome in this patient population [4,5]. Importantly, GLP-1 receptor agonists reduced cardiovascular events in high-risk patients with diabetes [6][7][8][9].…”

Gastrointestinal Incretins—Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-like Peptide-1 (GLP-1) beyond Pleiotropic Physiological Effects Are Involved in Pathophysiology of Atherosclerosis and Coronary Artery Disease—State of the Art

“…Recently, the research by Kahles et al [ 98 ] demonstrated that GLP-1 is a powerful biomarker of CV events and death in patients with MI. In this study, 918 patients hospitalized for MI (321 with STEMI and 597 with NSTEMI; mean age (SD) = 66.9 (12.7) years; 73.2% male) were observed for CV outcomes in long-term follow up.…”