The gut hormone glucose-dependent insulinotropic polypeptide is downregulated in response to myocardial injury.

BACKGROUND: The gut incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by enteroendocrine cells following food intake leading to insulin secretion and glucose lowering. Beyond its metabolic function GIP has been found to exhibit direct cardio- and atheroprotective effects in mice and to be associated with cardiovascular prognosis in patients with myocardial infarction. The aim of this study was to characterize endogenous GIP levels in patients with acute myocardial infarction. METHODS AND RESULTS: Serum concentrations of GIP were assessed in 731 patients who presented with clinical indication of coronary angiography. Circulating GIP levels were significantly lower in patients with STEMI (ST-elevation myocardial infarction; n=100) compared to clinically stable patients without myocardial infarction (n=631) (216.82 pg/mL [Q1-Q3: 52.37-443.07] vs. 271.54 pg/mL [Q1-Q3: 70.12-542.41], p = 0.0266). To characterize endogenous GIP levels in patients with acute myocardial injury we enrolled 18 patients scheduled for cardiac surgery with cardiopulmonary bypass and requirement of extracorporeal circulation as a reproducible condition of myocardial injury. Blood samples were drawn directly before surgery (baseline), upon arrival at the intensive care unit (ICU), 6 h post arrival to the ICU and at the morning of the first and second postoperative days. Mean circulating GIP concentrations decreased in response to surgery from 45.3 ± 22.6 pg/mL at baseline to a minimum of 31.9 ± 19.8 pg/mL at the first postoperative day (p = 0.0384) and rose again at the second postoperative day (52.1 ± 28.0 pg/mL). CONCLUSIONS: Circulating GIP levels are downregulated in patients with myocardial infarction and following cardiac surgery. These results might suggest nutrition-independent regulation of GIP secretion following myocardial injury in humans.

Glucagon-like peptide 1 levels predict cardiovascular risk in patients with acute myocardial infarction.

AIMS: Glucagon-like peptide 1 (GLP-1) is a gut incretin hormone inducing post-prandial insulin secretion. Glucagon-like peptide 1 levels were recently found to be increased in patients with acute myocardial infarction. Glucagon-like peptide 1 receptor agonists improve cardiovascular outcomes in patients with diabetes. The aim of this study was to assess the predictive capacity of GLP-1 serum levels for cardiovascular outcome in patients with myocardial infarction. METHODS AND RESULTS: In 918 patients presenting with myocardial infarction [321 ST-segment elevation myocardial infarction and 597 non-ST-segment elevation myocardial infarction (NSTEMI)] total GLP-1, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and the Global Registry of Acute Coronary Events (GRACE) score were assessed at time of hospital admission. The primary composite outcome of the study was the first occurrence of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Kaplan-Meier survival plots and univariable Cox regression analyses found GLP-1 to be associated with adverse outcome [hazard ratio (HR) of logarithmized GLP-1 values: 6.29, 95% confidence interval (CI): 2.67-14.81; P < 0.0001]. After further adjustment for age, sex, family history of cardiovascular disease, smoking, diabetes, hypertension, hypercholesterinaemia, glomerular filtration rate (GFR) CKD-EPI, hs-CRP, hs-Troponin T, and NT-proBNP levels the HR remained significant at 10.98 (95% CI: 2.63-45.90; P = 0.0010). Time-dependent receiver operating characteristic curve analyses illustrated that GLP-1 levels are a strong indicator for early events. For events up to 30 days after admission, GLP-1 proved to be superior to other biomarkers including hs-Troponin T, GFR CKD-EPI, hs-CRP, and NT-proBNP. Adjustment of the GRACE risk estimate by addition of GLP-1 increased the area under the receiver operating characteristic curve over time in NSTEMI patients. CONCLUSION: In patients hospitalized for myocardial infarction, GLP-1 levels are associated with cardiovascular events.