1Uniklinik RWTH Aachen Med. Klinik I - Kardiologie, Angiologie und Internistische Intensivmedizin Aachen, Deutschland; 2SYNLAB Holding Deutschland GmbH SYNLAB Akademie Mannheim, Deutschland
Background: The gut incretin hormone glucagon-like peptide 1 (GLP-1) induces post-prandial glucose-dependent insulin secretion. Clinical trials showed that GLP-1 receptor agonists improve cardiovascular outcomes in patients with diabetes at high cardiovascular risk. We found elevated GLP-1 levels to be associated with cardiovascular mortality in patients with acute myocardial infarction. The aim of this study was to analyze whether adjustment of the SMART (Second Manifestations of Arterial Disease) risk score by GLP-1 provides significant added value in the prediction of cardiovascular mortality in patients with coronary artery disease.
Methods: We measured circulating GLP-1 levels in 2326 patients with coronary artery disease who underwent coronary angiography at baseline (1997-2000) and are part of the Ludwigshafen Risk and Cardiovascular Health Study. The primary endpoint of our study was cardiovascular mortality.
Results: Multivariable Cox regression analysis found GLP-1 levels to be independently associated with cardiovascular mortality in patients with coronary artery disease (logarithmized GLP-1 tertile HR: 1.31; 95%-CI: 1.08–1.60; p=0.007; Harrell’s C-index: 0.76; multivariable model adjusted for age, sex, diabetes, smoking, hypertension, previous cardiovascular disease, eGFR CKD-EPI, hsCRP, LDL cholesterol, hs-TroponinT and NT-proBNP). Variable’s importance in the multivariable model was analysed and illustrated, proving the substantial higher influence of GLP-1 compared to other cardiovascular risk predictors like hs-TroponinT, LDL cholesterol, hsCRP, eGFR CKD-EPI, smoking, age and sex. The SMART risk score is a european guideline recommended tool for 10-year cardiovascular risk assessment in patients with clinical manifest atherosclerotic vascular disease. GLP-1 provides significant added value on top of the SMART risk score in risk prediction of cardiovascular mortality (delta Chi2: 12.29; logarithmized GLP-1 tertile HR: 1.32; 95%-CI: 1.09–1.61; p=0.004; Harrell’s C-index: 0.72). Furthermore, addition of GLP-1 to the SMART risk score leads to a better reclassification for medium-term cardiovascular risk prediction (continuous NRI: events 35.1%, non-events -7.9%).
Conclusion:
GLP-1 is a strong cardiovascular risk marker providing significant added value (improvement in risk discrimination, calibration, and reclassification) on top of the SMART risk score in patients with coronary artery disease.