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Quest for the Optimal Cardiovascular Risk Biomarker

March 23, 2020

Glucagon-like peptide 1 outperforms established cardiac markers as an early risk predictor for acute myocardial infarction.
A study in the European Heart Journal suggests that glucagon-like peptide 1 levels (GLP-1) could help stratify risk of acute myocardial infarction (MI), guiding more personalized treatment and better clinical outcomes. Squaring off against more established cardiac markers such as troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP), GLP-1 emerged as a top performer in predicting early cardiovascular events in hospitalized MI patients.
Experimental studies have shown associations between elevated GLP-1 levels and acute MI. In patients with diabetes, GLP-1 receptor agonists have been known to improve cardiac outcomes. Building on these results, researchers enrolled 918 patients with either ST-segment elevation MI or non-ST-segment elevation MI (NSTEMI). They assessed total GLP-1, NT-proBNP levels, and Global Registry of Acute Coronary Events (GRACE) scores for each patient upon admission to the hospital.
The study had three primary outcomes: first occurrence of cardiovascular death, nonfatal MI, or nonfatal stroke. Using Kaplan-Meier survival plots and univariable Cox regression analyses, the researchers found a definitive association between GLP-1 and adverse cardiac events. In other analysis, they also determined that GLP-1 was a strong marker for early cardiac events. Perhaps most significantly, GLP-1 bested four other markers —troponin T measured via high-sensitivity assay, glomerular filtration rate using the CKD-EPI equation, C-reactive protein measured with a high-sensitivity assay (hs-CRP), and NT-proBNP—in prognosticating events 30 days after hospital admission. “Moreover, admission GLP-1 levels added additional value to the GRACE risk score in NSTEMI patients,” the investigators noted.
GLP-1’s hazard ratio for adverse outcomes remained significant even after adjusting for a number of variables such as age, sex, family history of cardiovascular disease, smoking, diabetes, hypertension, hypercholesterinaemia, and other biomarkers. Future studies should focus on larger cohorts that include repeated GLP-1 measurements to better assess its value as a marker for MI patients, the researchers suggested.
The biomarker’s eventual impact on treatment regimens and outcomes for MI patients remains unknown at this point, wrote Leonardo Roever, MHS, MD, Gary Tse, PhD, Francesco Versaci, MD, and Giuseppe Biondi-Zoccai, MD, in a related editorial. Nevertheless, they expressed optimism that GLP-1 would establish itself as a routine part of clinical care, despite some challenges.
“I believe that with more studies, GLP-1 can be used with confidence to stratify the risk of MI,” Roever told.
Other experts also were encouraged by the results. The study makes an interesting connection between the gut pathology and acute coronary syndromes, Alan Wu, PhD, director of clinical chemistry and toxicology at the University of California, San Francisco told. “We are learning more and more of the importance of gastrointestinal issues with various diseases. The fact that GLP-1 appears to be protective,” is a finding that might have therapeutic implications. The measure to adjust hazard ratios to traditional risk factors and biomarkers makes these observations even more interesting, added Wu.