High apelin levels post-STEMI predict increased risk of adverse outcomes: insights from the INFINITY study

Abstract Background/Introduction Apelin, an endogenous peptide involved in regulating cardiovascular function, has been implicated in various cardiovascular diseases, including acute myocardial infarction (AMI). Some studies suggest that plasma apelin upon admission is decreased early after ST-elevation AMI (STEMI) indicating the inverse correlation of apelin with the presence and severity of coronary artery disease (CAD). However, other studies demonstrated a positive correlation of upon admission apelin with mortality at 6 months post-STEMI. The role of sustained high apelin levels in the post-STEMI period remains underexplored. Purpose The INFINITY study (INFlammatIoN amI sTudY) evaluates the role of a selected panel of inflammatory biomarkers in predicting long-term outcomes after AMI. This sub-study specifically investigates the prognostic value of plasma apelin in STEMI patients, examining its association with short-term (in-hospital, M0) and long-term (1, M1 and 6 months, M6) clinical outcomes, including cardiac death, noncardiac death, heart failure, and major adverse cardiovascular events (MACEs). MACEs were defined post hoc as non-fatal MI, unplanned revascularization, new-onset heart failure, angina or recurrent ACS requiring rehospitalization, and major bleeding. Methods Apelin levels were measured at three time points: upon admission (H0), 24 hours post-MI (H24), and 30 days post-MI (D30). Patients were followed for six months and categorized based on apelin levels at each time point, as well as the Area Under the Trapezoid (AUC) for apelin. Primary in-hospital endpoints included major bleeding (per BARC classification), new-onset heart failure (LVEF 40%), and MACEs (non-fatal MI, unplanned revascularization, recurrent ACS, heart failure, major bleeding). Long-term outcomes at 1 and 6 months included cardiac death, heart failure, and hospital readmission for ACS or heart failure. Cox proportional hazards regression models were applied to evaluate the association between apelin levels and clinical outcomes. Results Among 69 STEMI patients, high apelin levels upon admission associated with a statistically increased risk of in-hospital bleeding (p = 0.011). Those with sustained high apelin levels at 30 days post-MI had a significantly higher risk of hospital re-admission for heart failure or ACS (p = 0.006). Finally, elevated plasma apelin area under trapezoid (AUC) was strongly associated with a higher risk of hospital readmission for heart failure or ACS (p = 0.042). Conclusion Persistently high apelin levels 30 days post-STEMI are strongly associated with an increased risk of hospital readmission for heart failure or ACS. These findings suggest that apelin may serve as a valuable biomarker for identifying high-risk patients, potentially guiding early interventions. Targeting apelin signalling pathways could offer novel therapeutic strategies to improve long-term post-STEMI outcomes.Table 1 and 2 Figure 1