Circulating Amyloid and Misfolded Biomarkers in Early Myocardial Injury: A Systematic Review and Epistemic...

Misfolded proteins, including islet amyloid polypeptide (hIAPP), serum amyloid A (SAA), and amyloid-betas (Aβs) such as Aβ1-40 and Aβ1-42 oligomers, collectively referred to in our work as amyloid oligomers, have been implicated in the development of both metabolic and cardiovascular diseases. However, their potential role as early biomarkers of myocardial damage remains insufficiently explored. We conducted a systematic review following PRISMA guidelines and epistemic meta-analysis to investigate the association between misfolded protein oligomers and early myocardial injury. All English- and Spanish-language articles with titles, abstracts, or keywords relevant to the research topic and indexed in at least one of the following databases-PubMed, BIREME, or Web of Science-were included. A comprehensive search across major databases identified 30 eligible studies. Thirty studies met inclusion criteria, in humans and animals, and in vitro. Amyloid oligomers were consistently elevated in patients with acute myocardial infarction, type 2 diabetes, or coronary artery disease compared with controls. In specific individual cohorts, a higher SAA concentration correlated with major adverse cardiovascular events, where it acted as an independent predictor of mortality in reperfused AMI (RR 5.8; 95% CI: 1.3-27.7) and cardiac rupture (OR 8.8; 95% CI: 1.7-25.6). Our findings support the hypothesis that protein misfolding contributes to early myocardial injury and highlight its potential as a novel source of cardiometabolic biomarkers.