Proteomic profiling identifies novel independent relationships between inflammatory proteins and myocardial infarction.
Valdes-Marquez E., Clarke R., Hill M., Watkins H., Hopewell JC., PROCARDIS Consortium None.
BackgroundInflammation has been implicated in the pathogenesis of coronary heart disease (CHD), but the relevance and independence of individual inflammatory proteins is uncertain.ObjectiveTo examine the relationships between a spectrum of inflammatory proteins and myocardial infarction (MI).MethodsA panel of 92 inflammatory proteins was assessed using an OLINK multiplex immunoassay among 432 MI cases (diagnosed ResultsAmong the 92 proteins studied, 62 (67%) had plasma concentrations above the lower limit of detection in at least 50% of samples. Of these, 15 individual proteins were significantly associated with MI after covariate adjustment and correction for multiple testing. Five of these 15 proteins (CDCP1, CD6, IL1-8R1, IL-6 and CXCL1) were independently associated with MI, with up to 3-fold higher risks of MI per doubling in plasma concentrations. Findings were further validated using machine learning techniques and biologically focused analyses.ConclusionsThis study, demonstrating independent relationships between five inflammatory proteins and MI, provides important novel insights into the inflammatory hypothesis of MI and the potential utility of proteomic analyses in precision medicine.