Utility of S100A12 as an Early Biomarker in Patients With ST-Segment Elevation Myocardial Infarction

Abstract

Importance: S100A12 is a calcium binding protein which is involved in inflammation and progression of atherosclerosis.Objective: We sought to investigate the utility of S100A12 as a biomarker for the early diagnosis and prognostication of patients presenting with ST-segment elevation myocardial infarction (STEMI).Design, Setting, and Participants: S100A12 was measured in 1023 patients presenting to the emergency department with acute chest pain between June 2012 and November 2015. An independent cohort of 398 patients enrolled at 3 different hospitals served as a validation cohort.Main Outcomes and Measures: The primary clinical endpoint of interest was major adverse cardiac and cerebral events (MACCE) defined as a composite of all-cause death, MI, stroke, or hospitalization for heart failure.Results: A total of 438/1023 patients (42.8%) in the diagnosis cohort were adjudicated as STEMI, among whom plasma S100A12 levels increased within 30 min and peaked 1–2 h after symptom onset. Compared with high-sensitivity cardiac troponin T and creatine kinase-MB isoenzyme, S100A12 more accurately identified STEMI, especially within the first 2 h after symptom onset (area under the curve 0.963 compared with 0.860 for hscTnT and 0.711 for CK-MB, both P < 0.05). These results were consistent in the 243-patient validation cohort. The 1-year rate of MACCE was greatest in patients in the highest peak S100A12 tertile, intermediate in the middle tertile and least in the lowest tertile (9.3 vs. 5.7 vs. 3.0% respectively, Ptrend = 0.0006). By multivariable analysis the peak plasma concentration of S100A12 was an independent predictor of MACCE within 1 year after STEMI (HR, 1.001, 95%CI, 1.000–1.002; P = 0.0104).Conclusions and Relevance: S100A12 rapidly identified patients with STEMI, more accurately than other cardiac biomarkers, especially within the first 2 h after symptom onset. The peak plasma S100A12 level was a strong predictor of 1-year prognosis after STEMI.

Human Plasma Transcriptome Implicates Dysregulated S100A12 Expression: A Strong, Early-Stage Prognostic Factor in ST-Segment Elevated Myocardial Infarction: Bioinformatics Analysis and Experimental Verification

“…The increase of S100A12 protein level in blood, which is related to the fragility and rupture of atherosclerotic plaque, has been demonstrated to be a powerful predictor of the progression of stable coronary heart disease to acute coronary syndrome ( 17 , 36 ). In a recent multicenter prospective study, the protein level of S100A12 in peripheral blood was found to be a biomarker for early diagnosis and an independent predictor of major cardiovascular adverse events within 1 year after STEMI onset ( 37 ). In the present study, we innovatively used a strategy combining bioinformatics analysis and experimental validation to explore the correlation between S100A12 mRNA and protein levels and intra and out-of-hospital outcomes in patients with STEMI.…”

“…In our validation cohort, however, it was not shown that the protein level of S100A12 in plasma was an independent prognostic factor of in-hospital death and MACE during follow-up, although the level of the survival group was significantly higher than that of the death group. The reasons for the inconsistent conclusion in the two verifications may include: (1) S100A12, as an important early inflammatory index ( 37 ), could more effectively reflect the early myocardial inflammatory injury after STEMI onset, while in-hospital and long-term outcomes might be largely affected by multiple confounders, such as door-to-balloon time, intervention strategy (e.g., ischemic postconditioning), and the complexity of coronary artery lesions. In our center, relying on the advantages of extracorporeal life support center for critical disease, administration of extracorporeal membrane oxygenation has become a normal workflow in rescuing patients with cardiopulmonary failure in our center, which has successfully saved a considerable number of dying patients ( 39 , 40 ) and may thereby affect the predictive value of S100A12 on prognosis to a certain extent.…”

Bioinformatics analysis to identify potential biomarkers and therapeutic targets for ST-segment–elevation myocardial infarction-related ischemic stroke

“…The hub gene S100A12 has been shown to have a regulatory role in carotid plaque instability and the occurrence of major cardiovascular events in patients with stable coronary artery disease ( 36 ). Furthermore, S100A12 could more accurately diagnose patients with STEMI than other identified biomarkers, and the levels of S100A12 were negatively correlated with the prognosis of IS ( 37 , 38 ).…”

“…The hub gene S100A12 has been shown to have a regulatory role in carotid plaque instability and the occurrence of major cardiovascular events in patients with stable coronary artery disease (36). Furthermore, S100A12 could more accurately diagnose patients with STEMI than other identified biomarkers, and the levels of S100A12 were negatively correlated with the prognosis of IS (37,38). Additionally, previous studies have shown that posttreatment with sevoflurane may prevent myocardial ischemia/reperfusion damage through the upregulation of miR-145 and downregulation of GZMK expression (39).…”

Construction of Novel Gene Signature-Based Predictive Model for the Diagnosis of Acute Myocardial Infarction by Combining Random Forest With Artificial Neural Network

“…In this study, the top 11 key genes in DEGs were screened by the RF model based on MeanDecreaseGini. Furthermore, 10 of the 11 genes were also considered as AMI candidate genes in other studies: Acyl-CoA synthetase long-chain family member 1 (ACSL1) ( 31 ), nuclear factor interleukin-3-regulated (NFIL3) ( 32 ), interleukin-1 receptor-associated kinase 3 (IRAK3) ( 33 ), interleukin-1 receptor type 2 (IL1R2) ( 7 ), dysferlin ( DYSF) ( 32 ), S100A12 ( 34 ), B-cell lymphoma 6 (BCL-6) ( 35 ), mast cell-expressed membrane protein 1 ( MCEMP1 ) ( 36 ), serpin family A member 1 ( SERPINA1 ) ( 37 ), and intelectin-1 ( ITLN1 ) ( 38 ). Besides, we identified for the first time that zinc finger protein-36 (ZFP36) may get involve in the pathogenesis of AMI.…”