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Addition of Plasma Myeloperoxidase and Trimethylamine N-Oxide to the GRACE Score Improves Prediction of Near-Term Major Adverse Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction.

ABSTRACT: Background: The Global Registry of Acute Coronary Events (GRACE) risk score (GRS) is an established powerful model in predicting prognosis of patients with acute coronary syndrome. However, it does not contain pathophysiological biomarkers. Myeloperoxidase (MPO) and trimethylamine N-oxide (TMAO) are novel biomarkers of different pathophysiological processes of acute myocardial infarction, and each of them predicts risk of adverse clinical outcomes. We aimed to investigate whether the addition of MPO and TMAO could improve a GRS-based prediction model in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A prospective cohort of 444 consecutive patients with STEMI who underwent primary percutaneous coronary intervention were enrolled in this study. Plasma levels of MPO and TMAO were measured using samples collected before the interventional procedure. GRS at admission was calculated. Death and nonfatal myocardial infarction were recorded as major adverse cardiac events (MACEs). Kaplan-Meier survival analysis with Cox proportional-hazards regression was used to identify predictive values of MPO and TMAO. Area under the receiver-operator characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to evaluate the increment of predictive value for the combination of MPO and TMAO with GRS in predicting adverse clinical outcomes. Results: During 6 months follow-up, 27 patients suffered MACEs. Both MPO (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.11-5.87; p < 0.05) and TMAO (HR: 4.50, 95% CI: 1.78-11.40, p < 0.01) predicted MACEs at 6 months. The AUC for MPO, TMAO, GRS, and their combination in predicting risk of MACEs at 6 months is 0.642, 0.692, 0.736, and 0.760, respectively. The addition of MPO and TMAO significantly improved the net reclassification of GRS for predicting MACEs at 6 months (NRI: 0.42, p = 0.032). Conclusion: Plasma MPO and TMAO each predict near-term risk of adverse outcomes in patients with STEMI. Furthermore, the combination of MPO and TMAO with GRS enables more accurate prediction of cardiovascular events compared with GRS alone.

SUBMITTER: Tan Y

PROVIDER: S-EPMC8505536 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThis study is aimed at exploring the underlying molecular mechanisms of ST-segment elevation myocardial infarction (STEMI) and provides potential clinical prognostic biomarkers for STEMI.MethodsThe GSE60993 dataset was downloaded from the GEO database, and the differentially expressed genes (DEGs) between STEMI and control groups were screened. Enrichment analysis of the DEGs was subsequently performed using the DAVID database. A protein-protein interaction network was constructed, and hub genes were identified. The hub genes in patients were then validated by quantitative reverse transcription-PCR. Furthermore, hub gene-miRNA interactions were evaluated using the miRTarBase database. Finally, patient data on classical cardiovascular risk factors were collected, and plasma microRNA-146a (miR-146a) levels were detected. An individualized nomogram was constructed based on multivariate Cox regression analysis.ResultsA total of 239 DEGs were identified between the STEMI and control groups. Expression of S100A12 and miR-146a was significantly upregulated in STEMI samples compared with controls. STEMI patients with high levels of miR-146a had a higher risk of major adverse cardiovascular events (MACEs) than those with low levels of miR-146a (log-rank P = 0.034). Multivariate Cox regression analysis identified five statistically significant variables, including age, hypertension, diabetes mellitus, white blood cells, and miR-146a. A nomogram was constructed to estimate the likelihood of a MACE at one, two, and three years after STEMI.ConclusionThe incidence of MACEs in STEMI patients expressing high levels of miR-146a was significantly greater than in those expressing low levels. MicroRNA-146a can serve as a biomarker for adverse prognosis of STEMI and might function in its pathogenesis by targeting S100A12, which may exert its role via an inflammatory response. In addition, our study presents a valid and practical model to assess the probability of MACEs within three years of STEMI.

Project description:ImportanceChallenges to improving ST-segment elevation myocardial infarction (STEMI) care are formidable in low- to middle-income countries because of several system-level factors.ObjectiveTo examine access to reperfusion and percutaneous coronary intervention (PCI) during STEMI using a hub-and-spoke model.Design, setting, and participantsThis multicenter, prospective, observational study of a quality improvement program studied 2420 patients 20 years or older with symptoms or signs consistent with STEMI at primary care clinics, small hospitals, and PCI hospitals in the southern state of Tamil Nadu in India. Data were collected from the 4 clusters before implementation of the program (preimplementation data). We required a minimum of 12 weeks for the preimplementation data with the period extending from August 7, 2012, through January 5, 2013. The program was then implemented in a sequential manner across the 4 clusters, and data were collected in the same manner (postimplementation data) from June 12, 2013, through June 24, 2014, for a mean 32-week period.ExposuresCreation of an integrated, regional quality improvement program that linked the 35 spoke health care centers to the 4 large PCI hub hospitals and leveraged recent developments in public health insurance schemes, emergency medical services, and health information technology.Main outcomes and measuresPrimary outcomes focused on the proportion of patients undergoing reperfusion, timely reperfusion, and postfibrinolysis angiography and PCI. Secondary outcomes were in-hospital and 1-year mortality.ResultsA total of 2420 patients with STEMI (2034 men [84.0%] and 386 women [16.0%]; mean [SD] age, 54.7 [12.2] years) (898 in the preimplementation phase and 1522 in the postimplementation phase) were enrolled, with 1053 patients (43.5%) from the spoke health care centers. Missing data were common for systolic blood pressure (213 [8.8%]), heart rate (223 [9.2%]), and anterior MI location (279 [11.5%]). Overall reperfusion use and times to reperfusion were similar (795 [88.5%] vs 1372 [90.1%]; P = .21). Coronary angiography (314 [35.0%] vs 925 [60.8%]; P < .001) and PCI (265 [29.5%] vs 707 [46.5%]; P < .001) were more commonly performed during the postimplementation phase. In-hospital mortality was not different (52 [5.8%] vs 85 [5.6%]; P = .83), but 1-year mortality was lower in the postimplementation phase (134 [17.6%] vs 179 [14.2%]; P = .04), and this difference remained consistent after multivariable adjustment (adjusted odds ratio, 0.76; 95% CI, 0.58-0.98; P = .04).Conclusions and relevanceA hub-and-spoke model in South India improved STEMI care through greater use of PCI and may improve 1-year mortality. This model may serve as an example for developing STEMI systems of care in other low- to middle-income countries.

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Addition of Plasma Myeloperoxidase and Trimethylamine N-Oxide to the GRACE Score Improves Prediction of Near-Term Major Adverse Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction.

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