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en Cytochrome P450 2C19 Deficiency as the Sole Predictor of Major Adverse Cardiovascular Events in Post-COVID-19 Patients Aims: Post-COVID-19 syndrome increases the risk of major adverse cardiovascular events (acute myocardial infarction, deep vein thrombosis, ischemic stroke, and pulmonary embolism). We examined whether the cytokine-driven inflammatory milieu after COVID-19 continuously decreases circulating cytochrome P450 2C19 activity and whether this reduction independently predicts MACE risk in these patients. Materials & Methods: This prospective, single-center, case-control study was conducted at the Maysan Center for Heart Diseases and Surgery, Maysan Health Directorate, Amarah, Maysan Province, Iraq, from October 2022 to November 2024. A total of 210 adult participants were recruited from the outpatient cardiology and post-COVID-19 follow-up clinics of the Maysan Center for Heart Diseases and Surgery and divided into two groups (n=105 per group). Statistical analyses were conducted using SPSS 26 and GraphPad Prism 10. Findings: Case patients had significantly lower plasma cytochrome P450 2C19 activity than post-COVID-19 controls (0.531±0.114 vs. 0.812±0.071U/L; p<0.001; Cohen’s d=2.98). Cytochrome P450 2C19 activity was negatively correlated with hsCRP (r=0.481; p<0.001), IL-6 (r=0.512; p<0.001), and D-dimer (r=0.443; p<0.001). In ROC analysis, CYP2C19 activity showed excellent discrimination for major adverse cardiovascular events after COVID-19 (area under the curve=0.924; 95% CI: 0.889–0.959; p<0.001). Using an optimal cut-off of 0.6480U/L yielded sensitivity of 86.7% and specificity of 90.5%. Conclusion: Markedly reduced post–COVID-19 cytochrome P450 2C19 enzymatic activity is a standalone, highly reliable independent biomarker for predicting major adverse cardiac events. CYP2C19, Cytochrome P450, Post-COVID-19, Major Adverse Cardiovascular Events (MACE) , Myocardial Infarction, IL-6 149 155 http://ijwph.daneshafarand.org/browse.php?a_code=A--1-113&slc_lang=en&sid=3 A.K. Jasim 1003194753284600380569 1003194753284600380569 Yes Al-Manara College for Medical Sciences, University of Manara, Maysan, Iraq H.S. Hamadi 1003194753284600380570 1003194753284600380570 No Al-Manara College for Medical Sciences, University of Manara, Maysan, Iraq