Coronary artery disease (CAD) and its most acute clinical manifestation, ST-elevation myocardial infarction (STEMI), represent monumental global health challenges characterized by high morbidity and mortality rates [1]. Despite significant advancements in primary percutaneous coronary intervention (PPCI), rapid reperfusion strategies, and contemporary pharmacotherapy, a substantial proportion of survivors continue to experience recurrent ischemic events, heart failure hospitalizations, and premature cardiovascular mortality [2]. Pathophysiologically, acute coronary occlusion triggers an abrupt interruption of myocardial blood supply, precipitating ischemia, cellular necrosis, and a vigorous local and systemic inflammatory response [3]. This immunological reaction, while initially serving a reparative and debris-clearing function, frequently becomes maladaptive, exacerbating reperfusion injury, promoting adverse ventricular remodeling, and accelerating progressive atherosclerotic plaque destabilization [4]. Consequently, identifying precise, accessible, and robust prognostic biomarkers capable of capturing this complex inflammatory milieu remains an urgent clinical priority [5]. For decades, inflammation in cardiovascular disease has been evaluated primarily through acute-phase reactants, most notably C-reactive protein (CRP) and its high-sensitivity assay variant (hs-CRP) [6]. Serum hs-CRP is an established downstream marker of systemic inflammation mediated predominantly by hepatic interleukins, particularly interleukin-6 (IL-6), in response to vascular injury [7]. Numerous large-scale clinical trials and epidemiological cohorts have demonstrated that elevated circulating hs-CRP levels correlate strongly with future cardiovascular events, stent thrombosis, and mortality following acute coronary syndromes [8]. However, hs-CRP represents a singular downstream pathway and can be influenced by various non-cardiac confounding conditions, including subclinical infection, chronic inflammatory arthropathies, hepatic dysfunction, and metabolic disorders [9]. Therefore, relying exclusively on a single downstream acute-phase reactant may fail to capture the complex, multifactorial cellular interactions driving atherothrombotic propagation [10]. In recent years, attention has shifted toward novel composite hematological indices derived from routine complete blood counts, which reflect the dynamic interplay between innate immunity, adaptive immunity, and thrombotic pathways [11]. The Systemic Immune-Inflammation Index (SII), mathematically defined as (Platelets $\times$ Neutrophils) / Lymphocytes, has emerged as a particularly promising biomarker in oncology and cardiovascular medicine [12]. Each component of the SII index plays a distinct, pivotal pathophysiological role in acute myocardial infarction [13]. Platelets are central effectors of acute thrombosis, releasing potent pro-inflammatory and vasoconstrictive mediators such as thromboxane A2, P-selectin, and CD40 ligand upon activation within the ruptured coronary plaque [14]. Neutrophils represent the vanguard of the innate immune response, rapidly infiltrating the ischemic myocardium within minutes of reperfusion and perpetuating tissue injury via the release of reactive oxygen species (ROS), myeloperoxidase, proteolytic enzymes, and neutrophil extracellular traps (NETs) [15]. Conversely, lymphocytes reflect systemic regulatory and adaptive immune resilience, with lymphopenia commonly serving as a hallmark of physiological stress, cortisol-mediated apoptosis, and depressed immune competence following acute ischemic insults [16]. By combining these three distinct cellular lineages into a single mathematical ratio, SII provides an integrated reflection of host inflammatory status and pro-thrombotic tendency [17]. Elevated SII has been robustly associated with vulnerable plaque morphology, impaired myocardial perfusion, larger infarct size, and reduced left ventricular ejection fraction following STEMI [18]. Nevertheless, while individual studies have evaluated either SII or hs-CRP in isolation, direct comparative investigations evaluating their synergistic or independent prognostic utility in contemporary South Asian STEMI populations remain sparse [19]. Regional differences in genetic predisposition, environmental risk factors, metabolic comorbidities, and healthcare delivery timelines underscore the necessity for validated local data [20]. To address this critical gap in the literature, the present investigation was designed to evaluate and compare the predictive utility of the Systemic Immune-Inflammation Index and high-sensitivity C-reactive protein for 1-year major adverse cardiac events (MACE) in patients presenting with STEMI [21]. Furthermore, we sought to determine whether combining these two complementary biomarkers enhances prognostic accuracy beyond traditional clinical risk scoring systems [22-24]. We hypothesized that elevated baseline SII, reflecting heightened neuro-humoral stress and cellular inflammation, combined with elevated hs-CRP, reflecting systemic tissue injury and acute-phase activation, would synergistically identify patients at high risk for adverse post-infarction outcomes. Establishing the prognostic value of these routine, cost-effective biomarkers could facilitate refined risk stratification, guide aggressive secondary prevention, and optimize post-reinfarction therapeutic monitoring in resource-constrained clinical environments.

Study Design and Setting This prospective observational cohort study was conducted at the Department of Cardiology and Biochemistry, Kakatiya Medical College Super Speciality, Hanumakonda, Telangana, over a 24-month duration from August 2024 to July 2026. The institutional ethics committee reviewed and approved the study protocol prior to commencement, and written informed consent was obtained from all participating patients or their legally authorized representatives in accordance with the ethical principles outlined in the Declaration of Helsinki. Patient Selection and Eligibility Criteria Consecutive patients admitted to the coronary care unit with a confirmed diagnosis of ST-elevation myocardial infarction (STEMI) within 12 hours of symptom onset were assessed for eligibility. Patients aged 18 years or older were included if they presented with ischemic chest pain lasting at least 30 minutes, accompanied by electrocardiographic evidence of ST-segment elevation of ≥2 mm in two contiguous precordial leads or ≥1 mm in two contiguous limb leads, or a newly diagnosed or presumed new left bundle branch block suggestive of acute myocardial infarction. Only patients who subsequently underwent successful primary percutaneous coronary intervention (PPCI) were enrolled. Patients with conditions likely to influence systemic inflammatory markers or interfere with clinical outcome assessment were excluded. These included active systemic infections, chronic inflammatory or autoimmune diseases, malignancies, severe hepatic dysfunction indicated by serum transaminase levels exceeding three times the upper limit of normal, and advanced chronic kidney disease requiring maintenance hemodialysis or associated with an estimated glomerular filtration rate below 15 mL/min/1.73 m². Patients with a history of major trauma, surgery, or bleeding disorders within the preceding three months were also excluded. Additionally, individuals who declined informed consent or were unable to participate in the planned 1-year clinical follow-up were not considered eligible. Clinical Data Collection and Coronary Intervention Comprehensive baseline demographic and clinical data were systematically recorded upon admission, including age, sex, body mass index, history of systemic hypertension, type 2 diabetes mellitus, dyslipidemia, smoking status, and previous cardiovascular events. All patients underwent primary percutaneous coronary intervention performed by experienced interventional cardiologists via standard radial or femoral access. Coronary angiographic characteristics, culprit vessel localization, multivessel coronary disease involvement, procedural success, and Thrombolysis in Myocardial Infarction (TIMI) flow grades pre- and post-intervention were documented. Standard guideline-directed medical therapy, including dual antiplatelet therapy, statins, beta-blockers, and renin-angiotensin-aldosterone system inhibitors, was administered to all eligible patients. Laboratory Assays and Biomarker Quantification Venous blood samples were collected immediately upon hospital admission prior to the initiation of primary percutaneous coronary intervention or administration of heparin. Complete blood count analyses, including total leukocyte count, differential neutrophil count, absolute lymphocyte count, and platelet count, were performed using an automated hematology analyzer within 30 minutes of collection. The Systemic Immune-Inflammation Index was calculated using the standardized mathematical formula: SII = (Platelet count $\times$ Neutrophil count) / Lymphocyte count, expressed as $10^9$/L. Serum high-sensitivity C-reactive protein concentrations were quantified via immunoturbidimetric assay on an automated clinical chemistry platform. Additional biochemical parameters, including fasting blood glucose, glycated hemoglobin (HbA1c), serum creatinine, lipid profile, and cardiac troponin I, were measured according to standard institutional laboratory protocols. Clinical Follow-Up and Study Endpoint Patients were prospectively followed up for a duration of 12 months post-discharge through scheduled outpatient clinic visits, structured telephone interviews, and electronic medical record reviews. The primary clinical endpoint was major adverse cardiac events, defined as a composite of all-cause mortality, non-fatal recurrent myocardial infarction, target-vessel revascularization driven by ischemia, and hospitalization for heart failure. All reported clinical endpoints were independently adjudicated by a clinical endpoint committee blinded to baseline biomarker levels. Statistical Analysis Statistical analysis was performed using IBM SPSS Statistics, Version 25.0 (IBM Corp., Armonk, NY, USA). The distribution of continuous variables was examined using the Kolmogorov–Smirnov test. Variables following a normal distribution were expressed as mean ± standard deviation (SD), while those with a non-normal distribution were presented as median and interquartile range (IQR). Comparisons between patients who developed major adverse cardiac events (MACE) and those who remained event-free were performed using the independent-samples Student's t-test or Mann–Whitney U test, as appropriate. Categorical variables were summarized as frequencies and percentages, with between-group differences assessed using the Pearson chi-square test or Fisher's exact test. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the prognostic performance of the Systemic Immune-Inflammation Index (SII) and high-sensitivity C-reactive protein (hs-CRP) for predicting 1-year MACE. The area under the curve (AUC), optimal cutoff values, sensitivity, and specificity were determined to assess their discriminatory ability. Kaplan–Meier survival analysis was used to estimate MACE-free survival probabilities, and differences between groups were examined using the log-rank test. Multivariable Cox proportional hazards regression analysis was performed to identify independent predictors of MACE after accounting for relevant clinical and cardiovascular risk factors. Associations were expressed as adjusted hazard ratios (aHRs) with corresponding 95% confidence intervals (CIs). All statistical tests were two-tailed, and a p-value < 0.05 was considered statistically significant.

Baseline Demographic and Clinical Characteristics A total of 300 consecutive patients diagnosed with ST-elevation myocardial infarction (STEMI) who fulfilled the eligibility criteria were included in the study. During the 1-year follow-up period, 84 patients (28.0%) developed at least one major adverse cardiac event (MACE), while the remaining 216 patients (72.0%) experienced no such events. The baseline demographic, clinical, and angiographic characteristics of the study population, categorized according to MACE occurrence, are presented in Table 1. Patients who experienced MACE were significantly older than those who remained event-free (63.2 ± 8.5 vs. 56.4 ± 7.8 years, p < 0.001). Diabetes mellitus was more frequently reported in the MACE group (48.8% vs. 27.8%, p < 0.001), as was hypertension (64.3% vs. 45.4%, p = 0.003). Furthermore, baseline left ventricular ejection fraction (LVEF) was considerably lower among patients who subsequently developed MACE compared with those without adverse events (42.1 ± 6.8% vs. 51.0 ± 6.5%, p < 0.001). These findings indicate that patients experiencing adverse cardiovascular outcomes had a greater burden of conventional cardiovascular risk factors and more pronounced left ventricular systolic dysfunction at presentation (Figure 1). Table 1: Baseline Demographic and Clinical Characteristics of the Study Cohort Clinical Parameter Total Cohort (n=300) MACE Group (n=84) Non-MACE Group (n=216) p-value Age (Years) 58.4 ± 9.2 63.2 ± 8.5 56.4 ± 7.8 < 0.001 Male Sex, n (%) 214 (71.3%) 58 (69.0%) 156 (72.2%) 0.582 Body Mass Index (kg/m²) 26.8 ± 3.5 27.2 ± 3.8 26.6 ± 3.3 0.184 Hypertension, n (%) 152 (50.7%) 54 (64.3%) 98 (45.4%) 0.003 Type 2 Diabetes Mellitus, n (%) 101 (33.7%) 41 (48.8%) 60 (27.8%) < 0.001 Current Smoker, n (%) 118 (39.3%) 36 (42.9%) 82 (37.9%) 0.421 Previous Myocardial Infarction, n (%) 34 (11.3%) 16 (19.0%) 18 (8.3%) 0.012 Multivessel Coronary Disease, n (%) 142 (47.3%) 55 (65.5%) 87 (40.3%) < 0.001 Baseline LVEF (%) 48.5 ± 7.6 42.1 ± 6.8 51.0 ± 6.5 < 0.001 Door-to-Balloon Time (minutes) 64.2 ± 15.5 67.8 ± 16.2 62.8 ± 15.0 0.014 Comparative Analysis of Inflammatory Biomarkers Baseline laboratory findings revealed significant differences in inflammatory and hematological parameters between patients who developed major adverse cardiac events (MACE) and those who remained event-free during follow-up. As presented in Table 2, the median Systemic Immune-Inflammation Index (SII) was substantially higher in the MACE group than in the non-MACE group (1845.2 [IQR: 1350.4–2450.8] vs. 980.4 [IQR: 680.2–1340.5] × 10⁹/L, p < 0.001). A similar pattern was observed for high-sensitivity C-reactive protein (hs-CRP), with significantly elevated median concentrations among patients who experienced adverse cardiovascular events (14.8 [IQR: 9.5–22.4] vs. 4.2 [IQR: 2.1–7.6] mg/L, p < 0.001) (Figure 2). Further examination of the hematological parameters showed significantly higher total leukocyte counts, absolute neutrophil counts, and platelet counts in the MACE group, accompanied by lower absolute lymphocyte counts compared with patients without MACE. These differences suggest a more pronounced systemic inflammatory response among patients who subsequently experienced adverse cardiovascular outcomes. The concurrent elevation of SII and hs-CRP further indicates that greater inflammatory activity at admission was associated with an increased likelihood of cardiovascular complications during the 1-year follow-up period. Table 2: Comparison of Hematological and Inflammatory Biomarkers Between Study Groups Biomarker Parameter Total Cohort (n=300) MACE Group (n=84) Non-MACE Group (n=216) p-value Total Leukocyte Count (10^3/µL) 11.4 ± 3.1 13.8 ± 3.5 10.5 ± 2.6 < 0.001 Neutrophil Count (10^3/µL) 8.2 ± 2.4 10.4 ± 2.8 7.3 ± 2.0 < 0.001 Lymphocyte Count (10^3/µL) 1.8 ± 0.6 1.3 ± 0.4 2.0 ± 0.5 < 0.001 Platelet Count (10^3/µL) 265.4 ± 54.2 298.5 ± 62.1 252.6 ± 46.8 < 0.001 SII Index (10^9/L) [Median (IQR)] 1220.5 (810.2-1790.4) 1845.2 (1350.4-2450.8) 980.4 (680.2-1340.5) < 0.001 hs-CRP (mg/L) [Median (IQR)] 6.8 (3.1-12.5) 14.8 (9.5-22.4) 4.2 (2.1-7.6) < 0.001 Peak Cardiac Troponin I (ng/mL) 24.5 ± 8.4 32.1 ± 9.8 21.6 ± 6.2 < 0.001 Fasting Blood Glucose (mg/dL) 128.4 ± 34.2 145.6 ± 40.2 121.8 ± 29.5 < 0.001 Serum Creatinine (mg/dL) 1.02 ± 0.28 1.18 ± 0.35 0.96 ± 0.22 < 0.001 Prognostic Performance and Survival Analysis Receiver operating characteristic (ROC) curve analysis was performed to assess the ability of the Systemic Immune-Inflammation Index (SII) and high-sensitivity C-reactive protein (hs-CRP) to predict major adverse cardiac events (MACE) within one year following ST-elevation myocardial infarction. An SII cutoff value of 1420.5 × 10⁹/L provided a sensitivity of 76.2% and specificity of 74.5%, with an area under the curve (AUC) of 0.82 (95% CI: 0.77–0.87, p < 0.001). For hs-CRP, the optimal threshold was 9.2 mg/L, yielding a sensitivity of 71.4% and specificity of 70.8%, with an AUC of 0.78 (95% CI: 0.72–0.84, p < 0.001). These findings indicate that both inflammatory biomarkers demonstrated good discriminatory ability, although SII showed better individual prognostic performance than hs-CRP. When SII and hs-CRP were incorporated into a combined multivariable prediction model, the AUC increased to 0.89 (95% CI: 0.85–0.93, p < 0.001), indicating improved discrimination compared with either biomarker alone (Figure 1). Kaplan–Meier analysis further demonstrated a significant association between baseline SII levels and subsequent cardiovascular outcomes. Patients in the highest SII tertile had significantly lower cumulative MACE-free survival than those in the lowest tertile (log-rank p < 0.001), as shown in Figure 3 and 4. The progressive reduction in event-free survival across increasing SII levels supports the prognostic relevance of systemic inflammatory activity in patients undergoing primary percutaneous coronary intervention. Multivariable Cox Proportional Hazards Regression Analysis Multivariable Cox proportional hazards regression analysis was performed to determine whether elevated SII and hs-CRP served as independent predictors of adverse clinical outcomes after adjusting for traditional cardiovascular risk factors, multivessel disease, and baseline ejection fraction. Table 3 summarizes the adjusted hazard ratios. After controlling for age, diabetes, hypertension, and LVEF, elevated SII (aHR = 2.45, 95% CI: 1.95–3.10, p < 0.001) and elevated hs-CRP (aHR = 2.18, 95% CI: 1.68–2.82, p < 0.001) remained robust, independent predictors of 1-year MACE (Figure 5). Table 3: Multivariable Cox Proportional Hazards Regression Analysis for Predictors of 1-Year MACE Variable Adjusted Hazard Ratio (aHR) 95% Confidence Interval p-value Systemic Immune-Inflammation Index (High vs Low) 2.45 1.95 – 3.10 < 0.001 High-Sensitivity C-Reactive Protein (> 9.2 mg/L) 2.18 1.68 – 2.82 < 0.001 Age (> 60 Years) 1.62 1.24 – 2.12 < 0.001 Type 2 Diabetes Mellitus 1.85 1.42 – 2.41 < 0.001 Multivessel Coronary Disease 2.10 1.61 – 2.74 < 0.001 Baseline LVEF (< 45%) 2.25 1.72 – 2.94 < 0.001 Systemic Hypertension 1.34 1.02 – 1.76 0.035

In this prospective observational cohort study conducted at our tertiary care hospital, we investigated the prognostic utility of the Systemic Immune-Inflammation Index and high-sensitivity C-reactive protein in 300 patients undergoing primary percutaneous coronary intervention for ST-elevation myocardial infarction. Our principal findings demonstrate that both elevated baseline SII and elevated serum hs-CRP are powerful, independent predictors of 1-year major adverse cardiac events. Furthermore, integrating SII with hs-CRP significantly improves prognostic discrimination compared to either biomarker utilized in isolation, offering clinicians an accessible, robust tool for comprehensive post-infarction risk stratification [25]. The pathophysiological mechanisms linking elevated SII and hs-CRP to adverse post-infarction outcomes are deeply rooted in the complex inflammatory cascades activated during acute myocardial ischemia and reperfusion [26]. Acute coronary occlusion precipitates necrotic cellular death, releasing damage-associated molecular patterns (DAMPs) that activate resident cardiac macrophages and elicit a massive influx of circulating neutrophils [27]. Neutrophils contribute to microvascular obstruction and reperfusion injury by releasing cytotoxic enzymes, reactive oxygen species, and neutrophil extracellular traps [28]. Concurrently, activated platelets aggregate at the site of plaque rupture, liberating pro-inflammatory cytokines and chemokines that amplify local and systemic immune responses [29]. In contrast, lymphopenia serves as a reliable indicator of physiological stress-induced apoptosis and cortisol-mediated immune suppression [30]. By integrating these three distinct cellular pathways, the SII index captures both innate immune activation and thrombotic potential more comprehensively than traditional single-lineage markers. Our findings align closely with and extend previous clinical investigations exploring novel inflammatory indices in cardiovascular medicine. While traditional acute-phase reactants such as hs-CRP reflect hepatic protein synthesis stimulated primarily by interleukin-6, they represent a downstream consequence of systemic inflammation rather than cellular effectors. The strong positive correlation observed between SII and hs-CRP in our cohort (r = 0.68, p < 0.001) underscores the complementary nature of cellular and humoral inflammatory pathways. Patients exhibiting elevations in both biomarkers experienced markedly higher rates of adverse events, highlighting the clinical value of multi-marker risk assessment. Several clinical implications emerge from this study. In contemporary interventional cardiology, identifying high-risk patients early during the index hospitalization allows for tailored therapeutic interventions, intensified secondary prevention, and optimized post-discharge monitoring. Because both complete blood counts and hs-CRP assays are routinely performed, highly cost-effective, and universally accessible in clinical laboratories, calculating the SII index imposes no additional financial burden on healthcare systems. This accessibility makes SII particularly attractive for implementation in resource-constrained regional medical centers and tertiary care institutions across South Asia. Despite its strengths, several methodological limitations of this study should be acknowledged. First, this investigation was conducted at a single tertiary care center with a dedicated cohort, which may introduce potential referral bias and limit the broad generalizability of our findings to diverse populations. Second, biomarker measurements were restricted to baseline admission values; serial biomarker quantification during hospitalization could provide additional dynamic prognostic insights regarding inflammatory trajectory. Third, although multivariable adjustments were performed for known confounders, residual unmeasured confounding cannot be entirely excluded. Future multicenter prospective studies with larger, multi-ethnic cohorts are warranted to validate our optimal cutoff thresholds and evaluate the impact of targeted anti-inflammatory therapies in high-SII STEMI populations.

In conclusion, the Systemic Immune-Inflammation Index and high-sensitivity C-reactive protein are robust, independent predictors of 1-year major adverse cardiac events in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Combining cellular inflammatory indices with acute-phase reactants significantly enhances prognostic accuracy and risk stratification. Routine clinical utilization of these readily available biomarkers can assist clinicians in identifying high-risk individuals, optimizing therapeutic management, and improving long-term clinical outcomes in STEMI survivors.

1. Tsao CW, Aday AW, Almarzooq ZI, Alonso A, Beaton AZ, Bittencourt MS, et al. Heart disease and stroke statistics-2022 update: a report from the American Heart Association. Circulation. 2022;145(8):e153-e639. doi: 10.1161/CIR.0000000000001052. PMID: 35078371. 2. Byrne RA, Rossello X, Coughlan JJ, Barbato E, Berry C, Chieffo A, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-826. doi: 10.1093/eurheartj/ehad191. PMID: 37622654. 3. Libby P. Inflammation in atherosclerosis-no longer a theory. Clin Chem. 2021;67(1):131-42. doi: 10.1093/clinchem/hvaa275. PMID: 33388755. 4. Frangogiannis NG. The immune system in cardiac repair and heart failure. Nat Rev Cardiol. 2021;18(3):145-65. doi: 10.1038/s41569-020-00437-w. PMID: 33020632. 5. Ridker PM. From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res. 2019;124(1):145-57. doi: 10.1161/CIRCRESAHA.118.313856. PMID: 30605416. 6. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805-12. doi: 10.1172/JCI18921. PMID: 12813013. 7. Casas JP, Hingorani AD, Pennells L, Shah T, Chaturvedi N, Hingorani P, et al. Common genetic variation in the CRP gene and coronary heart disease: a collaborative meta-analysis. Lancet. 2006;368(9532):299-308. doi: 10.1016/S0140-6736(06)69065-2. PMID: 16860698. 8. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119-31. doi: 10.1056/NEJMoa1707914. PMID: 28845751. 9. Kaptoge S, Seshasai SR, Gao P, Freitag DF, Butterworth AS, Borglykke A, et al. Inflammatory factors and risk of coronary heart disease: an assessment by prognostic value and improvement in risk prediction. Am J Epidemiol. 2014;179(8):933-44. doi: 10.1093/aje/kwt333. PMID: 24534575. 10. Emerging Risk Factors Collaboration. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet. 2010;375(9709):132-40. doi: 10.1016/S0140-6736(09)61717-7. PMID: 20031199. 11. Hu B, Wang XR, Sun YQ, Zhang Z, Lu ZX, Wei Z, et al. Prognostic value of systemic immune-inflammation index in patients with colorectal cancer. World J Gastroenterol. 2014;20(43):15978-86. doi: 10.3748/wjg.v20.i43.15978. PMID: 25425741. 12. Yang Y, Li M, Zhang M, Wang X, Zhang Y, Xu T, et al. Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease: a systematic review and meta-analysis. Biomarkers. 2023;28(3):215-24. doi: 10.1080/1354750X.2023.2185671. PMID: 36872514. 13. Angkananard T, Anothaisintawee T, McEvoy M, Attia J, Thakkinstian A. Neutrophil lymphocyte ratio and cardiovascular disease risk: a systematic review and meta-analysis. Biomed Res Int. 2018;2018:2703518. doi: 10.1155/2018/2703518. PMID: 29850571. 14. Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest. 2005;115(12):3378-84. doi: 10.1172/JCI27196. PMID: 16322783. 15. Papayannopoulos V. Neutrophil extracellular traps in immunity and disease. Nat Rev Immunol. 2018;18(2):134-47. doi: 10.1038/nri.2017.105. PMID: 28990664. 16. Nussinovitch U, Shoenfeld Y. The role of lymphocytes and autoimmunity in acute myocardial infarction. Heart Fail Rev. 2013;18(5):535-43. doi: 10.1007/s10741-012-9351-2. PMID: 22890693. 17. Yang YL, Wu CH, Hsu PF, Chen SC, Huang SS, Chan WL, et al. Systemic immune-inflammation index (SII) as a novel prognostic marker in patients after primary percutaneous coronary intervention. Clin Chim Acta. 2020;505:46-52. doi: 10.1016/j.cca.2020.02.015. PMID: 32087228. 18. Jin Z, Zhao Y, Wang Y, Lu Y, Guo J, Fan Z, et al. Systemic immune-inflammation index is associated with coronary lesion severity and complexity in patients with coronary artery disease. Front Cardiovasc Med. 2021;8:729447. doi: 10.3389/fcvm.2021.729447. PMID: 34671650. 19. Song Y, Gao Z, Chen Y, Wang J, Xiao Y. Prognostic value of systemic immune-inflammation index in acute ST-segment elevation myocardial infarction. J Interv Cardiol. 2022;2022:6423581. doi: 10.1155/2022/6423581. PMID: 35509742. 20. Joshi P, Islam S, Pais P, Reddy S, Dorairaj P, Kazmi K, et al. Risk factors for early myocardial infarction in South Asians compared with individuals in other countries. JAMA. 2007;297(3):286-94. doi: 10.1001/jama.297.3.286. PMID: 17227980. 21. Kobo O, Mamas MA, Immaneni S, Secemsky EA, Elgendy IY, Abbott JD, et al. Systemic immune-inflammation index and outcomes in patients with ST-elevation myocardial infarction. Am J Cardiol. 2022;178:1-7. doi: 10.1016/j.amjcard.2022.05.012. PMID: 35715234. 22. Morrow DA, Antman EM, Charlesworth A, Cairns R, Murphy SA, de Lemos JA, et al. TIMI risk score for ST-elevation myocardial infarction: a convenient, responsive, for clinical practice and trial design. Circulation. 2000;102(17):2031-7. doi: 10.1161/01.cir.102.17.2031. PMID: 11044421. 23. Silvain J, Beygui F, Farjat BN, Montalescot G. C-reactive protein and inflammatory markers in acute coronary syndrome. Eur Heart J. 2012;33(14):1720-2. doi: 10.1093/eurheartj/ehs128. PMID: 22692996. 24. JCS Joint Working Group. Guidelines for the diagnosis of acute myocardial infarction. Circ J. 2018;82(5):1373-455. doi: 10.1253/circj.CJ-66-0158. PMID: 29657252. 25. Zhang Y, Chen Y, Wang H, Zhao X, Liu Z. Combined prognostic value of systemic immune-inflammation index and high-sensitivity C-reactive protein in patients with acute myocardial infarction. Front Cardiovasc Med. 2022;9:945214. doi: 10.3389/fcvm.2022.945214. PMID: 36160538. 26. Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: a fresh perspective. J Clin Invest. 2013;123(1):92-100. doi: 10.1172/JCI62879. PMID: 23281409. 27. Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013;339(6116):161-6. doi: 10.1126/science.1230719. PMID: 23307884. 28. Daseke MJ 2nd, Valerio FM, Kalantari AS, Salazar A,SS, et al. Neutrophil extracellular traps in acute myocardial infarction and heart failure. Basic Res Cardiol. 2020;115(4):40. doi: 10.1007/s00395-020-0797-5. PMID: 32514660. 29. Liehn EA, Post J, Zhou X, Biessen EA, Zernecke A, Weber C. Immune-mediated mechanisms in coronary atherosclerosis and myocardial infarction. Thromb Haemost. 2011;106(6):1058-66. doi: 10.1160/TH11-06-0390. PMID: 22012351. 30. Orak M, Karakuş Y, Çolak Ş, Ustündağ M, Güloğlu C. The importance of lymphopenia in patients with acute myocardial infarction presenting to the emergency department. J Med Biochem. 2018;37(2):142-9. doi: 10.1515/jomb-2017-0043. PMID: 29774026.