Background: Central Asia, including Uzbekistan, faces one of the highest burdens of cardiovascular mortality globally, with rates exceeding those in many other regions. The primary mechanism underlying acute coronary events is the rupture or erosion of vulnerable atherosclerotic plaques. Despite this, there has been a notable absence of studies in Central Asia that incorporate direct histological classification of plaques to differentiate between stable and unstable morphologies. This gap in research limits the understanding of region-specific risk factors and biomarkers. Methods: This prospective study, conducted between 2020 and 2023, enrolled 94 ethnic Uzbek men (mean age 58.5 ± 8.6 years) who were undergoing elective coronary artery bypass grafting (CABG) or endarterectomy procedures at a specialized cardiac center in Tashkent, Uzbekistan. Coronary artery segments obtained intraoperatively were histologically examined and classified according to the established criteria proposed by Virmani et al. [1]. To assess endothelial dysfunction and hemostatic parameters, plasma levels of monocyte chemoattractant protein-1 (MCP-1), endothelin-1, soluble vascular cell adhesion molecule-1 (sVCAM-1), asymmetric dimethylarginine (ADMA), homocysteine, plasminogen activator inhibitor-1 (PAI-1), and coagulation factors II, VII, XII, along with antithrombin III, were quantified using enzyme-linked immunosorbent assays (ELISA) and chromogenic substrates. Additionally, genetic polymorphisms including CCL2 rs1024611, SERPINE1 rs1799889, IL6 rs1800795, F7 rs6046, and F2 rs1799963 were genotyped via TaqMan real-time polymerase chain reaction (PCR). Statistical analyses included univariate comparisons, multivariable logistic regression, and receiver operating characteristic (ROC) curve assessments to identify independent predictors of plaque instability. Results: Histological analysis revealed unstable plaques in 55 patients (58.5% of the cohort). Patients with unstable plaques exhibited significantly elevated levels of MCP-1 (182.4 ± 68.1 pg/mL vs. 125.8 ± 52.3 pg/mL in stable plaques; p=0.019) [2] and increased factor XII activity (128.6 ± 22.4% vs. 98.7 ± 19.8%; p=0.017) [3]. Other markers, such as endothelin-1, sVCAM-1, ADMA, and PAI-1, showed trends toward higher levels in the unstable group but did not reach statistical significance. In multivariable logistic regression models adjusted for age, body mass index (BMI), hypertension, diabetes, smoking status, and lipid profiles, MCP-1 (odds ratio [OR] 1.009, 95% confidence interval [CI] 1.003–1.015, p=0.004) and factor XII activity (OR 1.014, 95% CI 1.006–1.023, p=0.001) emerged as independent predictors of unstable plaque morphology. Genetically, the carriage of the F7 rs6046 GG genotype was associated with a markedly increased risk (OR 5.12, 95% CI 1.89–13.86, p=0.001) [4], while the SERPINE1 rs1799889 4G/4G genotype conferred an OR of 4.91 (95% CI 1.62–14.91, p=0.005) [5]. A combined predictive model incorporating these biochemical and genetic factors yielded an area under the curve (AUC) of 0.879 in ROC analysis, indicating strong discriminatory power. Conclusion: Among ethnic Uzbek men, heightened plasma concentrations of MCP-1 and factor XII activity, coupled with specific risk genotypes in F7 and SERPINE1 genes, are strongly linked to histologically verified unstable atherosclerotic plaques. These findings underscore the potential for targeted biomarker screening and genetic profiling to identify high-risk individuals in Central Asian populations, paving the way for personalized preventive strategies against acute coronary events.

Vulnerable plaque, endothelial dysfunction, factor XII

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