Background: Vascular diseases, primarily chronic ischemic heart disease (CIHD) and cerebrovascular pathology, remain leading causes of mortality in Uzbekistan and Central Asia. Atherothrombosis, resulting from plaque destabilization and subsequent thrombosis, is the key mechanism underlying disease progression and cardiovascular complications. Biomarkers of coagulation, fibrinolysis, and extracellular matrix remodeling, as well as genetic determinants, may improve risk prediction; however, their prognostic value in regional populations has not been sufficiently studied.

Objective: To identify clinical, biochemical, and genetic predictors of cardiovascular complications in patients with CIHD, to develop a long-term risk stratification scale, and to evaluate factors influencing the efficacy of antiplatelet therapy.

Methods: A prospective observational study was conducted in 2023–2024 at the Republican Specialized Scientific-Practical Medical Center of Cardiology (Tashkent) and included 503 patients with stable CIHD. Clinical characteristics, biochemical markers of coagulation and fibrinolysis (D-dimer, plasmin–α2-antiplasmin complexes [PAP], matrix metalloproteinases MMP-2 and MMP-9), platelet reactivity, and genetic polymorphisms related to hemostasis, homocysteine metabolism, and antiplatelet drug response were assessed. Patients received aspirin, clopidogrel, or dual antiplatelet therapy according to clinical indications. Follow-up duration was at least 12 months. Primary endpoints included vascular death, acute coronary syndrome (ACS), ischemic stroke/transient ischemic attack (IS/TIA), peripheral arterial thrombosis, and revascularization. Statistical analysis was performed using Cox proportional hazards models and Kaplan–Meier survival analysis.

Results: During follow-up (mean 1.5 years), cardiovascular events occurred in 31% of patients. Independent clinical predictors included angina pectoris class II–III, previous myocardial infarction, multivessel coronary disease, history of IS/TIA, abnormal ankle–brachial index, body

mass index ≥31.6 kg/m², creatinine clearance <67 mL/min, and erosive gastritis. Based on these variables, a risk scale stratified patients into low-, intermediate-, and high-risk categories with event rates of 13%, 20%, and 39%, respectively. Percutaneous coronary intervention did not demonstrate superiority over optimal medical therapy and was associated with worse outcomes in the low-risk subgroup. Elevated D-dimer (OR 3.1), MMP-2 (OR 2.1), and PAP levels showed prognostic significance, with the highest risk observed when MMP-2 and PAP were elevated simultaneously (OR 3.6). Polymorphisms in homocysteine metabolism genes (MTHFR C677T, A1298C; TCN2 C776G) were associated with increased risk in a folate-dependent manner. Reduced clopidogrel efficacy was observed in carriers of CYP2C19*2 alleles, while dose escalation to 150 mg improved outcomes in poor metabolizers after PCI. Proton pump inhibitor co-administration was associated with increased thrombotic risk. Prolonged dual antiplatelet therapy beyond 12 months did not provide additional benefit.

Conclusion: An integrated approach combining clinical parameters, biomarkers, and pharmacogenetic testing improves long-term risk stratification and enables personalized antiplatelet therapy in patients with CIHD in Uzbekistan. Routine incorporation of genetic and biochemical markers may enhance secondary prevention strategies in stable coronary disease.

chronic ischemic heart disease, atherothrombosis, antiplatelet therapy

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