IMPACT OF EARLY CLINICAL AND BIOLOGICAL MARKERS ON SHORT-TERM FUNCTIONAL OUTCOMES IN CARDIOEMBOLIC STROKE

Abstract

Within the clinical subtypes of ischemic stroke, the cardioembolic form occupies a special place. This phenotype represents one of the most common ischemic stroke subtypes (accounting for up to 15–30%) and is characterized by the formation of thromboembolic material in the cardiac chambers or in the setting of cardiac rhythm disturbances, leading to sudden occlusion of cerebral vessels. Although the cardioembolic subtype has been widely investigated worldwide, a number of its clinical, pathobiological and genetic aspects remain relevant and insufficiently explored. The assessment of the association between polymorphisms of the MMP-9 (−1562 C/T) and MMP-12 (−82 A/G) genes and the severity and clinical course of cardioembolic stroke has expanded the regional scientific evidence base on stroke biology specific to the Central Asian population.

The aim of the study: To investigate the clinical-demographic, laboratory and genetic characteristics of cardioembolic stroke, with a particular focus on the impact of MMP-9 −1562 C/T and MMP-12 −82 A/G gene polymorphisms, inflammatory indices, and coagulation parameters on stroke severity and clinical outcomes.

Materials and methods. This study was designed to investigate the clinical course of cardioembolic stroke (CES), biological markers of inflammation, and the impact of MMP-9 and MMP-12 gene polymorphisms on stroke severity. The study was conducted as a single-center, population-based, prospective clinical and genetic investigation. A total of 196 patients hospitalized with acute ischemic stroke in the intensive neurology, intensive care/therapy, and neurology departments of the clinic of Tashkent State Medical University were enrolled. According to the TOAST classification, 97 patients were classified as having cardioembolic stroke (CES) and 99 patients as having atherothrombotic stroke (ATS). On the first day of hospitalization, leukocyte formula parameters obtained from the complete blood count were used in all patients to calculate inflammatory biomarkers, including the neutrophil-to- lymphocyte index (NLI), the platelet-to-lymphocyte index (PLI), and the lymphocyte-to-monocyte ratio (LMR). Written informed consent for genetic testing was obtained from all participants. Peripheral venous blood samples were used as biological material for molecular genetic analysis.

Results. According to the study findings, cardioembolic stroke was characterized by a more severe clinical course compared with atherothrombotic stroke in the investigated population. In the cardioembolic stroke (CES) group, a higher proportion of patients presented with severe neurological impairment (NIHSS ≥24). During dynamic follow-up (day 1, day 7 and 3 months), neurological deficit and the degree of functional limitation remained consistently higher in the CES group as assessed by the NIHSS and modified Rankin Scale (mRS) (p<0.01). Receiver operating characteristic (ROC) analysis confirmed the high discriminative ability of the NIHSS score on day 1 for predicting in-hospital mortality (AUC = 0.917), indicating the formation of a “severe clinical phenotype” of cardioembolic stroke. Molecular genetic analyses demonstrated a significant association between the MMP-12 rs2276109 (−82 A/G) polymorphism and cardioembolic stroke. Carriers of the A allele showed an approximately two-fold higher risk of CES in this cohort (OR≈2.1). In univariate analysis, the AG and GG genotypes exhibited a protective effect with respect to mortality (OR = 0.31; p<0.01), whereas the AA genotype was identified as a high-risk variant. The MMP-9 rs3918242 polymorphism did not demonstrate independent prognostic significance in the present sample. Inflammatory indices (NLI, PLI and LMR) and parameters of the hemostatic system were significantly higher in the CES group (p<0.001).

Conclusion. A higher proportion of patients in the cardioembolic stroke (CES) group presented with severe neurological impairment according to the NIHSS (≥24 points). An integrative diagnostic and prognostic model combining clinical (NIHSS, modified Rankin Scale), laboratory (inflammatory and coagulation markers), and genetic factors was developed. A stepwise increase in the risk of fatal outcome was observed with increasing genetic burden score (GBS). In particular, a high genetic burden (GBS ≥3) was associated with a 2.77-fold higher probability of death compared with a low genetic burden. This approach provides a scientific and practical basis for early stratification of patients with cardioembolic stroke into low-, intermediate- and high-risk groups, determination of individual prognosis, and selection of personalized treatment and follow-up strategies.