Features of circulating in the blood desquamated endotheliocytes at the patients with ischemic heart disease and hypertonic disease as well as their comorbidity

Abstract

Background and Rationale

Cardiovascular diseases (CVD) remain the leading cause of mortality worldwide, accounting for over 17.9 million deaths annually. In Ukraine, the situation is particularly critical, with standardized CVD mortality rates nearly twice the European average. Ischemic heart disease (IHD) and arterial hypertension (AH) are the two most prevalent forms of CVD, frequently coexisting in individual patients and forming comorbidity with particularly unfavorable prognosis. Endothelial dysfunction is recognized as a central pathophysiological mechanism underlying CVD development and progression, preceding structural vascular changes by years or decades.

Circulating desquamated endothelial cells (CEC) represent a direct marker of endothelial damage, with their enumeration in peripheral blood offering a relatively simple and accessible method for assessing endothelial dysfunction. However, the diagnostic and differential diagnostic value of CEC in combination with other cardiovascular biomarkers has not been comprehensively evaluated using multivariate statistical approaches.

Objective

To perform a comprehensive multivariate assessment of circulating desquamated endothelial cells and other cardiovascular risk biomarkers in patients with ischemic heart disease, arterial hypertension, and their comorbidity to identify specific pathophysiological profiles and develop a discriminant model for differential diagnosis.

Methods

The study included 142 participants divided into four groups: healthy controls (n=35), patients with isolated arterial hypertension (n=36), patients with isolated ischemic heart disease (n=35), and patients with IHD&AH comorbidity (n=36). A comprehensive assessment was performed including: enumeration of circulating desquamated endothelial cells using the Hladovec method; metabolic parameters (lipid profile, glucose, creatinine, urea); hemodynamic parameters (blood pressure, ankle-brachial index); hematological parameters (erythrocytes, hemoglobin, erythrocyte sedimentation rate, prothrombin index); and anthropometric parameters (body mass index). Integral indices were calculated: metabolic syndrome index, atherogenic indices of Klimov and Dobiášová-Frohlich, and entropic characteristics of lipid profiles.

Stepwise discriminant analysis was applied to identify the most informative biomarkers discriminating the four groups. Canonical roots were extracted to reveal underlying pathophysiological mechanisms. Classification functions were developed for diagnosis and differential diagnosis of IHD, AH, and their comorbidity. The accuracy of the classification model was evaluated using cross-validation.

Results

Circulating desquamated endothelial cell levels were significantly elevated in all patient groups compared to controls, with the highest values observed in patients with IHD&AH comorbidity (mean 4,850 cells/mL) compared to isolated IHD (3,920 cells/mL), isolated AH (2,780 cells/mL), and controls (1,240 cells/mL) (p<0.001 for all comparisons).

Stepwise discriminant analysis identified 18 most informative variables from the initial set of 28 parameters. Two significant canonical roots were extracted, explaining 87.3% and 12.7% of between-group variance, respectively. The first canonical root (Root 1) represented an "atherogenicity axis," strongly correlated with atherogenic indices (Klimov index: r=0.847; Dobiášová-Frohlich index: r=0.823), low-density lipoprotein cholesterol (r=0.791), triglycerides (r=0.756), and metabolic syndrome index (r=0.712). The second canonical root (Root 2) represented an "endothelial dysfunction/hemodynamics axis," most strongly associated with circulating desquamated endothelial cells (r=0.683), systolic blood pressure (r=0.645), ankle-brachial index (r=-0.587), and erythrocyte sedimentation rate (r=0.534).

The discriminant model demonstrated high classification accuracy: 91.4% for controls, 83.3% for isolated AH, 80.0% for isolated IHD, and 83.3% for IHD&AH comorbidity, with an overall accuracy of 84.5%. Cross-validation confirmed the stability of the model with minimal reduction in classification accuracy (82.4%).

Patients with isolated AH were characterized by elevated blood pressure parameters and moderately increased CEC levels, but relatively preserved lipid profiles. Patients with isolated IHD demonstrated pronounced dyslipidemia with high atherogenic indices, but less pronounced endothelial dysfunction markers. Patients with IHD&AH comorbidity exhibited the most unfavorable profile, combining severe dyslipidemia, marked endothelial dysfunction (highest CEC levels), elevated inflammatory markers (ESR), and hemodynamic abnormalities, reflecting the synergistic interaction of pathophysiological mechanisms.

Conclusions

This study demonstrates that circulating desquamated endothelial cells, assessed in combination with metabolic, hemodynamic, and hematological biomarkers using multivariate discriminant analysis, provide valuable information for the diagnosis and differential diagnosis of ischemic heart disease, arterial hypertension, and their comorbidity. The identification of two independent pathophysiological axes - "atherogenicity" and "endothelial dysfunction/hemodynamics" - supports the concept of multiple interacting mechanisms underlying cardiovascular disease development. The developed discriminant model with 84.5% accuracy represents a promising tool for comprehensive cardiovascular risk assessment and may facilitate early diagnosis, risk stratification, and therapeutic monitoring in clinical practice.