Evaluation of local vascular stiffness in patients with malignant neoplasms receiving immune checkpoint inhibitor therapy

Abstract

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become a key component of immunotherapy for malignant neoplasms; however, their use is associated with the risk of cardiovascular toxicity, presenting a significant challenge.

AIM: The study aimed to evaluate the effect of ICI therapy on local vascular stiffness parameters in patients with malignant neoplasms.

METHODS: This prospective study included 47 patients (27 men and 20 women) with a mean age of 59.5 ± 7.38 years, all of whom had been diagnosed with malignant neoplasms. The specific diagnoses included lung cancer (n = 30), melanoma (n = 6), urothelial carcinoma (n = 5), head and neck tumors (n = 5), and esophageal cancer (n = 1). The patients received therapy with ICIs, including nivolumab (n = 9), pembrolizumab (n = 23), and atezolizumab (n = 15). The control group included 20 individuals (10 men and 10 women) without malignant neoplasms, acute conditions, decompensated chronic non-communicable diseases, or acute or chronic infectious diseases. These individuals underwent evaluation as part of a preventive medical examination and screening. The control group was comparable to the study group in terms of age (59.3±6.52 years), sex distribution, and the prevalence of cardiovascular comorbidities. Ultrasound examination of the brachiocephalic arteries, calculation of local vascular stiffness parameters, and measurement of the ankle-brachial index were performed dynamically (before the initiation of anticancer drug therapy and three months after treatment initiation). The statistical analysis included descriptive statistics, Student’s t-test, the Mann–Whitney test, Fisher’s exact test, and Pearson’s chi-square (χ²) test. A significance level of p = 0.05 was used for all analyses.

RESULTS: An analysis of the structural and functional parameters of the vascular wall in patients undergoing ICI therapy demonstrated the progression of atherosclerotic changes in the carotid arteries. During anticancer therapy, an increase in common carotid artery stenosis was observed (p = 0.05) compared with the control group, along with a trend toward an increased number of visualized atherosclerotic plaques (p = 0.06). A tendency toward a decline in vascular wall distensibility (p = 0.07) was associated with an increase in Peterson’s modulus of elasticity (p = 0.05), Young’s modulus (p = 0.04), stiffness index (p = 0.09), and pulse wave velocity (p = 0.01). A significant decline in the ankle-brachial values index was identified (p = 0.001).

CONCLUSION: ICI therapy is associated with a greater severity of atherosclerotic lesions in the carotid arteries, increased local vascular stiffness, and a decrease in the ankle-brachial index.

Keywords

immune checkpoint inhibitors / malignant neoplasms / local vascular wall stiffness

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Funding

Russian Science FoundationРоссийский научный фонд(24-25-20035)

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