Endothelial function in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors is not related to cardiovascular risk assessed by the Systematic Coronary Risk Estimation 2 algorithm.

Abstract

Tyrosine kinase inhibitors (TKIs) revolutionized treatment of chronic myeloid leukemia (CML), but are endowed with negative effects on endothelial function. We aimed to characterize endothelial function in patients with CML treated with various TKIs. A total of 48 patients diagnosed with chronic‑phase CML treated with TKIs, such as imatinib, bosutinib, nilotinib, ponatinib, and asciminib were included. Endothelial function was assessed in the brachial artery and microcirculation based on flow‑mediated dilation (FMD), reactive hyperemia peripheral arterial tonometry (RH‑PAT) and flow‑mediated skin fluorescence (FMSF). Reactive hyperemia index, FMD, reactive hyperemia response (RHR), normoxia oscillatory index, and hyperemic response index did not differentiate between the group of patients with low / moderate risk in the Systematic Coronary Risk Estimation 2 (SCORE2), SCORE2‑Older Persons (SCORE2‑OP), and those with high / very high risk scores. Among the patients with low / intermediate risk based on the SCORE2 algorithm, some had lower (below the first quartile) values of the endothelial parameters, reflecting impaired endothelial function, as compared with the high / very high risk patient population. Lower values of the endothelial function parameters were associated with overall long‑term treatment with TKIs or ponatinib. Importantly, endothelial function assessed by FMSF (RHR) negatively correlated with total duration of TKI treatment, also after adjustment for age. Endothelial function in CML patients treated with TKIs was not related to cardiovascular risk based on SCORE2/SCORE2‑OP algorithms but correlated with CML‑specific factors, including duration of TKI treatment. FMSF‑based assessment of skin microcirculation was a sensitive method for detecting the vascular effects of TKIs.