Influence of atorvastatin therapy on biological markers and cardiovascular risk in patients with chronic lymphocytic leukemia in remission

Abstract

Purpose – to assess the impact of atorvastatin on plasma biomarkers and cardiovascular risk in patients with chronic lymphocytic leukemia in remission. Materials and methods. A total of 157 subjects with chronic lymphocytic leukemia in complete or partial remission were enrolled in the study. Atorvastatin at doses 20 mg/d and 40 mg/d were prescribed for patients with hypercholesterinemia, dyslipidemia and risk factors for coronary artery disease. Blood samples were collected for measurements of biomarkers such as galectin-3, VE-cadherin, VEGF-1, sCD40L, NT-proBNP and interleukin-6 by ELISA method at the time of inclusion into the study and after a 1-year follow-up. Cardiovascular events occurrence was assessed throughout a 3-year follow-up. Results. There were 170 clinical events occurred in 68 patients (43.3 %) within the follow-up, with the following distribution: 12 cardiovascular deaths, 17 life-threatening arrhythmias, 36 cardiac ischemic events, 9 strokes, 38 cases of chronic heart failure decompensation, and 58 hospital admissions for cardiovascular reasons. Patients were divided into two groups depending on the atorvastatin treatment. There were no differences in baseline levels of biomarkers between groups. Significant differences were observed in levels of galectin-3 (8.86 ± 5.62 ng/ml vs 16.74 ± 8.52 ng/ml; P = 0.035), VE-cadherin (0.76 ± 0.64 ng/ml vs 2.19 ± 1.66 ng/ml; P = 0.046) only in the group without atorvastatin treatment in the 1-year follow-up. Significant differences in levels of VEGF-1, IL-6, sCD40L, NT-proBNP were not revealed between groups during observation time. Atorvastatin treatment was associated with decreased cumulative cardiovascular event incidence with early differences in their occurrence between groups during the 3-year follow-up (log-rank test, χ 2 = 11.775, P = 0.001). Event-free survival were better in patients treated with atorvastatin 40 mg/d in comparison to patients treated with atorvastatin 20 mg/d (log-rank test, χ 2 = 6.147, P = 0.013) during the first year of follow-up. Conclusions. Among patients with chronic lymphocytic leukemia in remission, the key biomarkers of angiogenesis such as galectin-3 and VE-cadherin are associated with increased risk of cardiovascular events within 3-year follow up. Atorvastatin prevents an increase in angiogenesis biomarkers and reduces risk of cardiovascular events in this group of patients.