Atherosclerosis Risk Factors in Chronic Myeloid Leukemia Patients Under Durable Tyrosine Kinase Inhibitors Therapy

Intro:

Atherosclerotic cardiovascular diseases (aCVD) are widespread in the general population. Russia is among the countries with a very high risk of cardiovascular events. The aim of the retrospective study is to evaluate risk factors for aCVD in CML patients and in matched general population.

Materials and methods:

Overall 138 patients (men - n= 66; 48%) with chronic phase CML (CML-group) ≥18 years old, with history of at least one TKI therapy for ≥ 6 months were included to the study; the control group consisted of 1592 (men - n=567, 36%) conditionally healthy population - residents of St. Petersburg (Russia) ≥18 years old from epidemiological study ESSE-RF (Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation). Each CML patient was matched by gender, age, body mass index (fluctuations within +/-3) and the fact of major vascular events (angina pectoris, myocardial infarction, stroke) or diabetes mellitus) to 2 healthy control. All patients and healthy control underwent laboratory tests - level of C-reactive protein (CRP), fasting blood glucose (GLUC), total cholesterol (CHOL); instrumental studies - thickness of the intima-media complex (IMT), arterial wall stiffness index (CAVI) and brachial-ankle index (ABI).

Results:

In total, 120 and 240 cases were selected from the CML-group and control-group. Median age in both groups was 42.1+/-1.2 years. An average duration TKI therapy in CML-group at the time of inclusion in the study was 88 months. Patients were treated with only imatinib (n=28; 23%), nilotinib (n=5; 4%), dasatinib (n=2; 2%) or bosutinib (n=3; 2.5%). Other patients (n=82) patients received therapy with several (2-5) TKIs in various combinations, while the last TKI was: nilotinib (n=30), dasatinib (n=43); bosutinib (n=12) and ponatinib (n=7) cases with average time of treatment, respectively, 39 months, 28 months, 24 months and 2 months. In CML group 51 patients ever obtained nilotinib. Matched corresponding population was selected in the control group (n=102) for this NILO-group and analyzed separately due to the known risk for aCVD. Significantly higher median level of CRP and fasting glucose was detected in CML-group, as well as in NILO-group versus control-group (p<0,05), while the median level of total cholesterol was higher in control-group than in CML-group (p<0,05), but was equal to NILO-group (p=0.116). The median right- and left-side IMT was 0.74 mm versus 0.69 and 0.75 mm versus 0.7 mm in CML-group versus in control group, respectively (p = 0.038 and 0.116, respectively). The median IMT was significantly higher in NILO-group than in matched control-group: on the right side 0.8 mm versus 0.69 and on the left-side 0.82 mm versus 0.71 mm (p = 0.002 and 0.005, respectively). Median right-side and left-side CAVI 6.9 versus 7.4 and 7.0 versus 7.5, respectively, in CML group versus in control group (p = 0.002 and 0.009, respectively). Elevated CAVI >8 on at least one side was observed in 10 (8.3%) patients in CML group and in 44 (18%) cases among control-group; CAVI index on both sides was lower also in NILO-group than in control population (p<0.05). The median ABI on both sides was higher in whole CML-group and in NILO-group than in matched control-group (p<0.05).

Conclusions:

Patients with CML, including NILO-group, had more significant changes in markers of preclinical atherosclerosis (increased IMT, decreased ABI), higher levels of glycemia and markers of inflammation compared with matched control group. It is interesting that CAVI index and total cholesterol level was higher in matched population. We continue to analyze the impact of these metabolic and instrumental changes on the long-term cardiovascular safety in CML-group.

Shnalieva:Novartis: Consultancy; Biocad: Consultancy. Osipov:Biocad: Honoraria, Speakers Bureau; Astellas: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; GSK: Speakers Bureau; Dr.Reddy'S: Speakers Bureau; MSD: Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Lomaia:Novartis: Other: Travel, accommodation, and expenses, Speakers Bureau; Fusion Pharma: Speakers Bureau; Pfizer: Other: Travel, accommodation, and expenses, Speakers Bureau.