ABSTRACT
Imatinib, which has revolutionized chronic myeloid leukemia (CML) treatment, was suggested to improve lipid profile. Statins, a dyslipidemia drug, were reported to potentiate imatinib's antileukemic effect. However, analysis of imatinib combined with statins is lacking. We have retrospectively analyzed the normalization period of bcr-abl, blood counts, and lipids in 40 CML patients, 19 of which co-treated with statins, during short (<12 months) and prolonged (>12 months) imatinib treatment. Prior statins treatment did not hinder nor sensitized imatinib's anti-leukemic and lipid-lowering effects. CML cells (K562) treated with 1µM imatinib (24-96 h) were further assessed for the expression of central lipid-related genes by real-time PCR. HMGCoAR, LDL-R, and apobec1 expressions were significantly increased while CETP declined after 48-96 h. To conclude, imatinib produces an independent favorable lipid profile, which is not hindered by statins and is partly mediated via transcription regulation of genes involved in the clearance of plasma lipids.
Subject(s)
Antineoplastic Agents/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Protein Kinase Inhibitors/therapeutic use , Antineoplastic Agents/pharmacology , Biomarkers , Cell Line, Tumor , Drug Synergism , Fusion Proteins, bcr-abl/genetics , Gene Expression Regulation, Leukemic/drug effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Imatinib Mesylate/pharmacology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukocyte Count , Lipid Metabolism/drug effects , Lipid Metabolism/genetics , Lipids/blood , Protein Kinase Inhibitors/pharmacology , Transcription, Genetic , Treatment OutcomeABSTRACT
The present study was designed to assess the role of jugular venous distension (JVD) as a predictor of short- and long-term mortality in a "real-life" setting. The independent association between the presence of admission JVD and the 30-day, 1- and 10-year mortality was assessed among 2,212 patients hospitalized with acute heart failure (HF) who were enrolled in the Heart Failure Survey in Israel (2003). Independent predictors of JVD finding in study patients included: the presence of significant hyponatremia (odds ratio [OR] 1.48; p = 0.03), reduced left ventricular ejection fraction ([LVEF] OR 1.24; p = 0.03), anemia (OR 1.3; p = 0.01), New York Heart Association III to IV (OR 1.34; p <0.01) and age >75 years (OR 1.32; p = 0.01). The presence of JVD versus its absence at the time of HF hospitalization was associated with increased 30-day mortality (7.2% vs 4.9%, respectively; p = 0.02), 1-year (33% vs 28%, respectively; p <0.001), and greater 10-year mortality (91.8% vs 87.2%, respectively; p <0.001). Consistently, interaction term analysis demonstrated that the presence of JVD at the time of the index HF hospitalization was independently associated with a significant increased risk for 10-year mortality, with a more pronounced effect among younger patients, patients with reduced LVEF, preserved renal function, and chronic HF. In conclusion, in patients admitted with HF, JVD is associated with specific risk factors and is independently associated with increased risk of both short- and long-term mortality. These findings can be used for improved risk assessment and management of this high-risk population.
