Serum interleukin-6, cardiovascular disease, and mortality in chronic lymphocytic leukemia.

Abstract

6581 Background: Interleukin-6 (IL-6) plays an integral role in the process of aging and autoimmunity and contributes to the increased incidence of cardiovascular disease. IL-6 levels may be elevated in chronic lymphocytic leukemia (CLL) but whether these patients also have an increased incidence of cardiovascular disease leading to mortality is unknown. Methods: 193 patients (107 males, 86 females; ages, 37-92 yr (median, 67.6 yr) with CLL attending CancerCare Manitoba between 1/1/04 and 30/12/08 were evaluated. There were an equal number of patients aged < 65 yrs and ≥ 65 yrs. Serum IL-6 levels were determined by an ELISA assay. Cardiovascular disease was defined as any symptom referable to the cardiac, neurovascular or peripheral vascular system and/or vascular procedures. Results: Plasma IL-6 levels ranged from < 0.01 to 93.1 pg/mL (median, 1.43 pg/mL). The median plasma IL-6 level in 37 age- and sex-matched controls was 0.83 pg/mL (range, 0.06-8.11 pg/mL). Using a cut-off of 3 pg/mL to define an elevated IL-6 level, high IL-6 levels occurred in 23% of patients and levels correlated with Rai stage, β2-microglobulin and age. The median number of traditional cardiac risk factors did not differ between patients with high and low IL-6 (1.66 ± 1.1 vs. 1.52 ± 1.1, respectively). Patients with cardiovascular disease had increased IL-6 (p < 0.05) and there was a trend to a higher incidence of cardiovascular disease in patients with high IL-6 (36.4% vs. 22.8%, p = 0.07). In addition, patients with high IL-6 had considerably increased mortality as 31.8% of patients with high IL-6 died versus 12.8% for patients with low IL-6 (p = 0.003). This mortality difference was amplified in those ≥ 65 years old (42.8% vs. 10.4%, p = 0.0003). The major causes of death were progressive CLL, second malignancies, and infections. Conclusions: Thus, high levels of IL-6 in CLL are associated with a significantly increased risk of mortality and this is most evident in those ≥65 years old. Although cardiovascular disease is not the primary cause of death, it is associated with high levels of IL-6 and may contribute to progression of CLL. No significant financial relationships to disclose.