Atorvastatin Effect on Circulating and Leukocyte‐Produced CD40 Ligand Concentrations in People with Normal Cholesterol Levels: A Pilot Study

Study Objectives. To investigate whether atorvastatin decreases serum or leukocyte‐produced CD40 ligand (CD40L) levels and whether these effects are dependent on reduction in low‐density lipoprotein cholesterol (LDL) levels in people without overt dyslipidemia. Design. Prospective pilot study. Setting. University research center. Subjects. Twenty‐five normocholesterolemic volunteers (mean age 32 ± 11 yrs; 15 women, 10 men) without cardiovascular disease. Intervention. After a 2‐week drug‐free run‐in period, subjects received atorvastatin 80 mg/day orally for 16 weeks. Measurements and Main Results. All lipoprotein level measurements were performed with the subject in the fasting state. The CD40L concentrations were measured by immunofluorescence detection in serum and leukocyte culture supernates after 24‐hour incubation, and treatment effect was analyzed. Baseline mean ± SD total cholesterol, LDL, high‐density lipoprotein cholesterol, and triglyceride levels were 179 ± 33, 97 ± 29, 62 ± 20, and 102 ± 69 mg/dl, respectively. Mean changes in each of these levels, respectively, after 16 weeks of atorvastatin were −34%, −59%, +3%, and −23%. The median serum CD40L level was lower at 16 weeks (2.3 ng/ml, interquartile range [IQR] 1.2–5.0 ng/ml) than at baseline (3.0 ng/ml, IQR 2.1–3.7 ng/ml), but the change was not significant (p=0.24). However, atorvastatin significantly lowered CD40L produced from leukocytes by 57% (21 pg/mg of protein [IQR 10–38 pg/mg] vs 49 pg/mg [IQR 21–149 pg/mg], p=0.045). Effects were independent of reduction in cholesterol levels. Conclusion. Although atorvastatin did not significantly lower serum CD40L levels, significant reduction in leukocyte production was seen independent of degree of LDL reduction. These pilot data suggest a potential benefit in normocholesterolemic individuals that should be further investigated, and that leukocyte CD40L concentrations should be considered in the drug response.