Purpose. When administered separately, statin treatment and exercise training have anti-inflammatory effects. The purpose of this study was to determine the effect of combined rosuvastatin treatment and exercise training on markers/mediators of inflammation and lipid profile. Methods. 33 hypercholesterolemic and physically inactive subjects were randomly assigned to rosuvastatin (R; 8F, 9M) and rosuvastatin/exercise (RE; 9F, 7M) groups. A third group of physically active hypercholesterolemic subjects served as a control (AC; 9F, 7M). R and RE groups received rosuvastatin treatment (10 mg/d) for 20 weeks. The RE group completed 10-weeks of combined endurance (20 min @ 60-70% est. heart rate reserve) and resistive exercise training (80% 1 repetition maximum (RM)) from week 10 to week 20, while the R group remained sedentary. The AC group received no treatment and maintained habitual physical activity. Subjects consumed a prescribed diet 24 h prior to blood sampling and arrived at the laboratory (0600-0700 h) following an 8 h fast and three days of inactivity. Resting blood samples were obtained, and lipid profile and inflammatory mediators determined for all subjects, at week 0 (Pre), week 10 (Mid-prior to exercise training), and week 20 (Post-upon completion of exercise training program). Blood levels of creatine kinase (CK), and the liver enzyme alanine aminotransferase (ALT), were measured at two stages during the experimental trial; (1) at week 0 (Pre), after 5 and 10 weeks following the start of rosuvastatin treatment (R and RE groups), and (2) 48 hours after the 1 st and 5 th exercise bout (RE group only). Results. The RE group improved aerobic fitness (VO 2max : 29±6%). Strength measures also increased significantly for all exercises (8 RM Range: 30±4 - 57±10%; 1 RM Range: 16±3 - 20±17%). For example, 8 RM for the leg press increased by 47.6 kg in the RE group after the exercise training program. Total and low-density lipoprotein (LDL) cholesterol were lower in the RE and R groups at Mid and Post time points when compared to Pre (p < 0.05). Oxidized LDL (OxLDL) was lower in the R and RE groups at the Mid (R; 56±5 U/L, RE; 52±4 U/L) and Post (R; 63±6 U/L, RE; 48±2 U/L) time points, compared to Pre (R; 89±5 U/L, RE 83±4 U/L) (p<0.05). Also, at the Post time point, RE had lower oxLDL than R (48±2 U/L vs. 63±6 U/L, p<0.05). When groups were collapsed, high-density lipoprotein (HDL) was increased across time (p < 0.05). CK was significantly increased in the RE group 48 hours following the 1 st exercise bout (p < 0.05), and returned to baseline levels 48 hours after the 5 th exercise bout. There were no significant changes in ALT. Toll-like receptor (TLR) 4 expression on CD14+ monocytes was higher in the R group at the Post time point, compared to Pre (1.74±0.09 vs. 1.51±0.03 mean fluorescent intensity (MFI), p<0.05). The percentage of inflammatory monocytes was significantly lower in the RE group at the Post time point, compared to Pre (2.4±0.45% vs. 3.7±0.5%, p<0.05). There were no significant changes in C-reactive protein (CRP), sCD14, or lipopolysaccharide binding protein (LBP). Conclusion. Rosuvastatin treatment decreased oxLDL and increased monocyte TLR4 expression. The addition of an exercise training program resulted in a decrease in inflammatory monocyte percentage and oxLDL, suggesting an additive anti-inflammatory benefit. There was no abnormal sustained increase in CK or ALT suggesting that a combination of rosuvastatin and exercise training did not negatively influence muscle or liver health.
