Effects of Atorvastatin on Endothelial Function, Lipid Profiles and Inflammatory Markers in Healthy Dogs and Dogs with Congestive Heart Failure
HMG-CoA reductase inhibitors (statins) improve heart failure class and survival in people with congestive heart failure (CHF), independent of cholesterol reduction. Pleiotropic statin effects include antioxidant and anti-inflammatory properties, antiarrhythmic actions, and improvement of endothelial function. Impaired endothelium-dependent flow-mediated vasodilation (FMD) occurs in people with CHF and is a strong predictor of adverse outcome. The goals of this study were to evaluate the tolerability of atorvastatin in healthy dogs and in dogs with CHF, to determine whether dogs with CHF have endothelial dysfunction, and to evaluate the effects of atorvastatin on markers of endothelial function, systemic inflammation, and oxidative stress in dogs with CHF.
In part I of the study, employee-owned dogs that were healthy based on history, physical examination, CBC, biochemistry profile, and urinalysis (n=11) were treated with atorvastatin and reevaluated on days 14 and 30. Testing on each day included an examination and fasting CBC, biochemistry profile, and C-reactive protein (CRP) concentrations. FMD of the brachial artery was assessed in 6 of 11 dogs on days 0, 14 and 30. Ultrasonographic changes in arterial diameter and blood flow velocities were measured at 10, 15, 30, 45 and 60 sec after a 3-minute period of vessel occlusion. In part II of the study, client-owned dogs with ISACHC Class II or IIIa CHF (n=13) were administered atorvastatin at 2 mg/kg q 24 h for 8 weeks. All dogs were assessed on days 0 and 56 of the study via echocardiography, ECG, blood pressure (BP), and owner-completed FETCH questionnaires. CBC, biochemistry profiles, lipid fractionation, concentrations of 8-F2α-isoprostanes, NT-proBNP levels, and CRP were measured at each visit. FMD also was assessed in 5 of 13 dogs on days 0 and 56 of the study. Baseline parameters were compared between control and CHF dogs using Mann-Whitney-U tests, while pre- and post-atorvastatin data were analyzed using Wilcoxon signed ranks tests. At baseline, FMD assessment revealed a trend (p=0.06) towards a blunted change in the brachial artery velocity profile at 15 seconds in CHF dogs compared to healthy dogs. Atorvastatin was well-tolerated in control and CHF dogs and did not result in side effects or significant increases in hepatic transaminases or creatine kinase. Reductions in systolic BP (p=0.04), total serum cholesterol (p=0.01), non-HDL cholesterol (p=0.002) and total leukocytes (p=0.03) were noted in the CHF group after receiving atorvastatin. There were no significant changes in echocardiographic or FMD parameters or in FETCH scores. Healthy dogs also had a reduction in total cholesterol (p=0.01) after atorvastatin administration. Analysis of CRP, isoprostanes and NT-proBNP concentrations is pending. In conclusion, atorvastatin was well-tolerated at this dose in both groups of dogs and further investigation into the effects of statin therapy in dogs with CHF is warranted.