Atorvastatin improves cardiac function and remodeling in chronic non-ischemic heart failure: A clinical and pre-clinical study

Abstract

Abstract Aims The aim was to evaluate the cardio-protective effect of atorvastatin in combination with standard chronic heart failure (CHF) therapy that might improve cardiac function, remodeling, and further delay the progression of CHF in patients and rats. Methods and results CHF patients ( n = 20 per group) with left ventricular ejection fraction (LV-EF) n = 10 per group) received treatment for 4 weeks and were divided as follows: saline treated (control, 1 ml intraperitoneal, IP), doxorubicin treated (2.5 mg/kg, IP), atorvastatin–doxorubicin treated (10 mg/kg, orally), and digoxin–doxorubicin treated (0.02 mg/kg, orally). The same laboratory analysis including histopathology of heart tissues was performed on the rats. In patients, atorvastatin improved heart function (increased LV-EF%, LV-fraction shorting (LV-FS%), and E/A velocity ratio; decreased LV-end diastolic diameter (LV-EDD) and LV-end systolic diameter (LV-ESD)) and significantly reduced serum lipid profiles, cTnT, hs-CRP and MDA versus patient controls. In rats, atorvastatin improved signs of CHF, systolic blood pressure, reduced serum lipid profiles, cTnT, hs-CRP and tissue MDA; less cardiac necrosis and fibrosis with enhancement of neo-vascularization versus other doxorubicin-treated rats. Conclusions Atorvastatin with standard CHF therapy improved cardiac function and remodeling. Cardio-protective “pleiotropic” actions of atorvastatin are anti-inflammatory, anti-fibrotic and anti-oxidative. Thus, atorvastatin has a potential therapeutic value in the management of CHF patients.