Rosuvastatin added to standard heart failure therapy improves cardiac remodelling in heart failure rats with preserved ejection fraction

Abstract

AimsAlthough statins may provide potential therapeutic pathways for patients with heart failure with preserved ejection fraction (HFpEF), no studies have evaluated statins in combination with standard HF therapy, which would reflect clinical practice more closely. To address this question, we evaluated whether rosuvastatin added to a standard HF therapy provides additional improvement in cardiac structure and function in rats with hypertensive heart failure (SHHF). Methods and resultsTwo-month-old SHHF rats were randomly assigned to four groups: (i) non-treated SHHF rats; (ii) rosuvastatintreated SHHF rats; (iii) SHHF rats treated with quinapril plus torasemide plus carvedilol (considered as standard HF therapy); and (iv) SHHF rats treated with the combination of standard HF therapy and rosuvastatin. The administration of a standard anti-hypertensive HF therapy to SHHF rats for 17 months attenuated left ventricular (LV) chamber dilatation, cardiac hypertrophy, fibrosis, and inflammation compared with non-treated SHHF rats. Rosuvastatin alone prevented LV dilatation and cardiac inflammation similar to standard HF therapy-treated SHHF, despite being unable to normalize blood pressure (BP) or influence cardiac hypertrophy. However, and importantly, the addition of rosuvastatin to the standard HF therapy further prevented LV dilatation, preserved cardiac function, and normalized inflammation. ConclusionThese data show that the use of rosuvastatin plus a standard HF therapy results in a significant additional improvement in HF and cardiac remodelling in a rat model of HFpEF. These beneficial effects were independent of BP and plasma lipid changes, and seem to be due, at least in part, to decreased myocardial inflammation.--

Beneficial Effects of Rosuvastatin in Heart of C57Bl/6 Mice with Diet- Induced Metabolic Syndrome - A Preliminary Study

“…Consistent with our results, treatment with different classes of statins show beneficial effects in cardiac remodeling [32][33][34].…”

Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of ≥50%

“…This results in cardiomyocyte hypertrophy and interstitial fibrosis, leading to increased stiffness of the myocardium, as well as increased resting tension, which is indeed seen in patients with HFPEF. 22,32,33 There was no interaction between statin use and IHD or diabetes mellitus. This is consistent with the theory that HFPEF may represent a systemic proinflammatory state independent of these risk factors, 22 that is, in our patients, statins may have reduced this inflammation rather than having an effect on atherosclerosis or macrovascular disease per se.…”

Eplerenone enhances cardioprotective effects of standard heart failure therapy through matricellular proteins in hypertensive heart failure

“…More importantly, patients with hypertensive heart failure usually present impaired diastolic function, with only symptoms of diastolic heart failure, despite relative preserved left ventricular systolic function, although it can progress to combined diastolic and systolic heart failure [5,6]. Similar alterations are also seen in the spontaneously hypertensive heart failure (SHHF) rat, a genetic rat model that exhibits numerous pathologic, morphologic, and biochemical changes that parallel documented changes in patients with hypertension [7]. Accordingly, the first objective of this study was to investigate the effect of adding eplerenone to a standard pharmacological heart failure therapy (ACE inhibitor and diuretic and b-blocker) in the progression of heart failure over time using echocardiography in SHHF and normotensive rats.…”