What does this research mean for the field?

Cholesterol-lowering treatment with simvastatin and ezetimibe prevents heart valve inflammation and cholesterol infiltration only when initiated concurrently with a high-cholesterol diet, but is ineffective once lipid infiltration into the valve matrix has already occurred. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

August 1, 2020Open HeartOpen Access

Cholesterol induced heart valve inflammation and injury: efficacy of cholesterol lowering treatment

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Why the study?

Heart valves often undergo degeneration requiring replacement, sharing pathology with atherosclerosis; this study aimed to elucidate the role of inflammation triggered by cholesterol infiltration and crystal formation in heart valve injury.

Does treatment with simvastatin and ezetimibe prevent or reduce cholesterol-induced heart valve inflammation and injury in a rabbit model?

Structured PICO

Does treatment with simvastatin and ezetimibe prevent or reduce cholesterol-induced heart valve inflammation and injury in a rabbit model?

Population

Human diseased heart valves and New Zealand White male rabbits fed an enriched cholesterol diet

Intervention

Simvastatin and ezetimibe administered simultaneously with or 6 months after initiating a high-cholesterol diet

Comparator

Enriched cholesterol diet alone

Outcome

Valve inflammation (measured by C-reactive protein and RAM 11 tissue macrophage content) and cholesterol crystal presence/contentsurrogate

Early initiation of lipid-lowering therapy with simvastatin and ezetimibe prevents cholesterol infiltration and inflammation in heart valves in a rabbit model, but is ineffective once infiltration has already occurred.

Implication

Early combined therapy may limit experimental valve inflammation; leaves open human translation and optimal timing.

Abstract

BACKGROUND: Heart valves often undergo a degenerative process leading to mechanical dysfunction that requires valve replacement. This process has been compared with atherosclerosis because of shared pathology and risk factors. In this study, we aimed to elucidate the role of inflammation triggered by cholesterol infiltration and cholesterol crystals formation causing mechanical and biochemical injury in heart valves. METHODS: Human and atherosclerotic rabbit heart valves were evaluated. New Zealand White male rabbits were fed an enriched cholesterol diet alone or with simvastatin and ezetimibe simultaneous or after 6 months of initiating cholesterol diet. Inflammation was measured using C-reactive protein (CRP) and RAM 11 of tissue macrophage content. Cholesterol crystal presence and content in valves was evaluated using scanning electron microscopy. RESULTS: Cholesterol diet alone induced cholesterol infiltration of valves with associated increased inflammation. Tissue cholesterol, CRP levels and RAM 11 were significantly lower in simvastatin and ezetimibe rabbit groups compared with cholesterol diet alone. However, the treatment was effective only when initiated with a cholesterol diet but not after lipid infiltration in valves. Aortic valve cholesterol content was significantly greater than all other cardiac valves. Extensive amounts of cholesterol crystals were noted in rabbit valves on cholesterol diet and in diseased human valves. CONCLUSIONS: Prevention of valve infiltration with cholesterol and reduced inflammation by simvastatin and ezetimibe was effective only when given during the initiation of high cholesterol diet but was not effective when given following infiltration of cholesterol into the valve matrix.