Lipid Lowering in Aortic Stenosis

Helske, Satu; Otto, Catherine M

doi:10.1161/circulationaha.109.864421

Cited by 27 publications

(3 citation statements)

References 16 publications

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“…Thus, the presumption that plasma lipid-lowering therapy is of significant therapeutic value in the prevention and treatment of AS [72], [73] has suffered severely, as the results of clinical studies involving plasma lipid-lowering therapy have been uniformly unsuccessful in slowing AS progression [5], [6]. The results of the present study involving severely stenotic aortic valves indicate that plasma lipoprotein particles have accumulated and become extensively modified in the extracellular space of the diseased valves.…”

Section: Discussionmentioning

confidence: 65%

Modified Lipoprotein-Derived Lipid Particles Accumulate in Human Stenotic Aortic Valves

et al. 2013

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In aortic stenosis plasma lipoprotein-derived lipids accumulate in aortic valves. Here, we first compared the lipid compositions of stenotic aortic valves and atherosclerotic plaque cores. Both pathological tissues were found to be enriched in cholesteryl linoleate, a marker of extracellularly accumulated lipoproteins. In addition, a large proportion of the phospholipids were found to contain arachidonic acid, the common precursor of a number of proinflammatory lipid mediators. Next, we isolated and characterized extracellular lipid particles from human stenotic and non-stenotic control valves, and compared them to plasma lipoproteins from the same subjects. The extracellular valvular lipid particles were isolated from 15 stenotic and 14 non-stenotic aortic valves. Significantly more apoB-100-containing lipid particles were found in the stenotic than in the non-stenotic valves. The majority of the lipid particles isolated from the non-stenotic valves had sizes (23±6.2 nm in diameter) similar to those of plasma low density lipoprotein (LDL) (22±1.5 nm), while the lipid particles from stenotic valves were not of uniform size, their sizes ranging from 18 to more than 500 nm. The lipid particles showed signs of oxidative modifications, and when compared to isolated plasma LDL particles, the lipid particles isolated from the stenotic valves had a higher sphingomyelin/phosphatidylcholine –ratio, and also higher contents of lysophosphatidylcholine and unesterified cholesterol. The findings of the present study reveal, for the first time, that in stenotic human aortic valves, infiltrated plasma lipoproteins have undergone oxidative and lipolytic modifications, and become fused and aggregated. The generated large lipid particles may contribute to the pathogenesis of human aortic stenosis.

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Section: Discussionmentioning

confidence: 65%

Modified Lipoprotein-Derived Lipid Particles Accumulate in Human Stenotic Aortic Valves

et al. 2013

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“…However, defining aortic sclerosis has remained challenging due to the variable and qualitative nature of its description by echocardiographic evaluation. The prevalence of AVSc has been estimated at 25%–30% in patients > 65 years of age, and up to 40% in those > 75 years of age [9,10]. The presence of AVSc has been associated with a higher risk of cardiovascular events, including increased mortality.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Osteopontin Levels for the Identification of Asymptomatic Patients With Calcific Aortic Valve Disease

Grau

Poggio

Sainger

et al. 2012

The Annals of Thoracic Surgery

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Background Calcific Aortic Valve Disease (CAVD) is the most common etiology of acquired valve disease. Initial phases of CAVD include thickening of the cusps, whereas advanced stages are associated with biomineralization and reduction of the aortic valve area. These conditions are known as Aortic Valve Sclerosis (AVSc) and Aortic Valve Stenosis (AVS), respectively. Due to its asymptomatic presentation, little is know about the molecular determinants of AVSc. The aim of this study is to correlate plasma and tissue Osteopontin (OPN) levels with echocardiographic evaluation for the identification of asymptomatic patients at risk of CAVD. In addition, we aim to analyze the differential expression and biological function of OPN splicing variants as biomarkers of early and late stages of CAVD. Methods From Jan 2010 to Feb 2011, 254 patients were enrolled in the study. Subjects were divided in three groups based on transesophageal echocardiographic (TEE) evaluation: Controls (56 subjects), AVSc (90), and AVS (164). Plasma and tissue OPN levels were measured by IHC, ELISA and qPCR. Results Patients with AVSc have and AVS higher OPN levels compared to controls. OPN levels are elevated in asymptomatic AVSc patients with no appearance of calcification during TEE evaluation. Osteopontin splicing variants -a, -b, and -c are differentially expressed during CAVD progression and are able to inhibit biomineralization in a cell-based biomineralization assay. Conclusions The analysis of the differential expression of OPN splicing variants during CAVD may help in developing diagnostic and risk stratification tools to follow the progression of asymptomatic AV degeneration.

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“…Human trials studying the effect of lipid-lowering therapy on progression of aortic stenosis have failed to show clear effect. 48 49 50 51 There are no guidelines directing the use of lipid-lowering medications in aortic stenosis, but it is likely reasonable to consider in patients with coexisting risk factors for coronary artery disease. Hypertension should be treated as higher afterload has been associated with worse prognosis and the risk of syncope is low.…”

Section: Management Of Aortic Valvular Disease In the Elderlymentioning

confidence: 99%

Diagnosis and Management of Aortic Valvular Disease in the Elderly

2022

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Aortic valvular disease, including aortic stenosis and aortic regurgitation, is increasingly common with age. Due to the aging population, more elderly patients are presenting with aortic valve pathology and expectations for prompt diagnosis and efficacious treatment. The current paradigm for aortic valve disease is based on surgical or interventional therapy. In this review, we discuss the approach to diagnosing aortic valvular disease and the different options for treatment based on the most recent evidence.

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Lipid Lowering in Aortic Stenosis

Cited by 27 publications

References 16 publications

Modified Lipoprotein-Derived Lipid Particles Accumulate in Human Stenotic Aortic Valves

Modified Lipoprotein-Derived Lipid Particles Accumulate in Human Stenotic Aortic Valves

Analysis of Osteopontin Levels for the Identification of Asymptomatic Patients With Calcific Aortic Valve Disease

Diagnosis and Management of Aortic Valvular Disease in the Elderly

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