Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolemia (ASAP): a prospective, randomised, double-blind trial

Smilde, TJ; Wissen, Sanne van; Awollersheim, H; Trip,; Kastelein, J.J.P.; Stalenhoef, A.F.H.

doi:10.1016/s0140-6736(00)04053-8

Cited by 874 publications

(522 citation statements)

References 26 publications

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“…The many conflicting reports on the use of statins (3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors) to prevent or treat CAVD serve to illustrate this point 14, 15, 16. Although these LDL‐lowering drugs are considered an effective therapy for reducing the incidence or severity of CAD in both FH17, 18 and non‐FH populations,19, 20 randomized, prospective trials have failed to yield evidence that statins are effective at reducing the progression of CAVD 21, 22, 23. Even in individuals with FH, it remains unclear to what extent elevated LDL levels may contribute to initiation or progression of aortic valve disease.…”

Section: Introductionmentioning

confidence: 99%

Development of Aortic Valve Disease in Familial Hypercholesterolemic Swine: Implications for Elucidating Disease Etiology

Porras

Shanmuganayagam

Meudt

et al. 2015

JAHA

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BackgroundFamilial hypercholesterolemia (FH) is a prevalent hereditary disease associated with increased atherosclerosis and calcific aortic valve disease (CAVD). However, in both FH and non‐FH individuals, the role of hypercholesterolemia in the development of CAVD is poorly understood. This study used Rapacz FH (RFH) swine, an established model of human FH, to investigate the role of hypercholesterolemia alone in the initiation and progression of CAVD. The valves of RFH swine have not previously been examined.Methods and ResultsAortic valve leaflets were isolated from wild‐type (0.25‐ and 1‐year‐old) and RFH (0.25‐, 1‐, 2‐, and 3‐year‐old) swine. Adult RFH animals exhibited numerous hallmarks of early CAVD. Significant leaflet thickening was found in adult RFH swine, accompanied by extensive extracellular matrix remodeling, including proteoglycan enrichment, collagen disorganization, and elastin fragmentation. Increased lipid oxidation and infiltration of macrophages were also evident in adult RFH swine. Intracardiac echocardiography revealed mild aortic valve sclerosis in some of the adult RFH animals, but unimpaired valve function. Microarray analysis of valves from adult versus juvenile RFH animals revealed significant upregulation of inflammation‐related genes, as well as several commonalities with atherosclerosis and overlap with human CAVD.ConclusionsAdult RFH swine exhibited several hallmarks of early human CAVD, suggesting potential for these animals to help elucidate CAVD etiology in both FH and non‐FH individuals. The development of advanced atherosclerotic lesions, but only early‐stage CAVD, in RFH swine supports the hypothesis of an initial shared disease process, with additional stimulation necessary for further progression of CAVD.

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Section: Introductionmentioning

confidence: 99%

Development of Aortic Valve Disease in Familial Hypercholesterolemic Swine: Implications for Elucidating Disease Etiology

Porras

Shanmuganayagam

Meudt

et al. 2015

JAHA

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“…Further studies are warranted to confirm these results. p<0.001 Figure 3 p<0.001 Heart rate, bpm 69 (12) 69 (12) 69 (10) 68 (10) …”

Section: Discussionmentioning

confidence: 98%

Long-term treatment with low-dose metoprolol CR/XL is associated with increased plaque echogenicity: The Beta-blocker Cholesterol-lowering Asymptomatic Plaque Study (BCAPS)

et al. 2011

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“…Through a reference check one additional trial was identified 32) . Ultimately, this resulted in 15 CIMT trials for analyses 5, 7-10, 12, 13, 15, 16, 18,19,21,22,30,32) . For each drug used in the CIMT trials, the corresponding event trials were searched, resulting in 15 clinical event trials for lovastatin, pravastatin, fluvastatin, simvastatin, atorvastatin, torcetrapib, rosuvastatin and ezetimibe, as presented in Table 2 [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49] .…”

Section: Search Strategymentioning

confidence: 99%

Mean Common or Mean Maximum Carotid Intima-Media Thickness as Primary Outcome in Lipid-Modifying Intervention Studies

Doğan

Kastelein

Grobbee

et al. 2011

JAT

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Aim: Carotid intima-media thickness (CIMT) measurements are used as a disease outcome in randomized controlled trials that assess the effects of lipid-modifying treatment. It is unclear whether common CIMT or mean maximum CIMT should be used as the primary outcome. We directly compared both measurements using aspects that are of great importance in deciding which is most favorable for use in clinical trials.

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Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolemia (ASAP): a prospective, randomised, double-blind trial

Cited by 874 publications

References 26 publications

Development of Aortic Valve Disease in Familial Hypercholesterolemic Swine: Implications for Elucidating Disease Etiology

Development of Aortic Valve Disease in Familial Hypercholesterolemic Swine: Implications for Elucidating Disease Etiology

Long-term treatment with low-dose metoprolol CR/XL is associated with increased plaque echogenicity: The Beta-blocker Cholesterol-lowering Asymptomatic Plaque Study (BCAPS)

Mean Common or Mean Maximum Carotid Intima-Media Thickness as Primary Outcome in Lipid-Modifying Intervention Studies

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