Association of Angiotensin-Converting Enzyme With Low-Density Lipoprotein in Aortic Valvular Lesions and in Human Plasma

O’Brien, Kevin D.; Shavelle, David M.; Caulfield, Michael T.; McDonald, Thomas O.; Olin-Lewis, Katherine; Otto, Catherine M; Probstfield, Jeffrey L.

doi:10.1161/01.cir.0000035655.45453.d2

Cited by 272 publications

(207 citation statements)

References 35 publications

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“…Lipoproteins and inflammatory cells, such as macrophages and T cells,42 have been identified in early AV lesions,43 and inflammatory activity, visualized by positron emission tomography imaging, has been documented in patients with even mild stenosis 44. This lipid deposition has also been associated with increased angiotensin‐converting enzyme activity in the valve, with profibrotic effects 45. Furthermore, valvular interstitial cells can exhibit osteoblast‐like activity, thus leading to calcific deposition and valvular calcification over time 46.…”

Section: Discussionmentioning

confidence: 99%

Ideal Cardiovascular Health and the Prevalence and Severity of Aortic Stenosis in Elderly Patients

Sengeløv

Cheng

Biering‐Sørensen

et al. 2018

JAHA

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BackgroundThe relationship between ideal cardiovascular health reflected in the cardiovascular health score (CVHS) and valvular heart disease is not known. The purpose of this study was to determine the association of CVHS attainment through midlife to late life with aortic stenosis prevalence and severity in late life.Methods and ResultsThe following 6 ideal cardiovascular health metrics were assessed in ARIC (Atherosclerosis Risk in Communities) Study participants at 5 examination visits between 1987 and 2013 (visits 1–4 in 1987–1998 and visit 5 in 2011–2013): smoking, body mass index, total cholesterol, blood pressure, physical activity, and blood glucose. Percentage attained CVHS was calculated in 6034 participants as the sum of CVHS at each visit/the maximum possible score. Aortic stenosis was assessed by echocardiography at visit 5 on the basis of the peak aortic valve velocity. Aortic stenosis was categorized sclerosis, mild stenosis, and moderate‐to‐severe stenosis. Mean age was 76±5 years, 42% were men, and 22% were black. Mean percentage attained CVHS was 63±14%, and the prevalence of aortic stenosis stages were 15.9% for sclerosis, 4.3% for mild stenosis, and 0.7% for moderate‐to‐severe stenosis. Worse percentage attained CVHS was associated with higher prevalence of aortic sclerosis (P<0.001 for trend), mild stenosis (P<0.001), and moderate‐to‐severe stenosis (P=0.002), adjusting for age, sex, and race.ConclusionsGreater attainment of ideal cardiovascular health in midlife to late life is associated with a lower prevalence of aortic sclerosis and stenosis in late life in a large cohort of older adults.

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Section: Discussionmentioning

confidence: 99%

Ideal Cardiovascular Health and the Prevalence and Severity of Aortic Stenosis in Elderly Patients

Sengeløv

Cheng

Biering‐Sørensen

et al. 2018

JAHA

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“…Previous studies showed that ACE and angiotensin II type 1 receptor were upregulated when angiotensin II was expressed in the calcified human aortic valve compared with the normal valve. 21,22 An experimental study showed that in hypercholesterolemic rabbits, ARBs prevented lesion formation in the aortic valve, specifically preventing the accumulation of macrophages, myofibroblasts and osteoblasts, upregulation of osteopontin and ACE, and disruption of endothelial integrity. 23 Findings from these earlier studies and this study suggest that ARBs prevent progression of CAVD during the early stage.…”

Section: Prognostic Factors For Progression Of Early-stage Cavdmentioning

confidence: 99%

Prognostic factors for progression of early- and late-stage calcific aortic valve disease in Japanese: The Japanese Aortic Stenosis Study (JASS) Retrospective Analysis

Yamamoto

Yoshida

et al. 2010

Hypertens Res

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Calcific aortic valve disease (CAVD) is the most common etiology of acquired valvular heart disease, and hypertension is a principal underlying disease. The Japanese Aortic Stenosis Study (JASS) Retrospective Analysis is a retrospective observational study to clarify the prognostic factors for progression of CAVD in Japanese. Data from 556 subjects who met the following criteria were analyzed: (1) X50 years old; (2) calcification in any aortic valve leaflet or peak aortic jet velocity X2 m s À1 on an echocardiographic study performed between July 2004 and June 2007; and (3) availability of earlier echocardiographic data from within the previous 2-5 years to assess the progression of CAVD. The subjects were divided into two groups according to CAVD severity on the preceding echocardiographic examination. In early-stage subjects with calcification in one or zero leaflets who were without aortic stenosis on the preceding echocardiographic study (n¼157), the prognostic factors for progression were the following: (1) no use of angiotensin receptor blockers (ARB) and (2) use of warfarin. In late-stage subjects with calcification in two or three leaflets and/or aortic stenosis on the preceding echocardiographic study (n¼399), progression was observed in females and in subjects with low hemoglobin and a concentric left ventricle. There was no relation between medications and changes in CAVD. Prognostic factors for the progression of CAVD were different between the early and late stages. Initiation of ARB treatment during the early stage may be effective, and we should be vigilant about progression of CAVD in patients treated with warfarin.

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“…59,60 A subset of aortic valve lesion macrophages express ACE. 19,20 Surprisingly, a large proportion of valve lesion ACE colocalizes with LDL in the extracellular matrix. 19 Ang II also is localized to these regions, suggesting that the LDL-associated ACE is enzymatically active.…”

mentioning

confidence: 99%

Pathogenesis of Calcific Aortic Valve Disease

O’Brien

2006

ATVB

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254

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Background-Over the past 10 to 15 years, calcific aortic valve disease, which includes aortic sclerosis and aortic stenosis, has come to be recognized as an active process, based on: (1) epidemiologic studies demonstrating associations of specific risk factors with increased prevalence or rate of progression of aortic valve disease; (2) identification, in valve lesions, of histopathologic features of chronic inflammation, lipoprotein deposition, renin-angiotensin system components, and molecular mediators of calcification; and (3) identification of cell-signaling pathways and genetic factors that may participate in valve disease pathogenesis. These studies will be reviewed and organized into a proposed global hypothesis for the pathogenesis of calcific aortic valve disease. Key Words: aortic valve disease Ⅲ calcification Ⅲ lipoproteins Ⅲ matrix Ⅲ angiotensin II C alcific aortic valve disease is identified by thickening and calcification of the aortic valve leaflets in the absence of rheumatic heart disease. It is divided, on a functional basis, into aortic sclerosis, in which the leaflets do not obstruct left ventricular outflow, and aortic stenosis, in which obstruction to left ventricular outflow is present. Aortic sclerosis is present in more than 25% of patients over age 65 1 and is associated with a 50% increase risk of cardiovascular events. 2 Aortic stenosis is present in 2% to 5% of very elderly patients, 1,3 is the second most common indication for cardiac surgery, 4 and carries an 80% 5-year risk of progression to heart failure, valve replacement, or death. 5 Though the disease is associated with substantial clinical consequences, there currently is no effective therapy for the disease other than surgical aortic valve replacement.The lack of medical therapies for calcific aortic valve disease can be traced to at least two important issues, one intellectual, the other practical. The first was the long-held notion that calcific aortic valve disease was a "degenerative," and therefore unmodifiable, condition. 6 However, more recent studies have demonstrated convincingly that calcific aortic valve lesions have many features characteristic of an active pathobiological process, including chronic inflammation, 7-9 lipoprotein deposition, 10 -12 active calcification, [13][14][15][16][17][18] and renin-angiotensin system activation. 19,20 These features are present in both trileaflet and bileaflet aortic valve lesions. 21 Also, an emerging body of literature is investigating how genetic factors might influence disease development. [22][23][24][25] The second issue is that, for many years, there were no animal models that faithfully replicated the key histological features of the disease. Recently, rabbit models been developed, 16,26,27 with that of Rajamannan and colleagues already providing a number of novel insights. 16 -18,28,29 In particular, these models have implicated the Wnt 18 and Runx2/ Cbfa1 16,17,27 signaling pathways in disease pathogenesis. Only very recently has a purported mouse model of calcif...

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Association of Angiotensin-Converting Enzyme With Low-Density Lipoprotein in Aortic Valvular Lesions and in Human Plasma

Cited by 272 publications

References 35 publications

Ideal Cardiovascular Health and the Prevalence and Severity of Aortic Stenosis in Elderly Patients

Ideal Cardiovascular Health and the Prevalence and Severity of Aortic Stenosis in Elderly Patients

Prognostic factors for progression of early- and late-stage calcific aortic valve disease in Japanese: The Japanese Aortic Stenosis Study (JASS) Retrospective Analysis

Pathogenesis of Calcific Aortic Valve Disease

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