Autoantibodies and immune complexes to oxidation-specific epitopes and progression of aortic stenosis: Results from the ASTRONOMER trial

Capoulade, Romain; Chan, Kwan L.; Mathieu, Patrick; Bossé, Yohan; Dumesnil, Jean G.; Tam, James W.; Teo, Koon; Yang, Xiaohong; Witztum, Joseph L.; Arsenault, Benoît J.; Després, Jean‐Pierre; Tsimikas, Sotirios

doi:10.1016/j.atherosclerosis.2017.03.013

Cited by 6 publications

(3 citation statements)

References 34 publications

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“…In addition, in our study, we did not exclude patients with CHD, diabetes mellitus, and heart failure as the authors did in the ASTRONOMER sub-study. Similar to our study, patients with more progression of aortic valve stenosis were older than those with less progression [ 27 ]. A 15-year prospective study showed that a higher level of IgM autoAbs against MDA-LDL is associated with a lower risk of acute coronary syndrome and newly registered CVD [ 28 ].…”

Section: Discussionsupporting

confidence: 89%

“…In a subanalysis of the ASTRONOMER study, which included 220 patients with mild to severe aortic valve stenosis, there was no difference in the rate of progression of aortic valve stenosis depending on the tertile levels of IgG and IgM autoantibodies to LDL modified with MDA-LDL and apoB-IC. However, risk analysis of rapid progression of aortic valve stenosis showed a trend for higher IgG against to ApoB-IC levels and the lowest tertile of IgM against to MDA-LDL [ 27 ]. Thus, an increase in IgM levels has a protective effect, reducing the likelihood of aortic valve stenosis and its progression.…”

Section: Discussionmentioning

confidence: 99%

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Lipoprotein(a) and Its Autoantibodies in Association with Calcific Aortic Valve Stenosis

et al. 2023

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Aortic valve stenosis is the most common valvular heart disease in the Western world. Lipoprotein(a) (Lp(a)) is an independent risk factor of coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). The aim of this study was to assess the role of Lp(a) and its autoantibodies [autoAbs] in CAVS in patients with and without CHD. We included 250 patients (mean age 69 ± 3 years, males 42%) and divided them into three groups. There were two groups of patients with CAVS depending on the presence (group 1) or absence of CHD (group 2). The control group included the patients without CHD or CAVS. According to logistic regression analysis, levels of Lp(a), IgM autoAbs to oxidized Lp(a) (oxLp(a)), and age were independent predictors of CAVS. A concomitant increase in Lp(a) level (≥30 mg/dL) and a decrease in IgM autoAbs concentration (<9.9 lab. Units) are associated with CAVS with an odds ratio (OR) of 6.4, p < 0.01, and with CAVS and CHD with an OR of 17.3, p < 0.001. IgM autoantibodies to oxLp(a) are associated with calcific aortic valve stenosis regardless of Lp(a) concentration and other risk factors. Higher Lp(a) and lower IgM autoantibodies to oxLp(a) levels are associated with a much higher risk of calcific aortic valve stenosis.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Lipoprotein(a) and Its Autoantibodies in Association with Calcific Aortic Valve Stenosis

et al. 2023

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“…In addition, a recent study showed an effect of Lp(a) in the induction of calcification in vitro on HAVICs and an abnormal accumulation of apolipoproteins and phospholipids in diseased valves [ 30 ]. Given all this evidence on oxidized lipids and AS, the recent sub-study of the ASTRONOMER randomized clinical trial failed to find an association between autoantibody titers (which is an indirect measurement oxidation-specific epitopes) and progression of aortic stenosis or the need for AVR [ 31 ]. Another very recent study on CAVS samples revealed elevated Lp(a) and OxPL levels thanks to 18F-sodium fluoride positron emission tomography/computed tomography and, above all, found aortic valve microcalcification before the development of clinical manifestation of the pathology [ 32 ].…”

Section: Aortic Stenosis Pathobiology a Molecular Perspectivementioning

confidence: 99%

Aortic Valve Stenosis and Mitochondrial Dysfunctions: Clinical and Molecular Perspectives

Pedriali

Morciano

Patergnani

et al. 2020

IJMS

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Calcific aortic stenosis is a disorder that impacts the physiology of heart valves. Fibrocalcific events progress in conjunction with thickening of the valve leaflets. Over the years, these events promote stenosis and obstruction of blood flow. Known and common risk factors are congenital defects, aging and metabolic syndromes linked to high plasma levels of lipoproteins. Inflammation and oxidative stress are the main molecular mediators of the evolution of aortic stenosis in patients and these mediators regulate both the degradation and remodeling processes. Mitochondrial dysfunction and dysregulation of autophagy also contribute to the disease. A better understanding of these cellular impairments might help to develop new ways to treat patients since, at the moment, there is no effective medical treatment to diminish neither the advancement of valve stenosis nor the left ventricular function impairments, and the current approaches are surgical treatment or transcatheter aortic valve replacement with prosthesis.

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The association between aortic valve calcification, cardiovascular risk factors, and cardiac size and function in a general population

Khurrami

Møller

Dahl

et al. 2020

Int J Cardiovasc Imaging

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Autoantibodies and immune complexes to oxidation-specific epitopes and progression of aortic stenosis: Results from the ASTRONOMER trial

Cited by 6 publications

References 34 publications

Lipoprotein(a) and Its Autoantibodies in Association with Calcific Aortic Valve Stenosis

Lipoprotein(a) and Its Autoantibodies in Association with Calcific Aortic Valve Stenosis

Aortic Valve Stenosis and Mitochondrial Dysfunctions: Clinical and Molecular Perspectives

The association between aortic valve calcification, cardiovascular risk factors, and cardiac size and function in a general population

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