Does statin therapy impact the proximal aortopathy in aortic valve disease?

Gross, Tatiana Sequeira; Naito, Shigenori; Neumann, Niklas; Petersen, Johannes; Kuntze, Thomas; Reichenspurner, Hermann; Kodolitsch, Yskert Von; Girdauskas, Evaldas

doi:10.1093/qjmed/hcy129

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…Studies of BAV in the euploid population have linked increased cholesterol levels in BAV patients with aortic stenosis and linear correlation of low-density lipoprotein levels and ascending aorta diameter ( Alegret et al, 2015 ; Endo et al, 2015 ). BAV patients undergoing statin treatment were observed to have reduced progression of aortopathy following heart surgery, which was not found in the TAV counterparts ( Taylor et al, 2016 ; Sequeira Gross et al, 2018 ). An interesting connection can be found when we consider that TS individuals are at an increased risk for dyslipidemia which presents at an early age, although cholesterol levels improve following hormone replacement therapy ( Ross et al, 1995 ; Mavinkurve and O'Gorman, 2015 ).…”

Section: Discussionmentioning

confidence: 87%

DNA Methylation Analysis of Turner Syndrome BAV

Gutierrez

Davis²,

Nevonen³

et al. 2022

Front. Genet.

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Turner Syndrome (TS) is a rare cytogenetic disorder caused by the complete loss or structural variation of the second sex chromosome. The most common cause of early mortality in TS results from a high incidence of left-sided congenital heart defects, including bicuspid aortic valve (BAV), which occurs in about 30% of individuals with TS. BAV is also the most common congenital heart defect in the general population with a prevalence of 0.5–2%, with males being three-times more likely to have a BAV than females. TS is associated with genome-wide hypomethylation when compared to karyotypically normal males and females. Alterations in DNA methylation in primary aortic tissue are associated with BAV in euploid individuals. Here we show significant differences in DNA methylation patterns associated with BAV in TS found in peripheral blood by comparing TS BAV (n = 12), TS TAV (n = 13), and non-syndromic BAV (n = 6). When comparing TS with BAV to TS with no heart defects we identified a differentially methylated region encompassing the BAV-associated gene MYRF, and enrichment for binding sites of two known transcription factor contributors to BAV. When comparing TS with BAV to euploid women with BAV, we found significant overlapping enrichment for ChIP-seq transcription factor targets including genes in the NOTCH1 pathway, known for involvement in the etiology of non-syndromic BAV, and other genes that are essential regulators of heart valve development. Overall, these findings suggest that altered DNA methylation affecting key aortic valve development genes contributes to the greatly increased risk for BAV in TS.

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Section: Discussionmentioning

confidence: 87%

DNA Methylation Analysis of Turner Syndrome BAV

Gutierrez

Davis²,

Nevonen³

et al. 2022

Front. Genet.

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“…Moreover, a case-control study by Gracia Baena et al revealed that dyslipidemia was one of the cardiovascular risk factors associated with an increased risk of AVS [48]. However, there is also research indicating an insignificant relationship between TC, LDL-C, and TG and cross-sectional aortic diameters in individuals with BAV who underwent AVR [49]. Our results seem to be in agreement with the study of Alegret et al, which suggested that the concentration of Apo B could predict ascending aorta diameter in BAV patients [50].…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein(a) As a Potential Predictive Factor for Earlier Aortic Valve Replacement in Patients with Bicuspid Aortic Valve

et al. 2023

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Bicuspid aortic valve (BAV) affects 0.5–2% of the general population and constitutes the major cause of severe aortic valve stenosis (AVS) in individuals ≤70 years. The aim of the present study was to evaluate the parameters that may provide information about the risk of AVS developing in BAV patients, with particular emphasis on lipoprotein(a) (Lp(a)), which is a well-recognized risk factor for stenosis in the general population. We also analyzed the impact of autotaxin (ATX) and interleukin-6 (IL-6) as parameters potentially related to the pathomechanism of Lp(a) action. We found that high Lp(a) levels (>50 mg/dL) occurred significantly more frequently in patients with AVS than in patients without AVS, both in the group below and above 45 years of age (p = 0.036 and p = 0.033, respectively). Elevated Lp(a) levels were also strictly associated with the need for aortic valve replacement (AVR) at a younger age (p = 0.016). However, the Lp(a) concentration did not differ significantly between patients with and without AVS. Similarly, we observed no differences in ATX between the analyzed patient groups, and both ATX activity and concentration correlated significantly with Lp(a) level (R = 0.465, p < 0.001 and R = 0.599, p < 0.001, respectively). We revealed a significantly higher concentration of IL-6 in young patients with AVS. However, this observation was not confirmed in the group of patients over 45 years of age. We also did not observe a significant correlation between IL-6 and Lp(a) or between CRP and Lp(a) in any of the analyzed groups of BAV patients. Our results demonstrate that a high level of Lp(a), greater than 50 mg/dL, may be a significant predictive factor for earlier AVR. Lp(a)-related parameters, such as ATX and IL-6, may be valuable in providing information about the additional cardiovascular risks associated with developing AVS.

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“…Compared to thoracic aortic aneurysms, antihypertensive therapy (β-blockers or ACE inhibitors) cannot slow the progression of abdominal aortic aneurysms ( Lindeman and Matsumura, 2019 ). Statins are not currently included in the guidelines, but studies have shown that statin use can reduce the odds of ascending aortic dilatation in BAV ( Goel et al, 2011 ; Taylor et al, 2016 ; Sequeira Gross et al, 2018 ).…”

Section: Clinical Significancementioning

confidence: 99%

Aortic Dilatation in Patients With Bicuspid Aortic Valve

et al. 2021

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Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality. BAV aortic dilatation is associated with an increased risk of adverse aortic events and represents a potentially lethal disease and hence a considerable medical burden. BAV with aortic dilatation warrants frequent monitoring, and elective surgical intervention is the only effective method to prevent dissection or rupture. The predictive value of the aortic diameter is known to be limited. The aortic diameter is presently still the main reference standard for surgical intervention owing to the lack of a comprehensive understanding of BAV aortopathy progression. This article provides a brief comprehensive review of the current knowledge on BAV aortopathy regarding clinical definitions, epidemiology, natural course, and pathophysiology, as well as hemodynamic and clinically significant aspects on the basis of the limited data available.

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Does statin therapy impact the proximal aortopathy in aortic valve disease?

Cited by 6 publications

References 22 publications

DNA Methylation Analysis of Turner Syndrome BAV

DNA Methylation Analysis of Turner Syndrome BAV

Lipoprotein(a) As a Potential Predictive Factor for Earlier Aortic Valve Replacement in Patients with Bicuspid Aortic Valve

Aortic Dilatation in Patients With Bicuspid Aortic Valve

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