Statins for aortic valve stenosis

Thiago, Luciana; Tsuji, Selma Rumiko; Nyong, Jonathan; Puga, Maria Eduarda dos Santos; Góis, Aécio Flávio Teixeira de; Macedo, Cristiane R; Valente, Orsine; Atallah, Álvaro Nagib

doi:10.1590/1516-3180.20161346t1

Cited by 6 publications

(7 citation statements)

References 2 publications

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“…Calcific aortic valve disease (CAVD) is the most common heart valve disease and the principal cause of aortic stenosis (AS) in Western countries. Angiotensin converting enzyme (ACE) inhibitors have shown some promise but their efficacy in counteracting the progression of AS in the clinical setting is still uncertain [1,2], while statins, although able to counteract calcification in vitro, were found to be ineffective in large randomized clinical trials [3,4]. Currently, there is no pharmacological therapy specifically indicated for CAVD, which progresses rapidly, eventually requiring the replacement of the aortic valve.…”

Section: Introductionmentioning

confidence: 99%

COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification

Sega

Fortini

Cimaglia

et al. 2020

IJMS

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Calcific aortic valve disease (CAVD) is the result of maladaptive fibrocalcific processes leading to a progressive thickening and stiffening of aortic valve (AV) leaflets. CAVD is the most common cause of aortic stenosis (AS). At present, there is no effective pharmacotherapy in reducing CAVD progression; when CAVD becomes symptomatic it can only be treated with valve replacement. Inflammation has a key role in AV pathological remodeling; hence, anti-inflammatory therapy has been proposed as a strategy to prevent CAVD. Cyclooxygenase 2 (COX-2) is a key mediator of the inflammation and it is the target of widely used anti-inflammatory drugs. COX-2-inhibitor celecoxib was initially shown to reduce AV calcification in a murine model. However, in contrast to these findings, a recent retrospective clinical analysis found an association between AS and celecoxib use. In the present study, we investigated whether variations in COX-2 expression levels in human AVs may be linked to CAVD. We extracted total RNA from surgically explanted AVs from patients without CAVD or with CAVD. We found that COX-2 mRNA was higher in non-calcific AVs compared to calcific AVs (0.013 ± 0.002 vs. 0.006 ± 0.0004; p < 0.0001). Moreover, we isolated human aortic valve interstitial cells (AVICs) from AVs and found that COX-2 expression is decreased in AVICs from calcific valves compared to AVICs from non-calcific AVs. Furthermore, we observed that COX-2 inhibition with celecoxib induces AVICs trans-differentiation towards a myofibroblast phenotype, and increases the levels of TGF-β-induced apoptosis, both processes able to promote the formation of calcific nodules. We conclude that reduced COX-2 expression is a characteristic of human AVICs prone to calcification and that COX-2 inhibition may promote aortic valve calcification. Our findings support the notion that celecoxib may facilitate CAVD progression.

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Section: Introductionmentioning

confidence: 99%

COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification

Sega

Fortini

Cimaglia

et al. 2020

IJMS

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“…13 Some observational studies suggested that statin therapy may slow the progression of AVC. 32,33 A meta-analysis of 4 randomized controlled trials found no differences in the clinically relevant outcomes such as mean pressure gradient, valve area, freedom from valve replacement and death from cardiovascular causes between the statin group and the placebo group, 34 but the authors of the meta-analysis stated that "this issue is not over, mainly because the available evidence is based on studies which have limitations such as follow-up, randomization process, sample size and very elderly participants with many comorbidities". Indeed, the analyzed patients (n=269) in the meta-analysis had a mean age of 58 years, with asymptomatic mild aortic valve stenosis defined by maximum aortic valve velocity of 2.5-4.0 m/s.…”

Section: Resultsmentioning

confidence: 99%

Lipoprotein Particle Profiles Compared With Standard Lipids in the Association With Subclinical Aortic Valve Calcification in Apparently Healthy Japanese Men

Fujiyoshi

Hisamatsu

et al. 2021

Circ J

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egenerative calcific aortic valve disease is one of the most common heart diseases worldwide, and its prevalence has increased in developed countries as populations have aged. 1-3 If mild valve obstruction exists, the disease seems to progress inevitably to hemodynamically more altered states. Once the disease becomes symptomatic and severe, the prognosis without surgery is dismal. 4 The subclinical early stage of degenerative calcific aortic valve disease is characterized by aortic valve calcifi-cation (AVC). The pathophysiology of AVC involves an active process, similar to that of atherosclerosis, characterized by 3 primary processes: lipid accumulation, inflammation, and calcification. 5-8Nuclear magnetic resonance (NMR)-based lipoprotein assessment that simultaneously measures the concentrations and sizes of various lipoprotein particles, presents novel markers of atherosclerosis and/or cardiovascular disease. 9-12 Although some of these measures are correlated

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“…This finding is compatible with former studies showing no impact of statins on AS progression [ 25 , 26 ]. Recently, Thaigo et al presented a review showing lower values of P mean in patients who were under statin therapy, but they also agree the analyzed studies did not have high quality and concluded that the role of statin therapy in AS remained uncertain [ 27 ]. CRP values were also high in the slow progression group indicating increased inflammatory stress in these patients; this could be fairly explained by the increased inflammation status and higher comorbidities in these patients.…”

Section: Discussionmentioning

confidence: 99%

Association between Comorbidities and Progression of Transvalvular Pressure Gradients in Patients with Moderate and Severe Aortic Valve Stenosis

Salinger

Liú

et al. 2018

Cardiology Research and Practice

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Background Fast progression of the transaortic mean gradient (P mean) is relevant for clinical decision making of valve replacement in patients with moderate and severe aortic stenosis (AS) patients. However, there is currently little knowledge regarding the determinants affecting progression of transvalvular gradient in AS patients. Methods This monocentric retrospective study included consecutive patients presenting with at least two transthoracic echocardiography examinations covering a time interval of one year or more between April 2006 and February 2016 and diagnosed as moderate or severe aortic stenosis at the final echocardiographic examination. Laboratory parameters, medication, and prevalence of eight known cardiac comorbidities and risk factors (hypertension, diabetes, coronary heart disease, peripheral artery occlusive disease, cerebrovascular disease, renal dysfunction, body mass index ≥30 Kg/m2, and history of smoking) were analyzed. Patients were divided into slow (P mean < 5 mmHg/year) or fast (P mean ≥ 5 mmHg/year) progression groups. Results A total of 402 patients (mean age 78 ± 9.4 years, 58% males) were included in the study. Mean follow-up duration was 3.4 ± 1.9 years. The average number of cardiac comorbidities and risk factors was 3.1 ± 1.6. Average number of cardiac comorbidities and risk factors was higher in patients in slow progression group than in fast progression group (3.3 ± 1.5 vs 2.9 ± 1.7; P=0.036). Patients in slow progression group had more often coronary heart disease (49.2% vs 33.6%; P=0.003) compared to patients in fast progression group. LDL-cholesterol values were lower in the slow progression group (100 ± 32.6 mg/dl vs 110.8 ± 36.6 mg/dl; P=0.005). Conclusion These findings suggest that disease progression of aortic valve stenosis is faster in patients with fewer cardiac comorbidities and risk factors, especially if they do not have coronary heart disease. Further prospective studies are warranted to investigate the outcome of patients with slow versus fast progression of transvalvular gradient with regards to comorbidities and risk factors.

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Statins for aortic valve stenosis

Cited by 6 publications

References 2 publications

COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification

COX-2 Is Downregulated in Human Stenotic Aortic Valves and Its Inhibition Promotes Dystrophic Calcification

Lipoprotein Particle Profiles Compared With Standard Lipids in the Association With Subclinical Aortic Valve Calcification in Apparently Healthy Japanese Men

Association between Comorbidities and Progression of Transvalvular Pressure Gradients in Patients with Moderate and Severe Aortic Valve Stenosis

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