The role of inflammation and metabolic risk factors in the pathogenesis of calcific aortic valve stenosis
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REVIEW
The role of inflammation and metabolic risk factors in the pathogenesis of calcific aortic valve stenosis Maddalena Conte1,2 · Laura Petraglia1 · Pasquale Campana1 · Gerardo Gerundo1 · Aurelio Caruso2 · Maria Gabriella Grimaldi2 · Vincenzo Russo3 · Emilio Attena4 · Dario Leosco1,2 · Valentina Parisi1,2 Received: 17 June 2020 / Accepted: 8 August 2020 © The Author(s) 2020
Abstract Given the epidemiologic increase of aged population in the world, aortic stenosis (AS) represents now the most common valvular heart disease in industrialized countries. It is a very challenging disease, representing an important cause of morbidity, hospitalization and death in the elderly population. It is widely recognized that AS is the result of a very complex active process, driven by inflammation and involving multifactorial pathological mechanisms promoting valvular calcification and valvular bone deposition. Several evidence suggest that epicardial adipose tissue (EAT), the visceral fat depot of the heart, represents a direct source of cytokines and could mediate the deleterious effects of systemic inflammation on the myocardium. Importantly, obesity and metabolic disorders are associated with chronic systemic inflammation leading to a significant increase of EAT amount and to a pro-inflammatory phenotypic shift of this fat depot. It has been hypothesized that the EAT inflammatory state can influence the structure and function of the heart, thus contributing to the pathogenesis of several cardiac diseases, including calcific AS. The current review will discuss the recently discovered mechanisms involved in the pathogenesis of AS, with particular attention to the role of inflammation, metabolic risk factors and pro-fibrotic and pro-osteogenic signal pathways promoting the onset and progression of the disease. Moreover, it will be explored the potential role of EAT in the AS pathophysiology. Keywords Epicardial adipose tissue · Aortic stenosis · Inflammation · Aging
The evolving epidemiology of calcific aortic valve stenosis Aortic stenosis (AS) is the most common type of valvular heart disease in developed countries and its prevalence draamatically increases with age: in US population, the prevalence of moderate or severe AS ranges from 0.02 to 0.1% in subjects aged 18–44 years and from 2.8 to 4.6% in patients 75 years or older [1]. Similar trends are described Maddalena Conte and Laura Petraglia equally contributed. * Dario Leosco [email protected] 1
Department of Translational Medical Sciences, University of Naples Federico II, Via Pansini 5, 8031 Naples, Italy
2
Casa di Cura San Michele, Maddaloni, Italy
3
University of Campania Luigi Vanvitelli, Caserta, Italy
4
San Giuliano Hospital, Naples, Italy
in Europe. The EuroHeart Survey evaluated the incidence of valve disease among 92 centres across 25 countries. The mean age of patients with valve disease was 65 ± 14 years and AS was the most common valve disease, occurring in 43.1% of subjects [2]. As life expectancy and the aging population increase, th
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