Impact of Demographic Features, Lifestyle, and Comorbidities on the Clinical Expression of Hypertrophic Cardiomyopathy

Finocchiaro, Gherardo; Magavern, Emma; Sinagra, Gianfranco; Ashley, Euan A.; Papadakis, Michael; Tome-Esteban, M; Sharma, Sanjay; Olivotto, Iacopo

doi:10.1161/jaha.117.007161

Cited by 50 publications

(52 citation statements)

References 88 publications

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“…The initial defect causes a cascade of secondary molecular events, including the activation of the calcium-sensitive and stress-responsive molecular pathways that collectively mediate the programming of cardiac hypertrophy and induce the morphological and histological phenotypes that are recognized as HCM, principally represented by myocardial hypertrophy, myocyte disarray and myocardial fibrosis. The variability of the cardiac phenotype suggests that several epigenetic and environmental factors are involved in the pathogenesis of this disorder, but the mechanism by which the genetic mutation translates into the phenotype remains poorly understood [48]. Since the focus of HCM has typically been on myocardial hypertrophy, myocyte disarray and myocardial fibrosis, the role of inflammation and immune processes has been poorly characterized; however, it seems to have a pivotal role in the pathogenesis of HCM.…”

Section: Hypertrophic Cardiomyopathymentioning

confidence: 99%

Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

Monda

Palmiero

Rubino

et al. 2020

IJMS

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Cardiomyopathies (CMPs) represent a diverse group of heart muscle diseases, grouped into specific morphological and functional phenotypes. CMPs are associated with mutations in sarcomeric and non-sarcomeric genes, with several suspected epigenetic and environmental mechanisms involved in determining penetrance and expressivity. The understanding of the underlying molecular mechanisms of myocardial diseases is fundamental to achieving a proper management and treatment of these disorders. Among these, inflammation seems to play an important role in the pathogenesis of CMPs. The aim of the present study is to review the current knowledge on the role of inflammation and the immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.

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Section: Hypertrophic Cardiomyopathymentioning

confidence: 99%

Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

Monda

Palmiero

Rubino

et al. 2020

IJMS

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“…Так, в работе Ingles J, et al (2017) и в других многочисленных работах выявлено преобладание частоты АГ у пациентов старшего возраста с несемейной формой ГКМП [3, 5-8, 34, 35, 37]. Возраст дебюта является важной детерминантой особенностей клинического течения ГКМП [2,[38][39][40][41]. В результате проведенного исследования нами выявлена ассоциация генотипа СС и аллеля С полиморфного варианта rs2228145 гена IL6R с наличием АГ у пациентов с ГКМП с дебютом заболевания в возрас те ≥45 лет.…”

Section: Discussionunclassified

“…В последние годы механизмы патогенеза ГКМП рассматриваются с позиции вклада немодифицируемых детерминант (причинные мутации, возраст, пол) и потенциально модифицируемых факторов (коморбидность). Согласно данным метаанализа, приведенного в работе Finnochiaro G, et al (2017), дебют и особенности течения ГКМП у взрослых в возрасте до 45 лет во многом определяется причинными генетическими вариантами, экстремальной гипертрофией миокарда (гипертрофией >3 см) и высоким риском внезапной смерти [2]. В то же время дебют заболевания в старших возрастных группах нередко происходит под влиянием коморбидной патологии, в особенности факторов кардиометаболического риска, частота которых значимо увеличивается с возрастом [3].…”

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Cardiometabolic risk factors and their relationship with the interleukin-6 receptor gene polymorphism (rs2228145) in patients with hypertrophic cardiomyopathy

et al. 2020

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Aim. To analyze associations of interleukin-6 receptor gene (IL6R) polymorphism (rs2228145) with the clinical course characteristics of hypertrophic cardiomyopathy (HCM) in groups of patients with various cardiometabolic risk factorsMaterial and methods. The sample consisted of 123 patients with HCM. The age of the included patients ranged from 18 to 91 years (59 [41; 66.5]), of whom 59 were men, 64 — women. Two age groups were identified: the first group included patients from 18 to 44 years old, the second — 45 years and older. The control group consisted of 200 people without cardiovascular diseases and other severe comorbidities.For genetic testing, DNA was isolated from peripheral blood lymphocytes. Genotyping of the IL6R gene polymorphism (rs2228145) was carried out by realtime polymerase chain reaction.Results. A significant prevalence of CC genotype of the IL6R gene polymorphism (rs2228145) was revealed in patients aged ³45 years compared with the control group, which occurred in 14,1% and 3,0% of cases, respectively (CC:AC+AA, odds ratio (OR), 0,885, 95% confidence interval (CI), 1,051-0,691, p=0,006), and insignificant prevalence of C allele in this group, which does not reach the level of significance (A:C, OR, 0,870, 95% CI, 0,427-1,02, p=0,06). The prevalence of CC genotype (15,1% vs 3,0%) and C allele (39,0% vs 29,0%) was revealed in patients with HCM in combination with hypertension (HTN) compared with the control group (CC:AS+AA, OR=0,174, 95% CI, 0,047-0,650), p=0,004); (A:C, OR=0,638, 95% CI, 0,406-1,002), p=0,05).Conclusion. The relationship between the IL6R gene polymorphism (rs2228145) and HTN in patients with HCM was confirmed. The presence of CC genotype and C allele of the rs2228145 IL6R gene polymorphism is significantly more common in patients with HCM with the disease onset ³45 years of age. The presence of CC genotype and C allele of the IL6R gene polymorphism (rs2228145) is associated with HTN in patients with HCM.

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“…In healthy subjects harboring pathogenic genetic variants, phenotypic expression is likely to emerge only after interplaying with specific factors that modify the relationship with risk [65].…”

Section: Modifiers Of Clinical Expressionmentioning

confidence: 99%

Exploring the Continuum of Hypertrophic Cardiomyopathy—From DNA to Clinical Expression

et al. 2019

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The concepts underlying hypertrophic cardiomyopathy (HCM) pathogenesis have evolved greatly over the last 60 years since the pioneering work of the British pathologist Donald Teare, presenting the autopsy findings of “asymmetric hypertrophy of the heart in young adults”. Advances in human genome analysis and cardiac imaging techniques have enriched our understanding of the complex architecture of the malady and shaped the way we perceive the illness continuum. Presently, HCM is acknowledged as “a disease of the sarcomere”, where the relationship between genotype and phenotype is not straightforward but subject to various genetic and nongenetic influences. The focus of this review is to discuss key aspects related to molecular mechanisms and imaging aspects that have prompted genotype–phenotype correlations, which will hopefully empower patient-tailored health interventions.

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Impact of Demographic Features, Lifestyle, and Comorbidities on the Clinical Expression of Hypertrophic Cardiomyopathy

Abstract: No abstract

Cited by 50 publications

References 88 publications

Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

Cardiometabolic risk factors and their relationship with the interleukin-6 receptor gene polymorphism (rs2228145) in patients with hypertrophic cardiomyopathy

Exploring the Continuum of Hypertrophic Cardiomyopathy—From DNA to Clinical Expression

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