Affiliation:
1. Department of Physiology Amsterdam UMC Vrije Universiteit Amsterdam Amsterdam Cardiovascular Sciences Amsterdam The Netherlands
2. Department of Cardiology University of Groningen University Medical Center Groningen Groningen The Netherlands
3. Netherlands Heart Institute Utrecht The Netherlands
Abstract
Abstract
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and is characterized by asymmetric septal thickening and diastolic dysfunction. More than 1500 mutations in genes encoding sarcomere proteins are associated with HCM. However, the genotype‐phenotype relationship in HCM is incompletely understood and involves modification by additional disease hits. Recent cohort studies identify obesity as a major adverse modifier of disease penetrance, severity, and clinical course. In this review, we provide an overview of these clinical findings. Moreover, we explore putative mechanisms underlying obesity‐induced sensitization and aggravation of the HCM phenotype. We hypothesize obesity‐related stressors to impact on cardiomyocyte structure, metabolism, and homeostasis. These may impair cardiac function by directly acting on the primary mutation‐induced myofilament defects and by independently adding to the total cardiac disease burden. Last, we address important clinical and pharmacological implications of the involvement of obesity in HCM disease modification.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Reference162 articles.
1. New perspectives on the prevalence of hypertrophic cardiomyopathy;Semsarian C;J Am Coll Cardiol,2015
2. ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the task force for the diagnosis and management of hypertrophic cardiomyopathy of the European Society of Cardiology (ESC);Authors/Task Force members;Eur Heart J,2014
3. Genetic basis of hypertrophic cardiomyopathy: from bench to the clinics;Alcalai R;J Cardiovasc Electrophysiol,2008
4. Targets for therapy in sarcomeric cardiomyopathies;Tardiff JC;Cardiovasc Res,2015
5. Left ventricular outflow tract gradient is associated with reduced capillary density in hypertrophic cardiomyopathy irrespective of genotype;Guclu A;Eur J Clin Invest,2015
Cited by
18 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献