Progression of left ventricular hypertrophy and the angiotensin-converting enzyme gene polymorphism in hypertrophic cardiomyopathy

Doolan, Gavin; Nguyen, Lan Thi Ngoc; Chung, Jessica; Ingles, Jodie; Semsarian, Christopher

doi:10.1016/j.ijcard.2004.05.003

Cited by 39 publications

(26 citation statements)

References 36 publications

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“…10 -17 Several studies have demonstrated an association between the ACE insertion/deletion polymorphism and the AT1-R adenine/cytosine 1166 polymorphism and expression of LV hypertrophy. 10,[12][13][14][15][16] Carriers of ACE D (increased myocardial angiotensin II level) and AT1-R C (increased angiotensin II effect) alleles showed higher penetrance and degree of LV hypertrophy compared with patients with the ACE I and AT1-R A alleles. Only three studies reported a HCM-causing genotype with controversial results.…”

Section: Role Of Angiotensin II In Hcmmentioning

confidence: 99%

The Effects of Candesartan on Left Ventricular Hypertrophy and Function in Nonobstructive Hypertrophic Cardiomyopathy

Pěnička

Gregor

Kerekes³

et al. 2009

The Journal of Molecular Diagnostics

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Hypertrophic cardiomyopathy is caused by mutations in the genes that encode sarcomeric proteins and is primarily characterized by unexplained left ventricular hypertrophy, impaired cardiac function, reduced exercise tolerance, and a relatively high incidence of sudden cardiac death, especially in the young. The extent of left ventricular hypertrophy is one of the major determinants of disease prognosis. Angiotensin II has trophic effects on the heart and plays an important role in the development of myocardial hypertrophy. Here in a double-blind, placebo-controlled, randomized study, we show that the long-term administration of the angiotensin II type 1 receptor antagonist candesartan in patients with hypertrophic cardiomyopathy was associated with the significant regression of left ventricular hypertrophy, improvement of left ventricular function, and exercise tolerance. The magnitude of the treatment effect was dependent on specific sarcomeric protein gene mutations that had the greatest responses on the carriers of ß-myosin heavy chain and cardiac myosin binding protein C gene mutations. These data indicate that modulating the role of angiotensin II in the development of hypertrophy is specific with respect to both the affected sarcomeric protein gene and the affected codon within that gene. Thus, angiotensin II type 1 receptor blockade has the potential to attenuate myocardial hypertrophy and may, therefore, provide a new treatment option to prevent sudden cardiac death in patients with hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy (HCM) is a primary cardiac disease characterized by unexplained cardiac hypertrophy and a relatively high incidence of sudden cardiac death, especially in young people.1,2 The extent of left ventricular hypertrophy is one of the major determinants of symptoms and prognosis. 3,4 Angiotensin II has trophic effects on the heart and plays an important role in the development of myocardial hypertrophy. 5,6 Inhibition of angiotensin-converting enzyme (ACE) or the angiotensin II type 1 receptor (AT1-R) induced regression of myocardial hypertrophy in patients with hypertension or after myocardial infarction. [7][8][9] In HCM, ACE and AT1-R gene polymorphisms have been shown to be associated with severity of hypertrophy, a high incidence of atrial fibrillation and the risk of sudden cardiac death. -17Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter study to test the safety and effects of AT1-R antagonist candesartan in patients with nonobstructive HCM. We hypothesized that long-term use of candesartan would be associated with regression of left ventricular (LV) hypertrophy and improvement of LV function. Materials and Methods PatientsThis was a double-blind, placebo-controlled, randomized multicenter study. The study population consisted of 24 consecutive, genetically independent, adult (Ն18 years) patients (age 43 Ϯ 13 yrs; 46% males) with nonobstructive HCM, and normal ejection fraction (Ն60%) and sinus rhythm, who visited the participating in...

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Section: Role Of Angiotensin II In Hcmmentioning

confidence: 99%

The Effects of Candesartan on Left Ventricular Hypertrophy and Function in Nonobstructive Hypertrophic Cardiomyopathy

Pěnička

Gregor

Kerekes³

et al. 2009

The Journal of Molecular Diagnostics

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“…11 Indeed, the ACE D and the AT1-R C 1166 alleles have been reported as associated with increased LVH in HCM. [17][18][19] In previous follow-up studies of the predictors of LV systolic dysfunction in HCM, patients who developed systolic dysfunction had a greater LV wall thickness than patients who maintained normal systolic function at initial evaluation. 4-6 Thus, it is possible that these 2 RAS polymorphisms are associated not only with LVH but also with subsequent LV remodeling that can lead to development of systolic dysfunction and LV dilatation.…”

Section: Discussionmentioning

confidence: 99%

“…[17][18][19] Gene polymorphisms of ACE I/D were identified by PCR performed with a set of oligonucleotide primers flanking the polymorphic site in intron 16. To avoid mistyping, each sample found to have the DD genotype was subjected to a second round of independent PCR amplification with a primer pair that recognized an insertionspecific sequence, as described previously.…”

Section: Determination Of Ras-related Gene Polymorphismsmentioning

confidence: 99%

Impact of Renin-Angiotensin System Polymorphisms on Development of Systolic Dysfunction in Hypertrophic Cardiomyopathy - Evidence From a Study of Genotyped Patients -

Funada

Konno

Fujino

et al. 2010

Circ J

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“…An insertion or deletion of a 287bp DNA fragment in the ACE gene (ACEI/D) has been found to be an important modifier which may influence the clinical phenotype in cardiomyopathies. ACE I/D polymorphism has been shown to be associated with left ventricular hypertrophy (LVH) in untreated hypertension, complications of atherosclerosis (35) and HCM (36)(37)(38)(39)(40). D allele was shown to be associated with increased risk of cardiomyopathy in Asian Indians; HCM patients with DD genotype were found to be more susceptible to disease (38).…”

Section: Angiotensin Converting Enzyme (Ace)mentioning

confidence: 99%

“…DCM patients with ID genotype also showed significantly decreased left ventricular ejection fraction (LVEF) indicating a possible association of D allele in pathogenesis of DCM. It has been suggested that DD genotype may be an important biomarker of HCM and presence of the ACE gene I/D polymorphism may be an important marker to identify those individuals with HCM who are likely to have more progressive disease, and therefore at higher risk of adverse clinical outcomes (38,39). DD-ACE is considered a 'pro-LVH' modifier in HCM (41).…”

Section: Angiotensin Converting Enzyme (Ace)mentioning

confidence: 99%

Role of Modifier Genes in Idiopathic Cardiomyopathies

Khullar¹,

Hooda²,

Bahl³

2011

Atherosclerotic Cardiovascular Disease

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Progression of left ventricular hypertrophy and the angiotensin-converting enzyme gene polymorphism in hypertrophic cardiomyopathy

Cited by 39 publications

References 36 publications

The Effects of Candesartan on Left Ventricular Hypertrophy and Function in Nonobstructive Hypertrophic Cardiomyopathy

The Effects of Candesartan on Left Ventricular Hypertrophy and Function in Nonobstructive Hypertrophic Cardiomyopathy

Impact of Renin-Angiotensin System Polymorphisms on Development of Systolic Dysfunction in Hypertrophic Cardiomyopathy - Evidence From a Study of Genotyped Patients -

Role of Modifier Genes in Idiopathic Cardiomyopathies

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