Pharmacogenetic Interactions Between β-Blocker Therapy and the Angiotensin-Converting Enzyme Deletion Polymorphism in Patients With Congestive Heart Failure

McNamara, Dennis M.; Holubkov, Richard; Janosko, Karen; Palmer, Amy; Wang, Jue J.; MacGowan, Guy A.; Murali, Srinivas; Rosenblum, Warren D.; London, Barry; Feldman, Arthur M.

doi:10.1161/01.cir.103.12.1644

Cited by 168 publications

(33 citation statements)

References 20 publications

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“…The possible interactions between ACE I/D genotype and treatment with antihypertensive agents on blood pressure lowering, [25][26][27] total mortality, 28 regression of left ventricular hypertrophy, 29 -32 proteinuria, 33,34 stroke, 23 CHD and vascular events, 23 and dementia and cognitive decline 23 have been examined. Four of these studies suggested that the ACE DD genotype is more responsive to antihypertensive treatment 26,29,31,34 ; 2 studies suggested that the II genotype is more responsive 28,30 ; one study reports differences in blood pressure responses by genotype in men and women 27 ; and 4 studies report no significant ACE I/D genotype-by-treatment interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Four of these studies suggested that the ACE DD genotype is more responsive to antihypertensive treatment 26,29,31,34 ; 2 studies suggested that the II genotype is more responsive 28,30 ; one study reports differences in blood pressure responses by genotype in men and women 27 ; and 4 studies report no significant ACE I/D genotype-by-treatment interactions. 23,25,26,33 However, except for the PROGRESS trial, 23 most studies were small (ie, Ͻ100 patients), were observational (ie, subjects were not randomized to a treatment), and were restricted to surrogate markers of cardiovascular risk (ie, blood pressure, left ventricular mass, or proteinuria).…”

Section: Discussionmentioning

confidence: 99%

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Pharmacogenetic Association of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Blood Pressure and Cardiovascular Risk in Relation to Antihypertensive Treatment

et al. 2005

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Background-Previous studies have reported that blood pressure response to antihypertensive medications is influenced by genetic variation in the renin-angiotensin-aldosterone system, but no clinical trails have tested whether the ACE insertion/deletion (I/D) polymorphism modifies the association between the type of medication and multiple cardiovascular and renal phenotypes. Methods and Results-We used a double-blind, active-controlled randomized trial of antihypertensive treatment that included hypertensives Ն55 years of age with Ն1 risk factor for cardiovascular disease. ACE I/D genotypes were determined in 37 939 participants randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatments and followed up for 4 to 8 years. Primary outcomes included fatal coronary heart disease (CHD) and/or nonfatal myocardial infarction. Secondary outcomes included stroke, all-cause mortality, combined CHD, and combined cardiovascular disease. Fatal and nonfatal CHD occurred in 3096 individuals during follow-up.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic Association of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Blood Pressure and Cardiovascular Risk in Relation to Antihypertensive Treatment

et al. 2005

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“…Moreover, if this were to be combined with ␤ 1 -receptor blockade in subjects who also possess the ␤ 1 Arg389 high-functioning ␤ 1 -receptor polymorphism, then a study in left ventricular dysfunction or mild heart failure might well be able to detect an efficacy signal in a relatively small sample size. It has already been shown that a pharmacogenetic profile can predict response to ␤-blocking agents, 25 and the recent data of Small et al 24 suggest that responders to this form of therapy can be even further refined.…”

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confidence: 99%

Antiadrenergic Therapy of Chronic Heart Failure

Bristow

2003

Circulation

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“…33 Two small studies in 90 Czech and 84 Turkish subjects did, however, not detect an association between heart failure phenotype and ACE genotype. 24,26 Studies in Japanese 28,34 and Chinese patients 35 failed to associate this polymorphism with heart failure phenotype, whereas studies in blacks were contradictory.…”

Section: Renin-angiotensin-aldosterone Systemmentioning

confidence: 97%

Genetic polymorphisms and heart failure

Bleumink

Schut

Sturkenboom

et al. 2004

Genetics in Medicine

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Heart failure is a complex clinical syndrome. There is evidence for a genetic contribution to the pathophysiology of heart failure. Considering the fundamental role of neurohormonal factors in the pathophysiology and progression of cardiac dysfunction and hypertrophy, variants of genes involved in this system are logical candidate genes in heart failure. In this report, genetic polymorphisms of the major neurohormonal systems in heart failure will be discussed. Studies on polymorphisms of the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous polymorphisms that may be involved in the development or phenotypic expression of heart failure will be reviewed. Research on left ventricular hypertrophy is also included. The majority of genetic association studies focused on the ACE I/D polymorphism.Initial genetic associations have often been difficult to replicate, mainly due to problems in study design and lack of power. Promising results have been obtained with genetic polymorphisms of the RAAS and sympathetic system.Considering the evidence so far, a modifying role for these polymorphisms seems more likely than a role of these variants as susceptibility genes. Besides the need for larger studies to examine the effects of single nucleotide polymorphisms and haplotypes, future studies also need to focus on the complexity of these systems and study Heart failure is a complex clinical syndrome with high morbidity and mortality. 1,2 Impairment of cardiac function activates compensatory neurohormonal mechanisms, which at a later stage may accelerate progression of heart failure. 3 Coronary heart disease and hypertension are major underlying causes of heart failure. Other frequent underlying conditions include valvular heart disease and idiopathic dilated cardiomyopathy. It is difficult to predict who will develop heart failure in response to myocardial injury. Racial differences in occurrence and outcome of heart failure 4,5 and heritability estimates of variability in left ventricular mass of 28% to 65% 6,7 suggest a genetic contribution to the pathophysiology of left ventricular remodeling and heart failure.Many studies have been published on the role of single gene mutations in (familial) cardiomyopathies. 8,9 These Mendelian traits are by nature rare, and although important at an individual level and for the understanding of disease mechanisms, are of limited significance in terms of prediction of heart failure occurrence in the population. 10 Moreover, in patients with identical gene mutations clinical manifestations of cardiomyopathy may differ. This suggests that probably also environmental and/or other genetic factors play a role.In this report, genetic polymorphisms of major neurohormonal systems involved in the pathophysiology of heart failure will be discussed, including the renin-angiotensin-aldosterone system (RAAS), adrenergic receptor polymorphisms, endothelin (receptor) polymorphisms, and a group of miscellaneous...

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Pharmacogenetic Interactions Between β-Blocker Therapy and the Angiotensin-Converting Enzyme Deletion Polymorphism in Patients With Congestive Heart Failure

Cited by 168 publications

References 20 publications

Pharmacogenetic Association of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Blood Pressure and Cardiovascular Risk in Relation to Antihypertensive Treatment

Pharmacogenetic Association of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Blood Pressure and Cardiovascular Risk in Relation to Antihypertensive Treatment

Antiadrenergic Therapy of Chronic Heart Failure

Genetic polymorphisms and heart failure

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