Abstract:
OBJECTIVES:We sought to identify single nucleotide polymorphisms associated with mild statin-induced side effects. BACKGROUND:Statin-induced side effects can interfere with therapy. Single nucleotide polymorphisms in cytochrome P450 enzymes impair statin metabolism; the reduced function SLCO1B1*5 allele impairs statin clearance and is associated with simvastatin-induced myopathy with creatine kinase (CK) elevation. METHODS:The STRENGTH (Statin Response Examined by Genetic Haplotype Markers) study was a pharmacogenetics study of statin efficacy and safety. Subjects (n = 509) were randomized to atorvastatin 10 mg, simvastatin 20 mg, or pravastatin 10 mg followed by 80 mg, 80 mg, and 40 mg, respectively. We defined a composite adverse event (CAE) as discontinuation for any side effect, myalgia, or CK >3x upper limit of normal during follow-up. We sequenced CYP2D6, CYP2C8, CYP2C9, CYP3A4, and SLCO1B1 and tested 7 reduced function alleles for association with the CAE. RESULTS:The CAE occurred in 99 subjects (54 discontinuations, 49 myalgias, and 9 CK elevations). Sex was associated with CAE (percent female in CAE vs. no CAE groups, 66% vs. 50%, p < 0.01). SLCO1B1*5 was associated with CAE (percent with > or = 1 allele in CAE vs. no CAE groups, 37% vs. 25%, p = 0.03) and those with CAE with no significant CK elevation (p < or = 0.03). Furthermore, there was evidence for a gene-dose effect (percent with CAE in those with 0, 1, or 2 alleles: 19%, 27%, and 50%, trend p = 0.01). Finally, the CAE risk appeared to be greatest in those carriers assigned to simvastatin. CONCLUSIONS:SLCO1B1*5 genotype and female sex were associated mild statin-induced side effects. These findings expand the results of a recent genome-wide association study of statin myopathy with CK >3x normal to milder, statin-induced, muscle side effects.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Voora D,Shah SH,Spasojevic I,Ali S,Reed CR,Salisbury BA,Ginsburg GSdoi
10.1016/j.jacc.2009.04.053subject
Has Abstractpub_date
2009-10-20 00:00:00pages
1609-16issue
17eissn
0735-1097issn
1558-3597pii
S0735-1097(09)01713-6journal_volume
54pub_type
杂志文章,随机对照试验abstract::Patients with diabetes mellitus experience a more adverse outcome after acute myocardial infarction compared with nondiabetic patients, although the mechanisms responsible for these findings are not clear. From the Multicenter Investigation of the Limitation of Infarct Size (MILIS) study, the course of acute infarctio...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(89)90053-3
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abstract:OBJECTIVES:We sought to use quantitative markers of the regional left ventricular (LV) response to stress to infer whether diabetic cardiomyopathy is associated with ischemia. BACKGROUND:Diabetic cardiomyopathy has been identified in clinical and experimental studies, but its cause remains unclear. METHODS:We studied...
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abstract:OBJECTIVES:We evaluated the value of coronary flow reserve (CFR), as determined by transthoracic Doppler echocardiography (TTDE), for physiologic assessment of coronary artery stenosis severity, and we compared TTDE measurements with those obtained by exercise thallium-201 (Tl-201) single-photon emission computed tomog...
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doi:10.1016/s0735-1097(01)01167-6
更新日期:2001-04-01 00:00:00
abstract:OBJECTIVES:We sought to assess the ability of preload-adjusted maximal power measured by echocardiographic automated border detection (ABD) to quantify left ventricular (LV) contractility by determining the effects of alterations in preload, afterload and contractile state. BACKGROUND:Preload-adjusted maximal power ca...
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abstract::Although valved conduits have been used successfully in severe forms of right ventricular-pulmonary artery discontinuity, progressive valved conduit stenosis is an important clinical problem. To determine the feasibility of reducing right heart valved conduit stenosis with a balloon expandable stent, a baboon model wa...
journal_title:Journal of the American College of Cardiology
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doi:10.1016/0735-1097(90)90570-f
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更新日期:2010-10-12 00:00:00
abstract:OBJECTIVES:The objective of this study was to ascertain whether the reversal of low peak filling rates after administration of calcium channel blockers in patients with diastolic dysfunction indicates true improvement in the rate of ventricular relaxation and left ventricular end-diastolic pressure measured by invasive...
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abstract:OBJECTIVES:The study was done to test the ability to predict the extent of angiographically determined coronary artery disease (CAD) by quantification of coronary calcium using electron-beam computed tomography (EBCT) and to compare it with more conventional parameters for delineating the angiographic extent of CAD, th...
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journal_title:Journal of the American College of Cardiology
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doi:10.1016/0735-1097(88)92610-1
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journal_title:Journal of the American College of Cardiology
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journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1995-05-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(88)91533-1
更新日期:1988-03-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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更新日期:2013-12-17 00:00:00
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journal_title:Journal of the American College of Cardiology
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doi:10.1016/s0735-1097(97)00488-9
更新日期:1998-02-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(85)80207-2
更新日期:1985-12-01 00:00:00
abstract:OBJECTIVES:This study examined the predictors of in-hospital and 6-month outcome after different reperfusion strategies in acute myocardial infarction. BACKGROUND:Thrombolytic therapy and primary angioplasty are both widely applied as reperfusion modalities in patients with myocardial infarction. Although it is accept...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
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更新日期:1995-02-01 00:00:00
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更新日期:2018-04-24 00:00:00
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更新日期:2018-12-11 00:00:00
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更新日期:1996-07-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2003.10.037
更新日期:2004-03-17 00:00:00
abstract:OBJECTIVES:The aim of this study was to determine the prevalence and characteristics of ambulatory myocardial ischemia in patients with diabetes mellitus and to delineate the relation between the presence and severity of autonomic nervous system dysfunction and the incidence and time of onset of myocardial ischemia. B...
journal_title:Journal of the American College of Cardiology
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doi:10.1016/0735-1097(94)90855-9
更新日期:1994-10-01 00:00:00
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更新日期:2003-01-01 00:00:00
abstract::In 10 patients with moderate to severe hypertension, the hemodynamic effects of ergometric exercise and nicardipine, a dihydropyridine calcium channel antagonist, were characterized under basal conditions and after 1 week of therapy. The responses of plasma renin activity and catecholamines were also assessed. Nicardi...
journal_title:Journal of the American College of Cardiology
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更新日期:1987-09-01 00:00:00
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更新日期:1993-03-15 00:00:00
abstract:OBJECTIVES:The goal of this study was to evaluate the effect of smoking on the pharmacokinetics and pharmacodynamics (PD) of clopidogrel and prasugrel therapy. BACKGROUND:Major randomized trial data demonstrated that nonsmokers experience less or no benefit from clopidogrel treatment compared with smokers (i.e., the "...
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更新日期:2013-08-06 00:00:00
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更新日期:1996-08-01 00:00:00
abstract:OBJECTIVES:The aim of this study was to examine the effect of resolution from metabolic syndrome (MetS) between youth and adulthood on carotid artery intima-media thickness (IMT) and type 2 diabetes mellitus (T2DM). BACKGROUND:Published findings demonstrate that youth with MetS are at increased risk of cardio-metaboli...
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pub_type: 杂志文章,多中心研究
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更新日期:2012-10-23 00:00:00
abstract::Twenty-seven patients (mean age 57 +/- 7 years) underwent surgery for control of recurrent drug-refractory ventricular tachyarrhythmias (uniform ventricular tachycardia alone in 9 patients, ventricular tachycardia and ventricular fibrillation in 15 and ventricular fibrillation alone in 3) within 2 months of acute myoc...
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pub_type: 杂志文章
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更新日期:1990-07-01 00:00:00