13 results on '"James Shepherd"'
Search Results
2. Intensive Lipid-Lowering With Atorvastatin for Secondary Prevention in Patients After Coronary Artery Bypass Surgery
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Sanjiv J. Shah, John J.P. Kastelein, David A. DeMicco, Andrei Breazna, David D. Waters, Nanette K. Wenger, John C. LaRosa, James Shepherd, Philip J. Barter, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine
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Adult ,Male ,medicine.medical_specialty ,Atorvastatin ,Coronary Artery Disease ,law.invention ,Coronary Restenosis ,chemistry.chemical_compound ,Coronary artery bypass surgery ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Pyrroles ,cardiovascular diseases ,Myocardial infarction ,Coronary Artery Bypass ,Stroke ,Triglycerides ,Aged ,Cholesterol ,business.industry ,Anticholesteremic Agents ,Graft Occlusion, Vascular ,Cholesterol, LDL ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Treatment Outcome ,chemistry ,Heptanoic Acids ,Cardiology ,lipids (amino acids, peptides, and proteins) ,Female ,business ,Cardiology and Cardiovascular Medicine ,medicine.drug ,Artery - Abstract
OBJECTIVES: The aim of this post hoc analysis from the TNT (Treating to New Targets) trial is to determine whether patients with previous coronary artery bypass grafting (CABG) surgery achieved clinical benefit from intensive low-density lipoprotein (LDL)-cholesterol lowering. BACKGROUND: The development and progression of atherosclerosis is accelerated in coronary venous bypass grafts. METHODS: A total of 10,001 patients with documented coronary disease, including 4,654 with previous CABG, were randomized to atorvastatin 80 or 10 mg/day and were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event (cardiac death, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke). RESULTS: A first major cardiovascular event occurred in 11.4% of the patients with prior CABG and 8.5% of those without prior CABG (p < 0.001). In CABG patients, mean LDL-cholesterol levels at study end were 79 mg/dl in the 80-mg arm and 101 mg/dl in the 10-mg arm, and the primary event rate was 9.7% in the 80-mg arm and 13.0% in the 10-mg arm (hazard ratio 0.73, 95% confidence interval 0.62 to 0.87, p = 0.0004). Repeat revascularization during follow-up, either CABG or percutaneous coronary intervention, was performed in 11.3% of the CABG patients in the 80-mg arm and 15.9% in the 10-mg arm (hazard ratio 0.70, 95% confidence interval 0.60 to 0.82, p < 0.0001). CONCLUSIONS: Intensive LDL-cholesterol lowering to a mean of 79 mg/dl with atorvastatin 80 mg/day in patients with previous CABG reduces major cardiovascular events by 27% and the need for repeat coronary revascularization by 30%, compared with less intensive cholesterol-lowering to a mean of 101 mg/dl with atorvastatin 10 mg/day. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691)
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- 2008
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3. Intensive Lipid Lowering With Atorvastatin in Patients With Coronary Heart Disease and Chronic Kidney Disease
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Andrea Zuckerman, Daniel J. Wilson, John J.P. Kastelein, James Shepherd, Prakash Deedwania, Stephen Dobson, Andrei Breazna, Nanette K. Wenger, Vera Bittner, Tnt Trial Investigators, ACS - Amsterdam Cardiovascular Sciences, and Vascular Medicine
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medicine.medical_specialty ,education.field_of_study ,Cholesterol ,business.industry ,Atorvastatin ,Population ,Hazard ratio ,Renal function ,medicine.disease ,Gastroenterology ,Comorbidity ,Surgery ,chemistry.chemical_compound ,chemistry ,Internal medicine ,Relative risk ,medicine ,education ,business ,Cardiology and Cardiovascular Medicine ,Kidney disease ,medicine.drug - Abstract
Intensive Lipid Lowering With Atorvastatin in Patients With Coronary Heart Disease and Chronic Kidney Disease: The TNT (Treating to New Targets) Study James Shepherd, John J. P. Kastelein, Vera Bittner, Prakash Deedwania, Andrei Breazna, Stephen Dobson, Daniel J. Wilson, Andrea Zuckerman, Nanette K. Wenger, for the TNT (Treating to New Targets) Investigators In 9,656 patients with stable coronary heart disease (CHD) and low-density lipoprotein cholesterol levels
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- 2008
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4. Association of the Trp719Arg Polymorphism in Kinesin-Like Protein 6 With Myocardial Infarction and Coronary Heart Disease in 2 Prospective Trials
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Carmen H. Tong, Marc A. Pfeffer, Olga Iakoubova, James Shepherd, Frank M. Sacks, Charles M. Rowland, Chris J. Packard, Thomas J. White, Hannia Campos, Dov Shiffman, James J. Devlin, Todd G. Kirchgessner, Eugene Braunwald, Marc S. Sabatine, Bradford A. Young, and Andre R. Arellano
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medicine.medical_specialty ,business.industry ,Proportional hazards model ,Hazard ratio ,Absolute risk reduction ,Odds ratio ,medicine.disease ,Surgery ,Internal medicine ,Cohort ,medicine ,KIF6 ,Myocardial infarction ,Cardiology and Cardiovascular Medicine ,business ,Pravastatin ,medicine.drug - Abstract
Objectives We asked whether 35 genetic polymorphisms, previously found to be associated with cardiovascular disease, were associated with myocardial infarction (MI) in the CARE (Cholesterol and Recurrent Events) trial and with coronary heart disease (CHD) in the WOSCOPS (West of Scotland Coronary Prevention Study) trial and whether the risk associated with these polymorphisms could be reduced by pravastatin treatment. Background Identification of genetic polymorphisms associated with CHD may improve assessment of CHD risk and understanding of disease pathophysiology. Methods We tested the association between genotype and recurrent MI in the CARE study and between genotype and primary CHD in the WOSCOPS trial using regression models that adjusted for conventional risk factors: Cox proportional hazards models for the CARE study and conditional logistic regression models for a nested case-control study of the WOSCOPS trial. Results We found that Trp719Arg (rs20455) in KIF6 was associated with coronary events. KIF6 encodes kinesin-like protein 6, a member of the molecular motor superfamily. In placebo-treated patients, carriers of the KIF6 719Arg allele (59.4% of the CARE trial cohort) had a hazard ratio of 1.50 (95% confidence interval [CI] 1.05 to 2.15) in the CARE trial and an odds ratio of 1.55 (95% CI 1.14 to 2.09) in the WOSCOPS trial. Among carriers, the absolute risk reduction by pravastatin was 4.89% (95% CI 1.81% to 7.97%) in the CARE trial and 5.49% (95% CI 3.52% to 7.46%) in the WOSCOPS trial. Conclusions In both the CARE and the WOSCOPS trials, carriers of the KIF6 719Arg allele had an increased risk of coronary events, and pravastatin treatment substantially reduced that risk.
- Published
- 2008
5. INCREASED CARDIOVASCULAR EVENT RATE OBSERVED IN STABLE CORONARY PATIENTS WITH METABOLIC SYNDROME COMPLICATED BY CHRONIC KIDNEY DISEASE IS REDUCED BY INTENSIVE LIPID LOWERING WITH ATORVASTATIN
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Prakash C. Deedwania, James Shepherd, Daniel J. Wilson, and null on behalf of the TNT Investigators
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Cardiovascular event ,medicine.medical_specialty ,business.industry ,Atorvastatin ,medicine.disease ,Internal medicine ,medicine ,Cardiology ,Lipid lowering ,Metabolic syndrome ,business ,Cardiology and Cardiovascular Medicine ,Kidney disease ,medicine.drug - Published
- 2010
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6. Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study
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James, Shepherd, John J P, Kastelein, Vera, Bittner, Prakash, Deedwania, Andrei, Breazna, Stephen, Dobson, Daniel J, Wilson, Andrea, Zuckerman, and Nanette K, Wenger
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Adult ,Male ,Risk ,Anticholesteremic Agents ,Cholesterol, LDL ,Coronary Artery Disease ,Middle Aged ,Lipids ,Double-Blind Method ,Heptanoic Acids ,Atorvastatin ,Humans ,Kidney Failure, Chronic ,Female ,Pyrroles ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Triglycerides ,Aged ,Glomerular Filtration Rate - Abstract
This subanalysis of the TNT (Treating to New Targets) study investigates the effects of intensive lipid lowering with atorvastatin in patients with coronary heart disease (CHD) with and without pre-existing chronic kidney disease (CKD).Cardiovascular disease is a major cause of morbidity and mortality in patients with CKD.A total of 10,001 patients with CHD were randomized to double-blind therapy with atorvastatin 80 mg/day or 10 mg/day. Patients with CKD were identified at baseline on the basis of an estimated glomerular filtration rate (eGFR)60 ml/min/1.73 m(2) using the Modification of Diet in Renal Disease equation. The primary efficacy outcome was time to first major cardiovascular event.Of 9,656 patients with complete renal data, 3,107 had CKD at baseline and demonstrated greater cardiovascular comorbidity than those with normal eGFR (n = 6,549). After a median follow-up of 5.0 years, 351 patients with CKD (11.3%) experienced a major cardiovascular event, compared with 561 patients with normal eGFR (8.6%) (hazard ratio [HR] = 1.35; 95% confidence interval [CI] 1.18 to 1.54; p0.0001). Compared with atorvastatin 10 mg, atorvastatin 80 mg reduced the relative risk of major cardiovascular events by 32% in patients with CKD (HR = 0.68; 95% CI 0.55 to 0.84; p = 0.0003) and 15% in patients with normal eGFR (HR = 0.85; 95% CI 0.72 to 1.00; p = 0.049). Both doses of atorvastatin were well tolerated in patients with CKD.Aggressive lipid lowering with atorvastatin 80 mg was both safe and effective in reducing the excess of cardiovascular events in a high-risk population with CKD and CHD.
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- 2007
7. RELATIONSHIP BETWEEN BASELINE LIPOPROTEIN PARAMETERS AND CHRONIC KIDNEY DISEASE IN CORONARY PATIENTS
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Andrei Breazna, Matti J. Tikkanen, John C. LaRosa, James Shepherd, Prakash Deedwania, Terje J. Pedersen, Anders G. Olsson, David DeMicco, and Ingar Holme
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medicine.medical_specialty ,business.industry ,Internal medicine ,medicine ,Cardiology ,nutritional and metabolic diseases ,lipids (amino acids, peptides, and proteins) ,Cardiology and Cardiovascular Medicine ,medicine.disease ,business ,Baseline (configuration management) ,Kidney disease ,Lipoprotein - Published
- 2013
8. The metabolic syndrome is an independent predictor of cardiac events in WOSCOPS males
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Ian Ford, James Shepherd, and Gilbert L'Italien
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medicine.medical_specialty ,business.industry ,Internal medicine ,Cardiology ,Medicine ,Metabolic syndrome ,business ,Independent predictor ,medicine.disease ,Cardiology and Cardiovascular Medicine - Published
- 2003
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9. INTENSIVE ATORVASTATIN TREATMENT REDUCES CARDIOVASCULAR EVENTS (CVE) IN THOSE WITH DYSLIPIDEMIA, CORONARY HEART DISEASE (CHD) AND WITH MILD OR MORE ADVANCED CHRONIC KIDNEY DISEASE (CKD): AN ANALYSIS OF THE TNT, IDEAL AND ALLIANCE TRIALS
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Daniel J. Wilson, Andrei Breazna, James Shepherd, Michael J. Koren, and Terje R. Pedersen
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medicine.medical_specialty ,Ideal (set theory) ,Framingham Risk Score ,business.industry ,Atorvastatin ,medicine.disease ,Coronary heart disease ,Internal medicine ,Cardiology ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,Dyslipidemia ,Kidney disease ,medicine.drug - Published
- 2011
10. CARDIOVASCULAR EVENT RATES IN STABLE CORONARY PATIENTS WITH CHRONIC KIDNEY DISEASE, INCREASED BY THE PRESENCE OF OBESITY, ARE REDUCED BY INTENSIVE LIPID LOWERING WITH ATORVASTATIN
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Daniel J. Wilson, James Shepherd, and Prakash Deedwania
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Cardiovascular event ,medicine.medical_specialty ,business.industry ,Atorvastatin ,urologic and male genital diseases ,medicine.disease ,Obesity ,female genital diseases and pregnancy complications ,Internal medicine ,Cardiology ,medicine ,Lipid lowering ,Cardiology and Cardiovascular Medicine ,business ,Kidney disease ,medicine.drug - Published
- 2010
11. RETRACTED: Prediction of Cardiovascular Events in Statin-Treated Stable Coronary Patients by Lipid and Nonlipid Biomarkers
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James Shepherd, Scott M. Grundy, Philip J. Barter, David D. Waters, Gregory M. Preston, Weihang Bao, John J.P. Kastelein, Benoit J. Arsenault, Heiner Greten, Nanette K. Wenger, David A. DeMicco, John C. LaRosa, Prakash Deedwania, Amsterdam Cardiovascular Sciences, and Vascular Medicine
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Male ,medicine.medical_specialty ,Time Factors ,Statin ,medicine.drug_class ,Atorvastatin ,Population ,Myocardial Infarction ,Coronary Disease ,law.invention ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Pyrroles ,Myocardial infarction ,cardiovascular diseases ,education ,Retrospective Studies ,education.field_of_study ,Dose-Response Relationship, Drug ,business.industry ,Incidence ,Incidence (epidemiology) ,Cholesterol, HDL ,Cholesterol, LDL ,Middle Aged ,Prognosis ,medicine.disease ,Surgery ,Stroke ,C-Reactive Protein ,Death, Sudden, Cardiac ,Heptanoic Acids ,Cardiology ,Biomarker (medicine) ,Population study ,Female ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Follow-Up Studies ,medicine.drug - Abstract
This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).The main findings of the TNT Trial were published in 2005 (1). Since that time, members of the Steering Committee and other investigators have published 32 papers based upon additional analyses of TNT. The data for these papers were derived from analyses of the TNT clinical database, managed by Pfizer. The clinical database has been crosschecked many times and the data in it is valid. During the trial, blood samples were drawn from the patients at regular intervals for subsequent analysis. We performed a nested case-control study that included 507 patients who experienced a CV event and 1,020 control patients in the main biomarker analysis, and 496 patients who experienced a CV event and 1,117 control patients in the PCSK9 analysis. The biomarker database was separate from the clinical database. An anonymization code was run in 2007 to link patients from one database to the other.In late 2012, the TNT frozen blood samples were integrated into a large automated biobank that includes samples from other Pfizer trials. At that time discrepancies were noted among the samples, indicating that an error had occurred when the samples were anonymized in 2007. Further investigation revealed that the code created to manually anonymize the data was accidentally run twice. During the first run, anonymized subject identifiers were successfully assigned to both biosamples and clinical data. However, after this first run had passed quality control checks, the anonymization code was re-run inadvertently, replacing the first correct set of identifiers with a random and incorrect set. We do not understand how or why the code was re-run. The study team, who were blinded as to patient identity, thus reported on mismatched clinical and biomarker data. The investigators of the biomarkers study were puzzled that none of the 18 biomarkers were predictive of cardiovascular events. However we were reassured because on-treatment LDL-cholesterol, HDL-cholesterol and triglyceride levels were all strongly predictive of events, and we reported this in the paper. These lipid levels were part of the clinical database, and thus were not subject to the error that occurred with the biomarkers. In the PCSK9 analysis, PCSK9 levels were predictive of events in the atorvastatin 10-mg group (p = 0.039) but not in the 80-mg group. This finding, which we now realize is totally spurious, was not unexpected and raised no red flags. Similarly, the failure of vitamin D levels to predict events, as reported in the AHJ paper, was not surprising.Since the error was discovered, we have created a new anonymized clinical and biomarker database by restoring the original set of anonymized identifiers. We are currently reanalyzing the data according to our original study plans. However, the nested case-control feature of the original study design has been lost because the patient selection for biomarker sampling was random. Only approximately one tenth of patients now had an event, compared to one third in the original study design. Thus, the power to detect a difference in the level of a biomarker between patients with and without events has been attenuated.All authors of these manuscripts are anguished to have made this mistake and publishing incorrect information.
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12. Retraction notice to 'Prediction of cardiovascular events in statin-treated patients by lipid and non-lipid biomarkers' [J Am Coll Cardiol 2011;57:63–69]
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Prakash Deedwania, David A. DeMicco, Weihang Bao, Philip J. Barter, Heiner Greten, Nanette K. Wenger, John C. LaRosa, James Shepherd, David D. Waters, Gregory M. Preston, Scott M. Grundy, Benoit J. Arsenault, and John J.P. Kastelein
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Pathology ,medicine.medical_specialty ,Statin ,medicine.drug_class ,business.industry ,Internal medicine ,medicine ,Cardiology and Cardiovascular Medicine ,Lipid biomarkers ,business - Abstract
Benoit J. Arsenault, PhD,* Philip Barter, MD, PhD,† David A. DeMicco, PharmD,‡ Weihang Bao, PhD,‡ Gregory M. Preston, PhD,‡ John C. LaRosa, MD,§ Scott M. Grundy, MD, PhD,‖ Prakash Deedwania, MD, PhD,¶ Heiner Greten, MD,# Nanette K. Wenger, MD,** James Shepherd, MD,†† David D. Waters, MD,‡‡ John J. P. Kastelein, MD, PhD,* for the TNT Study InvestigatorsFrom the *Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; †The Heart Research Institute, Sydney, Australia; ‡Pfizer, Inc., New York, New York; §State University of New York Health Science Center, Brooklyn, New York; ‖University of Texas Southwestern Medical Center, Dallas, Texas; ¶Veterans Affairs Central California Healthcare System and University of California San Francisco School of Medicine, San Francisco, California; #Universitätsklinikum, Eppendorf, Germany; **Emory University School of Medicine, Atlanta, Georgia; ††University of Glasgow, Glasgow, United Kingdom; and the ‡‡San Francisco General Hospital, San Francisco, CaliforniaThis article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the author.The main findings of the TNT Trial were published in 2005 (1). Since that time, members of the Steering Committee and other investigators have published 32 papers based upon additional analyses of TNT. The data for these papers were derived from analyses of the TNT clinical database, managed by Pfizer. The clinical database has been crosschecked many times and the data in it is valid. During the trial, blood samples were drawn from the patients at regular intervals for subsequent analysis. We performed a nested case-control study that included 507 patients who experienced a CV event and 1,020 control patients in the main biomarker analysis, and 496 patients who experienced a CV event and 1,117 control patients in the PCSK9 analysis. The biomarker database was separate from the clinical database. An anonymization code was run in 2007 to link patients from one database to the other.In late 2012, the TNT frozen blood samples were integrated into a large automated biobank that includes samples from other Pfizer trials. At that time discrepancies were noted among the samples, indicating that an error had occurred when the samples were anonymized in 2007. Further investigation revealed that the code created to manually anonymize the data was accidentally run twice. During the first run, anonymized subject identifiers were successfully assigned to both biosamples and clinical data. However, after this first run had passed quality control checks, the anonymization code was re-run inadvertently, replacing the first correct set of identifiers with a random and incorrect set. We do not understand how or why the code was re-run. The study team, who were blinded as to patient identity, thus reported on mismatched clinical and biomarker data. The investigators of the biomarkers study were puzzled that none of the 18 biomarkers were predictive of cardiovascular events. However we were reassured because on-treatment LDL-cholesterol, HDL-cholesterol and triglyceride levels were all strongly predictive of events, and we reported this in the paper. These lipid levels were part of the clinical database, and thus were not subject to the error that occurred with the biomarkers. In the PCSK9 analysis, PCSK9 levels were predictive of events in the atorvastatin 10-mg group (p = 0.039) but not in the 80-mg group. This finding, which we now realize is totally spurious, was not unexpected and raised no red flags. Similarly, the failure of vitamin D levels to predict events, as reported in the AHJ paper, was not surprising.Since the error was discovered, we have created a new anonymized clinical and biomarker database by restoring the original set of anonymized identifiers. We are currently reanalyzing the data according to our original study plans. However, the nested case-control feature of the original study design has been lost because the patient selection for biomarker sampling was random. Only approximately one tenth of patients now had an event, compared to one third in the original study design. Thus, the power to detect a difference in the level of a biomarker between patients with and without events has been attenuated.All authors of these manuscripts are anguished to have made this mistake and publishing incorrect information.
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- View/download PDF
13. Association of the 719Arg Variant of KIF6 With Both Increased Risk of Coronary Events and With Greater Response to Statin Therapy
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James Shepherd, Frank M. Sacks, and Olga Iakoubova
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medicine.medical_specialty ,business.industry ,Anticholesteremic Agents ,education ,Kinesins ,Coronary Artery Disease ,Statin treatment ,Arginine ,Polymorphism, Single Nucleotide ,humanities ,Coronary heart disease ,Article ,Increased risk ,Risk Factors ,Internal medicine ,medicine ,Physical therapy ,KIF6 ,Humans ,Statin therapy ,Allele ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Cardiology and Cardiovascular Medicine - Abstract
We read with interest the editorial comment ([1][1]) accompanying 3 reports that described the association of the 719Arg allele of KIF6 with both increased risk of coronary heart disease and with response to statin treatment ([2–4][2]). However, we would like to comment on 2 assertions made in
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