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Coronary Artery Disease: HELP
Articles by L. Kristin Newby
Based on 28 articles published since 2010
(Why 28 articles?)
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Between 2010 and 2020, L. Kristin Newby wrote the following 28 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Guideline 2016 ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 2016

Levine, Glenn N / Bates, Eric R / Bittl, John A / Brindis, Ralph G / Fihn, Stephan D / Fleisher, Lee A / Granger, Christopher B / Lange, Richard A / Mack, Michael J / Mauri, Laura / Mehran, Roxana / Mukherjee, Debabrata / Newby, L Kristin / O'Gara, Patrick T / Sabatine, Marc S / Smith, Peter K / Smith, Sidney C / Halperin, Jonathan L / Levine, Glenn N / Al-Khatib, Sana M / Birtcher, Kim K / Bozkurt, Biykem / Brindis, Ralph G / Cigarroa, Joaquin E / Curtis, Lesley H / Fleisher, Lee A / Gentile, Federico / Gidding, Samuel / Hlatky, Mark A / Ikonomidis, John S / Joglar, José A / Pressler, Susan J / Wijeysundera, Duminda N. · ·J Thorac Cardiovasc Surg · Pubmed #27751237.

ABSTRACT: -- No abstract --

2 Guideline 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. 2016

Levine, Glenn N / Bates, Eric R / Bittl, John A / Brindis, Ralph G / Fihn, Stephan D / Fleisher, Lee A / Granger, Christopher B / Lange, Richard A / Mack, Michael J / Mauri, Laura / Mehran, Roxana / Mukherjee, Debabrata / Newby, L Kristin / O'Gara, Patrick T / Sabatine, Marc S / Smith, Peter K / Smith, Sidney C. · ·J Am Coll Cardiol · Pubmed #27036918.

ABSTRACT: -- No abstract --

3 Editorial Implications of High-Sensitivity Troponin Testing: Learning From Those Who Came Before Us. 2018

Newby, L Kristin / Lowenstern, Angela. ·Division of Cardiology, Department of Medicine, and the Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. Electronic address: kristin.newby@duke.edu. · Division of Cardiology, Department of Medicine, and the Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. ·J Am Coll Cardiol · Pubmed #29880122.

ABSTRACT: -- No abstract --

4 Editorial Sex, Region, and Outcomes After Revascularization. 2017

Newby, L Kristin. ·From the Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC. kristin.newby@duke.edu. ·Circ Cardiovasc Interv · Pubmed #28495900.

ABSTRACT: -- No abstract --

5 Editorial Back to the future: improving the use of guidelines-recommended coronary disease secondary prevention at the dawn of the precision medicine era. 2015

Rymer, Jennifer A / Newby, L Kristin. ·From Division of Cardiology, Department of Medicine (J.A.R., L.K.N.) and Duke Clinical Research Institute (L.K.N.), Duke University Medical Center, Durham, NC. · From Division of Cardiology, Department of Medicine (J.A.R., L.K.N.) and Duke Clinical Research Institute (L.K.N.), Duke University Medical Center, Durham, NC. kristin.newby@duke.edu. ·Circulation · Pubmed #25847978.

ABSTRACT: -- No abstract --

6 Editorial Applying the evidence in coronary disease secondary prevention: a call to action. 2014

Newby, L Kristin. ·Division of Cardiology, Department of Medicine and Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. Electronic address: kristin.newby@duke.edu. ·J Am Coll Cardiol · Pubmed #24184241.

ABSTRACT: -- No abstract --

7 Review Chronic Kidney Disease and Coronary Artery Disease: JACC State-of-the-Art Review. 2019

Sarnak, Mark J / Amann, Kerstin / Bangalore, Sripal / Cavalcante, João L / Charytan, David M / Craig, Jonathan C / Gill, John S / Hlatky, Mark A / Jardine, Alan G / Landmesser, Ulf / Newby, L Kristin / Herzog, Charles A / Cheung, Michael / Wheeler, David C / Winkelmayer, Wolfgang C / Marwick, Thomas H / Anonymous1091188. ·Division of Nephrology, Tufts Medical Center, Boston, Massachusetts. Electronic address: msarnak@tuftsmedicalcenter.org. · Department of Nephropathology, University Hospital Erlangen, Erlangen, Germany. · Division of Cardiology, New York University School of Medicine, New York, New York. · Minneapolis Heart Institute, Minneapolis, Minnesota. · Division of Nephrology, New York University School of Medicine, New York, New York. · College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia. · Division of Nephrology, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia, Canada. · Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California. · Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom. · Department of Cardiology, Charité Universitätsmedizin, Berlin, Germany. · Division of Cardiology, Department of Medicine and Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. · Division of Cardiology, Department of Medicine, Hennepin County Medical Center and University of Minnesota, Minneapolis, Minnesota; Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota. · Kidney Disease: Improving Global Outcomes, Brussels, Belgium. · University College London, London, United Kingdom. · Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas. · Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. Electronic address: tom.marwick@baker.edu.au. ·J Am Coll Cardiol · Pubmed #31582143.

ABSTRACT: Chronic kidney disease (CKD) is a major risk factor for coronary artery disease (CAD). As well as their high prevalence of traditional CAD risk factors, such as diabetes and hypertension, persons with CKD are also exposed to other nontraditional, uremia-related cardiovascular disease risk factors, including inflammation, oxidative stress, and abnormal calcium-phosphorus metabolism. CKD and end-stage kidney disease not only increase the risk of CAD, but they also modify its clinical presentation and cardinal symptoms. Management of CAD is complicated in CKD patients, due to their likelihood of comorbid conditions and potential for side effects during interventions. This summary of the Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference on CAD and CKD (including end-stage kidney disease and transplant recipients) seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of CAD in CKD and to identify knowledge gaps, areas of controversy, and priorities for research.

8 Review Failure to Launch: Targeting Inflammation in Acute Coronary Syndromes. 2017

Rymer, Jennifer A / Newby, L Kristin. ·Division of Cardiology, Department of Medicine, and Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. ·JACC Basic Transl Sci · Pubmed #30062164.

ABSTRACT: The importance of inflammation and inflammatory pathways in atherosclerotic disease and acute coronary syndromes (ACS) is well established. The success of statin therapy rests not only on potently reducing levels of low-density lipoprotein cholesterol, but also on the many beneficial, pleiotropic effects statin therapy has on various inflammatory mechanisms in atherosclerotic disease, from reducing endothelial dysfunction to attenuating levels of serum C-reactive protein. Due to the growing awareness of the importance of inflammation in ACS, investigators have attempted to develop novel therapies against known markers of inflammation for several decades. Targeted pathways have ranged from inhibiting C5 cleavage with a high-affinity monoclonal antibody against C5 to inhibiting the activation of the p38 mitogen-activated protein kinase signaling cascades. In each of these instances, despite promising early preclinical and mechanistic studies and phase 2 trials suggesting a potential benefit in reducing post-MI complications or restenosis, these novel therapies have failed to show benefits during large, phase 3 clinical outcomes trials. This review discusses several examples of novel anti-inflammatory therapies that failed to show significant improvement on clinical outcomes when tested in large, randomized trials and highlights potential explanations for why targeted therapies against known markers of inflammation in ACS have failed to launch.

9 Review 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention, 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease, 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, 2014 AHA/ACC Guideline for the Management of Patients With Non-ST-Elevation Acute Coronary Syndromes, and 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery. 2016

Levine, Glenn N / Bates, Eric R / Bittl, John A / Brindis, Ralph G / Fihn, Stephan D / Fleisher, Lee A / Granger, Christopher B / Lange, Richard A / Mack, Michael J / Mauri, Laura / Mehran, Roxana / Mukherjee, Debabrata / Newby, L Kristin / O'Gara, Patrick T / Sabatine, Marc S / Smith, Peter K / Smith, Sidney C. ·Focused Update writing group members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ACC/AHA Representative. Evidence Review Committee Chair. American Society of Anesthesiologists/Society of Cardiovascular Anesthesiologists Representative. American Association for Thoracic Surgery/Society of Thoracic Surgeons Representative. Society for Cardiovascular Angiography and Interventions Representative. ·Circulation · Pubmed #27026020.

ABSTRACT: -- No abstract --

10 Clinical Trial Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients. 2010

Rosenberg, Steven / Elashoff, Michael R / Beineke, Philip / Daniels, Susan E / Wingrove, James A / Tingley, Whittemore G / Sager, Philip T / Sehnert, Amy J / Yau, May / Kraus, William E / Newby, L Kristin / Schwartz, Robert S / Voros, Szilard / Ellis, Stephen G / Tahirkheli, Naeem / Waksman, Ron / McPherson, John / Lansky, Alexandra / Winn, Mary E / Schork, Nicholas J / Topol, Eric J / Anonymous15950674. ·CardioDx, Palo Alto, California, USA. ·Ann Intern Med · Pubmed #20921541.

ABSTRACT: BACKGROUND: Diagnosing obstructive coronary artery disease (CAD) in at-risk patients can be challenging and typically requires both noninvasive imaging methods and coronary angiography, the gold standard. Previous studies have suggested that peripheral blood gene expression can indicate the presence of CAD. OBJECTIVE: To validate a previously developed 23-gene, expression-based classification test for diagnosis of obstructive CAD in nondiabetic patients. DESIGN: Multicenter prospective trial with blood samples obtained before coronary angiography. (ClinicalTrials.gov registration number: NCT00500617) SETTING: 39 centers in the United States. PATIENTS: An independent validation cohort of 526 nondiabetic patients with a clinical indication for coronary angiography. MEASUREMENTS: Receiver-operating characteristic (ROC) analysis of classifier score measured by real-time polymerase chain reaction, additivity to clinical factors, and reclassification of patient disease likelihood versus disease status defined by quantitative coronary angiography. Obstructive CAD was defined as 50% or greater stenosis in 1 or more major coronary arteries by quantitative coronary angiography. RESULTS: The area under the ROC curve (AUC) was 0.70 ± 0.02 (P < 0.001); the test added to clinical variables (Diamond-Forrester method) (AUC, 0.72 with the test vs. 0.66 without; P = 0.003) and added somewhat to an expanded clinical model (AUC, 0.745 with the test vs. 0.732 without; P = 0.089). The test improved net reclassification over both the Diamond-Forrester method and the expanded clinical model (P < 0.001). At a score threshold that corresponded to a 20% likelihood of obstructive CAD (14.75), the sensitivity and specificity were 85% and 43% (yielding a negative predictive value of 83% and a positive predictive value of 46%), with 33% of patient scores below this threshold. LIMITATION: Patients with chronic inflammatory disorders, elevated levels of leukocytes or cardiac protein markers, or diabetes were excluded. CONCLUSION: A noninvasive whole-blood test based on gene expression and demographic characteristics may be useful for assessing obstructive CAD in nondiabetic patients without known CAD. PRIMARY FUNDING SOURCE: CardioDx.

11 Article In STEMI with multivessel CAD, complete revascularization reduced CV death or MI more than culprit lesion-only PCI. 2019

Lowenstern, Angela / Newby, L Kristin. · ·Ann Intern Med · Pubmed #31842221.

ABSTRACT: -- No abstract --

12 Article A Proposal for Modest Revision of the Definition of Type 1 and Type 2 Myocardial Infarction. 2019

de Lemos, James A / Newby, L Kristin / Mills, Nicholas L. ·Division of Cardiology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas (J.A.d.L.). · Division of Cardiology, Department of Medicine, Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (L.K.N.). · British Heart Foundation Centre for Cardiovascular Science and Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, United Kingdom (N.L.M.). ·Circulation · Pubmed #31765259.

ABSTRACT: -- No abstract --

13 Article Provocative biomarker stress test: stress-delta N-terminal pro-B type natriuretic peptide. 2018

Limkakeng, Alexander T / Leahy, J Clancy / Griffin, S Michelle / Lokhnygina, Yuliya / Jaffa, Elias / Christenson, Robert H / Newby, L Kristin. ·Division of Emergency Medicine, Duke University School of Medicine, Durham, North Carolina, USA. · Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA. · Department of Pathology, University of Maryland School of Medicine, Baltimore, USA. · Division of Cardiology, Department of Medicine, Duke Clinical Research Institute, Durham, North Carolina, USA. ·Open Heart · Pubmed #30364466.

ABSTRACT: Objective: Stress testing is commonly performed in emergency department (ED) patients with suspected acute coronary syndrome (ACS). We hypothesised that changes in N-terminal pro-B type natriuretic peptide (NT-proBNP) concentrations from baseline to post-stress testing (stress-delta values) differentiate patients with ischaemic stress tests from controls. Methods: We prospectively enrolled 320 adult patients with suspected ACS in an ED-based observation unit who were undergoing exercise stress echocardiography. We measured plasma NT-proBNP concentrations at baseline and at 2 and 4  hours post-stress and compared stress-delta NT-proBNP between patients with abnormal stress tests versus controls using non-parametric statistics (Wilcoxon test) due to skew. We calculated the diagnostic test characteristics of stress-delta NT-proBNP for myocardial ischaemia on imaging. Results: Among 320 participants, the median age was 51 (IQR 44-59) years, 147 (45.9%) were men, and 122 (38.1%) were African-American. Twenty-six (8.1%) had myocardial ischaemia. Static and stress-deltas NT-proBNP differed at all time points between groups. The median stress-deltas at 2  hours were 10.4 (IQR 6.0-51.7) ng/L vs 1.7 (IQR -0.4 to 8.7) ng/L, and at 4  hours were 14.8 (IQR 5.0-22.3) ng/L vs 1.0 (-2.0 to 10.3) ng/L for patients with ischaemia versus those without. Areas under the receiver operating curves were 0.716 and 0.719 for 2-hour and 4-hour stress-deltas, respectively. After adjusting for baseline NT-proBNP levels, the 4-hour stress-delta NT-proBNP remained significantly different between the groups (p=0.009). Conclusion: Among patients with ischaemic stress tests, static and 4-hour stress-delta NT-proBNP values were significantly higher. Further study is needed to determine if stress-delta NT-proBNP is a useful adjunct to stress testing.

14 Article Pooled RCTs: CABG reduces mortality more than PCI with DES in nondiabetic patients with multivessel CAD. 2016

Rymer, Jennifer A / Newby, L Kristin. ·Duke University Medical CenterDurham, North Carolina, USA. ·Ann Intern Med · Pubmed #27842388.

ABSTRACT: -- No abstract --

15 Article A registry-based randomized trial comparing radial and femoral approaches in women undergoing percutaneous coronary intervention: the SAFE-PCI for Women (Study of Access Site for Enhancement of PCI for Women) trial. 2014

Rao, Sunil V / Hess, Connie N / Barham, Britt / Aberle, Laura H / Anstrom, Kevin J / Patel, Tejan B / Jorgensen, Jesse P / Mazzaferri, Ernest L / Jolly, Sanjit S / Jacobs, Alice / Newby, L Kristin / Gibson, C Michael / Kong, David F / Mehran, Roxana / Waksman, Ron / Gilchrist, Ian C / McCourt, Brian J / Messenger, John C / Peterson, Eric D / Harrington, Robert A / Krucoff, Mitchell W. ·The Duke Clinical Research Institute, Durham, North Carolina. Electronic address: sunil.rao@duke.edu. · The Duke Clinical Research Institute, Durham, North Carolina. · Unity Health System, Rochester, New York. · University of South Carolina School of Medicine-Greenville, Greenville, South Carolina. · The Ohio State University Medical Center, Columbus, Ohio. · McMaster University, Hamilton, Ontario, Canada. · Boston University School of Medicine, Boston, Massachusetts. · Beth Israel Deaconess Medical Center, Boston, Massachusetts. · Mount Sinai Hospital, New York, New York. · Washington Hospital Center, Washington, DC. · Penn State Hershey Medical Center, Hershey, Pennsylvania. · The American College of Cardiology, Washington, DC. · Stanford University Medical Center, Palo Alto, California. ·JACC Cardiovasc Interv · Pubmed #25147030.

ABSTRACT: OBJECTIVES: This study sought to determine the effect of radial access on outcomes in women undergoing percutaneous coronary intervention (PCI) using a registry-based randomized trial. BACKGROUND: Women are at increased risk of bleeding and vascular complications after PCI. The role of radial access in women is unclear. METHODS: Women undergoing cardiac catheterization or PCI were randomized to radial or femoral arterial access. Data from the CathPCI Registry and trial-specific data were merged into a final study database. The primary efficacy endpoint was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding or vascular complications requiring intervention. The primary feasibility endpoint was access site crossover. The primary analysis cohort was the subgroup undergoing PCI; sensitivity analyses were conducted in the total randomized population. RESULTS: The trial was stopped early for a lower than expected event rate. A total of 1,787 women (691 undergoing PCI) were randomized at 60 sites. There was no significant difference in the primary efficacy endpoint between radial or femoral access among women undergoing PCI (radial 1.2% vs. 2.9% femoral, odds ratio [OR]: 0.39; 95% confidence interval [CI]: 0.12 to 1.27); among women undergoing cardiac catheterization or PCI, radial access significantly reduced bleeding and vascular complications (0.6% vs. 1.7%; OR: 0.32; 95% CI: 0.12 to 0.90). Access site crossover was significantly higher among women assigned to radial access (PCI cohort: 6.1% vs. 1.7%; OR: 3.65; 95% CI: 1.45 to 9.17); total randomized cohort: (6.7% vs. 1.9%; OR: 3.70; 95% CI: 2.14 to 6.40). More women preferred radial access. CONCLUSIONS: In this pragmatic trial, which was terminated early, the radial approach did not significantly reduce bleeding or vascular complications in women undergoing PCI. Access site crossover occurred more often in women assigned to radial access. (SAFE-PCI for Women; NCT01406236).

16 Article ACP Journal Club. Review: CABG reduces long-term mortality and morbidity more than PCI in multivessel coronary disease. 2014

Harskamp, Ralf E / Newby, L Kristin. · ·Ann Intern Med · Pubmed #24733226.

ABSTRACT: -- No abstract --

17 Article Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. 2014

Bhattacharya, Sayanti / Granger, Christopher B / Craig, Damian / Haynes, Carol / Bain, James / Stevens, Robert D / Hauser, Elizabeth R / Newgard, Christopher B / Kraus, William E / Newby, L Kristin / Shah, Svati H. ·Duke Global Health Institute, Durham, NC, USA; Duke Institute of Molecular Physiology, Durham, NC, USA. Electronic address: sayanti.bhattacharya@duke.edu. · Division of Cardiovascular Medicine, Duke University School of Medicine, Durham, NC, USA; Duke Clinical Research Institute, Durham, NC, USA. Electronic address: christopher.granger@duke.edu. · Duke Institute of Molecular Physiology, Durham, NC, USA. Electronic address: damian.craig@duke.edu. · Duke Institute of Molecular Physiology, Durham, NC, USA. Electronic address: carol.haynes@duke.edu. · Duke Institute of Molecular Physiology, Durham, NC, USA. Electronic address: james.bain@duke.edu. · Duke Institute of Molecular Physiology, Durham, NC, USA. Electronic address: rdjestev@duke.edu. · Duke Institute of Molecular Physiology, Durham, NC, USA. Electronic address: elizabeth.hauser@duke.edu. · Duke Institute of Molecular Physiology, Durham, NC, USA. Electronic address: newga002@mc.duke.edu. · Duke Institute of Molecular Physiology, Durham, NC, USA. Electronic address: william.kraus@duke.edu. · Division of Cardiovascular Medicine, Duke University School of Medicine, Durham, NC, USA; Duke Clinical Research Institute, Durham, NC, USA. Electronic address: kristin.newby@duke.edu. · Duke Global Health Institute, Durham, NC, USA; Duke Institute of Molecular Physiology, Durham, NC, USA; Division of Cardiovascular Medicine, Duke University School of Medicine, Durham, NC, USA; Duke Clinical Research Institute, Durham, NC, USA. Electronic address: svati.shah@duke.edu. ·Atherosclerosis · Pubmed #24401236.

ABSTRACT: OBJECTIVE: To validate independent associations between branched-chain amino acids (BCAA) and other metabolites with coronary artery disease (CAD). METHODS: We conducted mass-spectrometry-based profiling of 63 metabolites in fasting plasma from 1983 sequential patients undergoing cardiac catheterization. Significant CAD was defined as CADindex ≥ 32 (at least one vessel with ≥ 95% stenosis; N = 995) and no CAD as CADindex ≤ 23 and no previous cardiac events (N = 610). Individuals (N = 378) with CAD severity between these extremes were excluded. Principal components analysis (PCA) reduced large numbers of correlated metabolites into uncorrelated factors. Association between metabolite factors and significant CAD vs. no CAD was tested using logistic regression; and between metabolite factors and severity of CAD was tested using linear regression. RESULTS: Of twelve PCA-derived metabolite factors, two were associated with CAD in multivariable models: factor 10, composed of BCAA (adjusted odds ratio, OR, 1.20; 95% CI 1.05-1.35, p = 0.005) and factor 7, composed of short-chain acylcarnitines, which include byproducts of BCAA metabolism (adjusted OR 1.30; 95% CI 1.14-1.48, p = 0.001). After adjustment for glycated albumin (marker of insulin resistance [IR]) both factors 7 (p = 0.0001) and 10 (p = 0.004) remained associated with CAD. Severity of CAD as a continuous variable (including patients with non-obstructive disease) was associated with metabolite factors 2, 3, 6, 7, 8 and 9; only factors 7 and 10 were associated in multivariable models. CONCLUSIONS: We validated the independent association of metabolites involved in BCAA metabolism with CAD extremes. These metabolites may be reporting on novel mechanisms of CAD pathogenesis that are independent of IR and diabetes.

18 Article Aspirin exposure reveals novel genes associated with platelet function and cardiovascular events. 2013

Voora, Deepak / Cyr, Derek / Lucas, Joseph / Chi, Jen-Tsan / Dungan, Jennifer / McCaffrey, Timothy A / Katz, Richard / Newby, L Kristin / Kraus, William E / Becker, Richard C / Ortel, Thomas L / Ginsburg, Geoffrey S. ·Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina; Department of Medicine, Duke University, Durham, North Carolina. Electronic address: deepak.voora@duke.edu. · Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina. · Department of Medicine, Duke University, Durham, North Carolina. · Division of Genomic Medicine, The George Washington University/Medical Faculty Associates, Washington, DC. · Division of Cardiology, Department of Medicine, The George Washington University/Medical Faculty Associates, Washington, DC. · Institute for Genome Sciences & Policy, Duke University, Durham, North Carolina; Department of Medicine, Duke University, Durham, North Carolina. Electronic address: geoffrey.ginsburg@duke.edu. ·J Am Coll Cardiol · Pubmed #23831034.

ABSTRACT: OBJECTIVES: The aim of this study was to develop ribonucleic acid (RNA) profiles that could serve as novel biomarkers for the response to aspirin. BACKGROUND: Aspirin reduces death and myocardial infarction (MI), suggesting that aspirin interacts with biological pathways that may underlie these events. METHODS: Aspirin was administered, followed by whole-blood RNA microarray profiling, in a discovery cohort of healthy volunteers (HV1) (n = 50) and 2 validation cohorts of healthy volunteers (HV2) (n = 53) and outpatient cardiology patients (OPC) (n = 25). Platelet function was assessed using the platelet function score (PFS) in HV1 and HV2 and the VerifyNow Aspirin Test (Accumetrics, Inc., San Diego, California) in OPC. Bayesian sparse factor analysis identified sets of coexpressed transcripts, which were examined for associations with PFS in HV1 and validated in HV2 and OPC. Proteomic analysis confirmed the association of validated transcripts in platelet proteins. Validated gene sets were tested for association with death or MI in 2 patient cohorts (n = 587 total) from RNA samples collected at cardiac catheterization. RESULTS: A set of 60 coexpressed genes named the "aspirin response signature" (ARS) was associated with PFS in HV1 (r = -0.31, p = 0.03), HV2 (r = -0.34, Bonferroni p = 0.03), and OPC (p = 0.046). Corresponding proteins for the 17 ARS genes were identified in the platelet proteome, of which 6 were associated with PFS. The ARS was associated with death or MI in both patient cohorts (odds ratio: 1.2 [p = 0.01]; hazard ratio: 1.5 [p = 0.001]), independent of cardiovascular risk factors. Compared with traditional risk factors, reclassification (net reclassification index = 31% to 37%, p ≤ 0.0002) was improved by including the ARS or 1 of its genes, ITGA2B. CONCLUSIONS: RNA profiles of platelet-specific genes are novel biomarkers for identifying patients who do not respond adequately to aspirin and who are at risk for death or MI.

19 Article Antithrombotic therapy for atrial fibrillation and coronary artery disease in older patients. 2012

Hess, Connie N / Broderick, Samuel / Piccini, Jonathan P / Alexander, Karen P / Newby, L Kristin / Shaw, Linda K / Mahaffey, Kenneth W / Alexander, John H / Peterson, Eric D / Granger, Christopher B / Lopes, Renato D. ·Duke Clinical Research Institute, Durham, NC 27705, USA. ·Am Heart J · Pubmed #23067921.

ABSTRACT: BACKGROUND: Older patients with atrial fibrillation (AF) and coronary artery disease (CAD) face high risk of stroke and bleeding with antithrombotic therapy. Balancing safe and effective use of aspirin, clopidogrel, and warfarin in this population is important. METHODS: From the Duke Databank for Cardiovascular Disease, we identified patients with AF ≥65 years old with angiographically confirmed CAD from 2000 to 2010. Antithrombotic use was described across age and Congestive heart failure, Hypertension, Age >75 years, Diabetes, prior Stroke/transient ischemic attack (CHADS(2)) stroke risk and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) bleeding scores. Death and the composite of death, myocardial infarction, and stroke by antithrombotic strategy were reported. RESULTS: Of 2,122 patients ≥65 years old with AF and CAD, 477 (22.5%) were ≥80 years old; 1,133 (53.4%) had acute coronary syndromes. Overall rates of aspirin, clopidogrel, and warfarin use were 83.4%, 34.6%, and 38.9%, respectively. Compared with patients 65 to 79 years old, more patients ≥80 years old were at high stroke risk (CHADS(2) ≥2, 84.7% vs 57.8%) and high bleeding risk (ATRIA 5-10, 55.8% vs 23.3%). Warfarin use in both age groups increased with higher CHADS(2) scores and decreased with higher ATRIA scores. Of patients ≥80 years old with CHADS(2) ≥2, 150 (38.2%) received warfarin. Antithrombotic strategy was not associated with improved 1-year adjusted outcomes. CONCLUSIONS: Among older patients with AF and CAD, overall warfarin use was low. Patients ≥80 years old at highest stroke risk received warfarin in similar proportions to the overall cohort. Further investigation into optimizing antithrombotic strategies in this population is warranted.

20 Article Nighttime blood pressure dipping in postmenopausal women with coronary heart disease. 2012

Sherwood, Andrew / Bower, Julie K / Routledge, Faye S / Blumenthal, James A / McFetridge-Durdle, Judith A / Newby, L Kristin / Hinderliter, Alan L. ·Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA. sherw002@mc.duke.edu ·Am J Hypertens · Pubmed #22785406.

ABSTRACT: BACKGROUND: Blunted nighttime blood pressure (BP) dipping is prognostic of cardiovascular morbidity and mortality. This relationship may be stronger among women than men. The present study hypothesized that coronary artery disease (CAD) and advancing age would be associated with reduced BP dipping in postmenopausal women. The effects of daytime physical activity and nighttime sleep quality on BP dipping were also examined. METHODS: 54 postmenopausal women with CAD (≥50% occlusion of at least one major coronary vessel) and 48 age-matched (range 50-80 years) postmenopausal women without CAD (non-CAD) underwent 24-h ambulatory BP monitoring and actigraphic evaluations of daytime physical activity and nighttime sleep efficiency. RESULTS: Women with CAD evidenced higher nighttime systolic BP (SBP) (P = 0.05) and blunted SBP dipping (P = 0.017), blunted diastolic BP (DBP) dipping (P = 0.047), and blunted pulse pressure dipping (P = 0.01), compared to non-CAD women. Multivariable regression models showed that the presence of CAD, age, daytime physical activity, and nighttime sleep efficiency were independently related to the magnitude of SBP dipping, together accounting for 25% of its variability. DBP dipping showed similar associations. CONCLUSIONS: For postmenopausal women, the presence of CAD and advancing age are accompanied by blunted nighttime BP dipping, which may increase the risk of adverse cardiovascular events. Lifestyle changes that increase daytime physical activity and improve nighttime sleep quality may help improve cardiovascular risk by enhancing nighttime BP dipping.

21 Article Baseline metabolomic profiles predict cardiovascular events in patients at risk for coronary artery disease. 2012

Shah, Svati H / Sun, Jie-Lena / Stevens, Robert D / Bain, James R / Muehlbauer, Michael J / Pieper, Karen S / Haynes, Carol / Hauser, Elizabeth R / Kraus, William E / Granger, Christopher B / Newgard, Christopher B / Califf, Robert M / Newby, L Kristin. ·Division of Cardiovascular Medicine, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. svati.shah@duke.edu ·Am Heart J · Pubmed #22607863.

ABSTRACT: BACKGROUND: Cardiovascular risk models remain incomplete. Small-molecule metabolites may reflect underlying disease and, as such, serve as novel biomarkers of cardiovascular risk. METHODS: We studied 2,023 consecutive patients undergoing cardiac catheterization. Mass spectrometry profiling of 69 metabolites and lipid assessments were performed in fasting plasma. Principal component analysis reduced metabolites to a smaller number of uncorrelated factors. Independent relationships between factors and time-to-clinical events were assessed using Cox modeling. Clinical and metabolomic models were compared using log-likelihood and reclassification analyses. RESULTS: At median follow-up of 3.1 years, there were 232 deaths and 294 death/myocardial infarction (MI) events. Five of 13 metabolite factors were independently associated with mortality: factor 1 (medium-chain acylcarnitines: hazard ratio [HR] 1.12 [95% CI, 1.04-1.21], P = .005), factor 2 (short-chain dicarboxylacylcarnitines: HR 1.17 [1.05-1.31], P = .005), factor 3 (long-chain dicarboxylacylcarnitines: HR 1.14 [1.05-1.25], P = .002); factor 6 (branched-chain amino acids: HR 0.86 [0.75-0.99], P = .03), and factor 12 (fatty acids: HR 1.19 [1.06-1.35], P = .004). Three factors independently predicted death/MI: factor 2 (HR 1.11 [1.01-1.23], P = .04), factor 3 (HR 1.13 [1.04-1.22], P = .005), and factor 12 (HR 1.18 [1.05-1.32], P = .004). For mortality, 27% of intermediate-risk patients were correctly reclassified (net reclassification improvement 8.8%, integrated discrimination index 0.017); for death/MI model, 11% were correctly reclassified (net reclassification improvement 3.9%, integrated discrimination index 0.012). CONCLUSIONS: Metabolic profiles predict cardiovascular events independently of standard predictors.

22 Article Metabolic profiles predict adverse events after coronary artery bypass grafting. 2012

Shah, Asad A / Craig, Damian M / Sebek, Jacqueline K / Haynes, Carol / Stevens, Robert C / Muehlbauer, Michael J / Granger, Christopher B / Hauser, Elizabeth R / Newby, L Kristin / Newgard, Christopher B / Kraus, William E / Hughes, G Chad / Shah, Svati H. ·Division of Thoracic and Cardiovascular Surgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. ·J Thorac Cardiovasc Surg · Pubmed #22306227.

ABSTRACT: OBJECTIVE: Clinical models incompletely predict the outcomes after coronary artery bypass grafting. Novel molecular technologies can identify biomarkers to improve risk stratification. We examined whether metabolic profiles can predict adverse events in patients undergoing coronary artery bypass grafting. METHODS: The study population comprised 478 subjects from the CATHGEN biorepository of patients referred for cardiac catheterization who underwent coronary artery bypass grafting after enrollment. Targeted mass spectrometry-based profiling of 69 metabolites was performed in frozen, fasting plasma samples collected before surgery. Principal components analysis and Cox proportional hazards regression modeling were used to assess the relation between the metabolite factor levels and a composite outcome of postcoronary artery bypass grafting myocardial infarction, the need for percutaneous coronary intervention, repeat coronary artery bypass grafting, and death. RESULTS: During a mean follow-up period of 4.3 ± 2.4 years, 126 subjects (26.4%) experienced an adverse event. Three principal components analysis-derived factors were significantly associated with an adverse outcome on univariate analysis: short-chain dicarboxylacylcarnitines (factor 2, P = .001); ketone-related metabolites (factor 5, P = .02); and short-chain acylcarnitines (factor 6, P = .004). These 3 factors remained independently predictive of an adverse outcome after multivariate adjustment: factor 2 (adjusted hazard ratio, 1.23; 95% confidence interval, 1.10-1.38; P < .001), factor 5 (odds ratio, 1.17; 95% confidence interval, 1.01-1.37; P = .04), and factor 6 (odds ratio, 1.14; 95% confidence interval, 1.02-1.27; P = .03). CONCLUSIONS: Metabolic profiles are independently associated with adverse outcomes after coronary artery bypass grafting. These profiles might represent novel biomarkers of risk that can augment existing tools for risk stratification of coronary artery bypass grafting patients and might elucidate novel biochemical pathways that mediate risk.

23 Article Effect of heparin administration on metabolomic profiles in samples obtained during cardiac catheterization. 2011

Brunner, Michael P / Shah, Svati H / Craig, Damian M / Stevens, Robert D / Muehlbauer, Michael J / Bain, James R / Newgard, Christopher B / Kraus, William E / Granger, Christopher B / Sketch, Michael H / Newby, L Kristin. ·Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. ·Circ Cardiovasc Genet · Pubmed #22010138.

ABSTRACT: BACKGROUND: Metabolic profiling holds promise for early detection of coronary artery disease and assessing risk for ischemic events. Heparin is frequently administered (1) to treat acute coronary syndromes; and (2) during routine cardiac catheterization procedures. Because it stimulates lipolysis, heparin is a potential confounder of metabolic profiling in these populations. METHODS AND RESULTS: Using mass spectrometry and conventional immunoassays, we evaluated how unfractionated heparin administration affected 69 peripheral blood metabolites (acylcarnitines, amino acids, nonesterified fatty acids and their oxidation byproducts, conventional lipids, glucose, and C-reactive protein) in samples obtained pre- and postcardiac catheterization from 19 patients who received heparin and 10 patients who did not. Using unpaired t tests, we compared the changes in mean metabolite levels before and after the procedure between the nonheparin and heparin groups. Clinical characteristics of the nonheparin and heparin groups, indication for cardiac catheterization, procedure performed, and other periprocedural variables were similar. The mean change between pre- and postprocedure β-hydroxybutyrate (5.43 versus 66.84 μmol/L; P=0.009), ketones (21.17 versus 98.49 μmol/L; P=0.009), nonesterified fatty acids (0.37 versus 1.20 mmol/L; P=0.017), and triglycerides (-9.33 versus -36.50 mg/dL; P=0.007) was significantly different between the nonheparin and heparin groups, respectively. There were no significant differences between groups in the other metabolites measured. CONCLUSIONS: Heparin administration during cardiac catheterization induced changes in peripheral blood metabolites that were consistent with known lipolytic effects of heparin and define a metabolite signature associated with heparin administration. These findings are important for accurate interpretation of future metabolic profiling studies in populations exposed to heparin.

24 Article Polymorphisms associated with in vitro aspirin resistance are not associated with clinical outcomes in patients with coronary artery disease who report regular aspirin use. 2011

Voora, Deepak / Horton, John / Shah, Svati H / Shaw, Linda K / Newby, L Kristin. ·Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, NC 27710, USA. deepak.voora@duke.edu ·Am Heart J · Pubmed #21742104.

ABSTRACT: BACKGROUND: We hypothesized that single-nucleotide polymorphisms (SNPs) associated with heightened in vitro platelet function during aspirin exposure (which we define as "laboratory aspirin resistance") would be associated with greater risk for death, myocardial infarction (MI) or stroke among patients with coronary artery disease regularly using aspirin. METHODS: Duke Databank for Cardiovascular Disease patients with (n = 3,449, CATHeterization GENetics cohort) or without (n = 11,754, nongenetic cohort) banked DNA with ≥1 coronary stenosis >75% were followed up at 6 months, then annually for death, MI, or stroke occurring during periods of reported aspirin use. We evaluated associations of candidate SNPs from GNB3, PEAR1, ITGB3, VAV3, ITGA2, GPVI, PTGS1, F2R, THBS1, A2AR, and GP1BA with events during follow-up using Cox proportional hazards modeling adjusted for clinical characteristics associated with outcomes in the nongenetic cohort. RESULTS: Over a median of 3.5 years, 2,762 (24%) nongenetic cohort patients and 648 (19%) CATHeterization GENetics cohort patients had the composite outcome during reported aspirin use. No candidate SNPs were significantly associated with death, MI, or stroke in either univariable or multivariable analyses. A prospective analysis demonstrated 80% to 88% power to detect a hazard ratio of ≥1.3 for minor allele carriers. CONCLUSION: Patients with angiographically significant coronary artery disease regularly using aspirin and carrying SNPs associated with laboratory aspirin resistance were not at higher risk for death, MI, or stroke. Using these SNPs to guide more aggressive antiplatelet therapy is not justified by these results. Direct extrapolation from in vitro findings to the clinical setting should be avoided.

25 Article Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. 2010

Shah, Svati H / Bain, James R / Muehlbauer, Michael J / Stevens, Robert D / Crosslin, David R / Haynes, Carol / Dungan, Jennifer / Newby, L Kristin / Hauser, Elizabeth R / Ginsburg, Geoffrey S / Newgard, Christopher B / Kraus, William E. ·Department of Medicine, Duke University, Durham, NC, USA. svati.shah@duke.edu ·Circ Cardiovasc Genet · Pubmed #20173117.

ABSTRACT: BACKGROUND: Molecular tools may provide insight into cardiovascular risk. We assessed whether metabolites discriminate coronary artery disease (CAD) and predict risk of cardiovascular events. METHODS AND RESULTS: We performed mass-spectrometry-based profiling of 69 metabolites in subjects from the CATHGEN biorepository. To evaluate discriminative capabilities of metabolites for CAD, 2 groups were profiled: 174 CAD cases and 174 sex/race-matched controls ("initial"), and 140 CAD cases and 140 controls ("replication"). To evaluate the capability of metabolites to predict cardiovascular events, cases were combined ("event" group); of these, 74 experienced death/myocardial infarction during follow-up. A third independent group was profiled ("event-replication" group; n=63 cases with cardiovascular events, 66 controls). Analysis included principal-components analysis, linear regression, and Cox proportional hazards. Two principal components analysis-derived factors were associated with CAD: 1 comprising branched-chain amino acid metabolites (factor 4, initial P=0.002, replication P=0.01), and 1 comprising urea cycle metabolites (factor 9, initial P=0.0004, replication P=0.01). In multivariable regression, these factors were independently associated with CAD in initial (factor 4, odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74; P=0.02; factor 9, OR, 0.67; 95% CI, 0.52 to 0.87; P=0.003) and replication (factor 4, OR, 1.43; 95% CI, 1.07 to 1.91; P=0.02; factor 9, OR, 0.66; 95% CI, 0.48 to 0.91; P=0.01) groups. A factor composed of dicarboxylacylcarnitines predicted death/myocardial infarction (event group hazard ratio 2.17; 95% CI, 1.23 to 3.84; P=0.007) and was associated with cardiovascular events in the event-replication group (OR, 1.52; 95% CI, 1.08 to 2.14; P=0.01). CONCLUSIONS: Metabolite profiles are associated with CAD and subsequent cardiovascular events.

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