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    The Science and Medicine ofCirculatory Dysfunction andAcute Pressure Syndromes

    From Threat to TherapyThe Cardiovascular Specialists Perspective

    Investigation Innovation Application

    Jerrold H. Levy, MDProgram Co-Chairman

    Christopher B. Granger, MDProgram Chairman

    Professor, Department of Medicine I Division of Cardiology | Duke University Medical Center| Co-Director, Clinical Trials | Duke Clinical Research Institute (DCRI) | Durham, North

    Carolina

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    CME-accredited symposium jointly sponsored by the University ofMassachusetts Medical School and CMEducation Resources, LLC

    Commercial Support: Sponsored by an independent educational grantfrom The Medicines Company

    Mission statement: Improve patient care through evidence-basededucation, expert analysis, and case study-based management

    Processes: Strives for fair balance, clinical relevance, on-labelindications for agents discussed, and emerging evidence and

    information from recent studies

    COI: Full faculty disclosures provided in syllabus and at the beginningof the program

    Welcome and Program Overview

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    Program Educational Objectives

    As a result of this educational activity, physicians will:

    Learn to identify underlying chronic, acute, and perioperative precipitants of

    acute elevations in systemic blood pressure and how this syndrome presents

    across multiple cardiovascular disease states and patient populations.

    Learn about the vascular biology of hypertension and its implications for

    clinical practice.

    Learn to assess and implement optimal pharmacologic interventions for

    patients presenting with manifestations of vascular dysfunction and acute

    pressure syndromes.

    Learn to characterize, identify, and evaluate myriad, acute CV disease states

    producing serious and/or life-threatening elevations in systemic blood

    pressure, and optimal approaches for intravenous therapy.

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    Program Faculty

    Program Chairman

    Christopher B. Granger, MDProfessor

    Department of Medicine

    Division of Cardiology

    Duke University Medical Center

    Co-Director, Clinical Trials

    Duke Clinical Research Institute (DCRI)Durham, North Carolina

    Ernesto L. Schiffrin, MD, PhD,

    FRSC, FRCPC, FACPPhysician-in-Chief and Chairman

    Department of MedicineSir Mortimer B. Davis-Jewish General Hospital

    Canada Research Chair and Director

    Hypertension and Vascular Research Unit

    Lady Davis Institute for Medical Research

    Professor and Vice-Chair (Research)

    Department of Medicine, McGill UniversityMontreal, PQ, Canada

    Jerrold H. Levy, MDProfessor and Deputy Chair for Research

    Emory University School of Medicine

    Director of Cardiothoracic Anesthesiology

    Cardiothoracic Anesthesiology and Critical Care

    Emory Healthcare

    Atlanta, Georgia

    Charles V. Pollack Jr, MS, MD,

    FACEP, FAAEMChairman, Department of Emergency Medicine

    Pennsylvania Hospital

    Professor of Emergency MedicineUniversity of Pennsylvania

    School of Medicine

    Philadelphia, Pennsylvania

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    Faculty COI Disclosures

    Christopher B. Granger, MDEducational Grants and/or Research Support: Alexion, Astra Zeneca, Procter andGamble, sanofi-aventis, Novartis, The Medicines Company, Boehringer Ingelheim,

    Genentech, and Berlex

    Ernesto L. Schiffrin, MD, PhD, FRSC, FRCPC, FACP

    Grants/Research: Canadian Institutes of Health Research, Canadian Fund forInnovation, Merck-Frosst, Pfizer Cardiovascular AwardConsultant : Boehringer-

    Ingelheim, Bristol-Myers Squibb, Forest Pharmaceuticals, Novartis

    Jerrold H. Levy, MDGrant/Research Support: Alexion

    Consultant: Bayer HealthCare, Dyax, Novo Nordisk, and Organon

    Charles V. Pollack Jr, MA, MD, FACEP, FAAEMGrant/Research Support: GlaxoSmithKlineConsultant: The Medicines Company., Schering-Plough, Sanofi-Aventis, BMS,

    Genentech, Speakers Bureau: Schering-Plough, Sanofi-Aventis, BMS, Genentech

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    Acute Pressure Syndromes From Threat to Therapy

    Characterization, Epidemiology, and Approach to Acute BloodPressure Elevations Across the Cardiovascular Disease

    Continuum

    Giving Acute Hypertension the Hyperattention it Deserves

    Investigation Innovation Application

    Jerrold H Levy, MD, FAHAProfessor of Anesthesiology

    Emory University School of MedicineDeputy Chairman for Research

    Director, Cardiothoracic Anesthesiology

    Cardiothoracic Anesthesiology and Critical CareEmory Healthcare

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    Acute, Severe Hypertension

    Common

    Deadly and disabling

    Poorly studied

    Poorly managed

    Evidence that speed and degree ofcontrol relate to outcome

    Needs more attention Observed across multiple settings

    Better therapies required

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    72 million with

    hypertension

    1-2% with acutesevere hypertension

    Severe Hypertension

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    Prevalence of high blood pressure in adults

    by age and sex

    11.2

    55.4

    73.9

    23.2

    37.5

    49.1

    63.6

    69.5

    37.4

    6.4

    83.8

    18.3

    0.0

    10.0

    20.0

    30.0

    40.0

    50.0

    60.0

    70.0

    80.0

    90.0

    20-34 35-44 45-54 55-64 65-74 75+

    Percent

    ofPopulation

    Men Wom en

    Prevalence of Hypertension

    NHANES: 1999-2004.Source: NCHS and NHLBI.

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    Extent of awareness, treatment and control of

    high blood pressure by age

    52.3

    35.8

    24.6

    62.5

    39.8

    68.474.6

    34.3

    75.3

    0

    10

    20

    30

    40

    50

    60

    70

    80

    Awareness Treatment Controlled

    Percento

    fPopulation

    20-39 40-59 60+

    NHANES: 1999-2004.Source: NCHS and NHLBI.

    Hypertension: Awareness and Control

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    5,026 emergency departments

    113.9 million visits in 2003

    Presentation with severe hypertension in up to25% of patients in busy urban EDs

    Sullivan AF.Acad Emerg Med2004;11:454; IOM Emergency Medical Care Report 2006.

    Emergency Care of SevereBlood Pressure Elevation

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    Short-Term (2 to 6 month) Outcomes:A Deadly and Morbid Condition

    1. OASIS-5 NEJM2006.

    2. GUSTO IIb NEJM1996.

    3. GRACE JAMA 2007.4. IMPACT-HF J Cardiac Failure 2004.

    5. Cline DM.Acad Emerg Med2006.

    Acute Condition Death Rehospitalization

    ACS1,2,3 5-7% 30%

    CHF4 8.5% 26%

    Severe

    Hypertension5 5-6% 30%

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    Terminology and Definitions

    Severe Hypertension

    JNC VIII > 180/110

    End-organ Damage

    CHF

    ACS/AMI Renal failure

    Stroke and ICH

    Encephalopathy

    Aortic dissection

    Pre-eclampsia

    Other?

    plus

    Hypertensive Urgency Hypertensive Emergency

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    Spectrum of End-Organ Damage

    Zampaglione, B. Hypertension 1996;27:144-147.

    108 Hypertensive Emergencies*

    *All Caucasians

    End-Organ

    Damage TypeNo. of Cases %

    Cerebral Infarction 26 24.5%

    ICH or SAH 5 4.5%

    Encephalopathy 18 16.3%

    Acute Pulmonary Edema 24 22.5%

    Acute CHF 15 14.3%Acute MI 13 12.0%

    Aortic Dissection 2 2.0%

    Eclampsia 5 4.5%

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    Acute Severe HypertensionEpidemiology and Mortality

    1939: First study of the natural

    history of hypertensiveemergencies published

    Untreated hypertensive emergencieshad a 1-year mortality rate of 79%, withmedian survival of 10.5 months

    Varon J. CHEST2007; 131:19491962.

    Risk Factors

    History ofhypertension

    African Americans

    Elderly

    Men

    Noncompliance

    Historical

    Study

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    17/187Messerli F. N Engl J Med1995;332:1038-1039.

    St. Louis Post-DispatchApril 13, 1945

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    Blood Pressure of FDR

    Messerli F. N Engl J Med1995;332:1038-1039.

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    19/187Sokolow & Perloff. Circulation 1961;23:697-713.

    100

    80

    60

    40

    20

    0

    439 patients total

    Cumulative% Mortality

    1 2 3 4 5

    Time in Years

    BP I 150-200/90-110BP II 200-250/110-130

    BP III Over 250/130

    BP III

    BP II

    BP I

    38%

    18%

    8%

    Mortality and Severe Hypertension

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    Hypertensive Urgency or Emergency

    Total 865

    Reviews 190

    Randomized

    Clinical Trials 46

    ACS

    55,353

    3,518

    HU or HE

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    An Evaluation of PharmacotherapeuticRegimens Inadequately Studied

    Medline 1966-2001

    References from aboveExperts contacted

    Cochrane Library checked

    Randomized controlled trials

    Systematic review of cohort studiesIndividual cohort study

    Outcome Research

    600 Studies

    Identified

    Excluded

    Non-HumanBlood pressures too