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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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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