anthony n. demaria judith and jack white chair in cardiology founding director, sulpizio...

Anthony N. DeMariaAnthony N. DeMaria

Judith and Jack White Chair in CardiologyFounding Director, Sulpizio Cardiovascular

CenterUCSD School of Medicine

Judith and Jack White Chair in CardiologyFounding Director, Sulpizio Cardiovascular

CenterUCSD School of Medicine

(Adapted from Glagov et al.)

Coronary RemodelingCoronary Remodeling

Normalvessel

MinimalCAD

Progression

Compensatory expansionmaintains constant lumen

Expansion overcome:

lumen narrows

SevereCAD

ModerateCAD

Glagov et al, N Engl J Med, 1987.

Plaque Composition and RiskPlaque Composition and Risk

Stable Vulnerable

Eroded Ruptured

An Apparently Successful Angioplasty An Apparently Successful Angioplasty

PreinterventionPreintervention PostinterventionPostintervention

Coronary Heart Disease Risk Markers

Coronary Heart Disease Risk Markers

Modifiable Not

l Elevated LDL-C

l Low HDL-C

l Elevated blood

pressure

l Elevated triglycerides

Pyorala K, et al. Eur Heart J. 1994;15:1300-1331.

l Male gender

l Family history of CHD

l Age

l Personal history of CHD

l Thrombogenic factors– PAI-1– Fibrinogen– C-reactive

proteinl Dietl Tobacco smokingl Excess alcohol

consumptionl Physical inactivity

l Obesity

Metabolic Syndrome(3 components)

Metabolic Syndrome(3 components)

• Abdominal obesity• High trigycerides• Low HDL (good cholesterol)• High blood pressure• Elevated glucose

• Abdominal obesity• High trigycerides• Low HDL (good cholesterol)• High blood pressure• Elevated glucose

JAMA 1999;282:16, JAMA 2001;286:10.

Obesity Trends* Among U.S. Adults: BRFSS1985




JAMA 1999;282:16, JAMA 2001;286:10.



http://www.cdc.gov/brfss/#interactive

Obesity and Physical Inactivity in Children: A Call to Arms

Obesity and Physical Inactivity in Children: A Call to Arms

• US Children– 15% are overweight– Type 2 DM now exceeds

type 1

• 2/3 have 1 component of the Metabolic Syndrome– 10% have Metabolic

Syndrome

• US Children– 15% are overweight– Type 2 DM now exceeds

type 1

• 2/3 have 1 component of the Metabolic Syndrome– 10% have Metabolic

Syndrome

Pediatrics. August 2003De Ferranti et al. Circulation 2004; 110: 2494-2497

Hardee's "Monster Thickburger2 1/3-pound slabs of Angus beef

4 strips of bacon3 slices of cheese

MayonnaiseButtered sesame seed bun

1420 Calories107 g Fat

Portion DistortionPortion Distortion

Meal and Desert in One: Fried Ice Cream BurgerMeal and Desert in One: Fried Ice Cream Burger

Beware the Fried TwinkieBeware the Fried Twinkie

Deep Fried Butter BallsDeep Fried Butter Balls

Physical inactivity: A call to armsPhysical inactivity: A call to arms

Mortality According to Blood Pressure in Men Age 50 to 69

Mortality According to Blood Pressure in Men Age 50 to 69

0

50

100

150

200

250

158-167

148-157

138-147

128-137

98-127

98-10293-97

88-9283-87

68-82

Society of Actuaries. Blood Pressure Study, 1939.

Rat

io (

%)

of a

ctua

l to

exp

ecte

d

mor

tali

ty

Systolic blood pressure (mmHg)

Diasto

lic b

lood

pressu

re (m

mHg)

www.hypertensiononline.org

0

1

2

3

4

Rel

ativ

e ri

sk o

f C

HD

mor

tali

ty

He J, et at. Am Heart J. 1999;138:211-219.Copyright 1999, Mosby Inc.

<112

<71

Risk of CHD Death According to SBP and DBP in MRFIT

Risk of CHD Death According to SBP and DBP in MRFIT

1 2 3 4 5 6 7 8 9 10Decile

112-

71-

118-

76-

121-

79-

125-

81-

129-

84-

132-

86-

137-

89-

142-

92-

>151

>98

(lowest 10%) (highest 10%)SBP (mmHg)

DBP (mmHg)

Systolic blood pressure (SBP)

Diastolic blood pressure (DBP)


CHD=coronary heart disease

0123456789

Rel

ativ

e ri

sk o

f st

rok

e de

ath

<112

<71

Risk of Stroke Death According to SBP and DBP in MRFIT

Risk of Stroke Death According to SBP and DBP in MRFIT

1 2 3 4 5 6 7 8 9 10Decile

112-

71-

118-

76-

121-

79-

125-

81-

129-

84-

132-

86-

137-

89-

142-

92-

>151

>98

(lowest 10%) (highest 10%)SBP (mmHg)

DBP (mmHg)


Systolic blood pressure (SBP)

Diastolic blood pressure (DBP)

He J, et at. Am Heart J. 1999;138:211-219.Copyright 1999, Mosby Inc.

Intravascular Ultrasound

JAMA. 2004;291:1071-1080.

Effect of Intensive Compared With Moderate Lipid-Lowering Therapy on Progression of Coronary Atherosclerosis; A Randomized Controlled Trial

Steven E. Nissen, MD; E. Murat Tuzcu, MD; Paul Schoenhagen, MD; B. Greg Brown, MD; Peter Ganz, MD; Robert A. Vogel, MD; Tim Crowe, BS; Gail Howard, MS; Christopher J. Cooper, MD; Bruce Brodie, MD; Cindy L. Grines, MD; Anthony N. DeMaria, MD; for the REVERSAL Investigators

http://jama.ama-assn.org/cgi/content/full/291/9/1071?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=DeMaria&searchid=1081466018051_7666&stored_search=&FIRSTINDEX=0&journalcode=jama













http://jama.ama-assn.org/content/vol291/issue9/index.dtl

http://jama.ama-assn.org/content/vol291/issue9/index.dtl

Statin Trials Utilizing IVUS: REVERSALStatin Trials Utilizing IVUS: REVERSAL

Primary hypothesis• A large (vs moderate) reduction in LDL-C will cause

a greater decrease in the total atherosclerotic burden in patients with established CAD measured by IVUS

Secondary hypothesis• The reduction in plaque burden as assessed by

IVUS will be evident despite the absence of any angiographically apparent improvement

Primary hypothesis• A large (vs moderate) reduction in LDL-C will cause

a greater decrease in the total atherosclerotic burden in patients with established CAD measured by IVUS

Secondary hypothesis• The reduction in plaque burden as assessed by

IVUS will be evident despite the absence of any angiographically apparent improvement

Data on file, Pfizer Inc., New York, NY.

REVERSAL Trial REVERSAL Trial

79

110

0

20

40

60

80

100

120

Atorvastatin Pravastatin

LDL at follow-up p<0.001

AHA 2003, Orlando, FLAHA 2003, Orlando, FL

mg

/dL

151

188

0

50

100

150

200


Total-cholesterol at follow-up

p<0.001

mg

/dL

4345

0

10

20

30

40

50


HDL at follow-up p=0.06

mg

/dL


-0.4

2.7

-1

0

1

2

3

4


Change in atheroma volume

p=0.02 for change between atorvastatin vs pravastatin

Change in percent obstruction volume

p=0.0002 for change between atorvastatin vs pravastatin

0.2

1.6

0

1

1

2

2


AHA 2003, Orlando, FLAHA 2003, Orlando, FL


• Among patients with symptomatic CAD and elevated LDL, use of an aggressive lipid-lowering strategy through treatment with 80-mg atorvastatin was associated with a reduction in percent change in atheroma volume compared with a more moderate lipid-lowering strategy through treatment with 40-mg pravastatin

• Primary endpoint used an IVUS endpoint and the trial was not designed to assess mortality or clinical events, and a much larger trial would be needed to assess superiority of one statin over another for these endpoints

• Among patients with symptomatic CAD and elevated LDL, use of an aggressive lipid-lowering strategy through treatment with 80-mg atorvastatin was associated with a reduction in percent change in atheroma volume compared with a more moderate lipid-lowering strategy through treatment with 40-mg pravastatin

• Primary endpoint used an IVUS endpoint and the trial was not designed to assess mortality or clinical events, and a much larger trial would be needed to assess superiority of one statin over another for these endpoints

PRavastatin Or atorVastatin Evaluation and Infection

Therapy (TIMI 22)

PRavastatin Or atorVastatin Evaluation and Infection

Therapy (TIMI 22)

Changes from (Post-ACS) Baseline in Median LDL-C

Note: Changes in LDL-C may differ from prior trials: • 25% of patients on statins prior to ACS event• ACS response lowers LDL-C from true baseline

LD

L-C

(m

g/d

L)

20

40

60

80

100

120

Rand. 30 Days 4 Mos. 8 Mos. 16 Mos. Final

Pravastatin 40mg

Atorvastatin 80mg49%

21%

P<0.001

Median LDL-C (Q1, Q3)

95 (79, 113)

62 (50, 79)

<24h

All-Cause Death or Major CV Events in All Randomized Subjects

0 3 18 21 24 27 306 9 12 15

% with

Event

Months of Follow-up

Pravastatin 40mg(26.3%)

Atorvastatin 80mg(22.4%)

16% RR

(P = 0.005)

30

25

20

15

10

5

0

LDL Lowering to 60: Asteroid TrialLDL Lowering to 60: Asteroid Trial

Relation of LDL to Event Rate

O’Keefe et al; JACC, 2004

PRIMARY PREVENTION

y = 0.0599x - 3.3952

R2 = 0.9305p=0.0019

-1

0

1

2

3

4

5

6

7

8

9

10

55 75 95 115 135 155 175 195

LDL Cholesterol (mg/dL)

CH

D E

ven

ts (

%) WOSCOPS-P

AFCAPS-P

WOSCOPS-S

AFCAPS-S

ASCOT-P

ASCOT-S

Relation of LDL to Event Rate

O’Keefe et al; JACC, 2004

Comparative Cholesterol Levels

“Be There”: Making San Diego County a Heart Attack and Stroke-Free Zone

“Be There”: Making San Diego County a Heart Attack and Stroke-Free Zone

Anthony DeMaria, MDJudith and Jack White Chair in Cardiology

University of California, San DiegoChair, San Diego Right Care-Be There Campaign

Anthony DeMaria, MDJudith and Jack White Chair in Cardiology

University of California, San DiegoChair, San Diego Right Care-Be There Campaign

108

GR MH Tony 1st subm TJ edits 9Feb2012

BackgroundBackground

• Cardiovascular disease (CVD) remains the leading cause of death in the United States

• San Diego and CVD

– Heart disease and stroke together are the leading cause of death

• Nearly 5,000 deaths annually from heart disease (rate 112)

• Quick comparison of rates to those nationwide

• Risk factors have been identified for which effective interventions exist (ABCS)

• Cardiovascular disease (CVD) remains the leading cause of death in the United States

• San Diego and CVD

– Heart disease and stroke together are the leading cause of death

• Nearly 5,000 deaths annually from heart disease (rate 112)

• Quick comparison of rates to those nationwide

• Risk factors have been identified for which effective interventions exist (ABCS)

109

San Diego County Health and Human Services: Stakeholders in CVD Prevention

San Diego County Health and Human Services: Stakeholders in CVD Prevention

• Live Well San Diego • Live Well San Diego

110

http://www.sdcounty.ca.gov/hhsa/programs/sd/health_strategy_agenda/index.html

Communities Putting Prevention to Work (CDC grant) Reduce chronic disease by physical activity, nutrition, and

school environments Community Transformation Grant (CDC grant)

Tobacco free, active living, healthy eating, reduce hypertension and high cholesterol

Beacon Grant (NIH) Awarded across the country to serve as pilots for wide-scale use of health information technology through the Beacon Community program

How It All StartedHow It All Started

• Coordinated effort to improve quality– State Department of Managed Health Care– Medical groups beyond managed care organizations– UC Berkeley School of Public Health– Rand Health (GO Grant)

• Goal: Achieve national HEDIS 90% percentile targets– Blood pressure, lipids, blood sugar

• University of Best Practices meetings– Monthly meetings– Physicians, nurses, administrators, pharmacist– Discuss successful strategies– Now sharing data among group participants

• Coordinated effort to improve quality– State Department of Managed Health Care– Medical groups beyond managed care organizations– UC Berkeley School of Public Health– Rand Health (GO Grant)

• Goal: Achieve national HEDIS 90% percentile targets– Blood pressure, lipids, blood sugar

• University of Best Practices meetings– Monthly meetings– Physicians, nurses, administrators, pharmacist– Discuss successful strategies– Now sharing data among group participants

111

HEDIS, Healthcare Effectiveness Data and Information Set

Be There CampaignBe There Campaign

• Concept: “Heart Attack and Stroke-free Zone” – Audacious goal to capture attention– Extends the risk reduction efforts to all citizens– Actively engages persons in their own health (care)– Conveys ownership to population – Taps in to community pride

• Aim: Achieve both screening for risk factors and compliance with interventions

• Funding: $650,000; philanthropy• Steering Committee: Private-public partnership

• Concept: “Heart Attack and Stroke-free Zone” – Audacious goal to capture attention– Extends the risk reduction efforts to all citizens– Actively engages persons in their own health (care)– Conveys ownership to population – Taps in to community pride

• Aim: Achieve both screening for risk factors and compliance with interventions

• Funding: $650,000; philanthropy• Steering Committee: Private-public partnership

112

San Diego Demonstration ProjectGoing Emotional!

San Diego Demonstration ProjectGoing Emotional!

Emotional “tug” is critical for commitment to change one’s behavior

Benefit to those we love can be a bigger driver than benefit to oneself

Caring for one’s own health makes it possible to “be there”

for those we love!

Emotional “tug” is critical for commitment to change one’s behavior

Benefit to those we love can be a bigger driver than benefit to oneself

Caring for one’s own health makes it possible to “be there”

for those we love!

113

“When something is missing in your life,

it usually turns out to be someone”.

Robert Brault

Be There CampaignSteering Committee

• Anthony N. DeMaria, MD Judith and Jack White Chair in Cardiology, Professor of Medicine, University of California, San Diego, Editor-in-Chief, Journal of the American College of Cardiology, Chair, San Diego Right Care-Be There Campaign

• Daniel Dworski, MD, Medical Director, Scripps Medical Group

• Jim Dudl, MD, Vice-Chair, Steering Committee, Clinical Lead, Kaiser Care Management Institute

• James Dunford, MD, FACEP, City of San Diego Medical Director of Emergency Medical Services. President,San Diego American Heart Association

• Nora Faine, MD, MPH, Medical Director, Sharp Health Plan

• Scott Flinn, MD, Medical Director, Arch Medical Group

• Lawrence Friedman, MD, Medical Director, Managed Care, Ambulatory Care and Medical Group Quality and Safety, University of California, San Diego

• Anthony N. DeMaria, MD Judith and Jack White Chair in Cardiology, Professor of Medicine, University of California, San Diego, Editor-in-Chief, Journal of the American College of Cardiology, Chair, San Diego Right Care-Be There Campaign

• Daniel Dworski, MD, Medical Director, Scripps Medical Group

• Jim Dudl, MD, Vice-Chair, Steering Committee, Clinical Lead, Kaiser Care Management Institute

• James Dunford, MD, FACEP, City of San Diego Medical Director of Emergency Medical Services. President,San Diego American Heart Association

• Nora Faine, MD, MPH, Medical Director, Sharp Health Plan

• Scott Flinn, MD, Medical Director, Arch Medical Group

• Lawrence Friedman, MD, Medical Director, Managed Care, Ambulatory Care and Medical Group Quality and Safety, University of California, San Diego

• Lisa Gleason, MD CMIO, Cardiology Department Head, Naval Medical Center San Diego

• Hattie Rees Hanley, MPP, Right Care Initiative Project Director and Special Advisor to the Dean for Outcomes Improvement and Innovation, UC Berkeley School of Public Health and Department of Managed Health Care

• Elizabeth Helms, Executive Director, CA Chronic Care Coalition and Right Care San Diego Coordinator

• Susan Kaweski, MD, President, San Diego County Medical Society

• Jerry Penso, MD, Medical Director, Continuum of Care, Sharp Rees-Stealy Medical Group, Chair: University of Best Practices

• James Schultz MD, Council of Community Clinics

• Robert Smith, MD, Chief Medical Officer, Veteran’s Administration San Diego Medical Center

• Melissa J. Wilimas, Executive Director, American Heart Association

• Nick Yphantides, MD, MPH, Executive Medical Consultant, San Diego County Public Health and Human Services

• Lisa Gleason, MD CMIO, Cardiology Department Head, Naval Medical Center San Diego

• Hattie Rees Hanley, MPP, Right Care Initiative Project Director and Special Advisor to the Dean for Outcomes Improvement and Innovation, UC Berkeley School of Public Health and Department of Managed Health Care

• Elizabeth Helms, Executive Director, CA Chronic Care Coalition and Right Care San Diego Coordinator

• Susan Kaweski, MD, President, San Diego County Medical Society

• Jerry Penso, MD, Medical Director, Continuum of Care, Sharp Rees-Stealy Medical Group, Chair: University of Best Practices

• James Schultz MD, Council of Community Clinics

• Robert Smith, MD, Chief Medical Officer, Veteran’s Administration San Diego Medical Center

• Melissa J. Wilimas, Executive Director, American Heart Association

• Nick Yphantides, MD, MPH, Executive Medical Consultant, San Diego County Public Health and Human Services

114

Wireless Heart Monitors

Technology Integration Important differentiating component of the Campaign Incorporation of innovative medical and health related

technological advancements to enhance target user groups’ interest, adherence, and participation in the program

Wireless monitors to track exercise regime

Smart Phones to track and report vitals

115

Be There Campaign

Pill bottles that monitor medication adherence

Selected Implementation Activities

Detailed implementation tactics have been developed but as an overview, here is a summary of some of the patient engagement strategies that will be used by the “Be There San Diego” campaign

Recruit physicians using University of Best Practices

Screening events Shopping malls, pharmacies, schools, faith based groups

“Be There San Diego” Pins worn by pharmacists and medical office staff Bus to implement screening across county

Multimedia advertising campaign across all media platforms

Social media viral campaign to connect with community

116

117

Be There Campaign

Be There Campaign

118

Be There Campaign

119

Be There Campaign

120

Be There Campaign

122

Important Low HDL-C Facts:Independent Risk Factor for CHD

Important Low HDL-C Facts:Independent Risk Factor for CHD

• 70% of all infarctions occur in patients with low HDL-C (<45 mg/dl) based on the Framingham

• A 1 mg/dl increase in HDL-C reduces MI risk by 3-4%, based on Framingham

• Low HDL-C is identified as an independent CHD risk factor in the NCEP guidelines

• Low HDL-C was the second most important risk factor in 4S

• 70% of all infarctions occur in patients with low HDL-C (<45 mg/dl) based on the Framingham

• A 1 mg/dl increase in HDL-C reduces MI risk by 3-4%, based on Framingham

• Low HDL-C is identified as an independent CHD risk factor in the NCEP guidelines

• Low HDL-C was the second most important risk factor in 4S

HDL is a major Predictor of CADHDL is a major Predictor of CAD

0

20

40

60

80

100

120

<35 35 - 55 >55HDL-cholesterol (mg/dL)

Incid

ence

of C

HD

(per

100

0 in

6 y

ears

)n=4,407

Assmann G, et al. Atherosclerosis 1996;124(suppl):S11-S20.

Increased HDL and Reduced CHD Incidence

Increased HDL and Reduced CHD Incidence

Framingham Study

0

1

2

3

25 35 45 55 65 75 85

LDL 220 mg/ dlLDL 160 mg/ dlLDL 100 mg/ dl

Rel

ativ

e R

isk

of

CH

D

HDL (mg/dl)Kannel WB, Carter BL. Am Heart J 118 1989

100 160 2200.0

1.0

2.0

3.0

Ris

k of

CH

DLow HDL-C is an Independent Predictor of

CHD Risk Even When LDL-C is LowLow HDL-C is an Independent Predictor of

CHD Risk Even When LDL-C is Low

HDL-C(mg/dL)

LDL-C (mg/dL)

25

Gordon T et al. Am J Med 1977;62:707-714.

4565

85

Apo AI- MilanoApo AI- Milano

Nissen S. Jama 2004

Role of HDL for RegressionRole of HDL for Regression

Nichols et al; JAMA, 2007

Apo-A1 Milano; Plaque “Drano”Apo-A1 Milano; Plaque “Drano”

Ezetimibe in Enhance StudyEzetimibe in Enhance Study

Kastelein et al; NEJM, 2008

http://content.nejm.org/content/vol358/issue14/images/large/05f3.jpeg

http://content.nejm.org/content/vol358/issue14/images/large/05f2.jpeg

CAD: A Changing ParadigmCAD: A Changing Paradigm

Old Paradigm:

Focal disease

High grade stenoses account for morbidity and mortality

Rx: PCI and CABG

Old Paradigm:

Focal disease

High grade stenoses account for morbidity and mortality

Rx: PCI and CABG

New Paradigm:

Diffuse Disease of the entire artery

High grade stenoses cause angina- vulnerable plaques cause MI’s

Rx: Lipid lowering rx, ASA, ACE Inhibitors

CABG/PCI for angina, ischemic cardiomyopathy

New Paradigm:

Diffuse Disease of the entire artery

High grade stenoses cause angina- vulnerable plaques cause MI’s

Rx: Lipid lowering rx, ASA, ACE Inhibitors

CABG/PCI for angina, ischemic cardiomyopathy

Hunter/GathererHunter/Gatherer

ANDAND

anthony n. demaria judith and jack white chair in cardiology founding director, sulpizio...

Documents

obesity slide

obesity trends

elevated blood pressure

low hdlc

luminology angiography

elevated ldlc

elevated triglycerides

plaque composition