Geriatric Geriatric Cardiology: A Cardiology: A Global Growth Global Growth

IndustryIndustryJoseph S. Alpert, MDJoseph S. Alpert, MDDepartment of MedicineDepartment of Medicine

University of Arizona Health University of Arizona Health Sciences Center, Tucson, Sciences Center, Tucson,

ArizonaArizonaEditor-in-Chief, American Editor-in-Chief, American

Journal of MedicineJournal of Medicine

1. No major conflicts of interest, i.e., all honoraria <$5,000;

2. Consultations currently or previously performed: Sanofi-Aventis, Merck, Bristol-Myers-Squibb, Pfizer, Astra-Zeneca, McNeill, Organon, Berlex, Novartis, Ciba-Geigy, Roche, Exeter CME.

Potential Conflicts of Interest:

DEMOGRAPHICSDEMOGRAPHICS

Population Projections in Population Projections in the U.S.: 2000-2050the U.S.: 2000-2050

0

10

20

30

40

50

2000 2010 2020 2030 2040 2050

Popu

latio

n in

mill

ions

Women >65Men > 65Women > 85Men > 85

Hospital Mortality for Hospital Mortality for Cardiovascular CausesCardiovascular Causes

Total deathsTotal deaths

(in thousands) Age (in thousands) Age >> 6565

Acute MIAcute MI 7878 68 68 (87.2%)(87.2%)

ArrhythmiasArrhythmias 1717 12 12 (70.6%)(70.6%)

Heart failureHeart failure 4242 37 37 (88.1%)(88.1%)

Cerebrovascular diseaseCerebrovascular disease 6565 49 49 (75.4%)(75.4%)

Source: National Hospital Discharge Survey, 1998.

EFFECTS OF AGING ON EFFECTS OF AGING ON THE CARDIOVASCULAR THE CARDIOVASCULAR

SYSTEMSYSTEM

Principal Effects of Aging onPrincipal Effects of Aging onCardiovascular Structure and Cardiovascular Structure and

FunctionFunction Increased vascular + Increased vascular +

myocardial stiffnessmyocardial stiffness Decreased Decreased -adrenergic and -adrenergic and

baroreceptor responsivenessbaroreceptor responsiveness Impaired sinus node functionImpaired sinus node function Impaired endothelial functionImpaired endothelial function

Net effect - Large reduction in CV reserve

CV Changes: Max Exercise CV Changes: Max Exercise - Ages 20 and 80 Years- Ages 20 and 80 Years

Oxygen consumptionOxygen consumption Reduced ~ 50%Reduced ~ 50%

AV oxygen differenceAV oxygen difference Reduced ~ 25%Reduced ~ 25%

Cardiac outputCardiac output Reduced ~ 25%Reduced ~ 25%

Heart rateHeart rate Reduced ~ 25%Reduced ~ 25%

LV stroke volumeLV stroke volume Reduced ~ 15% to Reduced ~ 15% to 25%25%

LV end diastolic LV end diastolic volumevolume

No change or small No change or small decreasedecrease

LV end systolic LV end systolic volumevolume

Increased ~ 150%Increased ~ 150%

LV ejection fractionLV ejection fraction Reduced ~ 15%Reduced ~ 15%

Age Changes in Systolic Age Changes in Systolic and Diastolic BPand Diastolic BP

                                                                                   

Source: J Gerontol Med Sci 1997;52:M177-83

Conduction SystemConduction System

Increased elastic tissue, collagen Increased elastic tissue, collagen and fat, especially in the SA node and fat, especially in the SA node with marked reduction in SA node with marked reduction in SA node pacemaker cellspacemaker cells

Calcification of cardiac skeletonCalcification of cardiac skeleton Slowed conduction throughout the Slowed conduction throughout the

heartheart Hypertension, CAD, and amyloid Hypertension, CAD, and amyloid

infiltration amplify conduction infiltration amplify conduction abnormalitiesabnormalities

ArrhythmiasArrhythmias Marked increase in frequency of Marked increase in frequency of

supra-ventricular and ventricular supra-ventricular and ventricular ectopic beats ectopic beats

Short runs of SVT occur in 1/3 of Short runs of SVT occur in 1/3 of healthy older subjects on Holter healthy older subjects on Holter studiesstudies

Ventricular couplets occur in ~11% Ventricular couplets occur in ~11% and short runs of ventricular and short runs of ventricular tachycardia occur in ~4% of normal tachycardia occur in ~4% of normal persons > 60 yrpersons > 60 yr

In the absence of heart disease, none In the absence of heart disease, none of these arrhythmias are associated of these arrhythmias are associated with an adverse prognosiswith an adverse prognosisSource: Am J Cardiol 1992:70:748-51

Prevalence of Prevalence of Nonsustained SVT Nonsustained SVT

during Maximal Exerciseduring Maximal Exercise

Source: Am J Cardiol 1995;75:788-92

                                                                                   

Clinical ImplicationsClinical Implications Increased systolic BP and pulse Increased systolic BP and pulse

pressurepressure Increased prevalence of atrial Increased prevalence of atrial

fibrillation, heart failure, fibrillation, heart failure, especially heart failure with especially heart failure with preserved LV functionpreserved LV function

Increased prevalence of Increased prevalence of bradyarrhythmias and “sick sinus bradyarrhythmias and “sick sinus syndrome”syndrome”

Worse prognosis associated with Worse prognosis associated with all CV diseasesall CV diseases

Disease PresentationDisease Presentation Atypical symptomatologyAtypical symptomatology

- Chest pain less frequent- Chest pain less frequent

- Exertional dyspnea or fatigue - Exertional dyspnea or fatigue commoncommon

- ‘Gastrointestinal’ symptoms common- ‘Gastrointestinal’ symptoms common

- Confusion, dizziness, other CNS sx’s- Confusion, dizziness, other CNS sx’s Non-diagnostic ECG due to IVCD, Non-diagnostic ECG due to IVCD,

LVH, paced rhythm, electrolyte LVH, paced rhythm, electrolyte abnormalitiesabnormalities

CORONARY HEART CORONARY HEART DISEASE IN THE DISEASE IN THE

ELDERLYELDERLY

Prevalence of AHSD by Age Prevalence of AHSD by Age and Sex in the U.S. from 1988-and Sex in the U.S. from 1988-

9494

0%

5%

10%

15%

20%

25-44 45-54 55-64 65-74 75+

Male

Female

Age, years

Per

cen

t of

Pop

ula

tion

Source: National Health and Nutrition Examination Survey

Prognosis after AMI by Prognosis after AMI by AgeAge

Source: Circulation 1996;94:1826-33

Vaccarino et al Ann of Int Med 2001; 134: 173-181. Solid lines are men; dotted lines are women.

Vaccarino et al Ann of Int Med 2001; 134: 173-181. Solid lines are men; dotted lines are women.

Risk Stratification Post-Risk Stratification Post-MIMI

The Cooperative Cardiovascular Project risk The Cooperative Cardiovascular Project risk score (age > 65 years), GISSI, GUSTO score (age > 65 years), GISSI, GUSTO

FACTORS INCREASING MORTALITY:FACTORS INCREASING MORTALITY:

Older age groups - # 1Older age groups - # 1

Urinary incontinence; decreased functionality; Urinary incontinence; decreased functionality; peripheral vascular disease; low body mass peripheral vascular disease; low body mass index; renal insufficiency; decreased LV index; renal insufficiency; decreased LV functionfunction

Krumholz et al JACC 2001; 38: 453. Marchioli et al Eur Heart J 2001; 22: Krumholz et al JACC 2001; 38: 453. Marchioli et al Eur Heart J 2001; 22: 2085. Califf et al Circulation 2000; 101: 22312085. Califf et al Circulation 2000; 101: 2231..

0

100

60

70

80

50

90

Survival Free ofReinfarction or Stroke, (%)Survival Free ofReinfarction or Stroke, (%)

0

100

60

70

80

50

90

Year1 20

Year1 20

100

70

80

90

0

Overall Survival, (%)

YearYear1 20

100

70

80

90

Overall Survival, (%)

01 20

PCI, N = 46

SK, N = 41

Thrombolysis vs. Thrombolysis vs. Angioplasty in Older Angioplasty in Older

PatientsPatientsDeathDeathDeathDeath Death, re-MI, StrokeDeath, re-MI, StrokeDeath, re-MI, StrokeDeath, re-MI, Stroke

RR 5.2

De Boer et al., J Am Coll Cardiol 39:1723-De Boer et al., J Am Coll Cardiol 39:1723-8, 20028, 2002

p = 0.04 p = 0.003

LysisLysis PCIPCI00

22

44

66

88

1010

22 11

% of Pts.% of Pts.

LysisLysis PCIPCI00

22

44

66

88

1010

22 11

% of Pts.% of Pts.

LysisLysis PCIPCI00

22

44

66

88

1010

77

33

% of Pts.% of Pts.

LysisLysis PCIPCI00

22

44

66

88

1010

99

77

% of Pts.% of Pts.

PCI vs. Lysis Meta-PCI vs. Lysis Meta-AnalysisAnalysis23 Trials, 7739 Patients23 Trials, 7739 Patients

DeathDeath Re-MIRe-MI StrokeStroke

Weaver et al., JAMA 278:2093,1997;Weaver et al., JAMA 278:2093,1997;

Keeley et al., Lancet 361:13-20, Keeley et al., Lancet 361:13-20, 20032003

p = 0.0004p < 0.001p = 0.002

Primary Angioplasty for Primary Angioplasty for AMI in the Elderly: Pooled AMI in the Elderly: Pooled

Analysis from 3 TrialsAnalysis from 3 Trials

0%

5%

10%

15%

20%

< 70 > 70

Angioplasty

Thrombolysis

Age, years

Mor

tali

ty

Source: J Intervent Cardiol 1998;10:4A-10A

P=0.21

P=0.02

GUSTOGUSTOVV

00

11

22

33

0.50.5 0.40.4

1.11.1

2.12.1

rPA

rPA + Abciximab

PercentPercent

Age Age << 75 75 Age > 75Age > 75

Intracranial Intracranial HemorrhageHemorrhageTreatment by Age InteractionTreatment by Age Interaction

OR 0.76p = 0.26

OR 1.91p = 0.065

p = 0.033

GUSTOGUSTOVV

Higher risk with combination

Lower risk with combination

Years

6

2

0

4

3

5

1

40 9030 60 7050 80

Higher risk with combination

Lower risk with combination

40

Years

6

2

0

4

90

3

5

30 60 7050 80

1

The Age-Intracranial Hemorrhage The Age-Intracranial Hemorrhage InteractionInteraction

HIGHER RISK

LOWER RISK

Source: Am Heart J 2001:142:37-42

Reasons Reperfusion MissedReasons Reperfusion Missed

30% 30% nono reperfusion: reperfusion:

OROR

Age Age 75 752.42.4No CPNo CP3.23.2Prior CHFPrior CHF2.92.9Prior CABGPrior CABG2.32.3DMDM1.51.5

30% 30% nono reperfusion: reperfusion:

OROR

Age Age 75 752.42.4No CPNo CP3.23.2Prior CHFPrior CHF2.92.9Prior CABGPrior CABG2.32.3DMDM1.51.5

Eagle et al., GRACE Registry, Lancet 359:373–Eagle et al., GRACE Registry, Lancet 359:373–77, 200277, 2002

94 Hospitals in 14 Countries, N = 94 Hospitals in 14 Countries, N = 17631763

CARDIOVASCULAR CARDIOVASCULAR DRUG THERAPY IN THE DRUG THERAPY IN THE

ELDERLYELDERLY

Drug Therapy in the Drug Therapy in the Elderly:Elderly:

General ConsiderationsGeneral Considerations Decreased volume of distributionDecreased volume of distribution Decreased renal and hepatic Decreased renal and hepatic

clearanceclearance Altered drug pharmacodynamicsAltered drug pharmacodynamics Increased comorbidityIncreased comorbidity Increased risk of drug interactionsIncreased risk of drug interactions Paucity of data from clinical trialsPaucity of data from clinical trials

IN GENERAL, ELDERLY IN GENERAL, ELDERLY PATIENTS DO WELL PATIENTS DO WELL

WITH EVIDENCE-BASED WITH EVIDENCE-BASED MEDICAL AND MEDICAL AND

INTERVENTIONAL INTERVENTIONAL THERAPY ALTHOUGH THERAPY ALTHOUGH

MORBIDITY AND MORBIDITY AND MORTALITY ARE MORTALITY ARE HIGHER THAN IN HIGHER THAN IN

YOUNGER PATIENTSYOUNGER PATIENTS

Efficacy of Aspirin by Efficacy of Aspirin by Age: ISIS-2Age: ISIS-2

0%

5%

10%

15%

20%

25%

< 60 60-69 70+

Placebo

Aspirin

Age, years

Vas

cula

r M

orta

lity

at

35 D

ays

Source: Lancet 1988;II-349-60

Long-term Benefits of Long-term Benefits of AspirinAspirin

0%

5%

10%

15%

20%

25%

< 65 65+

Aspirin

Control

Age, years

Vas

cula

r E

ven

ts

Source: BMJ 1994;308:81-106

P < 0.00001

P < 0.00001

Clopidogrel in Non-ST-Clopidogrel in Non-ST-Elevation Acute Coronary Elevation Acute Coronary

Syndromes: CURE Syndromes: CURE Age, Age, yearsyears

PlacePlace

bobo

ClopidogClopidog

relrel

RelatiRelative ve

Risk*Risk*

Lives Lives Saved/ Saved/ 10001000

<< 65 65 7.6%7.6% 5.4%5.4% 0.710.71 2222

> 65> 65 15.3%15.3% 13.3%13.3% 0.870.87 2020

*Primary endpoint: CV death, nonfatal MI or CVA

Source: N Engl J Med 2001;345:494-502

Impact of Statins on Major Impact of Statins on Major Coronary EventsCoronary Events

4S4S

< 65< 65 26.4%26.4% 18.1%18.1% 0.660.66 8383

>> 65 65 33.4%33.4% 23.6%23.6% 0.660.66 9898

CARECARE

< 65< 65 25.6%25.6% 21.1%21.1% 0.810.81 4545

>> 65 65 28.1%28.1% 19.7%19.7% 0.680.68 8484

LIPIDLIPID

< 65< 65 13.4%13.4% 10.4%10.4% 0.770.77 3030

>> 65 65 19.7%19.7% 15.5%15.5% 0.790.79 4242

Placebo ActiveRelative

RiskEvents

Prevented

VALVULAR HEART VALVULAR HEART DISEASE IN THE DISEASE IN THE

ELDERLYELDERLY

Prevalence of AS in the Prevalence of AS in the ElderlyElderly

0%

5%

10%

15%

20%

White Hispanic

MenWomen

Source: Aronow WS et al. Am J Cardiol 2001;87:1131-3

Prevalence of AI in the Prevalence of AI in the ElderlyElderly

0%

10%

20%

30%

40%

White Hispanic

MenWomen

Source: Aronow WS et al. Am J Cardiol 2001;87:1131-3

AV Replacement: Age > AV Replacement: Age > 8080

0%

20%

40%

60%

80%

100%

30-days 1 year 5 years 10 years

Actuarial survival following AVR in 71 octogenarians

Source: Circulation 1989;80(suppl I):I-49-56

ConclusionsConclusions

There is rapid global growth in There is rapid global growth in the number of elderly patients the number of elderly patients with CV diseasewith CV disease

Mortality from CV disease is high Mortality from CV disease is high in elderly patientsin elderly patients

Evidence-based therapy is highly Evidence-based therapy is highly effective in elderly patientseffective in elderly patients

Careful selection and tailoring of Careful selection and tailoring of such therapies is mandatory for such therapies is mandatory for elderly patients with CV diseaseelderly patients with CV disease