Geriatric Cardiology: A Global Growth Industry Joseph S. Alpert, MD Department of Medicine University of Arizona Health Sciences Center, Tucson, Arizona Editor-in-Chief, American Journal 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:

DEMOGRAPHICS

Population Projections in the U.S.:

Hospital Mortality for Cardiovascular Causes Total deaths Total deaths (in thousands) Age > 65 (in thousands) Age > 65 Acute MI78 68 (87.2%) Acute MI78 68 (87.2%) Arrhythmias17 12 (70.6%) Arrhythmias17 12 (70.6%) Heart failure42 37 (88.1%) Heart failure42 37 (88.1%) Cerebrovascular disease65 49 (75.4%) Cerebrovascular disease65 49 (75.4%) Source: National Hospital Discharge Survey, 1998.

EFFECTS OF AGING ON THE CARDIOVASCULAR SYSTEM

Principal Effects of Aging on Cardiovascular Structure and Function Increased vascular + myocardial stiffness Increased vascular + myocardial stiffness Decreased  -adrenergic and baroreceptor responsiveness Decreased  -adrenergic and baroreceptor responsiveness Impaired sinus node function Impaired sinus node function Impaired endothelial function Impaired endothelial function Net effect - Large reduction in CV reserve

CV Changes: Max Exercise - Ages 20 and 80 Years Oxygen consumption Reduced ~ 50% AV oxygen difference Reduced ~ 25% Cardiac output Reduced ~ 25% Heart rate Reduced ~ 25% LV stroke volume Reduced ~ 15% to 25% LV end diastolic volume No change or small decrease LV end systolic volume Increased ~ 150% LV ejection fraction Reduced ~ 15%

Age Changes in Systolic and Diastolic BP Source: J Gerontol Med Sci 1997;52:M177-83

Conduction System Increased elastic tissue, collagen and fat, especially in the SA node with marked reduction in SA node pacemaker cells Increased elastic tissue, collagen and fat, especially in the SA node with marked reduction in SA node pacemaker cells Calcification of cardiac skeleton Calcification of cardiac skeleton Slowed conduction throughout the heart Slowed conduction throughout the heart Hypertension, CAD, and amyloid infiltration amplify conduction abnormalities Hypertension, CAD, and amyloid infiltration amplify conduction abnormalities

Arrhythmias Marked increase in frequency of supra- ventricular and ventricular ectopic beats Marked increase in frequency of supra- ventricular and ventricular ectopic beats Short runs of SVT occur in 1/3 of healthy older subjects on Holter studies Short runs of SVT occur in 1/3 of healthy older subjects on Holter studies Ventricular couplets occur in ~11% and short runs of ventricular tachycardia occur in ~4% of normal persons > 60 yr Ventricular couplets occur in ~11% and short runs of ventricular tachycardia occur in ~4% of normal persons > 60 yr In the absence of heart disease, none of these arrhythmias are associated with an adverse prognosis In the absence of heart disease, none of these arrhythmias are associated with an adverse prognosis Source: Am J Cardiol 1992:70:748-51

Prevalence of Nonsustained SVT during Maximal Exercise Source: Am J Cardiol 1995;75:788-92

Clinical Implications Increased systolic BP and pulse pressure Increased systolic BP and pulse pressure Increased prevalence of atrial fibrillation, heart failure, especially heart failure with preserved LV function Increased prevalence of atrial fibrillation, heart failure, especially heart failure with preserved LV function Increased prevalence of bradyarrhythmias and “sick sinus syndrome” Increased prevalence of bradyarrhythmias and “sick sinus syndrome” Worse prognosis associated with all CV diseases Worse prognosis associated with all CV diseases

Disease Presentation Atypical symptomatology Atypical symptomatology - Chest pain less frequent - Exertional dyspnea or fatigue common - ‘Gastrointestinal’ symptoms common - Confusion, dizziness, other CNS sx’s Non-diagnostic ECG due to IVCD, LVH, paced rhythm, electrolyte abnormalities Non-diagnostic ECG due to IVCD, LVH, paced rhythm, electrolyte abnormalities

CORONARY HEART DISEASE IN THE ELDERLY

Prevalence of AHSD by Age and Sex in the U.S. from Age, years Percent of Population Source: National Health and Nutrition Examination Survey

Prognosis after AMI by Age Source: Circulation 1996;94:

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

Risk Stratification Post-MI The Cooperative Cardiovascular Project risk score (age > 65 years), GISSI, GUSTO FACTORS INCREASING MORTALITY: Older age groups - # 1 Older age groups - # 1 Urinary incontinence; decreased functionality; peripheral vascular disease; low body mass index; renal insufficiency; decreased LV function Urinary incontinence; decreased functionality; peripheral vascular disease; low body mass index; renal insufficiency; decreased LV function Krumholz et al JACC 2001; 38: 453. Marchioli et al Eur Heart J 2001; 22: Califf et al Circulation 2000; 101: 2231.

Thrombolysis vs. Angioplasty in Older Patients DeathDeath Death, re-MI, Stroke RR 5.2 De Boer et al., J Am Coll Cardiol 39:1723-8, 2002 p = 0.04p = 0.003

PCI vs. Lysis Meta-Analysis 23 Trials, 7739 Patients DeathRe-MIStroke Weaver et al., JAMA 278:2093,1997; Keeley et al., Lancet 361:13-20, 2003 p = p < 0.001p = 0.002

Primary Angioplasty for AMI in the Elderly: Pooled Analysis from 3 Trials Age, years Mortality Source: J Intervent Cardiol 1998;10:4A-10A P=0.21 P=0.02

GUSTO V Intracranial Hemorrhage Treatment by Age Interaction OR 0.76 p = 0.26 OR 1.91 p = p = 0.033

GUSTO V The Age-Intracranial Hemorrhage Interaction HIGHER RISK LOWER RISK

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

Reasons Reperfusion Missed 30% no reperfusion: OR Age  No CP3.2 Prior CHF2.9 Prior CABG2.3 DM1.5 Eagle et al., GRACE Registry, Lancet 359:373– 77, Hospitals in 14 Countries, N = 1763

CARDIOVASCULAR DRUG THERAPY IN THE ELDERLY

Drug Therapy in the Elderly: General Considerations Decreased volume of distribution Decreased volume of distribution Decreased renal and hepatic clearance Decreased renal and hepatic clearance Altered drug pharmacodynamics Altered drug pharmacodynamics Increased comorbidity Increased comorbidity Increased risk of drug interactions Increased risk of drug interactions Paucity of data from clinical trials Paucity of data from clinical trials

IN GENERAL, ELDERLY PATIENTS DO WELL WITH EVIDENCE-BASED MEDICAL AND INTERVENTIONAL THERAPY ALTHOUGH MORBIDITY AND MORTALITY ARE HIGHER THAN IN YOUNGER PATIENTS

Efficacy of Aspirin by Age: ISIS-2 Age, years Vascular Mortality at 35 Days Source: Lancet 1988;II

Long-term Benefits of Aspirin Age, years Vascular Events Source: BMJ 1994;308: P <

Clopidogrel in Non-ST-Elevation Acute Coronary Syndromes: CURE Age, years Placebo Placebo Clopidogrel Clopidogrel Relative Risk* Lives Saved/ 1000 < %5.4% > %13.3% *Primary endpoint: CV death, nonfatal MI or CVA Source: N Engl J Med 2001;345:

Impact of Statins on Major Coronary Events 4S < %18.1% > %23.6% CARE < %21.1% > %19.7% LIPID < %10.4% > %15.5% PlaceboActive Relative Risk Events Prevented

VALVULAR HEART DISEASE IN THE ELDERLY

Prevalence of AS in the Elderly Source: Aronow WS et al. Am J Cardiol 2001;87:1131-3

Prevalence of AI in the Elderly Source: Aronow WS et al. Am J Cardiol 2001;87:1131-3

AV Replacement: Age > 80 Actuarial survival following AVR in 71 octogenarians Source: Circulation 1989;80(suppl I):I-49-56

Conclusions There is rapid global growth in the number of elderly patients with CV disease There is rapid global growth in the number of elderly patients with CV disease Mortality from CV disease is high in elderly patients Mortality from CV disease is high in elderly patients Evidence-based therapy is highly effective in elderly patients Evidence-based therapy is highly effective in elderly patients Careful selection and tailoring of such therapies is mandatory for elderly patients with CV disease Careful selection and tailoring of such therapies is mandatory for elderly patients with CV disease