2. FIGURE 80-1 United States population estimates projected from 2000 until 2050. Dark pink bars represent numbers of women older than 65 years, and dark blue bars represent numbers of men older than 65 years; lighter pink bars represent numbers of women older than 85 years, and lighter blue bars represent numbers of men older than 85 years in millions of people. )Source: U.S. Census Bureau.(

3. FIGURE 80-2 Prevalence of cardiovascular and other common chronic medical illnesses in older persons in the United States. Data are percentages. AF = atrial fibrillation; CAD = coronary artery disease; CVD = cardiovascular disease; HF = heart failure; high BP = hypertension (all forms); PAD = peripheral artery disease. Blue bars represent data for men older than 65 years, pink bars represent women older than 65 years, and yellow bars represent men and women older than 80 years

4. ↑ Left ventricular wall thickness Gross anatomy ↓ Left ventricular cavity size Endocardial thickening and sclerosis ↑ Left atrial size Valvular fibrosis and sclerosis ↑ Epicardial fat ↑ Lipid and amyloid deposition Histology ↑ Collagen degeneration and fibrosis Calcification of fibrous skeleton, valve rings, and coronary arteries Shrinkage of myocardial fibers with focal hypertrophy ↓ Mitochondria, altered mitochondrial membranes ↓ Nucleus/myofibril size ratio ↓ Protein elasticity Biochemical changes Numerous changes in enzyme content and activity affecting most metabolic pathways, but no change in myosin ATPase activity ↓ Catecholamine synthesis, especially norepinephrine ↓ Acetylcholine synthesis ↓ Activity of nitric oxide synthase Table 135.1 -- Effects of aging on the cardiovascular system.

5. Degeneration of sinus node pacemaker and transition cells Conduction system ↓ Number of conducting cells in the AV node and His-Purkinje system ↑ Connective tissue, fat, and amyloid ↑ Calcification around the conduction system ↓ Distensibility of large and medium-sized arteries Vasculature Impaired endothelial function Aorta and muscular arteries become dilated, elongated, and tortuous ↑ Wall thickness ↑ Connective tissue and calcification ↓ Responsiveness to β-adrenergic stimulation Autonomic nervous system ↑ Circulating catecholamines, decreased tissue catecholamines ↓ α-Adrenergic receptors in the left ventricle ↓ Cholinergic responsiveness Diminished response to Valsalva and baroreceptor stimulation ↓ Heart rate variability Modified from Stolker JM, Rich MW. Diagnosis and management of heart disease in the elderly. In Arenson C, Reichel W, eds. Reichel's Care of the Elderly. 6th ed. Lippincott Williams & Wilkins, 2009.

6. Figure 135.1 Prevalence of cardiac disease by age and gender. Prevalence of cardiovascular diseases (including coronary heart disease, heart failure, stroke, and hypertension) by age and gender in the United States, 1999 to 2002

7. Gradual ↓ in glomerular filtration rate (~8cc/min/decade( Kidneys Impaired fluid and electrolyte homeostasis ↓ Ventilatory capacity Lungs ↑ Ventilation/perfusion mismatching ↓ Cerebral perfusion autoregulatory capacity Neurohumoral system Diminished reflex responsiveness Impaired thirst mechanism ↑ Levels of coagulation factors Hemostatic system ↑ Platelet activity and aggregability ↑ Inflammatory cytokines and C-reactive protein ↑ Inhibitors of fibrinolysis and angiogenesis ↓ Muscle mass (sarcopenia( Musculoskeletal system ↓ Bone mass (osteopenia), especially In women Modified from Stolker JM, Rich MW. Diagnosis and management of heart disease in the elderly. In Arenson C, Reichel W, eds. Reichel's Care of the Elderly. 6th ed. Lippincott Williams & Wilkins, 2009. Table 135.2 -- Effects of aging on other organ systems

8. Figure 135.2 VO2 max as a function of age and gender. Peak treadmill oxygen consumption (VO2 max) as a function of age and gender in healthy subjects.

9. Figure 135.3 Annual rate of first heart attack. Annual rate of first heart attack by age, gender, and race in the Atherosclerosis Risk in Communities (ARIC) study, 1987 to 2000.

10. Figure 135.4 Clinical presentation of acute myocardial infarction in elderly patients. Clinical presentation of acute myocardial infarction in patients age 85 or older

11. Figure 135.5 Prevalence of atrial fibrillation by age and gender. Prevalence of atrial fibrillation by age and gender in a large health maintenance organization, 1996 to 1997.

12. Figure 135.8 Benefits of invasive therapy for the elderly. Benefits of invasive therapy for elderly subjects with non-ST-elevation acute coronary syndromes enrolled in the TACTICS-TIMI 18 trial.

13. FIGURE 80-3 Directly measured arterial waveforms from a peripheral artery (radial) and calculated aortic pressure waves for a young man aged 26 years in the upper panels and his 83-year-old grandfather in the lower panels. )Courtesy of Michael O’Rourke, MD, University of Sydney, Australia.(

14. CARDIOVASCULAR DISEASEORGANAGE-ASSOCIATED CHANGES Systolic hypertension Vasculature Increased intimal thickness Coronary artery obstruction Arterial stiffening Increased pulse pressure Increased pulse wave velocity Early central wave reflections Decreased endothelium-mediated vasodilation Peripheral artery disease Carotid artery obstruction Atrial fibrillation Atria Increased left atrial size Atrial premature complexes Sinus node dysfunction, sick sinus syndrome Sinus node Decreased maximal heart rate Decreased heart rate variability Type II block, third-degree block Atrioventricular node Increased conduction time Stenosis, regurgitationValvesSclerosis, calcification Left ventricular hypertrophyHeart failure (with or without preserved systolic function) Ventricular tachycardia, fibrillation Ventricle Increased left ventricular wall tension Prolonged myocardial contraction Prolonged early diastolic filling rate Decreased maximal cardiac output Right bundle branch block Ventricular premature complexes TABLE 80-1 Differentiation Between Age-Associated Changes and Cardiovascular Disease in Older People

15. TABLE 80-2 -- Guidelines for Medication Prescribing in Older Patients In general, loading doses should be reduced. Weight (or body surface area) can be used to estimate loading dose requirements. Weight differences between the sexes are greatest for white people. Use estimates of glomerular filtration to guide dosing of renally cleared medications and contrast agent administration. Reduce initial doses of metabolically or hepatically cleared drugs but titrate to effect. Time between dosage adjustments and evaluation of dosing changes should be longer in older patients than in younger patients. Routine use of strategies to avoid drug interactions is essential. Incorporation of reference materials, a team approach, and quality improvement efforts are effective strategies. Knowledge of effects of noncardiac medications is critical. Assessment of adherence and attention to factors contributing to nonadherence should be part of the prescribing process. Physicians must be familiar with the patient's source of prescription medication coverage and provide education and assistance with obtaining critical medications. Multidisciplinary approaches to monitoring of medication therapy may improve outcomes.

16. FIGURE 80-6 The relationship between the number of drugs consumed and drug interactions. Current guidelines for the pharmacologic management of patients with heart failure (HF) or myocardial infarction (post MI) place them at high risk for drug interactions. )From Schwartz JB: Clinical Pharmacology, ACCSAP V, 2003. As modified from Nolan L, O’Malley K: The need for a more rational approach to drug prescribing for elderly people in nursing homes. Age Aging 18:52, 1989; and Denham MJ: Adverse drug reactions. Br Med Bull 46:53, 1990.(

18. TABLE 80-4 -- Considerations for Pharmacologic Therapy for Older Patients with Hypertension and Other Disorders TOXICITY OR ADVERSE EFFECT CONSIDERATIONS EFFICACY CONSIDERATIONSHYPERTENSION + ACE, ARB, aldosterone, and renin antagonist interactions with NSAIDs —Arthritis Interactions with warfarin Atrial fibrillation ARB, ACE* Recurrent Beta blocker, calcium channel blocker (non-DHP(*,[†] Permanent Beta blockers, non-DHP calcium channel blockers —Atrioventricular block Calcium channel blocker, [†] ACE* Carotid disease or stroke Verapamil—Constipation Nitrates and postural hypotensionBeta blocker*,[†] calcium channel blocker*,[†] Coronary artery disease Clonidine [‡] Dementia

19. SSRIs and hyponatremia—Depression Chlorpropamide and hyponatremiaACE,*,[†] ARB,*,[†] CCB (non-DHP), beta blockerDiabetes ACE or ARB + renin inhibitor and hyperkalemia Beta blockerGlaucoma Thiazide diuretics* Gout Calcium channel blockers (possible)* ACE, ARB, aldosterone antagonist and hyperkalemia ACE,*,[†] ARB,*,[†] + loop diuretic,*,[†] beta blocker,*,[†] ? aldosterone antagonist*,[†],[?] Heart failure Diuretic (especially with SSRI)—Hyponatremia Diuretic—Incontinence Beta blockers, diureticsACE,* ARB,* calcium channel blocker*Metabolic syndrome ACE, ARB, aldosterone antagonist and hyperkalemia Beta blocker,*,[†] ? ACE,*,[†] ? aldosterone antagonist*Myocardial infarction Furosemide (bone loss) Thiazides (beta blocker, ACE neutral or protect); potassium (K) phosphate (versus KCl ) Osteoporosis Beta blocker (only if severe)Calcium channel blocker (DHP),*,[†] ACE + diuretics [ ∥ ] Peripheral artery disease

20. Alpha blocker, calcium channel blockers (DHP) Thiazide [?] Postural hypotension Alpha blocker [†] Prostatic hypertrophy Beta blocker Pulmonary disease (asthma, COPD) Aldosterone antagonists (? renin inhibitors) and hyperkalemia ACE,*,[†] ARB,*,[†] ACE + ARB; loop diuretic*,[†] Renal failure Thiazide, loop diuretics and hypokalemiaBeta blocker [†] Ventricular arrhythmias ACE = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; COPD = chronic obstructive pulmonary disease; NSAIDs = nonsteroidal anti-inflammatory drugs; DHP = dihydropyridine; SSRI = selective serotonin reuptake inhibitor. *Recommendations for second-line agents usually added to thiazide diuretics from Chobanian AV, Bakris GL, Black HR, et al: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The JNC 7 Report. JAMA 289:2560, 2003.†Mancia G, De Backer G, Dominiczak A, et al: 2007 Guidelines for the management of arterial hypertension. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 28:1462, 2007.‡Only available transdermal formulation for patients unable to swallow or who refuse oral medications.?Systolic heart failure only. ∥ Norgren L, Hiatt W, Dormandy J, et al: Inter-Society consensus for the management of peripheral arterial disease (TASC II). J Vasc Surg 45:S5A, 2007.?Nursing home patients.

21. Table 80-5 summarizes the approach to hypertension in older patients TABLE 80-5 -- Approach to Hypertension in Older Patients Systolic as well as diastolic hypertension should be treated; current recommendations are based on brachial artery measurements: Patients should be monitored for adverse effects and drug interactions, especially Current Controversies Note: Updated JNC 8 recommendations will be published soon and are expected to address some of these controversies.Note: Updated JNC 8 recommendations will be published soon and are expected to address some of these controversies. The focus should be on achieving blood pressure control, not initial therapy. Multiple medications are usually required in older patients, and combinations should be based on concomitant diseases. Drug dosing regimens should be adjusted for age and disease-related changes in drug metabolism and potential drug-drug interactions. Diastolic target is <90 mm Hg. Systolic target is <140 mm Hg for most (<150 mm Hg for patients older than 80 years). Postural hypotension and postprandial hypotension Hypovolemia with diuretics Hyperkalemia with ACE inhibitors, ARBs, aldosterone, renin antagonists

22. FIGURE 80-8 In-hospital mortality rates reported for revascularization procedures by age group. PCI = percutaneous coronary intervention of all types; CABG = coronary artery bypass graft surgery. (Data are from the National Cardiovascular Revascularization Network as reported by Alexander K, Anstrom K, Muhlbaier L, et al: Outcomes of cardiac surgery in patients ≥80 years: Results from the National Cardiovascular Network. J Am Coll Cardiol 35:731, 2000; Batchelor W, Anstrom K, Muhlbaier L, et al: Contemporary outcome trends in the elderly undergoing percutaneous coronary interventions: Results in 7,472 octogenarians. National Cardiovascular Network Collaboration. J Am Coll Cardiol 36:723, 2000; and the Society of Thoracic Surgeons data base, Bridges C, Edwards F, Peterson E, et al: Cardiac surgery in nonagenarians and centenarians. J Am Coll Cardiol 197:347, 2003.) Data were not available for PCI in patients older than 90 years. See text for further discussion of results for drug-eluting stents and newer surgical approaches.

28. FIGURE 80-5 Estimates of creatinine clearance with the Cockcroft and Gault formula (left panel) and estimates of glomerular filtration rate with the MDRD simplified algorithm (right panel) for men and women aged 45 to 85 years. For calculations, mean weight and height by decade were obtained from U.S. survey data (NHANES, http://www.cdc.gov ); serum creatinine is 1.0 mg/dL (average for older than 65 years in NHANES). Pink lines and circles represent estimates for women; blue lines and diamonds are estimates for men; lighter symbols are estimates for whites, and darker symbols represent estimates for African Americans. The shaded areas indicate GFR estimates of 30 to 59 mL/min/m2 classified as stage 3 renal disease or moderate GFR decrease. Cockcroft and Gault estimates show a steeper decline with age. Both formulas estimate lower clearance in women compared with men and higher clearances in African Americans compared with whites (based on average height and weights and the same creatinine concentration). (Modified from Schwartz JB: The current state of knowledge on age, sex, and their interactions on clinical pharmacology