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ΚΑΡΔΙΑΓΓΕΙΑΚΗ ΝΟΣΟΣ ΣΤΟΥΣ ΗΛΙΚΙΩΜΕΝΟΥΣ ΑΝΔΡΕΑΣ ΠΙΤΤΑΡΑΣ MD “ Seventy is old enough. After that there is too much risk.” Mark Twain Following the Equator, 1897 Introduction • Cardiovascular disease (CVD) is the leading cause of death in the elderly. • 5 out of every 6 deaths related to CVD occur in the elderly. • Nearly 2/3 of all myocardial infarctions and 80% of all deaths related to MI occur in persons over 65 years of age. Cardiovascular disease in the elderly • Coronary artery disease • Heart failure • Valvular heart disease • Atrial fibrillation Cardiovascular Health Study • Population-based study of risk factors for cardiovascular disease in older patients. • Participants > 65 were recruited from random samples of Medicare eligibility lists in four communities (CA, MD, NC and PA) • Presence of CVD was not an exclusion. J Am Geriatric Soc 2005; 53: 211-218 Cardiovascular Health Study • Original cohort ( n = 5201) enrolled in 1989-1990 • 2nd cohort ( n = 687) of predominately AA enrolled 3 years later to increase diversity • Combined cohort of 5,888 patients was 57.6% female and 15.7% African American • Average age at entry was 72.8 years +/- 5.6 Coronary artery disease Cardiovascular Health Study 10 yr incidence rates: CHD in women 40 35 30 25 65-69 70-74 75-79 80-84 20 15 10 5 0 Caucasian African American Cardiovascular Health Study 10 yr incidence rates: CHD in men 70 60 50 65-69 70-74 75-79 80-84 40 30 20 10 0 Caucasian African American Coronary artery disease in the elderly • Coronary heart disease (CHD) may often present atypically in the elderly. • Dyspnea or acute heart failure may be the initial manifestation of myocardial ischemia or infarction. • CHD is often undiagnosed or misdiagnosed in elderly patients. Acute coronary syndrome: Differences by age • 2133 consecutive acute coronary syndrome (ACS) patients from 26 hospitals participating in a nationwide survey • Three patient subgroups based on age: < 65 years 65 - 75 years > 75 years (n = 974) (n = 500) (n = 639) Am J Geriatric Cardiol 2004; 13: 188-196 Baseline characteristics of ACS patients: Differences by age 60 50 40 < 65 65-75 > 75 30 20 10 0 h/o angina h/o MI h/o CHF Initial symptoms & ECG findings in ACS patients: Differences by age 90 80 70 60 < 65 65-75 > 75 50 40 30 20 10 0 angina ST elevation ST depression In-hospital complications in ACS patients: Differences by age 30 25 20 < 65 65-75 > 75 15 10 5 0 CHF New BBB PAF In-hospital mortality in ACS patients: Differences by age 35 30 25 20 < 65 65-75 > 75 15 10 5 0 7 days 30 days 1 year In-hospital management in ACS patients: Differences by age 70 60 50 40 < 65 65-75 > 75 30 20 10 0 angiography stenting CABG Global Registry of Acute Coronary Events (GRACE) • Observational registry of patients admitted to hospital with acute coronary syndrome • 24,165 ACS patients (2/3 men) stratified into 4 age groups • 102 participating hospitals in 14 countries Am Heart J 2005; 149: 67-73 Global Registry of Acute Coronary Events (GRACE) • Patients > 65 more commonly had a past medical history of: angina previous MI CABG atrial fibrillation TIA/stroke heart failure hypertension Global Registry of Acute Coronary Events (GRACE) • Older patients demonstrated a higher incidence of non ST-segment elevation MI (NSTEMI) • Patients > 65 exhibited a significant delay in seeking treatment Comparison among age groups according to type of ACS 45 40 35 30 55-64 65-74 75-84 > 85 25 20 15 10 5 0 STEMI NSTEMI UA Hospital outcome among different age groups: GRACE 30 25 20 55-64 65-74 75-84 > 85 15 10 5 0 HF Shock Major bleed Hospital mortality associated with increasing age: GRACE 16 Adjusted OR ( 95% CI ) 14 12 10 55-64 65-74 75-84 > 85 8 6 4 2 0 Adjusted OR 55-64 65-74 75-84 > 85 2.77 4.95 8.04 15.7 (1.53 - 4.99) (2.78 - 8.79) (4.53 - 14.3) (8.77 - 28.3) Using GRACE risk model: SBP, initial serum creatinine, HR, cardiac enzyme, Kilip class STsegment deviation, cardiac arrest at arrival Hospital procedures: GRACE 60 50 40 55-64 65-74 75-84 > 85 30 20 10 0 Angio PCI CABG Medications prescribed during hospitalization: GRACE 100 90 80 70 60 50 40 30 20 10 0 55-64 65-74 75-84 > 85 ASA Beta blockers IIb/IIIa Acute Coronary Syndrome: Summary of Differences by Age • Frequency of no anginal pain/atypical pain as presenting symptom increased with age • Frequency of ST-segment elevation on admitting ECG decreased with age • Use of acute reperfusion strategies significantly declined with advancing age • Seven-day, 30-day and 1-year mortality increased with advancing age Some factors contributing to worse outcomes in elderly ACS patients • More extensive CAD and higher risk of previous MI • Increased risk of complications including heart failure, atrial fibrillation, ventricular rupture, bleeding or stroke Some factors contributing to worse outcomes in elderly ACS patients • Late presentation and/ or delayed recognition due to atypical symptoms and /or less classical ECG changes • Reduced utilization of EBM strategies • Increased co-morbidities, especially renal insufficiency and pulmonary diseases Results of Percutaneous Coronary Interventions (PCI) in the Elderly • Data from ACC national registry • 8828 PCI procedures performed on octogenarians (mean age 83.7 yrs) J Am Coll Cardiol 2002; 40: 394-402 Results of Percutaneous Coronary Interventions (PCI) in the Elderly • 93% angiographic success rate • 3.77% in-hospital mortality rate (1.35% inhospital mortality rate if no MI in the week preceding PCI • Most important predictor of in-hospital mortality was presence of an acute MI and time after MI CABG surgery in the elderly Elderly patients have a higher incidence of: • Left main disease • Multi-vessel disease • LV dysfunction • Re-operation as an indication for surgery • Concomitant valvular heart disease • Additional co-morbidities Post-op course in the elderly Combination of more advanced CAD and worse co-morbidities leads to increased mortality and higher rates of: • • • • • Intra-operative and post-operative MI Low output state and use of IABP Stroke, GI complications Wound infections Renal failure Heart failure HF in women: 10 year incidence rates/1000 person-years (CHS) 40 35 30 25 65-69 70-74 75-79 80-84 20 15 10 5 0 Caucasian African American HF in men: 10 year incidence rates/1000 person-years (CHS) 60 50 40 65-69 70-74 75-79 80-84 30 20 10 0 Caucasian African American Increasing prevalence of heart failure over past 20 years 6 5 4 3 # of HF pts in millions 2 1 0 1983 1988 1993 1998 2003 Major Public Health Problem • 5 million US patients have heart failure with 550,000 newly diagnosed cases/year • HF accounts for 12-15 million office visits and 6.5 million hospital days each year • 53,000 deaths/year from HF as primary cause and number steadily rising www.acc.org/clinical/guidelines/failure//index.pdf. Heart failure is predominately a disease of the elderly • 6-10% of patients over age 65 have HF. • Approximately 80% of patients hospitalized with HF are over age 65. • HF is the most common Medicare DRG. • More $$ spent for diagnosis and treatment of HF than for any other diagnosis Some potential reasons for the high prevalence of HF in the elderly • Age-related changes in ventricular function (particularly diastolic function) • Cumulative effects of hypertension and other cardiovascular disease risk factors. www.acc.org/clinical/guidelines/failure//index.pdf. Some potential reasons for the high prevalence of HF in the elderly • Less aggressive treatment of some cardiovascular risk factors in the elderly. • Elderly patients may often take medications that exacerbate HF symptoms. www.acc.org/clinical/guidelines/failure//index.pdf. Heart failure in the elderly • Like ACS, heart failure is often under recognized and inadequately treated in elderly patients. • Elderly HF patients may present with atypical symptoms & physical exam findings. www.acc.org/clinical/guidelines/failure//index.pdf. Heart failure symptoms in the elderly Less common • Dyspnea and orthopnea More common • Daytime oliguria & nocturia • Confusion, insomnia, irritability • Anorexia and GI disturbances • Non-specific complaints (often misdiagnosed as concomitant disease or age-related changes) Tresch Systolic function by gender among CHS participants with HF (Am J Cardiol 2001; 87: 413-419) HF in older vs. younger patients Characteristic Middle-aged Elderly Prevalence Gender Etiology LVEF Co-morbidities < 1% M>W CHD Impaired Fewer 6-10% W>M Hypertension Preserved Multiple Am J Geriatric Cardiol 2001; 9 (suppl) 97-111 Differential diagnosis of HF in patients with preserved LV function • Incorrect diagnosis • Inaccurate measurement of LV ejection fx • Primary valvular disease • Restrictive cardiomyopathy • Pericardial constriction www.acc.org/clinical/guidelines/failure//index.pdf Differential diagnosis of HF in patients with preserved LV function • Episodic/reversible LV systolic dysfunction • Severe hypertension • HF associated with high metabolic demand • COPD with right heart failure • Pulmonary hypertension with pulmonary vascular disorders Impact of age and gender on normal reference BNP levels 70 60 50 40 Men Women 30 20 10 0 45-54 55-64 65-74 > 74 Pharmacologic therapy for chronic systolic heart failure Diuretics Digoxin ACE-I Beta-blockers ARB Anti-aldosterone Isordil/hydralazine Improved symptoms Improved morbidity Improved morbidity & mortality Improved morbidity & mortality Improved morbidity & mortality Improved morbidity & mortality Improved morbidity & mortality Principles of treating patients with diastolic dysfunction • Control hypertension • Control tachycardia • Reduce central blood volume • Alleviate myocardial ischemia CHARM-Preserved Trial • 3023 patients (mean age 67 yrs) with Class II-IV heart failure and LVEF > 40% • Randomly assigned to placebo versus candesartan (target daily dose = 32 mg) • at 6 months, 2/3 of study patients achieved target treatment dose CHARM-Preserved Trial • Primary outcome = cardiovascular death or admission to hospital for HF. • Median follow-up = 36 months Number of HF admissions during CHARM-Preserved Trial 20 18 16 14 12 10 8 6 4 2 0 Placebo Candesartan 1 2 3 or more total Angiotensin receptor blockers in HF • Use of an ARB could be considered in patients with an ejection fraction > 40% to reduce the risk of hospitalization due to heart failure. Lancet 2003; 362: 754-755 Valvular heart disease 2006 Updated Guidelines for Management of Patients with Valvular Heart Disease • Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr., Faxon DP, et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease). Circulation 2006; 114: 450-527. also available online at http:// www.circulationaha.org Morphologic changes of elderly hearts Necropsy findings in 93 patients > 90 yrs. Finding Calcified aortic valve cusps Calcified mitral annulus Calcified papillary muscle % of patients 63 45 45 Roberts WC. Morphological features of the elderly heart in Cardiovascular Disease in the Elderly 3rd edition, Aronow WS, Fleg JL (eds) Marcel Dekker 2004 Cardiovascular Health Study: Prevalence of aortic sclerosis 60 50 40 Women Men 30 20 10 0 65-74 75-84 85+ Cardiovascular Health Study: Prevalence of aortic stenosis 7 6 5 4 Women Men 3 2 1 0 65-74 75-84 85+ Differences between young and old patients with valvular AS Characteristic Sex Etiology Valve Commissural fusion Systemic BP Pulse pressure Carotid upstroke Palpable LVH Young patientsOlder patients males > females males = females congenital or RHD calcific degen bicuspid tricuspid yes no usually low normal/ increase narrow frequently wide diminished, slow normal common uncommon Differences between young and old patients with valvular AS Characteristic Young patientsOlder patients Thrill Ejection click S4 Systolic murmur Location Atrial fibrillation AV calcium common common common harsh, rough upper sternum rare variable uncommon uncommon common musical apical 25 % common Tresch Clinical features of AS and their positive predictive value Features Likelihood ratios Slow rate of rise of carotid pulse 2.8 – 130 Mid to late peaking murmur 8.0 – 101 Decreased intensity of S2 3.1 – 50 JAMA 1997; 277: 564-571 Correlation of physical exam with severity of AS in elderly patients Exam finding ASEM Prolonged SM Late-peak SM Prolonged carotid A2 decreased/absent Mild 95 3 3 3 5 Moderate 100 63 63 33 49 Severe 100 84 84 53 74 Am J Cardiol 1991; 67: 776-777 Event rates per 1000 person-years for patients with sclerotic aortic valves Otto CM, et al. N Engl J Med 1999; 341: 142-147 40 35 30 25 normal sclerosis 20 15 10 5 0 stroke HF MI CV death All death Treatment of aortic stenosis • Therapeutic decisions in patients with AS are based primarily on presence or absence of symptoms. • After onset of symptoms (angina, heart failure or syncope) average survival is typically less than 2-3 years • AVR is the only effective Rx for severe AS Special considerations in elderly patients undergoing valve surgery Aortic stenosis • AVR should be considered in all elderly patients with symptoms caused by aortic stenosis. • Balloon valvotomy is not an acceptable alternative to aortic valve replacement. • Concomitant CAD and/or LV dysfunction are predictive of worse outcomes. Special considerations in elderly patients undergoing valve surgery Aortic stenosis • Some elderly females have a narrow LV outflow tract & small annulus that may need enlargement. • Heavy calcification of aortic valve, annulus or aortic root may require surgical debridement. • Excessive or inappropriate LVH may increase risk of peri-operative morbidity and mortality. Circulation 2006; 114: 450-527. Special considerations in elderly patients undergoing valve surgery Aortic regurgitation • Pure AR is uncommon in elderly patients. • Patients > 75 are more likely to develop symptoms or LV dysfunction at earlier stages of LV dilatation and may display more persistent LV dysfunction and HF symptoms after surgery. • Elderly patients with AR have worse postoperative survival rates than younger patients. Mitral regurgitation (MR) • Myxomatous degeneration and mitral annular calcification (MAC) are common etiologies for MR in the elderly. • Patients with MR may remain symptom free for many years (average interval from diagnosis to onset of symptoms = 16 years). • Most patients with chronic MR have mild mod symptoms and unlikely to need MVR. Marked increased prevalence of MAC in elderly patients 70 60 50 40 Men Women 30 20 10 0 62-70 71-80 81-90 Clinical characteristics of subjects with MAC: Framingham Heart Study • Older females with higher BMI • Higher SBP and more LVH on ECG • Increased % with diabetes, hyperlipidemia • More likely to have prevalent atrial fibrillation, heart failure and CVD Circulation 2003; 107: 1492-1496 Potential complications of mitral annular calcification • Conduction system disease • Arrhythmia, especially atrial fibrillation • Systemic emboli • Mitral regurgitation • Acquired mitral stenosis • Infective endocarditis Association of MAC with incidence of CV disease Incidence rates per 10,000 person-years 16 yrs of follow-up (adjusted for age and sex) Condition No MAC MAC Myocardial infarction Heart failure Incident CVD CV death All-cause death 113 153 268 162 443 225 383 554 428 847 (Circulation 2003: 107: 1492-1496) Mitral annular calcification predicts CV morbidity and mortality 900 800 700 600 500 No MAC MAC 400 300 200 100 0 MI HF CV death all death Are MAC and aortic valve sclerosis (ASc) markers of subclinical CVD ? • Vascular calcification is associated with CV risk factors & incident CV events • Burden of shared risk factors including age, HTN, DM, hyperlipidemia and obesity • MAC and ASc may function as bioassay for longitudinal exposure to CV risk factors. Features of MVP in the elderly • Isolated systolic clicks are rare • Holosystolic murmurs are common • Degree of regurgitation more severe c/w younger patients • Echo findings of pansystolic prolapse and flail valve leaflets are common Features of MVP in the elderly • Heart failure is a a problem, especially in elderly men with MVP • Onset of heart failure may be abrupt • At time of surgery, many patients have ruptured chordae Special considerations in elderly patients undergoing valve surgery • Elderly patients with MR fare less well with valve surgery than do patients with AS. • Operative mortality increases and survival is reduced in patients > 75 years, especially if valve replacement (versus repair) is performed or CAD is also present. Atrial fibrillation 2006 Updated Guidelines for Management of Patients with Atrial Fibrillation • Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines ( Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation). Circulation 2006; 114: 700-752. also available online at http:// www.circulationaha.org Atrial fibrillation • Prevalence increases with advancing age (6-8% of those over age 80 have AF) • Age-adjusted incidence is higher in men • Blacks have less than ½ the age-adjusted risk of developing AF c/w whites • Prevalence of AF increases with severity of HF or valve disease Prevalence of atrial fibrillation in US adults (ATRIA Study) • Approximately 2.3 x 106 US adults have AF • By 2050, the number of US adults with AF is projected to increase to 5.6 million – More than 50% of affected individuals will be 80 years of age or older JAMA 2001; 285: 2370-2375 Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) Trial Randomized multi-center trial of two approaches to the Rx of atrial fibrillation: • Cardioversion and treatment with antiarrhythmic drugs to maintain NSR; or • Allow atrial fibrillation to persist but control heart rate • Use of anticoagulant drugs was recommended in both approaches AFFIRM Trial • 4060 patients (mean age 69.7 yrs) • Male/Female ratio of 60/40 • Underlying cardiac diagnoses – Hypertension – Heart failure – % with normal LVEF 51% 23% 74% AFFIRM Trial: Summary of Results • Rhythm control strategy offered no survival advantage c/w rate control strategy (5-year mortality 23.8% vs. 21.3%) • Fewer hospitalizations in rate control group (73% vs. 80%, P <.001) and fewer adverse drug effects than rhythm control group N Engl J Med 2003: 347: 1825-1833 Risk stratification in AF patients using the CHADS 2 risk score Risk factors C Recent congestive heart failure H Hypertension A Age > 75 years D Diabetes mellitus S2 History of stroke or TIA Score 1 1 1 1 2 J Am Coll Cardiol 2004; 43: 929-935 CHADS2 risk score and adjusted stroke rate in NRAF 20 18 16 14 12 10 8 6 4 2 0 CHADS 2 score 0 1 2 3 4 5 6 Potential reasons for increased warfarin sensitivity in the elderly • • • • • • Concurrent drug therapy Heart failure Advanced malignancy Malnutrition Diarrhea Unsuspected vitamin K deficiency Hepatic abnormalities may increase warfarin sensitivity in the elderly • Decreased synthesis of vitamin K dependent clotting factors • Diminished albumin concentration (increases unbound fraction of warfarin) • Reduced intrinsic clearance of drug and/or decline in racemic warfarin clearance • Decreased liver size Additional background slides Effects of aging on the CV system Summary of principal effects of aging on cardiovascular system • Increased arterial and myocardial stiffness • Impaired beta adrenergic responsiveness • Impaired endothelial function • Reduced sinus node function • Decreased baroreceptor responsiveness • Net effect is marked reduction in CV reserve www.sgcard.org Clinical implications • Increased SBP and pulse pressure • Increased prevalence of atrial fibrillation • Increased prevalence of heart failure, especially HF with preserved LV function www.sgcard.org Clinical implications • Increased prevalence of bradyarrhythmias and “sick sinus syndrome” • Increased risk for syncope and falls • Impaired response to stress/illness www.sgcard.org Arterial changes with aging • Increased calcium, collagen & collagen cross-links • Increased intima-medial thickness • Increased vessel diameter • Decreased elastin • Increased systolic BP and pulse pressure • Increased vascular stiffness indices and pulse wave velocity • Net effect is increase in afterload Endothelial function and aging • Marked decline in endothelium-mediated vasodilation from age 40-70 • No change in vasodilator response to nitroglycerine • Age-related effects on endothelial function are exacerbated by HTN, dyslipidemia, CAD and HF. These effects are attenuated by regular aerobic exercise. Effect of age on stroke volume and LVEF with exercise • Impaired LV emptying with increased ESV index • Impaired LV filling with minimal change in EDV • Net effect: decrease in both stroke volume and LV ejection fraction • LVEF at peak exercise declines from 85% in 20’s to 70% in 80’s • Augmentation in EF from rest to peak exercise declines with age CV changes during maximum upright exercise between ages 20 and 80 Oxygen consumption AVO2 difference Cardiac output Heart rate LV stroke volume LVEDV LVESV LV ejection fraction reduced ~ 50 % reduced ~ 25 % reduced ~ 25 % reduced ~ 25 % reduced ~ 15 - 25 % NC/slight decrease increased ~ 150% reduced ~ 15% Changes on resting echo comparing normal subjects ages 20 and 80 LV wall thickness LV end diastolic diameter LV end systolic diameter Fractional shortening Peak E-wave velocity Peak A-wave velocity LA dimension Increased by ~ 30% No change No change No change Reduced ~ 50 % Increased ~ 50 % Increased ~ 10 % Circulation 1977; 56: 273-278 Effect of aging on diastolic function • Decrease in elastic properties of heart and great vessels (SBP, myocardial stiffness) • Decrease in rate of ventricular filling • Increase in cardiac fibrosis • Decline in active relaxation • Decrease in beta receptor density • Decline in peripheral vasodilatory capacity Effect of aging on conduction system • Increased elastic tissue and collagen • Marked decrease SA node pacemaker cells • Calcification of cardiac skeleton • Slowed conduction in AV node and proximal HisPurkinje system • Conduction abnormalities amplified by hypertension, CAD and amyloid infiltration ECG changes associated with aging • Modest increase in PR and QT intervals • Left shift in QRS axis • Increased prevalence of RBBB • Flattening of the ST segment • Decreased T-wave amplitude • No significant change in resting heart rate but marked reduction in HR variability www.sgcard.org Arrhythmias in the Elderly • Marked increase in frequency of SVT and PVCs • Short runs of SVT occur in 1/3 of healthy older subjects on 24 hour ambulatory monitoring • Ventricular couplets occur in ~ 11% and short runs of NSVT occur in about ~ 4% of healthy persons > 60 years of age • In the absence of heart disease, none of these arrhythmias are associated with adverse prognosis Am J Cardiol 1992; 70: 748-751