Age: A Major Risk Factor for Coronary Heart Disease (CHD)¹

The cardiovascular system undergoes significant changes as a person ages.¹ That's not surprising, given that the heart beats about 100,000 times in a typical day, and more than 2.5 billion times in a lifetime.¹ Changes in the structure and function of the heart and coronary blood vessels can increase the risk of developing certain cardiovascular diseases, including high blood pressure, atherosclerosis, and heart failure.¹ The signs and symptoms of CHD in older patients are due to disease progression superimposed on the normal physiologic effects of age on the cardiovascular system.²

Indeed, the incidence of heart disease and stroke increases sharply after age 65, and accounts for more than 40% of all deaths among people aged 65 to 74 and almost 60% among those 85 years and older.¹ Women in particular have a 32% lifetime risk of developing CHD after age 40.³ Additionally, CHD risk increases after menopause.⁴ Although the reasons for this increase have not been entirely elucidated, it may be related to the loss of estrogen's cardioprotective effect.^5-8

Many older people become disabled by CHD, which limits their activities and negatively impacts their quality of life.¹ Although age is an unmodifiable risk factor for heart disease, primary care physicians can help their patients reduce the impact of aging on their CHD risk by targeting other risk factors, such as physical inactivity, high blood pressure, and smoking (SOR: A).^2,9

How Aging Affects the Coronary Arteries

• Aging triggers thickening of the intima—the innermost arterial layer—and stiffening of the arterial walls.¹
  
• Aging blood vessels appear to have inadequate supplies of nitric oxide synthase (NOS), an enzyme required for nitric oxide production by vascular endothelial cells.¹
  
  • Nitric oxide is an important cell-signaling molecule involved in mediating vessel vasodilation.¹
    
  • Nitric oxide helps control atherosclerosis by preventing platelets and white blood cells from sticking to vessel walls.¹
    
• CHD is characterized by a narrowing of the coronary arteries from accumulative atherosclerosis, resulting in reduced blood flow and thus oxygen reaching the heart,¹ and the risk for having an occlusive plaque capable of causing an ischemic event increases with age.²
  
• Recent data from the Women's Ischemia Syndrome Evaluation (WISE) study found that coronary artery disease (CAD) may proceed differently in women; their arteries tend to have more diffuse disease than men's.¹⁰
  
  • This unique pathogenesis of CAD in women means that they often develop obstructive CAD 10 to 15 years later in life than do men.^11,12

Preventive Measures to Reduce Risk

• Absence of established risk factors at 50 years of age is associated with very low lifetime risk for cardiovascular disease (CVD) and markedly increased survival.¹³
• As shown in the figure below, 50-year-old women with optimal risk-factor levels had a substantially lower lifetime risk of CVD than those with ≥2 risk factors.¹³

• In the same study, women with optimal risk-factor levels had a median survival of more than 8 years longer than those with ≥2 risk factors.¹³
  
• Ideally, prevention efforts should begin decades before age 50 to reduce CHD risk later in life and improve healthy longevity (SOR: B).¹³
  
• The elderly can benefit greatly from initiation of secondary preventive measures to control CHD risk factors and reduce events (SOR: B).²

According to American Heart Association guidelines for CVD prevention in women, aspirin therapy (81 mg/day or 100 mg every other day) should be considered for women aged 65 years and older if their blood pressure is controlled and the benefit for ischemic stroke and myocardial infarction (MI) prevention is likely to outweigh the risk of gastrointestinal bleeding and hemorrhagic stroke.¹⁸

CHD Diagnosis in Older Women

• Diagnosis of CHD or MI can be difficult in older persons:
  
  • Dyspnea on exertion is a more common clinical symptom of CAD in older men and women than is chest pain.¹⁹
    
  • Older persons tend to describe chest pain as being less severe and of shorter duration.¹⁹
    
  • Acute angina may be due to underlying pulmonary edema rather than a heart attack.^2,19-23
    
• Older women are also at increased risk for suffering an unrecognized MI:
  
  • In a study of 110 older nursing home residents, the presenting symptoms of recognized acute MI and unrecognized healed MI were dyspnea in 35%, chest pain in 22%, neurologic symptoms in 18%, and gastrointestinal symptoms in 4%.²⁴
    
  • In the Framingham study, clinically unrecognized MI occurred in 35% of women aged 65 to 74 years, 36% of those aged 75 to 84 years, and 46% of those aged 85 to 95 years.²⁵
    
• Because age is an independent risk factor for CHD,¹⁵ there should be a higher level of suspicion of CHD (in other words, a higher pretest likelihood of CHD) in older women who present with nonanginal chest pain compared with younger women.
  
• Although current guidelines recommend the use of exercise testing for diagnosis of CAD,²⁶ women engage less often in physical exercise programs, have lower functional capacity, and have more functional decline during their menopausal years.¹¹
  
• Pharmacologic stress myocardial perfusion imaging is recommended as an alternative to exercise testing for the diagnosis and risk stratification of women who are unable to exercise adequately.¹¹

References
1. National Institutes of Health, National Institute on Aging. Aging Hearts & Arteries: A Scientific Quest. Bethesda, MD: US Department of Health and Human Services; 2005. NIH publication 05-3738. 2. Williams MA, Fleg JL, Ades PA, et al. Secondary prevention of coronary heart disease in the elderly (with emphasis on patients ≥75 years of age). An American Heart Association scientific statement from the Council on Clinical Cardiology Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation. 2002;105:1735-1743. 3. Lloyd-Jones DM, Larson MG, Beiser A, et al. Lifetime risk of developing coronary heart disease. Lancet. 1999;353:89-92. 4. Gaziano JM, Manson JE, Ridker PM. Primary and secondary prevention of coronary heart disease. In: Libby P, Bonow RO, Mann DL, et al. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 8th ed. Philadelphia, PA: Saunders Elsevier; 2008:1119-1148. 5. Shaw LJ, Bairey Merz CN, et al; WISE Investigators. Insights from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study: Part I–gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. J Am Coll Cardiol. 2006;47(suppl):S4-S20. 6. Barrett-Connor E. Menopause: Problems and interventions in the United States. In: Paoletti R, Crosignani PG, Kenemans P, et al, eds. Women's Health and Menopause: Risk Reduction Strategies. Dordrecht, The Netherlands: Kluwer Academic Publishers; 1997:9-13. 7. Adams MR, Kaplan JR, Manuck ST, et al. Inhibition of coronary artery atherosclerosis by 17-beta estradiol in ovariectomized monkeys. Arteriosclerosis. 1990;10:1051-1057. 8. Wagner JD, Clarkson TB, St. Clair RW, et al. Estrogen and progesterone replacement therapy reduces low density lipoprotein accumulation in the coronary arteries of surgically postmenopausal cynomolgus monkeys. J Clin Invest. 1991;88:1995-2002. 9. Hayes SN. Preventing cardiovascular disease in women. Am Fam Physician. 2006;74:1331-1340. 10. Pepine CJ, Kerensky RA, Lambert CR, et al. Some thoughts on the vasculopathy of women with ischemic heart disease. J Am Coll Cardiol. 2006;47:30S-35S. 11. Mieres JH, Shaw LJ, Arai A, et al. Role of noninvasive testing in the clinical evaluation of women with suspected coronary artery disease: consensus statement from the Cardiac Imaging Committee, Council on Clinical Cardiology, and the Cardiovascular Imaging and Intervention Committee, Council on Cardiovascular Radiology and Intervention, American Heart Association. Circulation. 2005;111:682-696. 12. Lerner DJ, Kannel WB. Patterns of coronary heart disease morbidity and mortality in the sexes: a 26-year follow-up of the Framingham population. Am Heart J. 1986;111:383-390. 13. Lloyd-Jones DM, Leip EP, Larson MG, et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation. 2006;113:791-798. 14. Chobanian AV, Bakris GL, Black HR, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206-1252. 15. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report. Circulation. 2002;106:3143-3421. 16. American Diabetes Association. Screening for type 2 diabetes. Diabetes Care. 2000;23:S20-S23. 17. Smith SC, Blair SN, Bonow RO, et al. AHA/ACC guidelines for preventing heart attack and death in patients with atherosclerotic cardiovascular disease: 2001 update: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology. Circulation. 2001;104:1577-1579. 18. Mosca L, Banka CL, Benjamin EJ, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. Circulation. 2007;115:1481-1501. 19. Aronow WS. Heart disease and aging. Med Clin North Am. 2006;90:849-862. 20. Tresch DD, Saelan K, Hoffman R. Elderly patients with late onset of coronary artery disease: clinical and angiographic findings. Am J Geriatr Cardiol. 1992;1:14-25. 21. Graham SP, Vetrovec GW. Comparison of angiographic findings and demographic variables in patients with coronary artery disease presenting with acute pulmonary edema versus those presenting with chest pain. Am J Cardiol. 1991;68:1614-1618. 22. Stone GW, Griffin B, Shah PK, et al. Prevalence of unsuspected mitral regurgitation and left ventricular diastolic dysfunction in patients with coronary artery disease and acute pulmonary edema associated with normal or depressed left ventricular systolic function. Am J Cardiol. 1991;67:37-41. 23. Tresch DD, Brady WJ, Aufderheide TP, et al. Comparison of elderly and younger patients with out-of-hospital chest pain. Clinical characteristics, acute myocardial infarction, therapy, and outcomes. Arch Intern Med. 1996;156:1089-1093. 24. Aronow WS. Prevalence of presenting symptoms of recognized acute myocardial infarction and of unrecognized healed myocardial infarction in elderly patients. Am J Cardiol. 1987;60:1182. 25. Vokonas PS, Kannel WB. Epidemiology of coronary heart disease in the elderly. In: Aronow WS, Fleg JL, eds. Cardiovascular Disease in the Elderly. 3rd ed. New York, NY: Marcel Dekker; 2004:189-214. 26. Gibbons RJ, Balady GJ, Bricker JT, et al. ACC/AHA 2002 guideline update for exercise testing: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing). http://www.acc.org/qualityandscience/clinical/guidelines/exercise/exercise_clean.pdf. Accessed May 14, 2009. 27. Rosamond W, Flegal K, Friday G, et al. Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. 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