Life Extension Magazine

Life Extension Magazine July 2006

Report

Aspirin

Aspirin’s Role in Heart Disease

Life Extension has repeatedly alerted its members to the lethal dangers of endothelial dysfunction, the key underlying factor in the progression of atherosclerosis, or hardening of the arteries. (See “Why Our Arteries Become Clogged as We Age,” Life Extension, October 2005.)

Endothelial dysfunction occurs when the blood vessel linings can no longer dilate in response to demands for increased blood flow. Emerging studies indicate that aspirin may protect against heart disease in part by improving endothelial function. In a study of 14 patients with coronary atherosclerosis, aspirin helped improve the ability of blood vessels to dilate, indicating an improvement in endothelial function. This led the study authors to suggest that aspirin therapy could help improve endothelial dysfunction and inhibit the advance of atherosclerosis.28

The heart depends on its coronary arteries for the oxygen supply that fuels this most vital of organs. Coronary heart disease occurs when normal blood flow through the arteries that feed the heart is slowed or interrupted by factors such as blood clots or plaque.

Preventing clots is another way that aspirin helps prevent heart attacks. By irreversibly blocking production of the clot-promoting biochemicals known as thromboxanes, aspirin prevents platelets in the blood from latching on to each other and forming a clot. A platelet has a life span of 10 days, and aspirin permanently impairs the platelet’s clotting ability.29 Aspirin helps blood flow more smoothly past any plaque that is narrowing an artery, and if a plaque ruptures, aspirin will reduce the likelihood of a clot clinging to it.30

Aspirin can also help prevent heart disease through its anti-inflammatory action. Inflammation participates in many disease processes in the body, including plaque accumulation in the arteries.31 The growth of plaque can obstruct blood flow through the arteries. If a plaque ruptures due to inflammation, it can trigger a heart attack.

A 2003 meta-analysis examined aspirin’s effects on primary heart-attack prevention (that is, the prevention of first heart attacks). In more than 55,000 men and women, aspirin use was associated with a 32% reduction in the risk of having a first heart attack, and with a 15% reduction in the risk of all major vascular events.32

A study presented at the 2005 meeting of the American Heart Association reported on the lifesaving benefits of aspirin therapy. This study examined nearly 9,000 women with stable heart disease, ranging in age from 50 to 79. During more than six years of follow-up, women taking aspirin were 25% less likely to die from heart disease and 17% less likely to die from any cause. Some women took 81 mg of aspirin daily, while others took 325 mg. The study authors stated that the two doses appeared to be similarly effective, but that higher doses of aspirin are associated with a greater risk of certain side effects, such as stomach bleeding.33

A meta-analysis published in 2006 examined the effects of aspirin therapy in preventing cardiovascular events in women and men. Examining data from more than 50,000 women, investigators determined that aspirin therapy was associated with a significant 12% reduction in cardiovascular events in women. Among more than 44,000 men, aspirin therapy produced a significant 14% reduction in all cardiovascular events and an even more impressive 32% reduction in heart attacks.34

According to the US Preventive Services Task Force, aspirin’s proven benefits are reason enough for people to start using it if they have at least a 6% chance of developing coronary heart disease in the next 10 years. By contrast, the American Heart Association recommends aspirin for people whose 10-year risk of developing coronary heart disease is 10% or higher, as long they have no medical contraindications for taking the drug. A doctor can help you calculate your cardiovascular risk based on factors such as tobacco use, cholesterol, and blood pressure.35,36 You can also assess your cardiovascular risk by using online risk factor calculators available at the American Heart Association website.

Life Extension strongly recommends that people who have already had a heart attack (or other episode of heart disease) discuss aspirin therapy with their doctor as part of a strategy to prevent future problems. Life Extension also suggests that people with no previous history of cardiovascular disease—but who are nevertheless at high risk for heart disease—strongly consider aspirin therapy in consultation with their personal physician. The recommended dose for preventing heart-related problems is 81-325 mg daily. Speak with your doctor about your personal needs before beginning aspirin therapy.

Aspirin and Stroke: Risk vs. Benefit

The brain requires a constant supply of oxygen from freshly flowing blood to convert glucose into energy.38 During a stroke, blood flow to part of the brain is cut off, and the damage from this interruption can cause death, disability, impaired speech, and myriad other adverse effects.

The most common type of stroke—known as ischemic stroke—occurs when an artery becomes blocked, limiting blood supply to areas of the brain. This type of stroke accounts for about 80% of stroke cases. The other 20% or so are cases of hemorrhagic stroke, which is caused by a blood vessel rupturing and spilling blood into the brain. Aspirin plays vastly different roles in these two types of stroke.

Aspirin helps to decrease the risk of ischemic stroke by keeping blood platelets from sticking together to form a clot, so that blood continues to flow past any narrowed spots in the arteries that feed the brain. However, some studies suggest that taking aspirin may cause a slight increase in a person’s chance of having a hemorrhagic stroke. The US Preventive Services Task Force estimates that if 1,000 people took aspirin for five years, as many as 2 would suffer a hemorrhagic stroke.39

A study published in March 2005 examined aspirin’s effects on women. Nearly 40,000 middle-aged and older women were assigned to take either placebo or 100 mg of aspirin every other day for 10 years. Women who took aspirin had a notable 24% reduced risk of ischemic stroke. In this study, however, aspirin use was associated with slightly higher risks of gastrointestinal bleeding and hemorrhagic stroke.40

ASPIRIN THERAPY: BALANCING BENEFITS AND SIDE EFFECTS

While aspirin therapy is known to reduce the incidence of cardiovascular events and ischemic stroke, it is also associated with an increased risk of certain adverse side effects, including peptic ulcer disease and hemorrhagic stroke.

For example, according to the US Preventive Services Task Force, if 1,000 people with a 1% risk of coronary heart disease took aspirin regularly for five years, this treatment would prevent 1-4 heart attacks, but would produce up to 2 cases of bleeding in the brain and 2-4 cases of major gastrointestinal bleeding. By contrast, if 1,000 people with a 5% (five times higher) risk of coronary heart disease events used aspirin therapy for five years, the treatment would prevent 6-20 heart attacks, but would contribute to up to 2 cases of bleeding in the brain and 2-4 major gastrointestinal bleeding events. Thus, the net benefit of aspirin therapy is increased in individuals with progressively greater degrees of cardiovascular risk.35

Chronic use of aspirin therapy has been associated with peptic ulcer disease and gastrointestinal bleeding. Concomitant use of cimetidine (Tagamet®) or antacids may help heal ulcerations. Some findings suggest that aspirin-induced damage to the gastrointestinal tract can be minimized by using enteric-coated tablets. Smaller doses of aspirin are generally less likely to induce gastrointestinal side effects.37 Consult your doctor to determine if you are a good candidate for aspirin therapy and what dosage may be best for you.

Another study reported in late 2005 examined the effects of aspirin therapy in more than 50,000 women who did not have coronary heart disease. Aspirin use was associated with a 17% reduction in the risk of suffering a stroke, and a 24% reduction in the risk of ischemic stroke. In this study, aspirin use did not appear to increase the risk of hemorrhagic stroke.33

Once your risk factors for stroke—like hypertension, high cholesterol, diabetes, or smoking—start adding up, you and your doctor need to discuss aspirin therapy, particularly as you grow older and advance into age groups that bear a heavier stroke risk. If you have suffered a hemorrhagic stroke, aspirin should not be used. In general, 81-325 mg of aspirin daily is used as part of a stroke-prevention program.

ASPIRIN'S OTHER CARDIOVASCULAR BENEFITS

Numerous recent studies suggest that aspirin is underutilized in the prevention and management of other conditions affecting the cardiovascular system.

Doctors know, for instance, that people who have conditions such as metabolic syndrome, kidney dialysis, peripheral arterial disease, and angina have elevated risks of cardiovascular disease and heart attacks. Research findings from the past two years indicate that aspirin therapy may help to mitigate the elevated cardiovascular disease risk experienced in these patient populations.41-44

Conclusion

Life Extension was at the forefront in advocating aspirin use to decrease cardiovascular risk, long before the mainstream medical community finally recognized the lifesaving benefits of aspirin.

Exciting new research findings support a disease-preventive benefit for aspirin in other potentially lethal conditions such as skin cancer, colon cancer, and Alzheimer's. Life Extension will continue to monitor ongoing research on aspirin and share with members important findings that are often overlooked by the mainstream medical establishment.

An overlooked staple of the medicine cabinet, aspirin continues to prove its value as one of our most powerful allies in fighting the deadly diseases that accompany aging.

Caution: Individuals with allergies to aspirin or other salicylates should not use aspirin. People with a history of bleeding disorders, hemorrhagic stroke, asthma, or ulcers should speak with a doctor before using aspirin. Consult a physician before using aspirin in combination with over-the-counter or prescription medications. Children and teenagers with symptoms of flu or chicken pox should not take aspirin.

References

1. Crofford LJ. Prostaglandin biology. Gastroenterol Clin North Am. 2001 Dec;30(4):863-76.

2. Available at: http://en.wikipedia.org/wiki/Thromboxane. Accessed May 8, 2006.

3. Bayer A. Clinicians’ Guide to Aspirin. London: Arnold; 1998.

4. Norman AW, Litwack G. Hormones. 2nd ed. Burlington, MA: Academic Press; 1997.

5. Available at: http://en.wikipedia.org/wiki/ Aspirin. Accessed May 8, 2006.

6. McGeer EG, Klegeris A, McGeer PL. Inflammation, the complement system and the diseases of aging. Neurobiol Aging. 2005 Dec;26 Suppl 1:94-7.

7. Dinarello CA. Interleukin 1 and interleukin 18 as mediators of inflammation and the aging process. Am J Clin Nutr. 2006 Feb;83(2):447S-55S.

8. Roberts LJ, Morrow JD. Analgesic-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout. In: Hardman JG, Limbird LE, eds. Goodman & Gilman’s the Pharmacological Basis of Therapeutics. 10th ed. New York: McGraw-Hill; 2001: 687-731.

9. Available at: http://www.answers.com/ nsaids. Accessed May 9, 2006.

10. Ulrich CM, Bigler J, Potter JD. Non-steroidal anti-inflammatory drugs for cancer prevention: promise, perils and pharmacogenetics. Nat Rev Cancer. 2006 Feb;6(2):130-40.

11. Itzkowitz SH, Yio X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol. 2004 Jul;287(1):G7-17.

12. Wang D, Dubois RN. Prostaglandins and cancer. Gut. 2006 Jan;55(1):115-22.

13. Bruce DF. Nutritional strategies for conquering colon cancer. Life Extension. March, 2005:48-56.

14. Available at: http://www.abc.net.au/worldtoday/content/2005/s1499391.htm. Accessed April 27, 2006.

15. Available at: http://www.emaxhealth.com/ 101/3662.html. Accessed April 27, 2006.

16. Rahme E, Ghosn J, Dasgupta K, Rajan R, Hudson M. Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer. BMC Cancer. 2005 Dec 12;5:159.

17. Schildkraut JM, Moorman PG, Halabi S, Calingaert B, Marks JR, Berchuck A. Analgesic drug use and risk of ovarian cancer. Epidemiology. 2006 Jan;17(1):104-7.

18. Baron JA, Cole BF, Sandler RS, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. 2003 Mar 6;348(10):891-9.

19. Sandler RS, Halabi S, Baron JA, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med. 2003 Mar 6;348(10):883-90.

20. van de Pol LA, Hensel A, Barkhof F, Gertz HJ, Scheltens P, van der Flier WM. Hippocampal atrophy in Alzheimer disease: age matters. Neurology. 2006 Jan 24;66(2):236-8.

21. Available at: http://www.nia.nih.gov/ Alzheimers/ResearchInformation/NewsReleases/Archives/PR1997/PR19970310NSAID.htm. Accessed April 27, 2006.

22. Ho L, Pieroni C, Winger D, et al. Regional distribution of cyclooxygenase-2 in the hippocampal formation in Alzheimer’s disease. J Neurosci Res. 1999 Aug 1;57(3):295-303.

23. Roman GC. Vascular dementia: distinguishing characteristics, treatment, and prevention. J Am Geriatr Soc. 2003 May;51(5 Suppl Dementia):S296-S304.

24. Zandi PP, Anthony JC, Hayden KM, et al. Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County Study. Neurology. 2002 Sep 24;59(6):880-6.

25. in ‘t, V, Launer LJ, Breteler MM, Hofman A, Stricker BH. Pharmacologic agents associated with a preventive effect on Alzheimer’s disease: a review of the epidemiologic evidence. Epidemiol Rev. 2002;24(2):248-68.

26. Etminan M, Gill S, Samii A. Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer’s disease: systematic review and meta-analysis of observational studies. BMJ. 2003 Jul 19;327(7407):128.

27. Nilsson SE, Johansson B, Takkinen S, et al. Does aspirin protect against Alzheimer’s dementia? A study in a Swedish population-based sample aged > or =80 years. Eur J Clin Pharmacol. 2003 Aug;59(4):313-9.

28. Husain S, Andrews NP, Mulcahy D, Panza JA, Quyyumi AA. Aspirin improves endothelial dysfunction in atherosclerosis. Circulation. 1998 Mar 3;97(8):716-20.

29. Available at: http://www.cnn.com/HEALTH/ library/DS/00691.html. Accessed May 8, 2006.

30. Steinhubl SR, Moliterno DJ. The role of the platelet in the pathogenesis of athero-thrombosis. Am J Cardiovasc Drugs. 2005;5(6):399-408.

31. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002 Mar 5;105(9):1135-43.

32. Eidelman RS, Hebert PR, Weisman SM, Hennekens CH. An update on aspirin in the primary prevention of cardiovascular disease. Arch Intern Med. 2003 Sep 22;163(17):2006-10.

33. Available at: http://foxnews.webmd.com/ content/article/115/111752.htm. Accessed April 27, 2006.

34. Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brown DL. Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials. JAMA. 2006 Jan 18;295(3):306-13.

35. Hayden M, Pignone M, Phillips C, Mulrow C. Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the US Preventive Services Task Force. Ann Intern Med. 2002 Jan 15;136(2):161-72.

36. Available at: http://www.americanheart.org/ presenter.jhtml?identifier=4704. Accessed April 26, 2006.

37. Savon JJ, Allen ML, DiMarino AJ Jr, Hermann GA, Krum RP. Gastrointestinal blood loss with low dose (325 mg) plain and enteric-coated aspirin administration. Am J Gastroenterol. 1995 Apr;90(4):581-5.

38. Bowman J. Strokes. Upper Saddle River, NJ: Prentice Hall; 2003.

39. Anon. Aspirin for the primary prevention of cardiovascular events: recommendation and rationale. Ann Intern Med. 2002 Jan 15;136(2):157-60.

40. Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005 Mar 31;352(13):1293-304.

41. Grundy SM. Metabolic syndrome: therapeutic considerations. Handb Exp Pharmacol. 2005;(170):107-33.

42. Dempster DW, Rosenstock JL, Scwimmer JA, Panagopoulos G, DeVita MV, Michelis MF. Underutilization of aspirin in hemodialysis patients for primary and secondary prevention of cardiovascular disease. Clin Nephrol. 2005 Nov;64(5):371-7.

43. Hankey GJ, Norman PE, Eikelboom JW. Medical treatment of peripheral arterial disease. JAMA. 2006 Feb 1;295(5):547-53.

44. Kelemen MD. Angina pectoris: evaluation in the office. Med Clin North Am. 2006 May;90(3):391-416.