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Managing Cardiovascular Risk in Older Women
by Barbara Messinger-Rapport, M.D., Ph.D.
Geriatric Times January/February 2003 Vol. IV Issue 1
The patient is a 74-year-old woman with hypertension, hypercholesterolemia and osteoporosis. She is on a statin and a diuretic. She has asked her physician if she can discontinue the hormone replacement therapy (HRT) that she has been taking since menopause 20 years ago. She has not had hot flashes in many years and has read that HRT can cause blood clots, heart attacks and breast cancer. She also wants to know if she should be on aspirin therapy to prevent heart attacks and strokes.
These issues are difficult, particularly regarding HRT, because the evidence for the benefit and harm of HRT is not as complete now as it will be in a few years, and application of the current evidence differs among clinicians, depending upon their enthusiasm for HRT. There is evidence, however, that interventions with antihypertensives, statins, antithrombotics and anticoagulants may have significant cardiovascular benefits for some older adults.
Interventions to reduce cardiovascular risk are very pertinent to older women in the United States. In women over the age of 65, heart disease is the leading cause of death and cerebrovascular disease is the third leading cause of death. This article summarizes the application of current evidence--including what is known currently about the cardiovascular effects of HRT--to the prevention and management of cardiovascular disease in older women.
Hypertension and Stroke
Stroke is the leading cause of severe disability in older adults. Multiple studies of diastolic and systolic hypertension demonstrate a stroke risk reduction with antihypertensive treatment in older women as well as men. Treatment of isolated systolic hypertension with a diuretic led to reductions in stroke, myocardiac infarction (MI), cardiovascular events and mortality (SHEP [Systolic Hypertension in the Elderly Program] Cooperative Research Group, 1991; Staessen et al., 1997). There was also evidence from the SHEP study of reduction in the incidence of proteinuria and congestive heart failure (CHF) (Kostis et al., 1997). From the Systolic Hypertension in Europe study, there was evidence of reduction in the incidence of dementia (Forette et al., 2002).
There is no age beyond which treatment does not yield a benefit in stroke reduction. For hypertension, the target blood pressure in older adults is the same as for younger adults (Joint National Committee, 1997), although the dose may need to be adjusted for reduced renal function and orthostasis, both of which increase with age. Despite this evidence, blood pressure control in older women often does not meet national guidelines.
Hyperlipidemia and CHD
The relationship of elevated cholesterol to coronary heart disease (CHD) in older women is controversial, and women were not well-represented in early trials of niacin, fibrates and bile acid sequestrants.
Statins. Women older than 65 who were enrolled in recent secondary prevention trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) demonstrated an approximate 15% to 34% reduction in relative risk for coronary events and 27% relative risk reduction in stroke (Kagansky et al., 2001). Older adults obtained at least as much or greater benefit as did their younger counterparts. Women with heart disease are often not on statins, despite the benefits demonstrated in intervention trials. For example, in the Heart and Estrogen/Progestin Replacement Study (HERS), which enrolled postmenopausal women with heart disease, 60% were not on statins. Of those 60%, 80% had low-density lipoprotein levels >100 and should have been on a statin (Herrington et al., 2002).
Primary prevention of cardiovascular events with statins was demonstrated in women as old as 73 in the Air Force/Texas Coronary Atherosclerosis Prevention Study trial (Downs et al., 1998) and in women as old as 80 in the Heart Protection Study trial (Collins et al., 2002). The latest recommendations by the Adult Treatment Panel for primary cardiovascular prevention suggest basing the decision to initiate therapy upon the Framingham risk scoring (low <10%, intermediate 10% to 20%, and high >20%) (Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001). The Framingham computation separates the male from the female risk but does not include an age group greater than 79 years, making it difficult to justify statins as primary prevention in women over age 80.
Antiplatelet therapy. A recent publication summarizing several sources of data suggested that the Framingham tables be used to compute the risk for five years, and those with risks e3% be offered aspirin preventive therapy (U.S. Preventive Services Task Force, 2002). Patients with diabetes fall into a separate high-risk category and should receive aspirin therapy as well.
ß-blockers. Despite data indicating efficacy in older adults, ß-blockers appear to be underused in the post-MI treatment of older women (Klungel et al., 2000). Older adults, women, minorities and those with low ejection fractions are least likely to receive b-blocker therapy (Mendelson and Aronow, 1997; Rathore et al., 2000; Rochon et al., 2000). Although the oldest patients on ß-blockers have a slightly smaller relative benefit, they have a greater absolute risk reduction compared with younger adults.
Nonpharmacologic interventions. Knowler et al. (2002) found that lifestyle changes had a greater advantage than did medication in older people in the Diabetes Prevention Program, and the high risk of CHD in older women with diabetes decreases after smoking cessation. Dietary restriction in older adults is controversial because of the risk of malnutrition, although one study suggested that reducing fat and sodium intake and consuming fruits, vegetables and low-fat dairy products might reduce reliance on antihypertensives (Appel et al., 1997).
Atrial Fibrillation
Atrial fibrillation (AF) affects 2.2 million people in the United States, with a mean age prevalence of 75 years. The mortality rate of adults with AF is double that of control subjects and is attributed mainly to stroke (Fuster et al., 2001). The risk of stroke increases with the number of risk factors, including CHF, hypertension or prior transient ischemic event. Diabetes and being older than 75 also increase the risk of thromboembolism (Albers et al., 2001). Anticoagulation with warfarin (Coumadin) to a target international normalized ratio (INR) of 2 to 2.5 offers women and men an approximately two-thirds reduction in stroke risk from atrial fibrillation (Albers et al., 2001). If the risk of anticoagulation is prohibitive, aspirin alone decreases the risk of stroke in the setting of atrial fibrillation by 23% in women and by 44% in men (Stroke Prevention in Atrial Fibrillation II Study, 1994).
HRT
Both physicians and the public have been barraged with contradictory information over past years on the purported benefits and harms of HRT, particularly following the 2002 discontinuation of the Women's Health Initiative (WHI) and the preliminary publication of interim data (Writing Group for the Women's Health Initiative Investigators, 2002). (See Sept/Oct 2002 Geriatric Times, p3, for more information--Ed.) Cardiovascular risks and benefits from HRT are summarized below.
Cardiac disease. Continuous-combined estrogen/progestin therapy (CCEPT) demonstrated no change in risk in the HERS study, which enrolled postmenopausal women with known CHD who were an average age of 67 years (Herrington et al., 2002; Hulley et al., 1998). In the WHI, CCEPT increased risk of CHD by 29% in healthy postmenopausal women with a mean age of 63.2 years (7.7% with prior CHD). The WHI study on estrogen replacement (Premarin) alone is ongoing.
Stroke. Relative risk of stroke increased by 41% in women in the WHI study, with an absolute risk increase of 0.8%. There was no significant increased risk in women in the HERS study.
Thromboembolism. Estrogen use, as well as selective estrogen receptor modulators, increased the relative risk of thromboembolic events by two- to threefold in multiple studies including WHI and HERS (Hulley et al., 1998). The absolute risk depended upon the age and comorbidities. Concomitant statin use appeared to reduce but not eliminate that risk in the HERS study.
Conclusions
Although the hypothetical patient's questions at the beginning of this article about cardiovascular risk are difficult, many of the answers lie in the basics. There does not seem to be an age at which one should discontinue managing hypertension, encouraging exercise and recommending tobacco cessation. The largest studies of isolated systolic hypertension have demonstrated benefit from diuretics and dihydropyridine calcium channel blockers in reducing stroke and cardiovascular events. Since the patient introduced at the beginning of this article is younger than 80, the Framingham estimation of risk can be used to help make decisions regarding her target cholesterol and the potential benefits of aspirin therapy. As for HRT, there appears to be no potential cardiac benefit, and her risk of breast cancer increases with duration of estrogen use. Prior to recommending discontinuation, however, the potential benefits of HRT on reducing the risk of fracture, colon cancer and Alzheimer's disease should be considered. The North American Menopause Society (NAMS) does recommend consideration of lower-than-standard doses of estrogen replacement, based on the Women's Health, Osteoporosis, Progestin, Estrogen study (NAMS, 2002).
For an older patient, clinical evidence is only part of the picture. Individual risk, adverse effects, polypharmacy, compliance and financial issues play an important role in deciding to start, continue or stop a medication.
Dr. Messinger-Rapport is assistant professor at the Case Western Reserve University School of Medicine and specializes in geriatric care at the Cleveland Clinic Foundation.References
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