Cardiovascular risk factors that predict coronary heart disease (CHD) in younger men and women seem to do so in older persons as well. Moreover, improvement or correction of risk has been shown to benefit the elderly. For example, in the followup of the Coronary Artery Surgical Study, those who had quit smoking the year before and continued not to smoke had lower death rates and a lower incidence of myocardial infarction (MI) than the smokers.(1) A recent double-blind, placebo-controlled trial has shown that in comparison with those given a placebo, elderly patients treated for elevated systolic blood pressure had significant reductions in nonfatal and fatal coronary events.(2) Yet confusion about whether to treat an elevated cholesterol persists because of the lack of clinical trials specifically targeting those over age 70.

ARGUMENTS FOR AND AGAINST TREATMENT

One source of confusion relates to the manner in which the risk of CHD is expressed. Epidemiologists talk about "relative risk," a statistical comparison of the risk of subjects with the highest cholesterol divided by the risk of those with the lowest cholesterol. Young subjects with hypercholesterolemia have an enhanced relative risk of coronary artery disease (CAD); relative risk is not shown to be increased as much in the elderly. On the other hand, the statistic comparing the risk of those with the lowest cholesterol subtracted from those with the highest cholesterol, the so-called "attributable risk," is substantial in the elderly owing to an increased likelihood of CHD in older populations, in which CHD is seen most often. Again, it must be stressed that while this suggests that effective cholesterol-lowering may, in fact, reduce cardiovascular risk in a 75-year-old high-risk patient, there is no conclusive evidence that this is so.

A second source of confusion is the large number of patients with high cholesterol in the eighth decade of life. In the Cardiovascular Health Study,(3) a sample of 4810 men and women ages 65-100 was randomly selected and subjects recruited from the United States Health Care Financing Administration Medicare eligibility lists. These subjects were not institutionalized, wheelchair-bound, currently receiving therapy for cancer, or currently taking lipid-lowering medications, and had not eaten in the preceding nine hours.

As Figure 1 shows, substantial numbers of the elderly population have cholesterol values above 200 mg/L. Do they all require therapy? Certainly not all patients with a high serum cholesterol are candidates for further evaluation and therapy. A useful question worth asking when evaluating any therapy is "are the benefits worth the risks or negative aspects?" The latter include cost, convenience, and side-effects of the therapy. Factors that suggest a more intensive therapeutic approach include either the presence of coronary disease or a high risk-factor profile, including hypertension, smoking, and/or diabetes.

What is the lipid profile of those over 65 with excess CAD? Castelli(4) noted in the Framingham Study population that serum triglycerides commonly exceeded 150 mg/L and high-density lipoprotein (HDL) was below 40 mg/L. Factors that would dissuade the physician from further evaluation and therapy include a "low-risk" profile for coronary disease or the presence of life-threatening illnesses or other co-morbidities that make consideration of coronary prevention a dispensable issue (e.g., dementia, degenerative neurologic disorders, institutionalization for various difficulties, problems with undernutrition or alcohol).

QUESTIONS OF COST-EFFECTIVENESS

Should cost-effective analyses enter into our decision to treat the 75-year-old with high cholesterol? We now know that 38 subjects need to be treated to prevent one death from CHD if efforts are confined to secondary prevention. By contrast, 675 individuals without CHD would require treatment if the emphasis is on primary prevention.(5) Thus, from a cost-effective point of view, restricting efforts to secondary prevention in the elderly might be the most efficient way to target those in whom CHD death might be prevented. Cost-effective analyses often lead to the notion of health care rationing, with its negative consequences for those who disproportionately occupy the ranks of older Americans; that is, women.(6) As Denke has carefully pointed out,(7) the more important question for both the individual and American society may be to ask, "What is the price society is willing to pay to reduce a retiree's chance of symptomatic heart disease or coronary death?"

EVALUATION AND TREATMENT PROCEDURES

If the decision is made that this is a functional, high-risk patient, then evaluation begins with a fasting lipoprotein profile to measure cholesterol, triglycerides, HDL cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c). These two lipoproteins give the best measure of risk and are essential to risk prediction. Secondary causes must be ruled out. Subtle degrees of hypothyroidism can be difficult to diagnose unless a thyroid-stimulating hormone (TSH) level is obtained. Nephrotic syndrome, obstructive jaundice, and diabetes are the other conditions to rule out. Medications like diuretics, steroids, estrogens, progestins, and beta-blockers affect lipid levels and must be considered in the overall evaluation. A family history of CHD, diabetes, and other risk factors should also be obtained.

Regrettably, controlled, randomized intervention trials involving diet, medication, or both have not been designed to answer the question of whether treatment is beneficial for the 75-year-old. Available data, however, do not show a lack of treatment efficacy among the oldest subjects in these trials. Diet remains the cornerstone of treatment for hypercholesterolemia at any age. A low-saturated-fat, low-cholesterol diet is the initial approach. The elderly often consume too much saturated fat and dietary cholesterol.(8) Careful follow-up is essential here. It must be remembered that nutritional issues are particularly important at the extremes of life, and overzealous restriction of fats may lead to excessive weight loss as well as calcium and protein inadequacies (if dairy products and meats are avoided because of their saturated-fat content). The elderly often have repetitive diets. dictated by convenience and cost, which create important barriers to change. If planned well, a low-fat diet can be less costly, but it may not be as easy to obtain some foods. A careful alcohol history is important, because while mild intake may be associated with reduced risk of coronary disease in epidemiologic studies, higher levels of alcohol use increase the risks for hypertension and stroke, accidents, cancer, and liver disease. Moreover, women and those of smaller body mass may not handle alcohol as well as their larger, male counterparts.

Drug therapy is not contraindicated in the elderly, but it should be reserved for those at highest risk. Those with existing CHD would appear to be prime candidates. Resins, which are constipating, are difficult to use in this age group. Niacin, gemfibrozil. and HMG-CoA reductase inhibitors are the drugs of choice. This latter group may have the best benefit:risk and cost:effectiveness ratios in those with CHD.(9) Cholesterol-lowering drugs rely on the liver for their metabolism; hepatic function must be carefully followed in the elderly patient undergoing drug therapy for hypercholesterolemia,

Since polypharmacy is more likely in older patients, care must also be taken to avoid drug combinations that interact in an adverse fashion. The use of niacin with an HMG-CoA reductase inhibitor carries an increased risk of myositis and/or liver toxicity and should be tried only after other, safer ways of lowering cholesterol have proven ineffective. Combining gemfibrozil with an HMG-CoA reductase inhibitor carries up to a 5% chance of myositis; again, these are used together only when the benefits would appear to outweigh the risks.

CONCLUSION

In dealing with the problem of treatment for a 75-year-old with a high cholesterol, the first step is a critical appraisal of the overall coronary and global health risk. In those patients found to be at the highest risk of a coronary event and who are fully functional, stepwise treatment of hypercholesterolemia holds the promise of being as useful as treatments directed toward correction of hypertension and cigarette smoking.

Acknowledgment. This work was supported in part by the Lipid Research and Education Fund at Northwestern University Medical School.

1. Hermanson B, Omenn GS, Kronmal RA, Gersh BJ. Beneficial six-year outcome of smoking cessation in older men and women with coronary artery disease. Results from the CASS registry. N Engl J Med 1988;319:1365-9

2. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program. JAMA 1991;265:3255-64

3. Manolio TA, Furberg CD, Wahl PW, et al. Eligibility for cholesterol referral in community-dwelling older adults. The Cardiovascular Health Study. Ann Intern Med 1992;116:641-9

4. Castelli WP, Wilson PWF, Levy D, Anderson K. Cardiovascular risk factors in the elderly. Am J Cardiol 1989;63:12H-19H

5. Silberberg JS, Henry DA. The benefits of reducing cholesterol levels: the need to distinguish primary from secondary prevention. 1. A meta-analysis of cholesterol-lowering trials. Med J Aust 1991;155:665-6,669-70

6. Jecker NS. Age-based rationing and women. JAMA 1991;266:3012-5

7. Denke M. Drug treatment of hyperlipidemia in elderly patients. Curr Opinion Lipidol 1993;4:56-62

8. Nestle M, Woteki C. Treatment of hypercholesterolemia in the elderiy: the case for dietary intervention. Cardiovasc Risk Factors 1992;2:191-9

9. Goldman L, Weinstein MC, Goldman PA, Williams LW. Cost-effectiveness of HMG-CoA reductase inhibition for primary and secondary prevention of coronary heart disease. JAMA 1991;265:1145-51

D. Stone is Associate Professor of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.

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