Managing Dyslipidemia in Older Adults
abstract & commentary
Synopsis: Evidence supports aggressive control of lipid disorders in persons older than age 65 up to age 85 since elevated LDL and total cholesterol are independent risk factors for coronary events. Diet, lipid-lowering medications, exercise, and weight loss may show results within 2-5 years of initiation and can decrease the risk of coronary events by up to 45%.
Source: Carlsson CM, et al. J Am Geriatr Soc 1999;47: 1458-1465.
Literature review of clinical trial data limited exclusively to subjects older than 65 years of age was summarized to evaluate both the importance of dyslipidemia as a risk factor for coronary heart disease (CHD) and the safety and efficacy of lipid-lowering interventions in this age group. Limited data for persons older than age 85 required the conclusions to be restricted to those younger than age 85. Women were included in many of the studies and some studies suggest that these conclusions may be even more significant for them than for men in this same age group.
Lipid and CHD risk associations in the elderly now appear to be supported by several studies. Recent data from the Framingham Heart Study (2051 participants > age 65 and 5209 aged 40-70 years) show that total cholesterol more than 306 mg/dL independently predicted future myocardial infarctions (MIs) and CHD deaths. High LDL levels were also associated with higher mortality, although this risk diminished with age. High HDL was associated with lower death rates across all age groups. A Kaiser Permanente study of 2746 men between ages 60-79 also showed the link between elevated lipids and increasing excess risk of CHD death with increasing age. No risk was initially suggested in one large epidemiologic study (EPESE) involving 6566 older adults and 40,666 total participants followed for seven years, but further analysis showed that comorbid conditions in persons approaching death had caused reductions in cholesterol levels, confusing the calculations. When these were excluded, the association between CHD death risk and elevated total cholesterol was significant at 1.57 relative risk.
Whether lowering lipid levels in the elderly is effective and safe is supported by literature showing exercise programs (e.g., 30-40 minutes aerobic exercise 3 times weekly for 12 weeks) that can improve HDL cholesterol up to 19% and decrease total cholesterol 6%; however, these changes may reverse when the exercise program is stopped. Weight loss is probably more significant, lowering total cholesterol levels 5%-20% through low fat, low cholesterol, and high-fiber diets, although malnutrition from excessively limited diets is also a concern in this age group.
Drug therapy is probably most effective, using HMG-CoA reductase inhibitors (statins), which studies show to be well tolerated in this age group. Five studies are reviewed with elderly subjects numbering from 142 to 1021 showing total cholesterol reductions from 17%-26%, and LDL reductions up to 36%. Estrogen replacement therapy for women can also lower total cholesterol to 14% and LDL to 24%. Side effects for these medications do not appear to be any more adverse than for younger patients.
Benefits of the lipid lowering are seen most clearly in older persons with known CHD; up to 28% in reduction of total mortality is seen compared to controls not treated. Another group of 1283 subjects older than age 65 in a randomized, double-blind, statin study for five years after acute MI showed 45% less cardiac death and 40% less stroke rate. For estrogen replacement, the ongoing HERS study has not yet demonstrated a benefit in subsequent CHD events.
For primary prevention of CHD events in persons without known pre-existing disease, studies are more controversial. One study that did show a benefit did not include elderly persons, and another showed a 28% lower incidence in major coronary events in those older than age 65 with average total cholesterol and below average HDL levels. The FAME trial using randomized Fluvastatin and diet aimed at ages 70-85 is now recruiting participants and will hopefully provide more guidance in the future.
Carlsson and colleagues conclude that fasting lipid levels should be used as screening tests, with therapy instituted as appropriate, for all persons younger than age 85 unless comorbid conditions would preclude even a short-term effect (2-5 years). National NCEP guidelines for lipid reduction should be followed (recently reviewed and reaffirmed: targeting a goal of LDL 130 mg/dL for primary prevention and < 100 mg/dL for known CHD secondary prevention).1,2 Diet and exercise should be given a four- to six-week trial and medications added as needed. For persons with known CHD, medications may be started as first-line therapy along with diet and exercise for a proven benefit of decreased risk of cardiac death, recurrent MI, and need for revascularization procedures.
COMMENT BY MARY ELINA FERRIS, MD
Given that CHD is the leading cause of mortality in older adults and an enormous source of hospital activity and expense, this summary of possible preventive strategies provides a useful guide. Although not all therapies that have been shown to work in younger populations can automatically be translated to the elderly, in this case the literature appears to support the efficacy of reducing CHD risk and mortality (and stroke risk) through lipid reductions even up to age 85, without published differences in medications’ adverse effects. An additional geriatric consideration that must be weighed in all newly initiated therapies is the effect on quality of life; i.e., if the person’s life expectancy from other illnesses is no greater than two to five years, the potential for causing more harm from the lipid-lowering treatment outweighs the possible benefit. Otherwise, it appears from this review that significant gains in CHD reductions are possible with more widespread management of dyslipidemia, particularly in older persons with pre-existing disease.
Clinicians who adopt more frequent monitoring of lipids should be prepared to find many abnormal results: up to 50% of persons older than age 65 qualify for dietary therapy and 10%-25% for pharmacotherapy in national nutritional surveys. The high frequency of dyslipidemia in older persons appears to be an aging-associated phenomenon and is not completely understood, possibly related to lipoprotein metabolism and hormonal changes. LDL cholesterol levels increase from puberty onward and even more for women after menopause. With aging, the clearance of LDL and the number of hepatic receptors decrease.
One area this article did not address is the importance of diabetes as a comorbidity and accelerator of lipid disorders, an extremely common problem in the elderly. New guidelines from the American Diabetes Association3 also urge more aggressive treatment of dyslipidemia to a goal of LDL less than 100 mg/dL, putting all persons with diabetes in the same category as those with pre-existing CHD. Although the diabetes guidelines do not specifically address treatment of the elderly, it would seem prudent from this article to also pursue abnormal lipids in elderly persons with diabetes as though they had known heart disease.
References
1. Steinberg D, Gotto AM. JAMA 1999;282:2043-2050.
2. National Cholesterol Education Progam Guidelines (NCEP): http://rover.nhlbi.nih.gov/guidelines/ index.htm.
3. American Diabetes Association. Diabetes Care 2000; 23(Suppl 1):S57-60.(Also available at http://journal. diabetes.org/FullText/Supplements/DiabetesCare/Supplement100/s57.htm).
Which of the following groups are recommended to have their LDL cholesterol levels decreased below 100 mg/dL to achieve proven risk reduction in coronary heart disease?
a. Males age 40-60 without known disease.
b. Females age 65-85 after menopause.
c. Males age 65-85 with previous coronary disease.
d. Diabetic males older than age 85.
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