Drug Therapy for Older Persons With Hypercholesterolemia and Vascular Disease: The Value of Secondary Prevention
Wilbert S. Aronow, MD, CMD

Older persons who have elevated serum low-density lipoprotein cholesterol levels despite dietary therapy and who have the following diseases should be treated with reductase inhibitor drug therapy: those with coronary artery disease, to reduce the incidence of new coronary events, stroke, intermittent claudication, and progression of carotid arterial disease; those with atherothrombotic brain infarction, to decrease the incidence of new stroke and coronary events; those with peripheral arterial disease, to reduce the incidence of new intermittent claudication and coronary events; and those with extracranial carotid arterial disease, to reduce the progression of carotid arterial disease and the incidence of new stroke and coronary events.

(Annals of Long-Term Care 1999;7[4]:135-139)

Coronary Artery Disease

Many studies have shown that a high serum total cholesterol level is a risk factor for the development of new coronary events in older men and women.1-7

Study Findings

Among persons age 65 and older with prior myocardial infarction (MI) in the Framingham Study,4 serum total cholesterol was most strongly related to death from coronary artery disease (CAD) and to all-cause mortality. In the Established Populations for Epidemiologic Studies of the Elderly research,8 serum total cholesterol was found to be a risk factor for death from CAD in older women but not in older men. At 40-month follow-up of 664 older men (mean age, 80 years) in a nursing home and at 48-month follow-up of 1488 older women (mean age, 82 years) in a nursing home, an increment of 10 mg/dL of serum total cholesterol significantly increased the relative risk of new coronary events 1.12 times in men and 1.12 times in women.2 In 1793 older men and women in a nursing home, there was a 1.28 times significantly greater probability of having CAD for an increment of 10 mg/dL of serum low-density lipoprotein (LDL) cholesterol.9

A low serum high-density lipoprotein (HDL) cholesterol level is also a risk factor for the development of new coronary events in older men and women.1-3,8-11 In the Framingham Study,4 in the Established Populations for Epidemiologic Studies of the Elderly investigation,8 and in 2152 older men and women in a nursing home,2 a low serum HDL cholesterol level was a more powerful predictor of new coronary events than was serum total cholesterol. At 40-month follow-up of 664 older men in a nursing home and at 48-month follow-up of 1488 older women in a nursing home, a decrement of 10 mg/dL of serum HDL cholesterol significantly increased the relative risk of new coronary events 1.70 times in men and 1.95 times in women.2 In 1793 older men and women in a nursing home, there was a 2.56 times significantly greater probability of having CAD for a decrement of 10 mg/dL of serum HDL cholesterol.9

Drug Treatment

At 5.4-year median follow-up of 4444 men and women (1021 were 65 to 70 years of age at study entry) with CAD and hypercholesterolemia, simvastatin, compared with placebo, reduced serum total cholesterol by 25% and serum LDL cholesterol by 35%, increased serum HDL cholesterol by 8%, and reduced total mortality, coronary death, major coronary events, and new or worsening angina pectoris.12-14 In men and women 65 to 70 years of age, simvastatin reduced all-cause mortality by 34%, CAD mortality by 43%, major coronary events by 34%, any atherosclerosis-related event by 33%, and revascularization procedures by 41% (Table I).13 Decreases in end-point events were similar in older and younger men and women.

At five-year follow-up of 4159 men and women (2129 were 60 to 75 years of age at study entry) with MI and serum total cholesterol levels lower than 240 mg/dL but serum LDL cholesterol levels of 115 mg/dL or higher, pravastatin, compared with placebo, reduced serum total cholesterol by 20% and serum LDL cholesterol by 28%, increased serum HDL cholesterol by 5%, and reduced major coronary events by 27% in men and women 60 to 75 years of age at study entry and by 20% in men and women younger than 60 years of age (Table I).15 Pravastatin reduced major coronary events by 46% in women and by 20% in men.15

Results from the LIPID Trial16 were recently published. In this study, 9014 men and women up to 75 years of age with MI or unstable angina pectoris and serum total cholesterol levels between 155 and 271 mg/dL were randomized to receive pravastatin or placebo.16 At 6.1-year follow-up, compared with placebo, pravastatin reduced all-cause mortality by 22%, death from CAD by 24%, fatal and nonfatal MI by 29%, and need for coronary artery revascularization by 20% (Table I).16

On the basis of the above data, older men and women with CAD who have elevated serum LDL cholesterol levels despite dietary therapy should be treated with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor therapy. The serum LDL cholesterol level should be decreased to 100 mg/dL or lower.17,18 Atherothrombotic Brain Infarction

There are conflicting data about the association of abnormal serum lipids with atherothrombotic brain infarction (ABI) in men and in women.19-25

Study Findings

In 559 men (mean age, 80 years) and 1275 women (mean age, 82 years) in a nursing home, there was a 1.06 times higher probability of having ABI for an increment of 10 mg/dL of serum total cholesterol and a 1.27 times higher probability of having ABI for a decrement of 10 mg/dL of serum HDL cholesterol.22

At 42-month follow-up of 664 men (mean age, 80 years) in a nursing home, there was no significant association between serum total cholesterol and new ABI and a borderline significant inverse association between serum HDL cholesterol and new ABI.23 However, at 48-month follow-up of 1488 women (mean age, 82 years) in a nursing home, there was a significant association between serum total cholesterol and new ABI and a significant inverse association between serum HDL cholesterol and new ABI.23

Drug Treatment

Despite the conflicting data about the association of abnormal serum lipids with ABI in men and women, HMG-CoA reductase inhibitor therapy has been demonstrated to reduce the incidence of new stroke in secondary prevention trials (Table II).12,15,16,24 At 5.4-year median follow-up of 4444 men and women in the Scandinavian Simvastatin Survival Study,12 simvastatin, compared with placebo, reduced the incidence of new cerebrovascular events by 30% (Table II). At five-year follow-up of 4159 men and women in the Cholesterol and Recurrent Events Trial,15 pravastatin, compared with placebo, reduced the incidence of new stroke by 31% (Table II). At 6.1-year follow-up of 9014 men and women in the LIPID Trial,16 pravastatin reduced the incidence of new stroke by 22%. A meta-analysis of 11 secondary prevention trials demonstrated that--compared with placebo--simvastatin, pravastatin, or lovastatin reduced serum total cholesterol by 22%, serum LDL cholesterol by 30%, and the incidence of new stroke by 32% (Table II).24

On the basis of the available data, older men and women with vascular disease who have elevated serum LDL cholesterol levels despite dietary therapy should be treated with HMG-CoA reductase inhibitor therapy to reduce the incidence of new stroke. Because older men and women with ABI are at increased risk for developing new coronary events,25-27 older men and women with ABI who have elevated serum LDL cholesterol levels despite dietary therapy should be treated with HMG-CoA reductase inhibitor therapy to decrease the incidence of new coronary events as well as new stroke.

Peripheral Arterial Disease

There are conflicting data about the association of hypercholesterolemia in men and women with peripheral arterial disease (PAD).22,28-33

Study Findings

Serum HDL cholesterol is inversely associated with PAD in men and women.22,29,31, 33 In 559 older men and 1275 older women in a nursing home, there was 1.24 times higher probability of having PAD for a decrement of 10 mg/dL of serum HDL cholesterol.

Drug Treatment

The Scandinavian Simvastatin Survival Study12 showed that, compared with placebo, simvastatin decreased the incidence of new intermittent claudication by 38%.Patients with PAD are also at increased risk for developing new coronary events.34-36 Therefore, older men and women with PAD and elevated serum LDL cholesterol levels despite dietary therapy should be treated with HMG-CoA reductase inhibitor therapy to reduce progression of PAD and to decrease the incidence of new coronary events.

Extracranial Carotid Arterial Disease

Many studies have shown that a high serum total cholesterol37-41 and a low serum HDL cholesterol37-43 are risk factors for extracranial carotid arterial disease (ECAD).

Study Findings

In a study of 175 persons (mean age, 81 years) with 40% to 100% ECAD and 888 persons (mean age, 81 years) without significant ECAD in a nursing home, multivariate analysis showed that serum total cholesterol (odds ratio = 1.014) and serum HDL cholesterol (inverse association; odds ratio = 0.982) were risk factors for ECAD.41

Drug Treatment

Many studies have demonstrated the beneficial effects of lipid-lowering drug therapy on progression of ECAD.14,44-46 The Scandinavian Simvastatin Survival Study14 showed that, compared with placebo, simvastatin reduced the incidence of new carotid bruit by 48%. Older men and women with ECAD are also at increased risk for developing new coronary events.47-49 Therefore, older men and women with 40% to 100% ECAD and elevated serum LDL cholesterol levels despite dietary therapy should be treated with HMG-CoA reductase inhibitor therapy to decrease the progression of ECAD and to reduce the incidence of new stroke and coronary events.

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About the Author:

Dr. Aronow is Corporate Medical Director of Hebrew Hospital Home, Bronx and Westchester County, NY, and Adjunct Professor of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, NY. Address for correspondence: Wilbert S. Aronow, MD, CMD, Medical Director, Hebrew Hospital Home, 801 Co-op City Blvd, Bronx, NY 10475.

Annals of Long-Term Care - ISSN: 1524-7929 - Volume 7 - Issue 04 - April 1999