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a Divisions of Cardiology and Geriatrics, Westchester Medical Center/New York Medical College, Valhalla
Wilbert S. Aronow, Cardiology Division, Westchester Medical Center/New York Medical College, 23 Pebble Way, New Rochelle, NY 10804 E-mail: WSAronow{at}aol.com.
NUMEROUS studies have demonstrated that hypercholesterolemia, increased serum low-density lipoprotein (LDL) cholesterol, and decreased serum high-density lipoprotein (HDL) cholesterol are risk factors for new coronary events in older persons (1)(2)(3)(4)(5)(6). Hypertriglyceridemia has been shown to be a risk factor for new coronary events in older women (2)(3). Although Maggi and colleagues (7) found in the Italian Longitudinal Study on Aging lower serum LDL cholesterol levels among older women with diabetes mellitus and higher insulin levels, atherogenic dyslipidemia is part of the metabolic syndrome (8) and should be treated with statin drug therapy alone, or in combination with gemfibrozil (8)(9).
Numerous studies have also demonstrated that treatment of hypercholesterolemia by 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors (statins) reduces cardiovascular events in older persons with hypercholesterolemia (1). Despite these data, the American College of Physicians guidelines published in 1996 recommended cholesterol screening to be optional except in middle-aged men (10). This encouraged some insurers, including Medicare, to refuse funding for cholesterol screening in older persons.
LaRosa and colleagues (11) published a meta-analysis of clinical trials from 1966 through 1998 showing the effects of statins on cardiovascular events in persons with hypercholesterolemia. For inclusion, a study had to meet the following criteria: (i) study participants were randomized to statin therapy or double-blind placebo; (ii) there was no intervention difference than use of a statin between the treatment and placebo groups; (iii) the intervention duration was at least 4 years; and (iv) clinical disease or death was the primary end point.
Data were abstracted from three secondary prevention trials (12)(13)(14)(15)(16)(17) and two primary prevention trials (18)(19). Major coronary events during treatment were abstracted as the primary outcome. Data were also abstracted on fatal coronary heart disease, cardiovascular disease deaths, noncardiovascular deaths, and all-cause deaths during treatment.
In the Scandinavian Simvastatin Survival Study (4S), 4444 persons with coronary heart disease (19% women and 23% 
65 years of age) and a mean serum LDL cholesterol level of 188 mg/dl were randomized to simvastatin or placebo (12)(13). Median follow-up was 5.4 years. In the Cholesterol and Recurrent Events (CARE) trial, 4159 persons with prior myocardial infarction (14% women and 31% 65 years of age) and a serum LDL cholesterol of 115 mg/dl (mean level of 139 mg/dl) were randomized to pravastatin or placebo (14)(15)(16). Median follow-up was 5.0 years. In the Long-Term Intervention With Pravastatin in Ischaemic Disease (LIPID) trial, 9014 persons with coronary heart disease (17% women and 39% 65 years of age) and a mean serum LDL cholesterol level of 150 mg/dl were randomized to pravastatin or placebo (17). Mean follow-up was 6.1 years. In the West of Scotland Coronary Prevention Study, 6595 middle-aged men up to 64 years of age with no heart disease and a mean serum LDL cholesterol of 192 mg/dl were randomized to pravastatin or placebo (18). Mean follow-up was 4.9 years. In the Air Force/Texas Coronary Atherosclerosis Prevention Study, 6605 persons (15% women and 21% 65 years of age) with no heart disease and a mean serum LDL cholesterol of 150 mg/dl were randomized to lovastatin or placebo (19). Mean follow-up was 5.2 years.
Pooled data from the five studies showed that statins caused a mean reduction in serum total cholesterol of 20%, in serum LDL cholesterol of 28%, and in serum triglycerides of 13%, and a mean increase in serum HDL cholesterol of 5%. Pooled data from these five studies showed that statins caused a 31% reduction in major coronary events (95% CI, 26%–36%) and a 21% reduction in all-cause mortality (95% CI, 14%–28%). The risk reduction in major coronary events was similar in women (29%) as in men (31%) and in persons aged 65 years (32%) and younger (31%). The absolute risk reduction in major coronary events per 1000 persons was 33 (13 to 52) for women and 37 (29 to 44) for men and 44 (30 to 58) for persons aged 65 years and 32 (24 to 40) for persons younger than 65 years.
The excellent meta-analysis by LaRosa and colleagues (11) demonstrated that reduction in serum LDL cholesterol by statins significantly decreased the risk of coronary heart disease and of all-cause mortality. This risk reduction was similar for men and women and for older and middle-aged persons. The absolute risk reduction in major coronary events per 1000 persons was 33 for women versus 37 for men and 44 for persons aged 65 years versus 32 for younger persons. These results are valid and clinically important.
The oldest persons at study entry in this meta-analysis were aged 75 years. At 7.4 years of median follow-up in the 4S study (a paper published since this meta-analysis), simvastatin significantly reduced all-cause mortality by 30% and coronary artery disease mortality by 38% (20).
In an observational study, 922 women and 488 men, mean age 81 years, with prior myocardial infarction and a serum LDL cholesterol 125 mg/dl treated with a statin (48%) or with no lipid-lowering drug (52%) were followed prospectively for the incidence of new coronary events (21). The attitudes of different physicians toward treating older persons with hypercholesterolemia determined whether or not statins were prescribed. At 36 months of mean follow-up, the use of statins caused a 50% significant independent reduction in new coronary events (21). Statins significantly reduced new coronary events in persons aged 60 to 70 years, 71 to 80 years, 81 to 90 years, and 91 to 100 years (21). The Cochran-Armitage test showed a significant trend in the reduction of new coronary events as the last level of serum LDL cholesterol decreased, with the lowest incidence of new coronary events occurring at serum LDL cholesterol levels <90 mg/dl (21).
This observational study also showed that use of statins caused a 60% significant independent reduction in new atherothrombotic brain infarction (ABI) (22). The significant reduction in new ABI occurred in persons aged 60 to 70 years, 71 to 80 years, and 81 to 90 years, but not in persons 91 to 100 years of age (22). The Cochran-Armitage test showed a significant trend in the reduction of new ABI as the last level of serum LDL cholesterol decreased, with the lowest incidence of new ABI occurring at serum LDL cholesterol levels <90 mg/dl (22).
The Post Coronary Artery Bypass Graft Trial investigated 1351 persons up to age 74 years who had undergone coronary artery bypass surgery and who had serum LDL cholesterol levels between 130 and 175 mg/dl (23). Persons were randomized to lovastatin and, if needed, cholestyramine to achieve serum LDL cholesterol levels between 93 and 97 mg/dl versus 132 to 136 mg/dl. At the 7.5-year follow-up, compared with moderate lipid-lowering therapy, reduction of serum LDL cholesterol to 93 and 97 mg/dl significantly reduced the composite end point of death from cardiovascular or unknown causes or nonfatal myocardial infarction, stroke, coronary angioplasty, or coronary artery bypass surgery by 24% (23).
The incidence of new stroke was significantly decreased by 30% in the 4S study (12), by 31% in the CARE study (24), by 56% in 576 postmenopausal women in the CARE study (15), and by 19% in the LIPID study (17). The 4S study also showed that simvastatin significantly reduced new or worsening angina pectoris by 26%, new intermittent claudication by 38%, one or more bruits by 30%, new carotid bruits by 48%, hospital days by 34%, and congestive heart failure by 19% (25)(26).
On the basis of the available data, the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults recommends reducing the serum LDL cholesterol to <100 mg/dl in persons with coronary heart disease, other clinical forms of atherosclerotic disease such as peripheral arterial disease, symptomatic carotid disease, and abdominal aneurysm, in persons with diabetes mellitus, in the metabolic syndrome, and in persons with two or more risk factors that confer a 10-year risk for coronary heart disease of >20% (9). Other coronary artery disease risk factors are age (45 years for men and 55 years for women), cigarette smoking, hypertension or being on hypertensive medication, serum HDL cholesterol <40 mg/dl, and family history of premature coronary artery disease in a first-degree relative (before age 55 in a related man and before age 65 in a related woman) (9). These guidelines recommend decreasing the serum LDL cholesterol to <130 mg/dl in persons with two or more risk factors that confer a 10-year risk for coronary heart disease of 
20% (9). These guidelines recommend reducing the serum LDL cholesterol level to <160 mg/dl in persons with no risk factors or one risk factor (9). These guidelines also recommend no age restriction for treatment of older persons with lipid-lowering drug therapy if they have coronary heart disease or are at higher risk for coronary heart disease because of multiple risk factors or advanced subclinical atherosclerosis (9).
Guo and colleagues (27) reported data from a large female population up to 84 years of age showing that high waist-to-hip ratio, high serum triglycerides, and low serum HDL cholesterol were associated with poor motor performance in women. These investigators suggested that reducing body weight, treating dyslipidemia, and maintaining regular physical exercise may be effective ways to prevent decline in motor performance in older women (27).
In addition to statins, the bile acid sequestrant cholestyramine (28), nicotinic acid (29), and the fibrate gemfibrozil (30) have been found to reduce cardiovascular events in persons with dyslipidemia. Policosanol is a cholesterol-lowering drug consisting of a mixture of eight higher aliphatic alcohols purified from sugar cane whose main component is octacosanol (31). Policosanol administered in a dose of 10 mg daily to older persons with type II hypercholesterolemia and more than one atherosclerotic risk factor reduced serum LDL cholesterol by 24% and serum total cholesterol by 16% and increased serum HDL cholesterol by 29% (31). Compared with placebo, policosanol also significantly improved cardiovascular capacity assessed using the Specific Activity Scale (31). The effect of policosanol on cardiovascular events in older persons needs to be investigated.
The author concurs with the conclusions reached by LaRosa and colleagues (11) after their excellent meta-analysis showing that reduction in serum LDL cholesterol associated with statin drug treatment significantly reduced the risk of coronary artery disease and of all-cause mortality. This risk reduction was similar for men and women and for elderly and middle-aged persons (11). The author also concurs with the recommendations made by the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (9).
Future geriatric research should include studies in which persons older than 80 years with hypercholesterolemia with and without cardiovascular disease should be randomized to statin drug therapy versus placebo. These studies should also investigate the optimal level of reduction of serum LDL cholesterol in older persons. In addition, observational data have shown that the use of statins was associated with a lower prevalence of vascular dementia and Alzheimer's disease and with a beneficial effect on the progression of cognitive impairment in older persons (32). Prospective, randomized, double-blind, placebo-controlled trials need to be performed to investigate the effect of statins on the development and progression of vascular dementia and of Alzheimer's disease.
Received February 5, 2002
Accepted February 12, 2002
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62 years. Am J Cardiol. 73:702-703. [Medline]
125 mg/dl treated with statins versus no lipid-lowering drug. Am J Cardiol. 89:67-69. [Medline]
125 mg/dl treated with statins versus no lipid-lowering drug. J Gerontol Med Sci 57A:M333-M335. This article has been cited by other articles:
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  W. S. Aronow Drug Treatment of Systolic and of Diastolic Heart Failure in Elderly Persons J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2005; 60(12): 1597 - 1605. [Abstract] [Full Text] [PDF]
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S. Sanal and W. S. Aronow Effect of an Educational Program on the Prevalence of Use of Antiplatelet Drugs, Beta Blockers, Angiotensin-Converting Enzyme Inhibitors, Lipid-Lowering Drugs, and Calcium Channel Blockers Prescribed During Hospitalization and at Hospital Discharge in Patients With Coronary Artery Disease J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2003; 58(11): M1046 - 1048. [Abstract] [Full Text] [PDF]
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W. S. Aronow Review Article: Treatment of Unstable Angina Pectoris/Non-ST-Segment Elevation Myocardial Infarction in Elderly Patients J. Gerontol. A Biol. Sci. Med. Sci., October 1, 2003; 58(10): M927 - 933. [Abstract] [Full Text] [PDF]
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M. Kesani, W. S. Aronow, and M. B. Weiss Prevalence of Multivessel Coronary Artery Disease in Patients With Diabetes Mellitus Plus Hypothyroidism, in Patients With Diabetes Mellitus Without Hypothyroidism, and in Patients With No Diabetes Mellitus or Hypothyroidism J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2003; 58(9): M857 - 858. [Abstract] [Full Text] [PDF]
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V. Suryadevara, S. G. Storey, W. S. Aronow, and C. Ahn Association of Abnormal Serum Lipids in Elderly Persons With Atherosclerotic Vascular Disease and Dementia, Atherosclerotic Vascular Disease Without Dementia, Dementia Without Atherosclerotic Vascular Disease, and No Dementia or Atherosclerotic Vascular Disease J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2003; 58(9): M859 - 861. [Abstract] [Full Text] [PDF]
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W. S. Aronow Commentaries on "Embracing Complexity: A Consideration of Hypertension in the Very Old" and Author's Response: Commentary J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2003; 58(7): M659 - 660. [Full Text] [PDF]
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W. S. Aronow and C. Ahn Elderly Diabetics With Peripheral Arterial Disease and No Coronary Artery Disease Have a Higher Incidence of New Coronary Events Than Elderly Nondiabetics With Peripheral Arterial Disease and Prior Myocardial Infarction Treated With Statins and With No Lipid-Lowering Drug J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2003; 58(6): M573 - 575. [Abstract] [Full Text] [PDF]
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S. Ghosh and W. S. Aronow Utilization of Lipid-Lowering Drugs in Elderly Persons With Increased Serum Low-Density Lipoprotein Cholesterol Associated With Coronary Artery Disease, Symptomatic Peripheral Arterial Disease, Prior Stroke, or Diabetes Mellitus Before and After an Educational Program on Dyslipidemia Treatment J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2003; 58(5): M432 - 435. [Abstract] [Full Text] [PDF]
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W. A. Banks and J. E. Morley Memories Are Made of This: Recent Advances in Understanding Cognitive Impairments and Dementia J. Gerontol. A Biol. Sci. Med. Sci., April 1, 2003; 58(4): M314 - 321. [Full Text] [PDF]
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J. E. Morley Editorial: Hot Topics in Geriatrics J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2003; 58(1): M30 - 36. [Full Text] [PDF]
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W. S. Aronow, C. Ahn, and H. Gutstein Reduction of New Coronary Events and New Atherothrombotic Brain Infarction in Older Persons With Diabetes Mellitus, Prior Myocardial Infarction, and Serum Low-Density Lipoprotein Cholesterol >=125 mg/dl Treated With Statins J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2002; 57(11): M747 - 750. [Abstract] [Full Text] [PDF]
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W. S. Aronow Guest Editorial: What Is the Appropriate Treatment of Hypertension in Elders? J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2002; 57(8): M483 - 486. [Full Text] [PDF]
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