Wilbert S. Aronow, MD, FACC, FAHA, AGSF, Department of Medicine, Divisions of Cardiology, Geriatrics, and Pulmonary/Critical Care, New York Medical College, Valhalla, NY, USA.

Randomized, double-blind, placebo-controlled studies and observational studies have documented that statins reduce mortality and major cardiovascular events in high-risk persons with hypercholesterolemia. The Heart Protection Study showed that statins reduced mortality and major cardiovascular events in high-risk persons regardless of the initial level of serum lipids, age, or gender. The updated National Cholesterol Education Program (NCEP) III guidelines state that in very-high-risk patients, a serum low-density lipoprotein (LDL) cholesterol level of <1.81 mmol/L (<70 mg/dL) correct is a reasonable clinical strategy, regardless of age. When a high-risk person has hypertriglyceridemia or low serum high-density lipoprotein cholesterol, consideration can be given to combining a fibrate or nicotinic acid with an LDL cholesterol–lowering drug. For moderately high-risk persons, the serum LDL cholesterol should be reduced to <2.59 mmol/L 2.59 (<100 mg/dL). When LDL cholesterol–lowering drug therapy is used to treat high-risk persons or moderately high-risk persons, the serum LDL cholesterol should be reduced by at least 30–40%. High-risk older persons should be treated with lipid-lowering drug therapy according to NCEP III updated guidelines to reduce cardiovascular morbidity and mortality. The LDL cholesterol should be reduced to <4.14 mmol/L (<160 mg/dL)correct in persons at low risk for cardiovascular disease.
Key words: lipids, statins, lipid-lowering drugs, atherosclerotic vascular disease.

Wilbert S. Aronow, MD, Department of Medicine, Cardiology, Geriatrics, and Pulmonary/Critical Care Divisions, New York Medical College, Valhalla, NY, USA.

Randomized, double-blind, placebo-controlled studies and observational studies have demonstrated that statins reduce mortality and major cardiovascular events among high-risk older adults with hypercholesterolemia. The Heart Protection Study showed that statins reduced mortality and major cardiovascular events in high-risk persons regardless of the initial level of serum lipids, age, or gender. The updated National Cholesterol Education Program (NCEP) III guidelines state that among very high-risk patients a serum LDL cholesterol level of less than 70 mg/dl (1.8 mmol/l) is a reasonable clinical strategy, regardless of age. When a high-risk person has hypertriglyceridemia or low serum HDL cholesterol, consideration can be given to combining a fibrate or nicotinic acid with an LDL cholesterol-lowering drug. For moderately high-risk persons (having two or more risk factors and a 10-year risk for CHD of 10-20%) the serum LDL cholesterol should be reduced to less than 100 mg/dl (2.6 mmol/l). When LDL cholesterol-lowering drug therapy is used to treat high-risk persons or moderately high-risk persons, the serum LDL cholesterol should be reduced at least 30-40%.
Key words: lipids, statins, lipid-lowering drugs, coronary heart disease, atherosclerotic vascular disease, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides.

D. Larry Sparks, PhD, Senior Scientist and Head, Roberts Laboratory for Neurodegenerative Disease Research, Sun Health Research Institute, Sun City, AZ, USA.

The primary care physician is often pressed with first-line treatment of Alzheimer’s disease (AD). A number of FDA-approved therapies are available. Emerging data indicate that circulating cholesterol levels may influence progression of the dementing disorder. A recent pilot, proof-of-concept, placebo-controlled clinical trial suggests that the cholesterol-lowering medication atorva-statin provides benefit in treating mild-to-moderate AD. Although not approved for the treatment of AD, statin therapy might be considered in the setting of elevated cholesterol levels--even when LDL/HDL ratios are acceptable.
Key words: Alzheimer’s disease, cholesterol, statins, dementia, atorvastatin.

Raymond Fung, MD, BSc, Fellow, Division of Endocrinology, University of Toronto, Toronto, ON.

Lorraine L. Lipscombe, MD, FRCPC, Clinical Associate, Research Fellow, Division of Endocrinology, Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, Toronto, ON.

The prevalence of diabetes has been increasing significantly in the last several years, especially in the older population. Cardiovascular disease (CVD) represents the most important complication of diabetes in this age group, as up to 80% of persons with diabetes die from CVD. The treatment of dyslipidemia and hypertension are both key in ameliorating CVD risk. Recent randomized controlled trials have included older persons with diabetes and have demonstrated that both statin therapy for dyslipidemia and antihypertensive agents are highly effective and safe in preventing CVD in this population. This review will examine the evidence for treatment in both areas, outlining the special considerations in the aged.

Key words: diabetes mellitus, cardiovascular disease, statins, hypertension, cholesterol.

James Shepherd, MD, PhD, Institute of Biochemistry, Royal Infirmary, Glasgow, Scotland, UK.

In the last two decades the prevalence of stroke, diabetes mellitus, and heart disease has increased significantly as a tangible index of aging in the population. All these diseases are increasing the strain on community health care and social services. Policy-makers need to understand and monitor these trends in order to make informed and cogent decisions about the management of this growing problem. This review highlights some of the key health issues facing older adults in regard to vascular disease and statin therapy in the hope that enlightened debate will inform decision makers in resource allocation for this important and growing segment of society.

Key words: statins, PROSPER, vascular risk reduction, economic evaluations, cholesterol.

Gustavo A. Cardenas, MD, Carl J. Lavie, MD and Richard V. Milani, MD, Department of Cardiology, Ochsner Medical Institutions, New Orleans, LA, USA.

Substantial data from epidemologic, lipid intervention and serial coronary angiographic studies have established the importance of high-density lipoprotein cholesterol (HDL-C) on cardiovascular risk. Low levels of HDL-C should be treated with non-pharmacologic therapy, including weight reduction and aerobic exercise training. Persistently low levels of HDL-C can be treated with niacin therapy, fibrates (especially if the triglyceride levels are elevated) and the statin family of medications. For every 1% increase in HDL-C, one would expect a greater than 3% reduction in vascular risk.
Key words: high-density lipoprotein, niacin, fibrates, statins, exercise.

Milita Crisby, MD, PhD, Neurotec Department, Division of Geriatric Medicine, Stockholm, Sweden.

The interaction of genetic and multiple environmental factors contributes to the development of Alzheimer disease (AD). Hypertension and hypercholesterolemia have been identified as risk factors for ischemic heart disease (IHD). Recent epidemiological data also have revealed an association between hypercholesterolemia and AD. Experimental models of AD and in vitro studies have shown that cholesterol modulates the amyloidogenic pathway in favour of production and deposition of amyloid in the brain. Dysregulation of the lipid metabolism in the brain due to apolipoprotein E4 or 24-hydroxylase polymorphisms has been observed in patients with AD and related dementias. Furthermore, observational studies have revealed that statin use could have a potential role in the prevention of AD.
Key words: cholesterol, statins, lipid-lowering, Alzheimer disease, neurodegeneration.

While investigating the benefits of statin therapy in the seldom studied elderly, the PROSPER study found that pravastatin reduced the risk of coronary disease as it has in studies of middle-aged people, yet unlike previous studies, did not have a clear effect on risk of stroke.

The benefits of statins have been demonstrated for the primary and secondary prevention of both coronary and cerebrovascular events, but most of this evidence has involved middle-aged people. The rationale for such treatment in those older than 70 years is less clear, since the association between cholesterol levels and risk of coronary artery disease diminishes with increasing age, and the frequency of stroke is associated with hypertension rather than with cholesterol. However, there has been enough conflicting evidence to challenge these concepts such that investigators launched the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) to look more closely at the efficacy of statin therapy in older people. The researchers set out to determine whether pravastatin reduces the risk of cardiac events, stroke, cognitive decline and disability in those with existing (secondary prevention) and those at high risk of developing (primary prevention) vascular disease.

A total of 5,804 men and women 70-82 years old were recruited if they had pre-existing vascular disease or a high risk of developing vascular disease due to smoking, hypertension or diabetes. Of these, 2,891 were randomized to treatment with pravastatin 40mg per day and 2,913 to placebo. Plasma total cholesterol levels had to be 4.0-9.0mmol/L and their triglyceride concentration less than 6.0mmol/L. Every three months, lipoprotein profiles were measured, and every year an electrocardiogram was recorded and cognitive function tests and disability assessments were performed. Follow-up was 3.2 years on average and the primary outcome was the combined endpoint of definite or suspect death from coronary heart disease, non-fatal myocardial infarction and fatal or non-fatal stroke. Secondary outcome was a separate examination of coronary and cerebrovascular components, while tertiary outcomes included disability and cognitive function.

Pravastatin was found to reduce the risk of the primary endpoint by 15% (relative reduction; p=0.014), yet this risk reduction was largely attributable to a reduction in risk of coronary events only. Upon separation, investigators noted a 19% reduction in coronary events (p=0.006) but no discernable effect on cerebrovascular events (p=0.81). Reductions, although non-significant, were found in transient ischemic attacks and the frequency of revascularization procedures among participants taking pravastatin. There were no observed differences between treatment and placebo groups in all-cause mortality or rates of hospital admissions for heart failure. Furthermore, serious adverse events were reported with similar frequency in both groups, and cognitive function declined at the same rate.

The overall reduction in the primary endpoint in pravastatin-treated subjects was less than predicted because of the lack of effect on rates of stroke. This finding was not, however, due to pravastatin's inability to lower low-density lipoprotein (LDL) cholesterol; at three months LDL cholesterol was 34% lower in treated subjects and after two years remained 33% lower than levels measured in placebo subjects. Researchers propose that the lack of effect on stroke might be due to a lack of statistical power, or may be a consequence of the short duration of the trial since other research suggests that stroke benefit from statin therapy does not begin to appear until after three years (whereas coronary risk reduction is an early event).

Extrapolating results from the PROSPER study to clinical practice is difficult. Although it provides clear evidence that statin therapy in elderly individuals reduces the risk of coronary disease, as it does in middle-aged people, a clear result on stroke would require a longer period of treatment if indeed statins are even beneficial for this indication in the elderly.

Source

1. Shepherd J, Blavw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623-30.

K. Farcnik, MD, FRCP(C), Psychiatrist, Division of Geriatric Psychiatry, University of Toronto, Toronto, ON.
M. Persyko, PsyD, CPsych, Division of Geriatric Psychiatry, University of Toronto, Toronto, ON.

Significant work has been done in the treatment of Alzheimer disease (AD) since cholinesterase inhibitors (CI) were approved in Canada five years ago. This has led to a better understanding of these drugs in terms of their different properties, therapeutic efficacy and indications for switching, and their use has since been extended to the treatment of AD with vascular pathology. Other treatments for AD, such as estrogens and non-steroidal anti-inflammatory drugs (NSAIDs), have also been evaluated further, while newer treatments, including a vaccine for AD, are currently in development. Although research outcomes have not always been positive, a significant effort is being made to achieve greater impact in a disease that is becoming ever more prevalent.

Cholinesterase Inhibitors
Currently, the CIs are the only class of drugs that have been proven efficacious in the symptomatic treatment of AD.¹ There are two types of CIs: acetyl and butyryl. Butyrylcholinesterase levels in the brain increase with the progression of AD, whereas levels of the enzyme acetylcholinesterase decrease.² The CIs approved in Canada that have demonstrated efficacy as well as a favourable safety profile are donepezil, rivastigmine and galantamine.

Cynthia Jackevicius, BScPhm, MSc
Practice Leader,
Pharmacy Department,
Associate, Women's Health Program,
University Health Network-Toronto General Hospital,
Assistant Professor,
University of Toronto, Toronto, ON.

Coronary heart disease (CHD) is a major economic burden on the health care system, with the total cost of the morbidity and mortality associated with cardiovascular disease in Canada estimated at $18.0 billion in 1994.¹ Effective prevention and treatment decrease morbidity and mortality associated with CHD. A controversial issue in recent years has been whether the reduction of cholesterol results in a decline in subsequent CHD events and mortality in patients older than 65 years of age.² Several observational studies have suggested that elevated cholesterol levels may not be a significant cardiovascular risk factor in older people. However, a recent study investigated this hypothesis and found that after adjustment for risk factors and indicators of frailty, such as low serum albumin, elevated total cholesterol levels do predict increased risk for death from CHD in older adults.³

Three recently published, landmark trials focusing on the benefits of statins in the prevention of secondary coronary events showed that statins improve patient outcomes with minimal adverse effects.