cardiovascular disease prevention, older adults, risk factors



  1. Klieman, Linda MSN, ANP
  2. Hyde, Shauna MS, RD, CDE
  3. Berra, Kathy MSN, ANP, FAAN


Preventing cardiovascular events in older persons presents unique challenges to clinicians. Cardiovascular disease accounts for a large amount of disability and mortality in older persons. Older persons are often faced with unique and multiple challenges to health, including cognitive decline, social isolation, financial constraints, and physical disabilities. As more and more older persons are enrolled in studies that aim to better understand coronary heart disease and its prevention, new information is becoming available that allow clinicians to improve outcomes in the older adult. The most recent updates in the area of medical management, as well as updates of recommendations for lifestyle changes, including physical activity and dietary recommendations for older persons at risk, are presented in this article.


Article Content

The vast majority of deaths due to coronary heart disease (CHD) occur in people aged 65 and older, with 84% of CHD mortality occurring in persons 65 years or older.1 Coronary heart disease and stroke account for close to 6 million hospitalizations each year and result in disability for 10 million Americans older than 65 years.2 Of the 71,300,000 Americans living with cardiovascular disease, 38% are over the age of 65.3


Contributions to increased mortality from myocardial infarction (MI) in older adults include an increased incidence of comorbid conditions, relatively more extensive CHD, and lesser use of beneficial therapies, including a substantial underuse of medications shown to improve MI survival (eg, aspirin, [beta]-blocking drugs, and angiotensin-converting enzyme [ACE] inhibitors).4


There is great room for improvement in the prevention and management of CHD in the older adult. In considering lifestyle and medial therapies for older adults, it is important to remember that "older adults" are not a homogeneous group. Many differences exist including a 30- to 40-year age span, the presence of comorbid conditions, the use of concomitant medications, as well as social and demographic factors. This article will focus on the benefits of lifestyle change and medical therapies in the secondary prevention of CHD in older (>=65 years) adults. We acknowledge that recommendations for all adults must take into consideration their chronological age, their health status, and their personal goals and wishes.


Lifestyle Changes for Improved Health in Older Adults

Physical Activity

The benefits of physical activity are many. Regular aerobic physical activity increases functional capacity and plays a role in both primary and secondary prevention of CHD. Exercise positively affects lipid abnormalities, hypertension, diabetes, weight, and obesity. Resistance training helps maintain strength, muscle mass, bone mineral density, and functional capacity. In addition to the physical benefits of exercise, physical activity is also associated with improvements in various indexes of psychologic functioning.5 There is a direct relationship between physical inactivity and cardiovascular mortality, and physical inactivity is a risk factor for coronary artery disease.6 These benefits are also seen in older adults who are regularly active and in those who undertake regular physical activity.


Scientific evidence demonstrates that physical activity can reduce the incidence of CHD.7 Physical activity both prevents and improves many CHD risk factors, including hypertension, insulin resistance, glucose intolerance, elevated triglycerides, low high-density lipoprotein cholesterol (HDL-C), and obesity. When combined with weight loss, physical activity also decreases levels of low-density lipoprotein cholesterol (LDL-C).7 These benefits also have been shown in older adults. Gill et al8 demonstrated that in both observational studies and randomized controlled trials, persons 75 years and older experienced benefits. In the observational studies, benefits included reductions in morbidity and mortality, less functional decline, less mobility disability, less CHD, and increases in active life expectancy. The randomized controlled trials demonstrated improvements in functional outcomes, including reduced falls and fear of falling.


Physical Activity Counseling

Regular physical activity is critical in the management of all CHD risk factors and, as a result, should play aprominent role when counseling older adults. For older adults with or without CHD, special consideration must be taken in regard to comorbidities (eg, chronic obstructive pulmonary disease, atrial fibrillation, ischemic coronary symptoms, peripheral vascular disease, osteoarthritis, osteoporosis, emotional status, neurologic impairment, and visual disabilities) in order to provide a safe exercise prescription.9 Because changes in cardiovascular status are common with aging, guidelines for exercise should include a comprehensive physical examination, a review of all medications, an exercise test for those at risk for a cardiovascular event, and other evaluations as indicated by overall health status and comorbidities. In general, it is recommended that all adults participate in regular physical activity (30 minutes of moderate physical activity on most and preferably all days of the week).7 All exercise prescriptions must include specific information about the type(swimming, walking, biking), the intensity (low, moderate), the frequency (days per week), and the duration (continuous, short bouts, total length of time per day). Strength and flexibility training are important components of a comprehensive program.7-10


Patients With Coronary Heart Disease

Several meta-analyses have concluded that comprehensive, exercise-based cardiac rehabilitation reduces mortality rates in patients after MI.11-13 However, it has yet to be established whether exercise training is also associated with a reduction of morbidity or mortality in the older adult with CHD. The British Heart Study examined light-to-moderate activity in 5,934 men (mean age 63 years) with CHD. Results showed that men participating in physical activity over 5 years had significantly lower all-cause mortality compared with the sedentary group.14 A meta-analysis of 48 randomized trials comparing exercise-based rehabilitation with usual medical care showed that exercise-based cardiac rehabilitation was associated with lower total and cardiac mortality rates compared with medical care.15 These finding also applied to persons older than 65 years. Favorable trends were noted for a lower incidence of nonfatal MI and revascularization procedures in cardiac patients who received exercise-based rehabilitation, but these trends did not achieve statistical significance.


Referral rates for older adults, especially older women, to cardiac rehabilitation are lower compared with younger adults. This is despite the evidence that exercise training decreases risk factors, improves survival, and improves quality of life.4 It is important for providers to improve the utilization of cardiac rehabilitation programs in order to maximize the health potential of older adults with coronary artery disease and other cardiovascular conditions.


Nutrition for Dyslipidemia

The National Cholesterol Education Program recommends a multifaceted approach to diet and lifestyle, called therapeutic lifestyle changes (TLC), aimed at improving lipid levels, and thus, decreasing the risk of CHD.16 The essential features of TLC are described in Table 1. Therapeutic lifestyle changes are recommended in all high-risk patients whenever the LDL-C level is >=100 mg/dL. Furthermore, any person at high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level.

Table 1 - Click to enlarge in new windowTABLE 1 Features of Therapeutic Lifestyle Changes

Saturated Fatty Acids, Cholesterol, and Trans-Fatty Acids

There is substantial evidence that dietary saturated fatty acids, cholesterol, and trans-fatty acids increase LDL-C. Low-density lipoprotein cholesterol-lowering can be achieved by reducing saturated fatty acids to less than 7% of total calories and consuming less than 200 mg/d of cholesterol.16 Currently, there is no numerical limit for dietary trans-fatty acids, however, as trans-fatty acids are not essential and pro vide no known health benefit, it is recommended by the Institute of Medicine's Food and Nutrition Board to consume as little trans-fat as possible.17


Monounsaturated and Polyunsaturated Fatty Acids

Monounsaturated fatty acids are a form of unsaturated fatty acid that can replace saturated fatty acids. Substituting saturated fatty acids with cis-monounsaturated fatty acids has been shown to yield a decrease in LDL-C with little or no decrease in HDL-C.18 National Cholesterol Education Panel, Adult Treatment Panel III (ATP III) recommends an intake of monounsaturated fatty acids of up to 20% of total calories. Similar to monounsaturated fatty acids, polyunsaturated fatty acids reduce LDL-C levels when substituted for saturated fatty acids.18



When carbohydrate is substituted for saturated fatty acids, LDL-C levels fall. However, a high intake of carbohydrates (eg, >60% of total calories) is accompanied by a reduction in HDL-C and an increase in triglyceride levels.19-21 Therefore, ATP III recommends that carbohydrate intake should be limited to 60% of total calories for persons with risk factors for the metabolic syndrome where triglyceride levels are often elevated.



Viscous (soluble) dietary fiber can reduce LDL-C levels. In contrast, insoluble fiber does not affect LDL-C.22 ATP III recommends a diet that contains a minimum of 5 to 10 grams of soluble fiber per day and even higher intakes of 10 to 25 grams per day can be beneficial.


Plant Sterols and Plant Stanols

Studies have demonstrated the LDL-lowering effect of plant sterols and plant stanols. Plant sterols are isolated from soybean and tall pine-tree oils. Hydrogenating plant sterols produces plant stanols. Stanol/sterol esters at dosages of 2 to 3 g/d lower LDL-C levels 6% to 15% with little or no change in HDL-C or triglyceride levels.23 ATP III recommends 2 g/d of plant stanols/sterols as a therapeutic option to enhance LDL-C lowering.


Metabolic Syndrome

After LDL-C lowering has been implemented, nutrition therapy should address the risk factors of the metabolic syndrome (Table 2).16 Management of the metabolic syndrome focuses on reversing its primary causes-overweight/obesity and physical inactivity. A caloric level should be recommended which will promote weight loss. In addition to a decrease in total calories, nutrition therapy should also target macronutrient levels as well. Carbohydrate intakes should be limited to no more than 60% of total calories with lower intakes (50% of calories) appropriate for persons with elevated triglycerides or low HDL-C. 16

Table 2 - Click to enlarge in new windowTABLE 2 The Metabolic Syndrome

Nutrition for the Management of Hypertension

Diet composition is one of many factors that affect the development and management of hypertension in older adults. Diet modifications have been shown to be effective in lowering blood pressure.24 The Dietary Approaches to Stop Hypertension study (DASH) tested nutrients as they occur together in food. The DASH study showed that a diet low in saturated fat, cholesterol, and total fat, and that emphasizes fruits, vegetables, and low-fat dairy foods reduces blood pressure. The DASH-Sodium Study investigated the effect of reduced dietary sodium intake on blood pressure as participants followed either the DASH diet or an eating plan typical of what many Americans consume.25 The largest reductions in blood pressure were seen in the DASH diet with a sodium intake of 1,500 mg/d. This can be accomplished by reading food labels, avoiding processed foods, and by using alternative seasonings to salt. The PREMIERE study supports the DASH approach to blood pressure control.26 PREMIER showed that in adults with stage 1 hypertension (120 to 159 mm Hg and 80 to 95 mm Hg), lifestyle (DASH diet) and behavioral interventions lowered blood pressure.


A recent randomized controlled trial compared the effects of substituting some of the carbohydrate of the DASH diet with either protein (about half from plant sources) or unsaturated fat (predominantly monounsaturated fat) on blood pressure and serum lipids in generally healthy persons aged 30 years and older (mean age 53.6 years) having hypertension or prehypertension.27 All diets resulted in reduced blood pressure, LDL-C, and estimated CHD risk when compared with baseline.


Compared with the higher carbohydrate diet, the higher protein diet (protein accounted for 25% of total calories vs 15%) further significantly decreased mean systolic blood pressure and LDL-C. Triglyceride and HDL-C levels were also significantly lowered in the higher protein versus higher carbohydrate diet. Compared with the higher carbohydrate diet, the higher unsaturated fat diet (fat accounted for 37% of total calories vs 27%) further significantly decreased systolic blood pressure and had no effect on LDL-C. This diet also showed a significant increase in HDL-C and a decrease in triglycerides compared with the higher carbohydrate diet. The estimated 10-year CHD risk was lower and similar on the higher protein and higher unsaturated fat diets compared with the higher carbohydrate diet.27


Excessive alcohol is an important risk factor for hypertension. All adults should be counseled to limit alcohol intake (no more than 1 ounce of ethanol or 24 ounces of beer or 10 ounces of wine per day for men or 0.5 ounce of ethanol or 12 ounces of beer or 5 ounces of wine per day for women).28


Medical Nutrition Therapy for Diabetes

Nutrition therapy is an integral component of diabetes mellitus (DM) management. The nutrition recommendations for persons with DM are determined by considering treatment goals and the lifestyle changes the diabetic patient is willing and able to make and maintain (Tables 3 and 4).29,30 Older persons with DM should receive individualized medical nutrition therapy (MNT) preferably by a registered dietitian familiar with the components of MNT for diabetes. Clinicians should strongly support and encourage these physical activity and nutrition modifications in older adult patients.

Table 3 - Click to enlarge in new windowTABLE 3 Goals of Medical Nutrition Therapy for Older Adult Patients with Diabetes
Table 4 - Click to enlarge in new windowTABLE 4 Macronutrient Recommendations for Patients With Diabetes

Weight Management

An estimated 97 million adults in the United States are overweight or obese, a condition that substantially raises the risk of morbidity from hypertension, dyslipidemia, DM, CHD, and stroke.31 Obesity is a risk factor for second coronary events in older men and women with CHD.4 This is primarily due to the clustering of dyslipidemia, hypertension, and insulin resistance in older overweight individuals. Therefore, weight loss has the potential to act as a multifactorial risk reduction intervention in older adults.


Unfortunately, few data are available that describe the effect of either increased physical activity orhypocaloric diets as a means of impacting obesity in older patient with CHD. However, weight loss induced by exercise or caloric restriction in older adults is associated with similar improvements in cardiac risk factors as seen in younger patients. Therefore, there is reason to expect a reduction in secondary coronary events.4


A clinical decision to forgo obesity treatment in an older adult should be guided by an evaluation of the potential benefits of weight reduction for day-to-day functioning and reduction of the risk of future cardiovascular events, as well as the patient's motivation for weight loss.32


A combined intervention of behavior therapy, a low-calorie diet, and increased physical activity provides the most successful therapy for weight loss and weight maintenance.31



Statistics from the Centers for Disease Control and Prevention for 1999 through 2000 show that 40.1% of men and 26.8% of women older than 65 smoked cigarettes. Among this group, African Americans outnumbered Hispanics, Latinos, and whites.33 The American Heart Association (AHA) recommends complete smoking cessation for everyone.34 The known benefits of smoking cessation, including reduced risk of lung and other cancers, reduction in CHD and CHD-related events, and reduction of chronic obstructive lung disease are well documented. Smoking cessation has been shown to improve peripheral circulation and therefore reduce the symptoms of peripheral arterial disease.35 Among smokers who quit at age 65, men gained 1.4 to 2.0 years of life and women gained 2.7 to 3.4 years.36 Pulmonary function improves with smoking cessation, even in the older population.37


The International Tobacco Control Policy Evaluation Survey (ITCPES) examined factors associated with older smokers' (9,000 adult smokers aged 60 years and above) intention to quit smoking using data gathered via a random digit dialed telephone survey. It was hypothesized that older smokers would perceive themselves as being less vulnerable to the harm of smoking (self-exempting beliefs); be less concerned about the health effects of smoking; be less confident about being able to quit successfully (self-efficacy); not perceive any health benefit of quitting; hence, be less willing to want to quit. Controlling for possible confounders, the hypotheses were all confirmed. Reported considerations for quitting revealed that price of cigarettes, health professional advice, inexpensive quitting medication, and information on health risks were important predictors of quitting intention. The authors concluded that the findings have important implications for developing strategies for encouraging older smokers to give up smoking.38


Patients aged 65 years or more are less likely to be prescribed any form of smoking cessation therapy compared with those younger than 65 years.39 When used with caution, it appears that the combination of buproprion with nicotine replacement therapy can be safe in older patients.40 Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and excreted by the kidneys. The risk of toxic reaction to this drug may be greater in patients with impaired renal function and those with a history of seizure disorders. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.40


It should also be noted that buproprion should be used with great caution in patients with severe hepatic disease. Coadministration of bupropion with certain drugs should be approached with caution. These drugs include beta-blockers, certain antiarrhythmics, monoamine oxidase (MAO) inhibitors, drugs that lower seizure threshold, certain antipsychotics and antidepressants, warfarin, and theophylline.40


Medical Therapies for High-Risk Older Adults

Lipid Management

In 2001, ATP III described the benefits of LDL-C-lowering therapy in older persons with established CHD.16 The recommendations were based on several large studies which included significant numbers of older persons.41-43 ATP III recommends <100 mg/dL as the optimal level for LDL-C for all adults.16 This recommendation is based on significant evidence that lowering LDL-C results in reductions in recurrent MI and coronary death, coronary artery procedures, and stroke.16


In 2004, ATP III was updated based on new and compelling data. The update recommends an "optional LDL-C goal" of <=70 mg/dL for persons at "very high risk (Table 5)."44 The update also summarizes research that would extend the recommendations to older adults.

Table 5 - Click to enlarge in new windowTABLE 5 Criteria for Identifying Very High Risk Patients in the Treatment of Dyslipidemia

Much research has focused on the use of statins in the treatment of older patients. Although statins are generally safe and well tolerated in older people, it remains important to initiate therapy at low doses to minimize adverse effects with gradual titration until the target LDL-C level is safely reached.45 When statins are combined with medications that are known substrates or inhibitors of CYP3A4 (eg, nefazodone) or agents such as gemfibrozil or niacin, the risk of adverse effects (ie, myositis and, in severe cases, rhabdomyolysis) is significantly increased. Statins that do not undergo CYP3A4 metabolism should be considered for individuals receiving medications metabolized by that isoenzyme.45


Knowing that lowering LDL-C is effective in reducing the risk for CHD in older adults, clinicians should consider LDL-C lowering as a major emphasis in their treatment of older adults with CHD and those at high risk for the development of CHD. However, several obstacles exist. Firstly, traditional risk factor assessment with Framingham scoring declines in predictive power as we age.16 In a study of older (>65 years), high-risk men and women, Kuller et al46 found that subclinical disease was present in 36% of women and 38.7% of men over age 65, and that this finding increased with age. Their methods included using a combined index based on electrocardiogram and echocardiogram abnormalities, carotid artery wall thickness and stenosis based on carotid ultrasound, decreased ankle-brachial blood pressure, and positive response to a Rose Questionnaire for angina or intermittent claudication.46 Surely, the ability to determine subclinical atherosclerosis would aid the clinician greatly in determining which patients to target more aggressively. However, at present, these methods are not widely available, nor have specific guidelines been generated for their use.16


ATP III highlights the importance of treating LDL-C first, as it is most significantly related to the development of CHD.16 The management of hypertriglyceridemia and low HDL-C deserve attention, as they are common, and their treatment becomes more complicated in the older patient.


The goal for serum triglycerides in all patients is <150 mg/dL. An HDL-C level of <40 mg/dL is considered a major risk factor for CHD. Low HDL-C is often seen in association with elevated triglycerides. Non-HDL-C has been defined by ATP III as a secondary target of therapy to take into account the atherogenic potential associated with remnant lipoproteins in patients with hypertriglyceridemia. When triglycerides are >200 mg/dL), non-HDL-C should be calculated and considered as a secondary target (Table 6). Elevated triglycerides are categorized as borderline high triglycerides (150 to 199 mg/dL), high triglycerides (200 to 499 mg/dL), or very high triglycerides (>500 mg/dL). There are no specific recommendations for medical therapies based on current research for older patients. Thus, borderline high triglycerides are treated with aggressive lifestyle changes. High triglycerides can generally be treated with lifestyle and statin therapy, which lowers triglycerides by 20% to 40%. Very high triglycerides may require treatment with a fibrate or nicotinic acid.16

Table 6 - Click to enlarge in new windowTABLE 6 The Calculation of Non-HDL-C

Fibrates can lower triglycerides by an average of 74% in people with severe hypertriglyceridemia.16 Fibrates also raise HDL-C by 15% to 25%. Low-density lipoprotein cholesterol typically increases with fibrates by 5% to 30%, so they often need to be used in conjunction with a statin. Nicotinic acid lowers triglycerides by 20% to 50%, raises HDL-C by 20% to 30%, and LDL-C generally remains unchanged or modestly lowered. The safety profile for these medications in older persons is not well studied. A post hoc analysis of the VA-HIT study47 evaluated gemfibrozil safety in patients with chronic renal insufficiency and found it could be safely used in patients with chronic renal insufficiency. The participants in this group were all under the age of 74, with an average age of 67. No studies to date have examined safety of nicotinic acid use specifically in older patients.


It is important not to neglect the detection and treatment of conditions that can result in secondary dyslipidemias, especially in older persons. These conditions include hypothyroidism, nephrotic syndrome, obstructive liver disease, and other renal disorders, including renal failure.16



The prevalence of systolic hypertension (>140 mm Hg) rises with increasing age, whereas the presence of diastolic hypertension (>90 mm Hg) appears to peak at about age 55, and then declines with advancing age.28,48 Isolated systolic hypertension is the most prevalent form of hypertension in older adults.48 More than 50% of people over the age of 60 years, especially women, are hypertensive.49 Currently, blood pressure control rates (systolic blood pressure [SBP] <140 mm Hg and diastolic blood pressure [DBP] <90 mm Hg) are only about 20% in older hypertensive individuals, largely due to poor control of SBP.28


Systolic blood pressure provides more appropriate classification and risk stratification than DBP in the elderly. Largely due to the incidence of isolated systolic hypertension in older adults, SBP alone correctly classified the blood pressure stage in 94% of adults over the age of 60, whereas DBP alone correctly classified 66%. Therefore, SBP is superior to DBP as a way to stratify patients in order to target treatment in older persons. Treatment of hypertension in older adults with CHD should follow the recommendations of the Joint National Commission on the detection and control of hypertension VII (JNC VII). The blood pressure (BP) goal for all persons is <140/90 mm Hg with "optimal" blood pressure (BP) >defined as <120/80 mm Hg. In hypertensive patients with diabetes or renal disease, the BP goal is 130/80 mm Hg.28


Antihypertensive therapy has been shown to reduce stroke incidence by 35% to 40%, MI incidence by 20% to 25%, and heart failure by an average of 50%. Two studies, the SHEP study and the Syst-EUR study, demonstrated significant benefits to hypertension treatment in the older adult. The SHEP study enrolled patients over age 60 with hypertension (pretreatment SBP >160 and DBP >90). They found that participants treated with chlorthalidone (with or without a beta-blocker) had a 36% reduction in stroke, a 54% reduction in heart failure, a 27% reduction in MI, and a 32% reduction in overall CHD when compared with placebo.50 Syst-EUR had similar findings of 41% reduction in stroke and 31% reduction in CHD events when comparing nitrendipine to placebo.51


A large international trial evaluating the effect of antihypertensive therapy on incidence of stroke and cognitive function (HYpertension in the Very Elderly Trial [HYVET]) in patients 80 years and older may provide more definitive information regarding the risk and benefits in this population.


Analyses of treatment trials in the older adult by the Hypertension Trialists group suggest that the initial choice of agents is not as important as the degree of blood pressure (BP) reduction achieved.52 Pharmacologic therapy selection should seek to treat other conditions (compelling indications) and should be based on the severity of hypertension, presence of risk factors, and target organ damage.4 Compelling indications for the choice of certain agents can be seen in Table 7.28

Table 7 - Click to enlarge in new windowTABLE 7 Compelling Indications for Individual Drug Classes in the Treatment of Hypertension

A significant number of older people have widely variable blood pressure with exaggerated high and low extremes. Clinicians should consider a slow titration approach in the patient who has variable blood pressure.28


Because declining kidney function is more prevalent in the older adult than in younger persons, it is important to note the recommendations for patients with chronic kidney disease. Chronic kidney disease is defined as either the presence of albuminuria (>300 mg/d) or a reduced glomerular filtration rate of <60 (corresponding to a serum creatinine of >1.5 mg in men or >1.3 mg in women). The National Kidney Foundation indicates that most patients with chronic kidney disease should receive an ACE inhibitor or an angiotensin receptor blocker in combination with a diuretic (most likely a loop diuretic rather than a thiazide).53


Stroke Prevention

About 80% of strokes are a result of an ischemic event, of which 50% of cases are related to atherothrombotic diseases of intracerebral or extracerebral arteries, about 20% are related to embolism of cardiac origin, and 25% are a result of occlusion of one of the small deep perforating cerebral arteries.54 Hypertension, heart disease, thoracic aorta and carotid atherosclerosis are the main causes of ischemic stroke in the elderly. Secondary stroke prevention is addressed elsewhere in this issue.54


Diabetes Mellitus

It is currently estimated that 20% of patients over 65 years have DM, and this number can be expected to grow rapidly in the future.29 Older persons with DM have higher rates of premature death, functional disability, and coexisting illnesses such as hypertension, CHD, and stroke than those do without DM.55,56 Further, the presence of DM is a strong predictor for the occurrence of secondary coronary events in older patients with CHD.57 Older adults with diabetes are at greater risk than other older persons for other common geriatric syndromes such as depression, cognitive impairment, urinary incontinence, injurious falls, and persistent pain.29


Prevention or Delay of Diabetes

Several studies have been published in recent years demonstrating the benefit of lifestyle modification or glucose-lowering medication to prevent or delay the onset of type 2 diabetes in persons with impaired fasting glucose. Of particular relevance is the Diabetes Prevention Program (DPP).58 In the DPP, 20% of participants were 60 years or older. Participants were randomized to 1 of 3 treatment groups: (1) an intensive lifestyle intervention program, (2) standard lifestyle recommendations plus metformin, or (3) standard lifestyle recommendations plus placebo. A 58% relative reduction in the progression to diabetes was seen in the lifestyle group, and a 31% relative reduction in the progression of diabetes was observed in the metformin group compared with placebo. The findings of the DPP were particularly impressive for persons 60 years or older. For older adults, the development of diabetes was prevented or delayed by 71% in the intensive lifestyle intervention group and by 11% in the metformin group as compared with placebo.


Diabetes Management in the Older Adult

In 2003, evidence-based guidelines that specifically targeted the needs of older persons with DM were published by the California Healthcare Foundation in conjunction with the American Geriatric Society.59 The treatment goals of older adults with DM are similar to those of younger persons; however, the care of older adults is complicated by their clinical and functional heterogeneity. Some older adults with DM are frail and have other underlying chronic conditions, substantial DM-related comorbidity, or have limited physical or cognitive functioning. On the other hand, others have little comorbidity and are active. Consideration must also be given to the patient's daily schedule, physical activity, eating patterns, social situation, personality, and cultural factors.59


Patients who can be expected to live long enough to reap the benefits of long-term intensive DM management and who are active, cognitively intact, and willing to undertake the responsibility of self-management should be encouraged to do so and be treated using the goals for younger adults. The American Diabetes Association (ADA) recommends glycemic control to attain an HbA1c of 7% or less, preprandial glucose of 90 to 130 mg/dL, and peak postprandial glucose of <180 mg/dL.29


For patients having DM, control of hyperglycemia is important. However, older individuals may have greater reductions in morbidity and mortality by controlling cardiovascular risk factors rather than tight glycemic control alone. For older adults having advanced DM complications, life-limiting comorbid illness, or cognitive or functional impairment, it is reasonable to set less intensive glycemic target goals. These patients are less likely to benefit from reducing the risk of microvascular complications and more likely to suffer serious adverse effects from hypoglycemia.59


Older patients with DM can be treated with the same drug regimens as younger patients, but special care is required in prescribing and monitoring drug therapy. Metformin is often contraindicated because of renal insufficiency or heart failure. Sulfonylureas and other insulin secretagogues can cause hypoglycemia. Insulin can also cause hypoglycemia as well as require good visual and motor skills and cognitive ability of the patient or a caregiver. Thiazolidinediones should not be used in patients with chronic heart failure. Drugs should be started at the lowest dose and gradually titrated until targets are reached or side effects develop. In regard to concomitant medical therapies for blood pressure and lipid control, the potential benefits must always be weighed against potential risks.59



The American Heart Association, American College of Cardiology, and American College of Physicians (ACC/AHA/ACP) recommend that beta-blockers should be started and continued indefinitely in all patients after MI and acute coronary syndrome, regardless of age, in the absence of contraindications.60,61


Beta-blockers have been shown to reduce overall mortality in both short-term early-intervention and long-term late-intervention prospective randomized trials in patients who have experienced an MI.62 Multiple studies have clearly demonstrated that beta-blockers provide a greater reduction in post-MI mortality in older persons (>=60-65 years) than in younger persons.45 A pooled analysis from 3 of the largest placebo-controlled trials of long-term beta-blockade, including patients up to the age of 75 years, revealed a 6% absolute reduction (from 14.9% to 8.9%) in mortality in the older subgroup (65-75 years) compared with a 2.1% decrease (from 7.6% to 5.5%) observed in the younger subgroup (<65 years).45


Beta-blockers are underutilized in older persons with CHD.45 The National Cooperative Cardiovascular Project (CCP) found that of 45,308 Medicare patients >=65 years, only 50% of eligible patients were prescribed beta-blocker therapy. After stratifying forage, beta-blockers were prescribed in 53.2% of patients aged 65 to 74 years, 48.7% of patients aged 75 to 84 years, and 40.3% in those 85 years. The 1-year mortality rate for patients prescribed beta-blockers was 7.7% compared with 12.6% for those not prescribed beta-blockers (P < .001).


Several relative contraindications are important to keep in mind when using these agents in the elderly. First, beta-blockers may inhibit insulin release and mask the signs of hypoglycemia. Use of beta-blockers may also exacerbate symptoms in patients with pulmonary disease, Raynaud disease, or peripheral vascular disease. The benefits of beta-blockers in the prevention of CHD may outweigh these potential risks. Careful monitoring is necessary to prevent adverse events and maintain quality of life. It is also important when recommending or prescribing beta-blockers to begin with low doses and slowly titrate to target doses based on the patient's clinical response.45


Angiotensin Converting Enzyme Inhibitors

Angiotensin converting enzyme (ACE) inhibitors serve multiple roles in secondary prevention for older patients. They have been shown to be effective for blood pressure control and stroke prevention,54 for patients with left ventricular dysfunction following and MI,45 for the improvement of symptoms in heart failure,45 and for renal protection in patients with diabetes.29 Several studies, including SMILE,63 SAVE,64 AIRE,65 and HOPE,66 examined mortality in patients post-MI after treatment with ACE inhibitor versus placebo. With and without the presence of heart failure, ACE inhibitors greatly reduced both short (6 weeks' outcome) and long-term (15 months) mortality. Most significant were the findings for older participants in these studies, where mortality was reduced more significantly than for younger participants.45


Angiotensin converting enzyme inhibitors should be initiated at low doses in the older adult and slowly titrated to target doses. This class of medications should also be used cautiously in individuals with acute kidney failure, those receiving concomitant potassium supplements or potassium-sparing medications due to the risk of hyperkalemia, and individuals receiving concomitant nonsteroidal anti-inflammatory drug (NSAID) therapy, especially chronic nonsteroidal anti-inflammatory drug use, due to the risk of acute kidney failure. Angiotensin converting enzyme inhibitors must also be added cautiously to concomitant antihypertensive agents to avoid hypotension.45



Long-term aspirin therapy significantly reduces the risk of MI, stroke, and vascular death among patients with CHD. The 1994 Antiplatelet Trialists' Collaboration (ATC)67 meta-analysis looked at results of randomized trials of antiplatelet therapy among more than 54,000 high-risk patients with evidence of CHD. These trials included patients with prior MI, stroke, transient ischemic attacks, unstable angina, stable angina, revascularization surgery, angioplasty, atrial fibrillation, valvular disease, and peripheral vascular disease. Aspirin therapy reduced the risk of subsequent vascular events (nonfatal MI plus nonfatal stroke plus vascular death) by about 25%. This benefit was statistically significant in older patients.68


The ATC found no evidence that higher doses of aspirin or any other oral antiplatelet regimen were more effective than medium-dose aspirin.67 Based on these findings, the ACC/AHA/ACP recommend aspirin 75 to 325 mg/d for all patients after a coronary event in the absence of contraindications.62 In the trials of stroke and transient ischemic attack, higher doses (650 to 1,300 mg/d) were used, but in trials of post-MI patients, lower doses (75 to 325 mg/d) appeared equally beneficial in reducing risks of subsequent stroke.62


Since the ATC's 1994 report, the TASS69 study has shown that ticlopidine versus aspirin results in a 21% decrease in stroke compared with aspirin treatment. The CAPRIE70 study showed that clopidogrel is comparable in effect to aspirin in preventing stroke in patients with CHD, peripheral arterial disease, or history of stroke. Several studies have shown that antiplatelet therapy is underutilized for secondary prevention in older persons. Although aspirin should be used cautiously among patients at high risk for bleeding, it should be prescribed in persons with CHD and continued indefinitely in these older patients without contraindications.68


There are several concerns when using aspirin therapy in older adults. Aspirin should be used cautiously among individuals with a history significant for peptic ulcer disease, gastrointestinal bleeding, or hemorrhagic stroke. nonsteroidal anti-inflammatory drugs, warfarin, and clopidogrel can all increase risk for bleeding, and should be used with caution in conjunction with aspirin therapy. Patients should be reminded to take aspirin with food to minimize the risk of gastrointestinal irritation or bleeding. The risks must be weighed against benefits for each individual before aspirin is prescribed, and careful monitoring is necessary to minimize the occurrence of adverse events.68


Special Issues With Older Patients

The available data suggest that reducing modifiable risk factors is effective for secondary prevention of CHD in older patients. Yet secondary prevention approaches for older adults are underused. The reasons for this are multiple and complex. Future challenges need to focus on improving the implementation of known beneficial therapies to older patients with CHD and at high risk for its development.


Older patients with CHD have other unique barriers to adequate treatment of their risk factors. Older patients tend to have more health problems than their younger counterparts. This translates into a large number of medications being taken by the older adult. Studies conducted in a variety of settings have shown that patients over 65 years use an average of 2 to 6 prescribed medications and 1 to 3.4 nonprescribed medications daily.71 Nurses are in a unique position to educate and assist older patients in managing their medications because of our holistic perspective. Barriers to understanding and adhering to a medication regimen include beliefs, illiteracy, vision impairment, cognitive decline, depression, physical handicaps, low level of education, and financial constraints.


Many interventions for improving adherence have focused on patient barriers and factors related to the characteristics of the drug regimen. Several devices, such as calendar charts, blisterpaks, and compartmentalized trays, all designed to assist with the organization of complex drug regimens, have been shown to improve adherence in intervention studies in older populations.72 Newer devices such as digital alarms are also available, although older persons may prefer to use simpler devices such as organizer trays.72


Several interventions involving enhanced direct patient/care-provider interaction have also shown varying levels of effectiveness. For example, a pharmacist-led information session before discharge from the hospital was found to be effective for patients on complex medication regimens.72 Comprehensive counseling with a nurse, in conjunction with a medication review and recommendations for modification of regimens by a geriatric cardiologist, resulted in a 15% improvement in adherence.72 One-time in-home medication counseling provided by nurses was not found to be effective, but adherence did improve when follow-up telephone calls were added to the intervention.72 The beneficial effects of interventions arising from direct patient/care-provider contact may decline over time, suggesting that successful interventions should include an ongoing component.72


Other significant obstacles for the older adult in managing their medical conditions include cost of drug treatment and other medical care, lack of social support, physical handicaps, depression, and decline in cognitive function. In many instances, the patient can benefit from having a case manager. Case management of CHD risk factors has been shown to positively affect risk factors in several studies conducted on patients with CHD.73,74



As our population ages and the prevalence of CHD rises, it will be our challenge to provide both access to care as well as age-appropriate healthcare. Fortunately, an increasing number of investigators are including older patients in clinical trials and are demonstrating the benefits, risks, and costs of preventive strategies for cardiovascular disease prevention and treatment. Nursing plays a critical role in the care of the older adult, and thus, must take a leadership position in determining better methods of care through research efforts and implementation of appropriate therapies.




1. National Health and Nutrition Examination Survey III (NHANES III, 1988-94), CDC/NCHS. [Context Link]


2. National Center for Health Statistics. Current Estimates from the National Health Interview Survey, 1995. Hyattsville, Md: US Department of Health and Human Services, CDC; 1998. DHS Publication No. (PHS) 98-1527. [Context Link]


3. Thom T, Haase N, Rosamond W, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics-2006 update: a report from the American Heart Association Statistics. Committee and Stroke Statistics Subcommittee. Circulation. 2006;113:e85-e151. [Context Link]


4. Williams MA, Fleg JL, Ades PA, et al. Secondary prevention of coronary heart disease in the elderly (with emphasis on patients (>=75 years of age). An American Heart Association Scientific Statement from the Council on Clinical Cardiology Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention. Circulation. 2002;105:1735. [Context Link]


5. Lavie CJ, Milani RV. Effects of cardiac rehabilitation programs on exercise capacity, coronary risk factors, behavioral characteristics, and quality of life in a large elderly cohort. Am J Cardiol. 1995;76:177-179. [Context Link]


6. Fletcher GF, Balady G, Blair SN, et al. Statement on exercise: benefits and recommendations for physical activity programs for all Americans. A statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart Association. Circulation. 1996;94:857-862. [Context Link]


7. Thompson PD, Buchner D, Pina IL, et al. Exercise and physical activity in the prevention and treatment of atherosclerotic CHD: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation. 2003;107:3109-3116. [Context Link]


8. Gill TM, DiPeitro L, Krumholz HM. Role of exercise stress testing and safety monitoring for older persons starting an exercise program. JAMA. 2000;284:342-349. [Context Link]


9. Williams MA. Exercise testing in cardiac rehabilitation: exercise prescription and beyond. Cardiol Clin. 2001;19:415-431. [Context Link]


10. Brennan FH. Exercise prescriptions for active seniors. Phys Sports Med. 2002;30:19-29. [Context Link]


11. O'Connor GT, Buring JE, Yusuf S, et al. An overview of randomized trials of rehabilitation with exercise after myocardial infarction. Circulation. 1989;80:234-244. [Context Link]


12. Oldridge NB, Guyatt GH, Fischer ME, et al. Cardiac rehabilitation after myocardial infarction: combined experience of randomized clinical trials. JAMA. 1988;260:945-950. [Context Link]


13. Jolliffe JA, Rees K, Taylor RS, et al. Exercise-based rehabilitation for coronary heart disease. Cochrane Database Syst Rev. 2001;1:CD001800. [Context Link]


14. Wannamethee SG, Shaper AG, Walker M. Physical activity and mortality in older men with diagnosed coronary heart disease. Circulation. 2000;102:1358-1363. [Context Link]


15. Taylor RD, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review of meta-analysis of randomized trials. Am J Med. 2004;116:682-697. [Context Link]


16. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497. [Context Link]


17. Institute of Medicine. Letter Report on Dietary Reference Intakes for Trans Fatty Acids. Washington, DC: National Academy Press; 2002. [Context Link]


18. Mensink RP, Katan MB. Effects of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb. 1992;12:911-919. [Context Link]


19. Garg A. High-monousaturated-fat diets for patients with diabetes mellitus: a meta-analysis. Am J Clin Nutr. 1998;67:577S-582S. [Context Link]


20. Turley ML, Skeaff CM, Mann JI, Cox B. The effect of a low-fat, high-carbohydrate diet on serum high density lipoprotein cholesterol and triglyceride. Eur J Clin Nutr. 1998;52:728-732. [Context Link]


21. Knopp RH, Walden CE, Retzlaff BM, et al. Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic men. The Dietary Alternatives Study. JAMA. 1997;278:1509-1515. [Context Link]


22. Anderson JW, Hanna TJ. Impact of nondigestible carbohydrates on serum lipoproteins and risk for CHD. J Nutr. 1999;129:1457S-1466S. [Context Link]


23. Vuorio AF, Gylling J, Turtola H, Kontula K, Ketonen P, Miettinen TA. Stanol ester margarine alone and with simvastatin lowers serum cholesterol in families with familial hypercholesterolemia caused by the FH-North Karelia Mutation. Arterioscler Thromb Vasc Biol. 2000;20:500-506. [Context Link]


24. Appel LJ, Moore TJ, Obarzanek E, et al. For the DASH Collaboratice Research Group. A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med. 1997;336:1117-1124. [Context Link]


25. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertensio (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3-10. [Context Link]


26. Elmer PJ, Obarzanek E, Vollmer WM, et al. Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial. Ann Intern Med. 2006;144(7):485-495. [Context Link]


27. Appel LJ, Sacks FM, Carey VJ, et al. Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids. Results of the OmniHeart randomized trial. JAMA. 2005;294:2455-2464. [Context Link]


28. Chobanian AV, Bakris GL, Black HR, et al; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC Guidelines). Hypertension. 2003;42:1206-1252. [Context Link]


29. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28:S4-36. [Context Link]


30. American Diabetes Association. Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care. 2003;26:S51-S61. [Context Link]


31. National Institutes of Health. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults-the evidence report. NIH Pub. No. 98-4083. Bethesda, Md: National Heart, Lung and Blood Institute; 1998:262 pages. [Context Link]


32. The Practical Guide: Identification, Evaluation and Treatment of Overweight and Obesity in Adults. NHLBI Obesity Education Initiative Expert Panel on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults; 2002. NIH Publication No. 02-4084. [Context Link]


33. Health, United States 2003, with Chartbook on Trends of Health in Americans. 2003. Available at: Accessed on January 18, 2006. [Context Link]


34. Smith S, Blair S, Criqui M, et al. Preventing heart attack and death in patients with coronary disease. JACC. 1995;26:292-294. [Context Link]


35. Baumgartner I. Systemic antiatherosclerotic treatment for the peripheral arterial occlusive disease patient. Expert Opin Pharmacother. 2005;6(13):2181-2192. [Context Link]


36. Taylor D, Hasselblad V, Henley J, Thun M, Sloan F. Benefits of smoking cessation for longevity. Am J Public Health. 2002;92:990-996. [Context Link]


37. Keller C, Fleury J. Health Promotion for the Elderly. Thousand Oaks, Calif: Sage Publications; 2000. [Context Link]


38. Yong H, Borland R, Siahpush M. Quitting-related beliefs, intentions, and motivations of older smokers in four countries: findings from the International Tobacco Control Policy Evaluation Survey. Addict Behav. 2005;30(4):777-788. [Context Link]


39. Williams D, Bennet K, Heery A, Feely J. Initial uptake and evidence of safe prescribing practice with buproprion (Zyban). Pharmacoepidemiol Drug Saf. 2004;13(6):411-415. [Context Link]


40. Physician's desk reference; 2005, GlaxoSmithKline. RL-2217. [Context Link]


41. Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349-1357. [Context Link]


42. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:138-139. [Context Link]


43. Sacks FM, Pfeffer MA, Moye LA, et al, for the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;(335):1001-1009. [Context Link]


44. Grundy SM, Cleeman JI, Merz CN, et al; National Heart, Lung, and Blood Institute; American College of Cardiology Foundation; American Heart Association. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation. 2004;110:227-239. [Context Link]


45. Dornbrook-Lavender K, Roth M, Pieper J. Secondary prevention of coronary heart disease in the elderly. Ann Pharmacother. 2003;37(12):1867-1876. [Context Link]


46. Kuller L, Borhani N, Furberg C, et al. Prevalence of subclinical atherosclerosis and CHD and association with risk factors in the Cardiovascular Health Study. Am J Epidemiol. 1994;139:1164-1179. [Context Link]


47. Rubins HB, Robins SJ, Collins D, et al, for the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med. 1999;341:410-418. [Context Link]


48. Fair J. Cardiovascular risk factor modification: is it effective in older adults? J Cardiovasc Nurs. 2003;18(3):161-168. [Context Link]


49. The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997;157:2413-2446. [Context Link]


50. 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 (SHEP). JAMA. 1991;265:3255-3264. [Context Link]


51. Staessen JA, Fagard R, Thijs L, et al. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet. 1997;350:757-764. [Context Link]


52. Neal B, MacMahon S, Chapman N. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: Results of prospectively designed overviews of randomized trials. Blood Pressure Lowering Treatment Trialists' Collaboration. Lancet. 2000;356:1955-1964. [Context Link]


53. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 suppl 1):S1-S290. [Context Link]


54. Andrawes W, Bussy C, Belmin J. Prevention of cardiovascular events in elderly people. Drugs Aging. 2005;22(10):859-876. [Context Link]


55. Schwartz AV, Hillier TA, Sellmeyer DE, et al. Older women with diabetes have a higher risk of falls: a prospective study. Diabetes Care. 2002;25:1749-1754. [Context Link]


56. Songer TJ. Disability in diabetes. In: Harris MI, Cowie CC, Stern MP, eds. Diabetes in America. 2nd ed. Bethesda, Md: National Institutes of Health; 1995:259-282. [Context Link]


57. Vokonas PS, Kannel WB. Diabetes mellitus and coronary heart disease in the elderly. Clin Geriatr Med. 1996;2:69-78. [Context Link]


58. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403. [Context Link]


59. Brown AF, Mangione CM, Saliba D, Sarkisian CA. Guidelines for improving the care of the older person with diabetes mellitus. J Am Geriatr Soc. 2003;51:S265-S280. AACE Diabetes Guidelines. Endocr Pract. 2002;8(suppl 1). [Context Link]


60. Gibbons RJ, Chatterjee K, Daley J, et al. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients with Chronic Stable Angina). J Am Coll Cardiol. 1999;33:2092-2097. [Context Link]


61. Ryan TJ, Antman EM, Brooks NH, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol. 1999;34:890-911. [Context Link]


62. Rich MW. Therapy for acute myocardial infarction. Clin Geriatr Med. 1996;12:141-168. [Context Link]


63. Ambrosioni E, Borghi C, Magnani B. The effect of the angiotensin-converting-enzyme inhibitor zofenopril on mortality and morbidity after anterior myocardial infarction. N Engl J Med. 1995;332:80-85. [Context Link]


64. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results from the Survival and Ventricular Enlargement Trial. N Engl J Med. 1992;327:669-677. [Context Link]


65. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993;342:821-828. [Context Link]


66. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342:145-153. [Context Link]


67. Antiplatelet Trialists Collaboration. Collaborative overview of randomized trials of antiplatelet treatment, I: prevention of vascular death, MI and stroke by prolonged antiplatelet therapy in different categories of patients. Br Med J. 1994;308:235-246. [Context Link]


68. Hennekens C, Dyken M, Fuster V. Aspirin as a therapeutic agent in CHD. A statement for healthcare professionals from the American Heart Association. Circulation. 1997;96:2751-2753. [Context Link]


69. Hass WK, Easton JD, Adams HP Jr, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. N Engl J Med. 1989;321:501-507. [Context Link]


70. CAPRIE Steering Committee. A randomised, blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329-1339. [Context Link]


71. Stewart R, Cooper J. Polypharmacy in the aged. Practical solutions. Drugs Aging. 1994;4(6):449-461. [Context Link]


72. Vik SA, Maxwell CJ, Hogan DB. Measurement, correlates, and health outcomes of medication adherence among seniors. Ann Pharmacother. 2003;38(2):303-312. [Context Link]


73. Haskell WL, Alderman EL, Fair JM, et al. Effects of intensive multiple risk factor reduction on coronary atherosclerosis and clinical cardiac events in men and women with coronary artery disease. The Stanford Coronary Risk Intervention Project (SCRIP). Circulation. 1994;89:975-990. [Context Link]


74. Campbell N, Ritchie L, Thain J, Deans H, Rawles J, Squair J. Secondary prevention in coronary heart disease: a randomised trial of nurse led clinics in primary care. Heart. 1998;80(5):447-452. [Context Link]