Cardiovascular Issues in the Older Adult
The Elderly and Peripheral Arterial Disease
This article is the fourth in a continuing series on cardiovascular issues in the older adult. The third article in the series, “Atrial Fibrillation in the Elderly: A Review,” was published in the May issue of Clinical Geriatrics. The remaining articles in the series, to be published in future issues of the Journal, will discuss such topics as heart failure, hypertension, and devices for heart rhythm disorders.
Peripheral arterial disease (PAD), defined as abnormal blood flow to the lower extremities, is a major cause of morbidity and mortality in the United States, especially among the elderly.1 Potential limb loss is one of the most recognized concerns in patients with PAD, but the link between PAD and cardiovascular disease may not be as widely appreciated. Without proper diagnosis and treatment, patients with PAD are at risk for poor outcomes, yet PAD is often underdiagnosed and undertreated. The reason for this disparity between the significance of PAD and the lack of optimal management is manifold, including insufficient vascular training and poor awareness of both the disease and its treatment options.2 These limitations may result in claudication being misinterpreted as a natural sign of aging, the underappreciation of atypical presentations of PAD, or the underdiagnosis of PAD in sedentary individuals. It is critical that we overcome these limitations since PAD, especially in older patients, carries significant risks of morbidity and mortality. This review focuses on the special considerations for elderly patients with PAD and how these considerations can affect the presentation, diagnosis, and treatment of PAD.
Diseases that disproportionately affect the elderly, such as PAD, have special significance for a variety of reasons. First, the US population is growing older; it is estimated that between 1900 and 1994 the number of people ≥65 years living in the United States increased eleven-fold while the nonelderly population increased only three-fold.3 It is projected that the number of elderly Americans will more than double to 80 million by the middle of this century.3 This creates important challenges such as meeting the higher demand for healthcare and adapting health systems to the nation’s changing needs. An aging population in good health will translate to better quality of life and prolonged independence for elderly individuals and less strain on the health systems. In order to promote healthy aging, it is imperative that we improve outcomes of diseases that affect the elderly.
PAD affects approximately 5 to 10 million Americans and is a leading cause of disability among people >50 years and among those with diabetes.4 The prevalence of PAD increases with age; it occurs in 3% of people <60 years, but its prevalence increases to 15% to 20% among individuals >70 years.5 PAD carries significant risks of pain, limited mobility, and adverse vascular outcomes such as stroke and myocardial infarction. Compared with the general population, patients with PAD have a three-fold increase in all-cause mortality and a six-fold increase in mortality from cardiovascular disease.5-7 Despite the significant risk of cardiovascular complications in patients with PAD, PAD is often overlooked or undertreated. As many as 46% of patients with PAD receive no risk factor control, partly because of limited appreciation for the cardiovascular risk seen in PAD.8
Risk factors for PAD can be categorized as modifiable or nonmodifiable (Table 19). Race clearly plays a role, as those of African descent are at an increased risk for the development and progression of PAD.6 However, the likelihood of developing PAD is more complex than simply possessing risk factors. In a study from the United Kingdom, people of South Asian descent had poorer risk factor profiles than the British population as a whole, but PAD was less prevalent in South Asian individuals than in white individuals in the general population.10 Further studies are needed to elucidate the intricacies of risk factor interactions. Meanwhile, it is important to minimize modifiable risk factors for PAD, including smoking, diabetes mellitus, hypertension, dyslipidemia, and sedentary lifestyle, through early identification and effective interventions.
PAD is often accompanied by arterial stenosis, a narrowing of the arteries that impairs blood flow. The effects of arterial stenosis are amplified in the elderly, who have baseline deterioration in oxidative capacity, muscle mass, and capillary density.11 The stenosis alters the distal pressure needed for muscle activity. When a peripheral limb is exercised, blood flow increases as a result of greater cardiac output and vasodilation at the tissue level. In claudication, resting blood flow is not impaired, but during exercise, blood flow does not increase sufficiently to meet muscle demand. When metabolic demands exceed available blood flow, patients experience claudication.9
In a healthy extremity, the mean blood pressure drop from the heart to the ankles is a few mm Hg. As the pressure travels distally, the systolic pressure increases due to the higher resistance from the smaller vessels. Thus, a healthy ankle may have a higher blood pressure reading than an arm and there should be no change in blood pressure with exercise. Arteries in an extremity afflicted with PAD, however, have either one or multiple stenotic segments that reduce pressure, resulting in lower blood pressure at the ankle than that of a healthy extremity. In patients with PAD, this pressure difference becomes more pronounced with exercise.7,9 This is the basis behind the ankle-brachial index (ABI).
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The diagnosis of PAD often begins with symptoms of muscle fatigue, discomfort, or pain in leg muscles when walking. Up to 50% of patients with PAD are asymptomatic, and 30% to 40% have atypical leg pain or pain at rest.5,6,12 Atypical leg pains often seen in the elderly include limb heaviness, numbness, or soreness. In 5% of cases, PAD leads to ischemic ulcers or gangrene.6 In patients with leg ulcers, PAD is underdiagnosed as the etiology, leading to delayed therapeutic referral and occasional iatrogenic harm from the use of compression therapy with elastic bandages, a treatment contraindicated in patients with PAD.13
When evaluating an elderly patient, the routine review of systems should include asking about the patient’s history of limb symptoms.6 Once a history of intermittent claudication is established, it is crucial to determine how much exercise triggers the onset of pain. This can be measured in terms of street blocks and helps to establish a baseline against which to measure improvement with therapy. To help distinguish vascular claudication from the neurogenic claudication seen with spinal stenosis, it is important to establish whether the pain is reproducible within the same muscle groups and whether it ceases within 2 to 5 minutes; symptoms from spinal stenosis may take longer to resolve.9 The location of the pain may help to predict the sites of the arterial lesions. For example, PAD is most common in the distal superficial femoral artery and causes pain in the calf muscles; PAD in the aortoiliac arteries affects the thigh and buttock muscle groups.9
Just as patients who present with chest pain or transient ischemic attack would be evaluated for vascular disease, patients who present with claudication should also be assessed for vascular disease elsewhere. Their cardiovascular disease risk factors should be managed aggressively.6
There are several different modalities for diagnosing PAD (Table 26,14).
Digital Subtraction Angiography
Digital subtraction angiography (DSA) remains the gold standard for assessing PAD. DSA is a relatively invasive procedure that allows visualization of even poorly opacified distal vessels. Inherent risks of DSA include hemorrhage, infection, arterial dissection, and cholesterol embolization. The iodinated contrast dye used may also induce an allergic reaction or cause nephropathy. The risk of developing nephropathy is greater in patients with underlying renal insufficiency. Carbon dioxide is sometimes used as an alternative contrast agent when performing DSA in patients with renal insufficiency, but it greatly limits the diagnostic value of the examination. Because of these risks, DSA is only indicated when intervention is expected.6
The ABI should be the first diagnostic test used in patients with clinically suspected PAD. It is quick and inexpensive and can be easily performed in an outpatient office setting (Table 39).
The ABI is measured while the patient is in a supine position, with a blood pressure cuff placed around the ankle. The cuff is inflated and deflated as a handheld Doppler device is used to measure systolic pressure in the posterior tibial artery and in the dorsalis pedis artery. The higher of these two ankle readings is then divided by the higher of two upper extremity brachial pressure readings to determine the ABI for each lower extremity. An ABI of 1.0 to 1.29 is considered normal, and an ABI of 0.91 to 0.99 is considered borderline or equivocal. An ABI value of between 0.41 and 0.90 suggests mild to moderate PAD, while a value of ≤0.40 suggests severe disease.6
The ABI contributes diagnostic and prognostic information. Having an ABI of ≤0.90 nearly doubles a patient’s 10-year risk of all-cause mortality, cardiovascular mortality, and major coronary events as compared with overall risk for these events across all risk categories of the Framingham Risk Score.6,15 Lower ABI scores are also associated with a worse prognosis.6,7
The ABI has been validated as a diagnostic tool and has an approximate sensitivity of 79% to 95% and specificity of 96% to 100%.6,16,17 The diagnostic sensitivity of the ABI measurement can be increased by adding provocative exercise testing. A typical protocol calls for measuring ABI before and after the patient walks on a treadmill at 2 miles per hour with a 10% to 12% incline until the onset of claudication pain or until 5 minutes have elapsed.5,18
Contraindications to exercise testing include a history of advanced heart failure, advanced chronic obstructive pulmonary disease, uncontrolled hypertension, severe aortic stenosis, or evidence of chest pain or shortness of breath with minimal to no exertion.5,18 Alternatively, active pedal plantar flexion while standing may be useful for patients who are unable to undergo treadmill testing.19
ABI values of ≥1.30 are not diagnostic and are observed in patients with diabetes, renal insufficiency, and advanced age—presumably due to stiff, calcified, noncompressible vessels. In these patients, the toe-brachial index (TBI), which is measured using a small cuff on the proximal aspect of the great or second toe, may be useful because medial calcinosis generally spares the digital vessels.20 A TBI of <0.70 is considered suggestive of PAD.5,6 Interestingly, studies have also associated an ABI of >1.40 with higher mortality risk.6,7
Some experts believe that ABI screening should be recommended for all patients age >70 years and for those between the ages of 50 and 69 years who have a history of smoking or diabetes.6,7 However, the U.S. Preventive Services Task Force says that there is insufficient evidence to recommend routine ABI screening.21
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Segmental Pressure Measurements
Taking the concept of the ABI a step further, blood pressure cuffs can be placed sequentially down a lower extremity rather than just at the ankle. With this method, the cuffs are generally placed in four positions: the upper thigh, lower thigh, upper calf, and lower calf. A pressure gradient of 15 to 30 mm Hg or more across adjacent segments is suggestive of arterial stenosis localized to that region.22 This examination, as with the ABI test, is not useful in patients with noncompressible vessels.
Pulse Volume Recording
In addition to measuring segmental pressures, blood pressure cuffs can be used to evaluate the pulsatility of vascular inflow. The cuffs are inflated and connected to a plethysmographic device to measure changes in limb volume with each cardiac cycle. If the pulse volume recording (PVR) shows decreases in upstroke and amplitude of the measured tracing as compared with PVR measured using a brachial cuff as the reference standard, stenosis might be affecting the proximal arterial segment. The PVR is useful as an adjunct to segmental pressure measurements since it is effective in patients with noncompressible vessels. Both examinations are commonly used together, which increases diagnostic accuracy to as high as 97%.23
Doppler ultrasound (DUS) is the only imaging method that is completely safe. DUS has the advantage of not only providing anatomical information regarding any stenosis found, but also allowing assessment of its hemodynamic significance based on the Doppler characteristics of flow across the stenosis. Sensitivity and specificity can reach ≥90%, but the examination relies on satisfactory visualization of the arteries.24,25 DUS is a time-consuming procedure, and diagnostic quality is operator-dependent. Some centers use DUS for preoperative planning, but they frequently complement it with additional imaging studies, negating any theoretical cost advantages of DUS.26,27
Magnetic Resonance Angiography
Contrast-enhanced magnetic resonance angiography (MRA) is a widely accepted technique for imaging peripheral vascular disease. It is noninvasive but has a sensitivity and specificity of >90% as compared with angiography.28 MRA is unsafe to use with most pacemakers and certain medical devices and therefore some patients are excluded from undergoing this diagnostic procedure. In addition, the smaller size of the bore used in MRA can elicit claustrophobia in a small proportion of patients. The gadolinium contrast agent used with MRA was previously believed to be free of the nephrotoxic effects associated with iodinated contrast, and, in fact, gadolinium was sometimes used as an alternative contrast agent for DSA in patients with renal insufficiency. We now know that gadolinium can induce nephrogenic systemic fibrosis in patients with renal insufficiency, a potentially fatal condition.29 This is a particularly troubling development since patients with PAD often have concomitant renal disease. Noncontrast MRA techniques are currently investigational.
Computed Tomography Angiography
Computed tomography angiography (CTA) compares favorably with MRA as an alternative diagnostic tool, although it does involve the use of a potentially nephrotoxic iodinated contrast agent. Sensitivity and specificities achieved with CTA are also >90%.30 CTA has the added advantage of surveying the surrounding tissues and has demonstrated that some popliteal artery stenosis and occlusions are due to aneurysms, popliteal entrapment, and cystic adventitial disease.31 CTA can be the default fallback diagnostic tool for patients with metallic devices, and it is less susceptible than MRA to image artifact from clips, stents, and prosthesis.
While recommendations for the prevention and treatment of PAD do not vary based on age, elderly patients with PAD may be less likely to receive the recommended therapy. In elderly patients, leg symptoms may be overlooked as signs of aging even though older patients with PAD are more likely to be asymptomatic due to a reduced level of activity; hence, symptomatic elderly patients may have advanced disease.1 Poor risk modification may place patients at risk for disease progression and the need for revascularization.
One of the most effective, inexpensive—and often neglected—interventions for PAD is a supervised exercise program. Exercise programs that are structured and supervised are effective at improving symptoms of claudication, especially among the elderly. This is especially true for patients with intermittent claudication.32 In a study of patients with a mean age of 68 years, exercise programs significantly increased the distance they could walk before experiencing pain.33 Even small modifications in physical activity level can slow the progression of PAD-associated physical disability. Of note, unsupervised exercise programs have consistently been found not to improve claudication symptoms.34 However, a lack of resources and referral options can be barriers to accessing a supervised exercise program.
Medical management of PAD should also focus on lowering cardiovascular risk with therapies to help manage lipids, hypertension, and diabetes. A treatment program needs to include tobacco cessation efforts and cholesterol therapy, with the goal of reducing low-density lipoproteins to <100 mg/dL, and antiplatelet therapy should be considered.7
Tobacco cessation is crucial because tobacco use is a critical risk factor for increasing progression of PAD, event rates, amputations, and costs. Treatment options include behavior modification therapy, over-the-counter nicotine replacement products, and medical therapies such as bupropion and varenicline. A recent randomized controlled trial concluded that an intensive smoking cessation program was associated with a major increase in smoking abstinence among patients with PAD.35 The study’s intensive smoking cessation program included educating patients about the association between smoking and PAD, cognitive-behavioral counseling, providing information on pharmacologic treatments, and securing a tobacco-cessation sponsor from the patient’s social network. In comparison, the control group received only verbal advice to quit smoking and a list of smoking cessation programs; only 6.8% of participants in the control group quit smoking compared to 21.3% in the intensive program.35
Antiplatelet therapy, such as clopidogrel or aspirin, remains controversial. A meta-analysis concluded that treatment with aspirin alone or with dipyridamole resulted in a statistically nonsignificant decrease in cardiovascular events, the study’s primary end point.36 However, antiplatelet therapy did result in a significant reduction in nonfatal stroke.36 A reasonable approach would be to use aspirin in those patients with PAD and additional evidence of cardiovascular disease.
Current guidelines also support the use of cilostazol to help improve exercise performance in patients with claudication. TransAtlantic Inter-Society (TASC)-II guidelines recommend first-line pharmacotherapy with cilostazol for 3 to 6 months to treat claudication.5 Cilostazol is not as effective as a supervised exercise training program, however, and may cause headaches; it is also contraindicated in those with congestive heart failure.6 Previously, pentoxifylline was considered an alternative to cilostazole, but it has been shown to have only marginal clinical effectiveness.6
Important consideration must be given to diagnosing and treating leg ulcers properly in patients with PAD. Many leg ulcers associated with PAD do not heal with conservative measures, and the majority of these patients benefit from revascularization. Past studies have suggested that conservative wound healing may not be possible in patients with an ankle pressure of ≤80 mm Hg, although it is likely that ankle pressure alone is not a sufficient basis for making such a prognosis.13 The presence of leg ulcers should prompt a thorough vascular assessment of the patient and an appropriate referral to initiate a step-wise therapy plan that could lead to eventual revascularization. Referral to a vascular specialist is indicated for patients with severe symptoms and for those with critical limb ischemia, indicated by rest pain, a nonhealing ulcer due to impaired perfusion, or gangrene.6
Although bypass surgery remains an important treatment option for severe PAD, many patients are ineligible because they have diffuse arterial occlusions, no suitable veins for grafting, and multiple underlying comorbidities.37 Minimally invasive interventional radiological (IR) procedures can be equally as effective as surgery and may impart less mortality and morbidity.6,38,39 This is especially important for elderly patients, who are often poor surgical candidates due to comorbidities. Additionally, IR procedures may be repeated as needed and used to revascularize multiple vessels. Unfortunately, short-term angiographic vascular restenosis is high with IR, and infrapopliteal occlusion has a 1-year recurrence rate of 50%, resulting in a high number of repeat procedures.39,40 IR procedures remain an option for very frail elderly patients, however.
While infrapopliteal use of bare metal stents is safe, it is associated with significant neointimal hyperplasia and early restenosis.38,40,41 The success of drug-eluting stents in coronary arteries has led to increased use of drug-eluting stents in the peripheral arteries, and recent clinical data show favorable results at 6- and 12-month follow-up, with significantly higher angiographic patency and fewer reinterventions as compared with the use of bare metal stents.39,40
Other Special Considerations in the Elderly
As the US population ages, diseases that affect the elderly are likely to rise in prevalence. In particular, dementia is predicted to impose a significant disease burden on the elderly and on healthcare costs. There is strong evidence that atherosclerotic vascular disease plays a role in the onset and progression of cognitive impairment. Studies have shown that PAD is an independent risk factor for increased cognitive decline.42 Hence, optimal treatment targeted at primary and secondary prevention of PAD is important when seeking to preserve cognitive function.
Another special consideration with the elderly population is the expanding disproportion in the ratio of women to men. The ratio of women to men is high in this demographic and continues to increase in the oldest elderly age group.3 As a result, it is becoming increasingly common to see women with morbidities due to diseases that are more prevalent among the elderly, such as PAD.32 Efforts to improve PAD detection and risk factor modification should include such topics as the potential harmful effects of hormone replacement therapy (HRT) on peripheral vascular events and procedural outcomes. As the prevalence of cardiovascular disease correlates positively with age in women, and it has been suggested that estrogen might have vasoprotective properties.32 However, multiple large trials have failed to demonstrate beneficial effects from HRT on PAD.32,43 Since most women who present with PAD are postmenopausal, it is important to counsel patients that HRT is unlikely to protect against the development of PAD. HRT may also place patients at risk for poor procedural outcomes because of increased risk for thromboembolic events following a vascular intervention.43
PAD is a major public health burden and accounts for a large proportion of vascular disease in the United States. PAD is associated with increased morbidity and mortality and should not be considered part of the normal aging process. With an estimated prevalence of 15% to 20% in those ≥70 years, the overall prevalence and burden of disease will continue to grow as the US population ages. PAD is currently underdiagnosed and undertreated, yet there are simple, effective ways to screen for, diagnose, and treat PAD. If PAD becomes severe, surgery is an option; however, advanced age and concomitant illness may be a deterrent to surgery. Recent improvements in percutaneous interventions, along with appropriate medical therapy, offer hope to individuals with PAD, particularly elderly patients.
The authors report no relevant financial relationships.
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