A 52-Year-Old Woman With Diabetes and Claudication

DR DALEY: Mrs D is a 52-year-old mother of 2 children who has progressive pain in her right leg while walking. She lives in Boston and has her health care insurance through Massachusetts Medicaid and Medicare.

Mrs D has had insulin-dependent diabetes mellitus for 29 years, complicated by peripheral neuropathy, retinopathy, and nephropathy with nephrotic range proteinuria. She has had 1 atrophic kidney since childhood and has required chronic hemodialysis since June 1997. She has had hypertension since age 16 years. The patient has long-standing coronary artery disease with a history of 2 myocardial infarctions. She had percutaneous transluminal angioplasty for chronic angina without relief, followed by coronary artery bypass graft for triple vessel disease, including significant stenosis of the left anterior descending artery, in June 1997. She had an episode of congestive heart failure in 1995 with an ejection fraction of 0.25. She has hyperlipidemia and has tried several lipid-lowering agents, but has been unable to tolerate them because of adverse effects. Most recently she discontinued treatment with gemfibrozil because of gastrointestinal side effects. She has an 80 pack-year history of smoking and stopped smoking in the summer of 1997. Family history is significant for her father who died of coronary artery disease at age 53 years and for her mother who had diabetes mellitus, coronary artery disease, and renal failure requiring dialysis.

Mrs D also has temporal lobe epilepsy and has experienced several episodes of major unipolar depression requiring hospitalization. She has a multinodular goiter and is euthyroid. She has a history of peptic ulcer disease, chronic gastroparesis, and gastroesophageal reflux disease with severe, chronic nausea.

Despite her multiple, chronic illnesses, Mrs D has been an avid sportswoman and athlete since childhood. In the spring of 1997, she noted right calf pain and cramping when running to first base during softball games. She then developed progressive pain in her right leg after walking 25 to 35 ft. She notes the onset of pain after walking for 1 minute, and after walking 25 ft, describes the pain as severe. The pain limits her activities; for example, she now parks closer to her destinations because she cannot walk more than 10 to 25 ft without experiencing disabling pain. She has no rest or nocturnal pain.

Her current medications include furosemide (80 mg daily), metoclopramide hydrochloride (10 mg daily), NPH insulin, aspirin (325 mg daily), cisapride (10 mg 4 times daily), phenytoin (100 mg 3 times daily), metoprolol tartrate (50 mg twice daily), and epoetin alfa on dialysis.

On physical examination, Mrs D is pale and appears chronically ill but not depressed. Vascular examination is significant for bilateral carotid bruits and an absent right popliteal and pedal pulse. Vascular access for dialysis has been placed in both arms. Laboratory examination is significant for the following levels: serum urea nitrogen, 30.3 mmol/L (85 mg/dL); creatinine, 522 µmol/L (5.9 mg/dL); random blood glucose, 9.1 mmol/L (164 mg/dL); fasting total cholesterol, 5.61 mmol/L (217 mg/dL); high-density lipoprotein, 1.32 mmol/L (51 mg/dL); low-density lipoprotein, 3.57 mmol/L (138 mg/dL); triglycerides, 1.58 mmol/L (140 mg/dL); and hematocrit, 0.33.

Noninvasive studies of her carotid arteries show a 60% to 69% stenosis of the left carotid artery. Pelvic contrast magnetic resonance angiography showed a 70% stenosis of the left common iliac artery, 30% to 40% stenosis of the right common iliac artery, and an occlusion of the right popliteal artery just above the knee joint. Lower-extremity magnetic resonance angiography showed an obstruction of the distal right superficial femoral artery about 8.5 cm above the knee joint with good reconstitution. The trifurcation and the remaining vascular structures of the lower extremities appear normal.

A vascular surgeon diagnosed claudication in her right leg secondary to superficial femoral artery disease and recommended surgery. A trial of exercise was unsuccessful because Mrs D developed leg pain so severe she was unable to walk and angina. Mrs D has largely recovered from her coronary bypass surgery, aside from some vascular access problems, and she is awaiting surgery for claudication.

MRS D: One day I was walking along, then all of a sudden I started to cramp up badly and could not go any further. This happened more than once, and I realized there was something severely wrong. It was a turning point for me because I could deal with everything else I had, but when it came to this really debilitating condition, it just set me back. It scared me, and I realized I had to do something. I knew I needed some heart work done, but I had put it off because I knew that if I did it, I would wind up on dialysis. But I gave in to it because I want my leg fixed so badly.

You can't do these surgeries all at once. The whole point is I want to be able to walk. I need that normalcy, because it takes everything away from me. It restricts me from going anywhere. People have no idea how much it matters when you can't walk. I can now go about 35 ft, but coming back 35 ft is tough. It's nerve-wracking, because it makes you feel old. And it enlightens you when you realize that something is stopping you from walking. It scared me quite a bit.

I consider myself a reasonably strong person and able to handle things. But when you don't have control of your health, don't know what's going to happen, and have a doctor that you're unsure of, you lose some control over your life. That can do things to you. I think a lot of patients get so scared that they bring on more symptoms of other things. I've seen people in hospitals be frightened because they're not communicating with their doctors, or the doctors are not communicating with them.

DR S: Mrs D is a middle-aged woman I've known for about 5 years. When she first came to me, her main issues were diabetes and chronic heart disease. She had a couple of heart attacks in the preceding few years. She was an avid smoker. She also had some renal insufficiency, in part because of a congenital problem and also diabetes. She also had significant nausea and gastrointestinal problems. There were a number of active issues, as well as some inactive ones such as her temporal lobe epilepsy, and she was taking a host of medications.

When I first met her, despite her smoking history, cardiac history, and some unstable angina, she was interested in participating in competitive sports. She was participating on a local softball team. Even at that time, she was having some significant calf cramping with exercise when running to first base, but she was still trying to do it. Over the years, the peripheral vascular disease issue was sidelined by progressive renal insufficiency, coronary disease, and development of more significant chest pain. Recently she became concerned, however, because her right calf problems became much worse. They now limit her from doing even her usual day-to-day activities, let alone her sports.

Mrs D is an incredibly strong woman. She has weathered many different storms during her lifetime. With regard to her medical condition, she has had repeated challenges from dealing with her diabetes, to dealing with heart disease over a long period, to dealing with dialysis, to now dealing with a problem with an arteriovenous fistula that is not functioning well. She has some ischemic symptoms in her hand and is looking toward another surgery for this peripheral vascular disease. She has certainly experienced mood swings and has felt depressed. But overall, given everything that she has had to deal with, she is actually doing quite well.

It would be helpful for me as a primary care doctor to have a vascular surgeon's perspective on when arteriography is warranted and also when proceeding to surgery is warranted. Often our patients have what they consider intolerable symptoms, but they are still able to walk, push themselves to the point of pain, and get around. When do you decide to try to do something anatomically to fix this problem?

What are the epidemiology, prevalence, and pathophysiology of occlusive peripheral vascular disease? What are the options for medical and/or surgical therapy for this patient? What can she expect in terms of restoration of functional status and relief from pain after treatment? What does the future hold for the diagnosis and treatment of atherosclerotic peripheral vascular disease? What would you recommend for her? What can she expect in the future?

DR MCDANIEL: Though not all patients with symptoms from lower-extremity arterial insufficiency are as medically complicated as Mrs D, intermittent claudication is a common problem in general practice, since it is present in 5% to 7% of the US population older than 65 years.¹

Patients with lower-extremity arterial occlusive disease (LEAOD) exhibit a wide variety of clinical presentations, from those with definite but hemodynamically insignificant disease with no symptoms to those with complete arterial occlusion and gangrene requiring amputation. Patients with advanced anatomic LEAOD may vary widely in the severity of their reported symptoms because (1) atherosclerotic plaque must occupy at least 75% of the arterial lumen before it significantly affects blood flow, (2) many individuals with significant axial arterial occlusion develop collateral blood supply sufficient to alleviate symptoms substantially, (3) symptoms occur in direct proportion to the patient's attempted activity level, and (4) perceptions of discomfort differ among individuals.

Decision making is relatively straightforward at the extremes: patients with minimal disease and no symptoms require no active intervention, while those with extensive gangrene may require major amputation to salvage their lives. A large group of individuals, however, has disease of intermediate severity for whom decision making and prognostication are not easy given our present state of knowledge. Mrs D and patients with claudication like her are members of that group.

The most common initial symptom of LEAOD, as was true in Mrs D's case, is intermittent claudication. Derived from the Latin claudicare, to limp, the salient features of this symptom complex were defined by the World Health Organization Expert Committee on Cardiovascular Diseases and Hypertension, then formalized in the epidemiological work of Rose (Table 1).² Each criterion is designed to exclude patients with lower-extremity pain not related to arterial insufficiency: pain originating in a joint, neuropathic pain, and spinal stenosis with neurogenic claudication. This simple sequence of questions is reasonably specific but not completely sensitive in identifying patients with claudication of arterial origin. In Rose's pilot work,² 34 (92%) of 37 patients with documented intermittent claudication (and none of 18 controls) were identified as having intermittent claudication by the questionnaire. In subsequent work comparing this methods of case identification with objective diagnostic methods and physician interview^{3 - 4} (McDaniel, unpublished data, 1992), however, the Rose questionnaire would have identified only 30% to 60% as having intermittent claudication.

Because the long-term implications for patients with stable intermittent claudication like Mrs D are quite different from those for patients with more severe arterial insufficiency, clinicians making this diagnosis need to ensure that the ischemia is not so severe as to cause pain at rest (and therefore oxygen supply [to the foot] is never sufficient), or so severe as to be associated with loss of tissue either spontaneously or from minor trauma. The latter characteristics warrant urgent referral for consideration of revascularization because of the risk of limb loss.⁵

For many patients, as for Mrs D, the development of intermittent claudication is perceived mainly as a functional limitation and not as a manifestation of significant systemic disease. Clinicians should recognize the symptom as much for its systemic prognostic significance as for its functional significance.

Patients are typically about 66 years of age by the time they develop symptomatic intermittent claudication from atherosclerosis.⁶ The presence of intermittent claudication identified by the Rose² questionnaire approximately triples the cardiovascular mortality rate during follow-up.⁷ When objective measures rather than questionnaires are used to identify patients with LEAOD, however, the relative risk of cardiovascular death during follow-up compared with age-matched controls without LEAOD increases to about 7.⁸ Overall, the mortality rate for patients with symptomatic intermittent claudication is about 7% per year of follow-up, with death due to cardiovascular disease in about 80% of cases.⁶ Following infrainguinal bypass, the presence of diabetes (all other significant variables being equal) increases the relative risk of late (>30 days) death by about 2-fold.⁹ End-stage renal disease requiring hemodialysis is associated with an annual mortality of about 15% per year,¹⁰ which is increased by preexisting cardiac disease¹¹ and diabetes.¹² Although a patient's main concern is frequently the lower-extremity symptoms, we should concern ourselves also with the systemic disease. Prognostication for individuals is fraught with hazard, but Mrs D's annual mortality risk is greater than that of other patients with claudication, but without her extensive comorbidities.

The folk wisdom is that intermittent claudication that manifests itself at a young age carries an even more ominous prognosis than when it appears in the older population. The younger patient with LEAOD is relatively rare, however, a host of congenital and nonatherosclerotic causes can lead to the development of lower-extremity ischemia. Some, such as popliteal entrapment, are easily treated and are not manifestations of a systemic disorder. Systemic abnormalities leading to diffuse arterial occlusive disease are much more serious¹³ and need to be considered when a young patient complains of intermittent claudication. Hyperlipidemias, hypercoagulable states, hyperhomocysteinemia, and elevated levels of lipoprotein(a) have all been identified in patients who develop symptomatic atherosclerosis before age 45 years, and clearly have systemic implications if found to be causative of the LEAOD. Hyperlipidemia can lead to systemic atherosclerosis,¹⁴ and increasing evidence also demonstrates that elevated levels of lipoprotein(a)¹⁵ and hyperhomocysteinemia¹⁶ are causative factors in the development of atherosclerosis. Evidence that other hypercoagulable states, such as congenital deficiencies in endogenous anticoagulants, cause premature atherosclerosis is less firm,^{15 ,17} though when present, such deficiencies seem to worsen the outcome of treatment for LEAOD.^{18 - 19} Hyperhomocysteinemia, relatively inexpensive to screen for and easy to treat in patients with normal renal function with small doses of vitamin B₆ or folic acid,²⁰ should be screened for in any patient who develops manifestations of atherosclerosis before reaching 50 years of age. Special consideration must be given to the possible existence of hyperhomocysteinemia in dialysis-dependent patients with chronic renal failure such as Mrs D, because the prevalence of homocysteine levels greater than the 95th percentile of normal is 85% in this group.²¹ Though the relationship between hyperhomocysteinemia and atherosclerosis is under debate,²² there is strong evidence^{21 ,23} that it may be an independent risk factor for symptomatic atherosclerosis in patients with end-stage renal failure and therefore may warrant treatment. Higher doses of folate (as much as 10 mg/d²⁴ rather than 0.65 mg/d²⁵ ) are required to normalize homocysteine levels in the presence of renal failure.

Mrs D is relatively young and wishes to be physically active both playing softball and looking after her grandchildren, so she has important concerns about her lower-extremity symptoms. Pooled data from large published series⁶ indicate that, in general, intermittent claudication portends only a modest risk of limb loss, with major amputation ensuing at a rate of less than 1% per year of follow-up. Data obtained from survivors with continued claudication show considerable variability in continued symptoms: from 31% to 63% may be improved or stable, and from 8% to 47% may develop worse claudication. The presence of diabetes may darken this relatively benign prognosis, increasing the likelihood of symptom progression in 5 years from 19% to 35%^{26 - 27} and the chance of major amputation in 5 years from 3% to 21%.^{27 - 28} Unfortunately, existing literature does not support creating a prediction rule robust enough to guide Mrs D's decision making by helping her to understand the probable course her symptoms will take without specific treatment.

Current treatment options for intermittent claudication are myriad and can generally be characterized into 2 classes: treatment of the claudication symptoms alone or treatment of the anatomic arterial obstruction as a means to treat the symptoms.

Patients and physicians often find it more attractive to treat a symptom with medication and than with a lifestyle change. For intermittent claudication, only 1 drug, pentoxifylline, has proven effective enough to be approved for this use by the Food and Drug Administration. This drug has many effects, including inhibition of platelet degranulation, decrease in circulating fibrinogen level, decrease in neutrophil aggregation, and increase in erythrocyte membrane fluidity,²⁹ but the precise mechanism by which it can increase pain-free walking distance is not known. It is therefore difficult to predict which patients might benefit from its use. Overall, depending on age, sex, comorbidity profile, and duration of symptoms before starting therapy, about two thirds of patients with claudication can expect the drug to increase pain-free walking distance by at least 50% within 8 to 24 weeks.³⁰ However, the magnitude of its effect may not seem clinically important to patients. Of a series of 130 patients with claudication taking pentoxifylline,³¹ less than 20% found the medication effective enough to be worth paying for the drug after a trial period of use.

Though it is tempting to believe that vasodilator therapy might be useful in the treatment of intermittent claudication, its efficacy has not been demonstrated in randomized blinded trials because the physiological vasodilation that occurs in response to ischemia is likely the maximum that can be achieved. Antiplatelet and anticoagulant strategies have proven similarly ineffective, though the former clearly has a longevity benefit in the presence of concurrent coronary occlusive disease.³² Many drugs have been tested for efficacy in intermittent claudication, but to date none has consistently had the desired effect.³³ Levopropionylcarnitine (thought to improve skeletal muscle utilization of metabolic substrates) and cilostazol (a phosphodiesterase inhibitor) are undergoing further clinical trials of their efficacy in improving walking distance for intermittent claudication.

Exercise therapy is perhaps a more efficacious treatment for symptoms of intermittent claudication, because it offers systemic benefits as well as the opportunity to expose patients to new ideas about self-care. Even a patient's best intentions will often flag, so, if available, a supervised exercise program is preferable.³⁴ The program should focus mainly on walking, but may include strength training and general conditioning, as well as a health education component. Most patients with claudication, without comorbid conditions that limit walking, can expect to double their pain-free walking distance by participating for at least 12 weeks in such a program.³⁴

Taking the direct approach of reducing symptoms by modifying the anatomical cause has great theoretical appeal for the active patient, such as Mrs D, whose main concern is the limitation of walking distance. Various alternatives, both percutaneous and open, exist. At present, in routine clinical practice, the more widely used percutaneous options include various combinations of thrombolysis, balloon angioplasty, rotational atherectomy, and stent placement. Percutaneous performance of bypass grafts remains experimental in 1998. The range of possible options and variation in the anatomy of individual patients make prediction of probable short- and long-term results difficult. The more experience the profession has with a therapy, the better estimation one can make of probable results.

The results of balloon angioplasty of arteries under various conditions are the best quantified of these techniques in the literature.^{35 - 36} Primary care physicians must keep in mind that percutaneous interventions are most likely to be successful in focal lesions (with stenosis yielding a more favorable outcome than short-segment occlusions) and in vessels with high flow rates. Percutaneous interventions are thus attractive for the treatment of intermittent claudication because patients with this moderate symptom complex are more likely to have a mild burden of disease than patients with limb-threatening ischemia. Complication rates of percutaneous interventions by experienced practitioners are also low. Mrs D's predominant lesion, a relatively unusual one, is a short segment occlusion of the superficial femoral artery, which may be treated with thrombolysis and balloon angioplasty or stent: in this case, expected patency rate at 2 years is between 40% and 60%.^{35 ,37 - 38} She might expect a complication rate of about 3%,³⁵ a mortality rate of about 1%,³⁵ and a relatively short time to functional recovery (several days at most).³⁵

The results of open surgery for intermittent claudication for patients like Mrs D are well quantified regarding graft-artery patency and the risk of operative death or limb loss, but poorly quantified regarding overall functional outcome. Typically, patients with intermittent claudication will require either aortofemoral reconstruction or femoropopliteal bypass to achieve relief of symptoms. From aortobifemoral bypass (independent of indication for surgery), patients without diabetes and renal failure should expect more than 85% 5-year graft patency and 60% 5-year survival, with little risk (5% to 6% at 2 years' follow-up) of limb loss and about 5% operative mortality risk.³⁹ Depending on the graft material, patients undergoing femoral to supragenicular popliteal bypass for claudication can expect between 65% and 85% 5-year primary graft patency.³⁵ The risk of limb loss in this specific population is not known, but is generally considered low and roughly similar to the nonoperated population of patients with claudication. Operative mortality for infrainguinal bypass is between 1% and 5%.³⁵ When retrospectively interviewed, 80 (82%) of 97 patients undergoing various open procedures for claudication reported satisfaction with the results of their operations.⁴⁰ How these results pertain to Mrs D, given her multiple comorbidities, is uncertain.

Postoperative recovery time from any operation is idiosyncratic, but patients typically require 4 to 6 weeks to recover full function from any open revascularization. Perioperative complications are not uniformly reported, making relative quantification among operation types difficult.⁴¹ The estimate for risk of complication following infrainguinal bypass (3% to 13%) derived from literature review by Hunink et al³⁵ seems appropriate as a baseline. The need for postoperative endocarditis prophylaxis is determined by whether prosthetic material is implanted. Long-term incisional pain and bothersome chronic lower extremity edema are not prominent problems, but do play a small role in choosing between open revascularization and other potential therapies.

A patient's decision to undergo intervention for intermittent claudication occurs at a perceived threshold where pain and functional limitations are great enough to risk the morbidity and mortality of the intervention. Determining where this threshold is reached can be problematic. It requires knowledge of (1) the probability of immediate death, limb loss, or other complications occurring as a result of the intervention; (2) the probability that pain and functional limitations will progress, remain stable, or improve without specific intervention; and (3) the probabilities that pain and functional limitations will improve, remain stable, or worsen with the intervention.

Opinions in the medical community differ about the optimal therapy for intermittent claudication. In 1988, we surveyed family practice physicians about the care of a 68-year-old man with uncomplicated claudication. These clinicians were members of the Dartmouth Primary Care Cooperative Information Project, a group of freestanding medical practices engaged in primary care delivery and research,^{42 - 43} including the development and testing of measures of functional health.^{44 - 45} A prototypical patient with claudication was described (Table 2). Questions were then posed about the appropriateness of referral to a vascular surgeon and whether the primary care clinician would agree with the surgeon's recommendation for angioplasty or bypass. The response to our survey (Table 2) demonstrated a clear lack of consensus concerning the appropriate action to be taken for this hypothetical patient, confirming great variability among physicians in the management of claudication.

Some new data are now available to bear on Mrs D's decision. A small study of patients with claudication and short femoral or iliac stenoses or occlusion, randomized either to percutaneous angioplasty or to aspirin therapy and "advice on smoking and exercise," demonstrated no significant difference between these treatments after 2 years with regard to walking distance or quality of life.⁴⁶ A careful formal decision analysis of a 65-year-old man with concomitant coronary artery disease and an occluded superficial femoral artery indicates that some improvement in quality-adjusted life expectancy (6 to 7 years as opposed to 4.5 years) can be gained by either angioplasty or bypass as opposed to no treatment.⁴⁷ Unfortunately, the latter analysis did not consider a structured exercise program.

Mrs D has claudication, not imminent limb threat, and a good deal of determination to continue to be active. She also has comorbid conditions placing her in a high-risk group for both early mortality and suboptimal outcome of intervention for her lower-extremity disease. Chief among these risk factors is her chronic renal failure. Debate rages in the vascular surgery literature about whether to offer limb revascularization to patients with limb threat and chronic renal failure, given the generally dismal results (90% operative and 38% 2-year survival).⁴⁸ Whether these data pertain to Mrs D, who is not in a limb salvage situation, is not known.

Mrs D is in a difficult situation. She has severe systemic disease and highly symptomatic, though not presently limb-threatening, LEAOD. She has a hemodynamically significant, though asymptomatic, left common iliac stenosis, multiple levels of right lower-extremity disease (at least common iliac and superficial femoral-popliteal artery occlusion), and an asymptomatic but hemodynamically significant left internal carotid artery stenosis.

Mrs D needs, in concert with Dr S and other advisers she trusts, to consider the big picture—the probable duration of her life and the qualities she wishes her life to have. If walking is her most important priority, she might better increase her walking distance by engaging in a structured exercise program than by embarking on anatomic interventions, given the multiple sites of her anatomic disease and its bilaterality. Should such a program fail to allow her the mobility she desires, further investigation concerning the hemodynamic significance of the right iliac artery stenosis would inform a decision about whether this needs to be addressed before considering options for relieving the superficial femoral artery occlusion. Regardless of the choice she makes concerning her lower extremities, she needs to learn about the symptoms of cerebral ischemia and perhaps participate in a surveillance program for her carotid artery disease.

If Mrs D had failed an exercise program and were willing to risk graft failure to gain more blood flow and improve walking distance, and if the right iliac artery lesion proved not to be hemodynamically significant or was durably treatable by balloon angioplasty, she would have a choice between percutaneous interventional strategies and femoral-popliteal bypass. She has an anatomically unusual lesion (a short segment of distal superficial femoral artery occlusion with normal runoff), which might make balloon angioplasty a tempting first step. Overall, however, angioplasty for claudication with superficial femoral artery occlusion has a worse long-term patency rate (27% to 43% patent at 5 years) than angioplasty performed for claudication with superficial femoral artery stenosis (62% to 73% patent at 5 years).³⁵ Following surgical bypass with saphenous vein or prosthetic material, she could expect a 5-year patency rate of roughly 70% to 90%.³⁵ Table 3 provides approximate charges of treatment.

If the patient's preferences did not inform this decision, I would recommend preliminary percutaneous balloon angioplasty. The rationale for this choice is that she might benefit for a meaningful period; the complication rate is low; and her collateral pattern is such that thrombosis of the angioplasty site, should it occur, is unlikely to leave her any worse than she is at present.

Is such a strategy (trial of formal exercise program, possibly followed by balloon angioplasty if the ipsilateral iliac lesion is not hemodynamically significant and if contralateral symptoms are not likely to cause significant functional limitation) socially responsible? I believe it is. First, the likelihood is high that Mrs D will be able to double her walking distance if she completes the structured exercise program, and this increment in walking distance will meet her needs, especially if she is appropriately counseled by Dr S and her vascular surgeon. Second, Mrs D's highest priority is increasing her walking distance—in her mind, this was such a high priority that she quit smoking and risked coronary artery bypass and lifelong hemodialysis in order to become eligible for a regimen that would increase her walking distance. Balloon angioplasty appears to be the most cost-effective first anatomic intervention for claudication with superficial femoral artery occlusion.⁴⁷ If Mrs D failed a structured exercise program, would most experienced vascular surgeons offer the option of anatomic intervention? Some might argue against intervention because her life expectancy is limited by her overall burden of disease, revascularization carries exceedingly high risks in the presence of dialysis-dependent renal failure, and claudication is not a significant symptom. Careful quantitative analysis of this specific decision,⁴⁷ however, taking into account a range of annual mortality risks approaching those of Mrs D's indicates that balloon angioplasty would be a cost-effective strategy given Mrs D's strong desire to improve her ability to walk longer distances.

Mrs D has spunk, a caring and talented array of physicians in a world-class medical care system, and good insurance coverage. She is in a better position than many less ill people to consider and plan for the quality of her life. She is fortunate she lives in an era beyond 1959, when a leading surgeon told the World Conference of Angiology that "[w]omen seldom require to have their walking distance increased because they rarely walk far without stopping to gossip or look into shop windows."⁴⁹ Despite her multiple medical problems, she may yet return to first base.

AN INTERNIST: My colleagues and I have had patients who are glad they can walk after surgery, but are upset about the pain in the incision. They say they would not have undergone surgery if they had known. What about the incidence and treatment of incisional pain?

DR MCDANIEL: Neuralgia in long harvesting incisions is an occasional problem. Generally it resolves over a period of about a year. It is important when we counsel patients about revascularization to talk about skin numbness, incisional pain, and the concept that incisions begin to settle down after about 6 months to 1 year. Patients often believe that when they go home, their incisions are healed. Edema is even more of a problem than incisional pain. It is important for patients to know this beforehand, as it largely resolves with external support and commonsense measures after about 3 to 6 months. Edema is also a common chronic problem for patients who have had saphenectomy for coronary bypass grafting.

DR S: Do you think there would be any benefit to having a patient like this consider hormonal therapy at this juncture?

DR MCDANIEL: A 25-year MEDLINE search on the use of hormone replacement therapy that I conducted produced no information on its specific effect on LEAOD. It may help Mrs D's overall well-being and energy and help her avoid progression of arterial occlusive disease, but we do not have specific information about its effect on lower-extremity disease.

DR PARKER: There is clearly evidence that lowering low-density lipoprotein cholesterol below 2.59 mmol/L (100 mg/dL) has helped prevent coronary events in patients with known atherosclerosis. Is there any analogous information in peripheral vascular disease?

DR MCDANIEL: No, although we believe data derived from the coronary circulation can be extrapolated to other atherosclerotic beds. We do have increasing evidence that oxidized low-density lipoprotein is the bad actor. The sales of vitamin E have skyrocketed, and since metallic iron is a potent oxidizing agent and active on low-density lipoprotein, there is increasing interest in reducing iron stores to a minimum to prevent progression of disease. The acronym for the Department of Veterans Affairs study of this hypothesis is FEAST (Iron [Fe] in Atherosclerosis Trial), in which patients are routinely phlebotomized to reduce their systemic oxidation potential. We do not know if it will be effective for LEAOD.

AN INTERNIST: If prosthetic grafts are used, is there any need for warfarin sodium or other medications to help keep the graft patent?

DR MCDANIEL: I know of no evidence that postoperative use of warfarin improves the patency of infrainguinal prosthetic bypass grafts. There may also be a significant incidence of bleeding complications, which would negate any patency benefit. In terms of aspirin and vein bypass, as best we can tell, the major role for aspirin is not so much to decrease intimal hyperplasia in the graft, but to decrease the cardiac morbidity in patients with anatomic coronary disease. There's an important role for β-blockers in that regard as well.