Skip to main content. Contemporary management of peripheral arterial disease: I. Cardiovascular risk-factor modification. Author s : Heather L. Creager, MD. Author and Disclosure Information Heather L. PAD itself rarely causes death unless an ischemic limb is untreated for too long , but it can cause substantial morbidity and disability. Individuals with PAD have a reduced peak exercise capacity that limits their range of physical functioning.
For example, they have less capacity to walk than otherwise similar individuals without PAD. If they have progressed to intermittent claudication, they have substantial limitations on their capacity to walk. These rates went up sharply with age and were higher among men than women, among non-Hispanic blacks than among non-Hispanic whites or Mexican Americans, and in individuals with diabetes than nondiabetic individuals.
A more recent systematic review of U. The majority of individuals with PAD are asymptomatic. According to several large population studies, the prevalence of symptomatic PAD i. Prevalence increases sharply among older individuals—to 6 percent among those ages 64 to 69 and 7 percent among those ages 70 to 74 Norgren et al. Intermittent claudication is approximately twice as common among PAD patients with diabetes.
PAD in nondiabetic patients also progresses more quickly and is more likely to involve distal vessels, and the need for amputation because of critical leg ischemia is 5 to 10 times higher Norgren et al. The physical examination of patients presenting with pain during exercise includes checking for abnormal leg pulses, for bruits, and for cool or ulcerated skin. However, physical examination findings are not sufficient for a diagnosis of PAD, even combined with a history of risk factors, such as smoking, high blood pressure, or high cholesterol Criqui et al.
However, contrast angiography is invasive and carries some risk. The most common method to establish or rule out a diagnosis of lower extremity PAD is the ABI because it is reasonably accurate, has good sensitivity and excellent specificity, and is easy to perform, inexpensive, and noninvasive.
The ABI is the ratio of systolic blood pressure at the ankle to the systolic blood pressure in the brachial artery of the upper arm. Normal ABI values are between 1. An ABI of 0. ABI values of 0. Values of 0. A 20 percent or greater decrease in the ABI after exercise is also diagnostic for PAD, and the more severe the disease, the longer it takes for the ankle pressure to return to normal after exercise Gerhard-Herman et al.
Studies of the sensitivity, specificity, and accuracy of the ABI as a tool to diagnose peripheral artery blockage of 50 percent or more, using contrast angiography as the standard, have found that the ABI has a sensitivity of 72 to 95 percent, specificity of 96 to percent, positive predictive value of 90 to percent, negative predictive value of 96 to 99 percent, and overall accuracy of 98 percent Hirsch et al.
In unselected populations, sensitivity is about 80 percent and specificity is about 96 percent higher values are from studies that compare extremes: patients scheduled for intervention with young healthy controls Criqui and Ninomiya, The highest brachial and ankle blood pressure readings are used in clinical practice and are required by the current listing for PAD.
However, two recent studies have found that the ABI based on the average pressure in each ankle has the strongest statistical association with leg function Allison et al. One of the studies, the Multi-Ethnic Study of Atherosclerosis MESA , compared three ways to measure ankle pressure in a given leg to compute the ABI: 1 the higher of the dorsalis pedis artery and posterior tibial artery pressures, 2 the lower of the dorsalis pedis artery and posterior tibial artery pressures, and 3 the mean of these two ankle pressures Allison et al. The prevalence of PAD in the study population was three times higher using the lower pressure than.
The MESA study also calculated the sensitivity and specificity of the alternative ABIs in predicting several subclinical measures of atherosclerosis e. The finding was that using the ABI based on the lower pressure reading is more sensitive, but less specific than the ABI based on the higher pressure the average of the two pressures was intermediate. In other words, using the higher pressure reading results in a specificity of 98 to 99 percent, which results in few false positives. However, the lower sensitivity leads to more false negatives.
On the other hand, while using the lower pressure value is more sensitive, it is less specific and results in more false positives. The major limitation of the ABI as a diagnostic test is its inability to obtain accurate results with incompressible arteries due to medial calcification, which can occur in patients with conditions such as diabetes or chronic kidney disease.
When the ABI is greater than or equal to 1. The TBI procedure is similar to the ABI procedure except that it is performed with a photoplethysmograph infrared light sensor and a very small blood pressure cuff placed around the toe. A TBI less than 0. Ischemic rest pain is common when toe pressures are less than 30 mm Hg Rutherford et al. A case-control study of 56 men with stable claudication and toe pressures less than 40 mm Hg found that 34 percent progressed to rest pain, ulceration, or gangrene over 31 months, compared with 9 percent of age-, sex-, and race-matched controls, and that those with diabetes had the highest incidence of deterioration Bowers et al.
The ABI has been in use in clinical practice for some time, but it remains more likely to be found in a specialized vascular laboratory than in primary care settings Mohler et al. This test is relatively inexpensive and can be done in 15 minutes or less by a trained nurse Criqui et al. Nevertheless, two-thirds of the participants in a recent program to implement the ABI measurement in primary care outpatient clinics had not measured the ABI of patients prior to participation.
They reported that moderate to major barriers to administering the ABI included time constraints 56 percent , lack of reimbursement 45 percent , and limited staff availability 45 percent Mohler et al. The TBI is rarely measured in primary care because measurement of toe pressure is more time consuming and technically difficult and requires additional equipment Brooks et al. Other noninvasive, inexpensive, and relatively safe diagnostic methods that provide diagnostic discrimination include segmental pressure measurements, pulse volume recordings, duplex ultrasonography, Doppler waveform analysis, and ABI after exercise testing Hirsch et al.
Segmental pressure measurements help to identify the location of arterial blockages. Pulse volume recording is another useful technique for diagnosing PAD, especially in people with incompressible arteries. Continuous-wave Doppler ultrasound measurements of blood flow with duplex imaging are useful in assessing PAD severity and location. Pulse volume recording and Doppler ultrasound are often used to assess the results of revascularization. Exercise treadmill tests are used to diagnose PAD, provide objective evidence of the degree of the functional limitations of PAD, identify any non-PAD exercise limitations, and determine the safety of prescribing an exercise program, as well as to measure the response to therapy.
Generally, the treadmill should be programmed to provide a progressive workload beginning at a less intense level than used for healthy individuals and patients with coronary heart disease, such as the Gardner-Skinner, Hiatt, or Naughton protocols. ABI values should be determined before and after the test to ensure that the claudication symptoms are due to PAD and not to other causes Hirsch et al. Treadmill testing is not suitable for patients who, due to age or other reasons, are not able to exert themselves enough to allow reliable results. In such cases, a 6-minute walk test may be used to obtain an objective assessment of functional limitation and response to therapy Hirsch et al.
The drop in ankle pressure with this test correlates quite highly with that seen during a standard treadmill test Amirhamzeh et al. Also well recognized was the idea that aggressive risk factor modification was needed to lower the incidence of cardiovascular events, especially heart attack and stroke, stemming from the systemic atherosclerosis that a diagnosis of PAD strongly signals Belch et al.
These steps are prescribed primarily to reduce the likelihood of a heart attack or stroke, but they may also slow atherosclerosis of the lower limbs, and thus slow, halt, or reverse the progressive loss of functional capacity and the development of critical limb ischemia and limb loss. Ideally, patients with PAD should be treated aggressively for their underlying atherosclerosis.
Treatment includes smoking cessation, taking antihypertensive and lipid-lowering medications, controlling diabetes when present, and taking blood-thinning medications such as aspirin or clopidogrel. Specific findings include the following:. However, a meta-analysis did not find that smoking cessation improved maximal treadmill walking distance Girolami et al. A recent study found that only 33 percent of PAD patients were receiving beta-blockers, 29 percent angiotensin-converting enzyme, or ACE, inhibitors, and 31 percent cholesterol-lowering medications, and that only 46 percent had a hemoglobin A1c of less than 7 percent Rehring et al.
Many studies have shown that supervised exercise training doubles pain-free walking distance and maximal walking time on average Hirsch et al. The supervised exercise training should be performed for a minimum of 30 to 45 minutes, at least 3 times per week, for 12 or more weeks Class I Recommendation, Level of Evidence: A Hirsch et al. However, few such programs exist because of lack of reimbursement by health insurers. Cilostazol, a phosphodiesterase inhibitor, was approved by the Food and Drug Administration FDA in for the treatment of claudication after it was shown in six controlled clinical trials to increase pain-free and maximal constant-load treadmill walking distances by 65 to 98 percent and 40 to 76 percent, respectively Regensteiner et al.
The same meta-analysis found that patients on cilostazol reported significantly greater gains in community walking distances and speeds according to the Walking Impairment Questionnaire than did patients on placebo. Therefore, the guidelines recommend that a therapeutic trial of cilostazol should be considered in all patients with lifestyle-limiting claudication Class I Recommendation, Level of Evidence: A.
Cilostazol cannot be used in patients with heart failure, however, because of possible adverse side effects Hirsch et al. Pentoxifylline mg three times per day may be considered as second-line alternative therapy to cilostazol to improve walking distance in patients with intermittent claudication, although improvement has been shown to be better with cilostazol Class IIb Recommendation, Level of Evidence: A Hirsch et al. No other medications are recommended at this time, or have been approved by FDA, although a number are being developed and tested.
The most common side effects of cilostazol are gastrointestinal complaints, including nausea or change in stool characteristics. Side effects usually lessen with continued use Carman and Fernandez, A study of long-term effects of cilostazol did not find increased mortality or serious bleeding events Hiatt et al. The most common side effects of pentoxifylline are also gastrointestinal Carman and Fernandez, The absolute gains in distance from medication are modest.
For example, patients taking cilostazol were able to walk an average of additional meters on a graded treadmill test before they were forced to stop by symptoms instead of meters Regensteiner et al. Revascularization should be considered for patients with severe, lifestyle-limiting symptoms, such as severe claudication or rest pain despite medical therapy for 3 months. Endovascular procedures e. Surgical revascularization for claudication is rarely indicated.
Patients are initially treated with an endovascular intervention, and bypass surgery is an option only if that fails. According to the guidelines, surgical interventions are indicated for individuals with claudication symptoms who have a significant functional disability that is vocational or lifestyle limiting, who are unresponsive to exercise or pharmacotherapy, and who have a reasonable likelihood of symptomatic improvement Class I Recommendation, Level of Evidence: B Hirsch et al.
Blood carries oxygen and nutrients needed for the body to live and function. PAD results in reduced blood flow to the muscles and nerves of the lower extremities.
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In advanced cases, the reduced flow of blood can cause muscle pain, weakness, and numbness when an individual walks or even,. A person with advanced PAD may also develop leg ulcers that will not heal. In the most severe instances, the muscles may die and the lower leg or foot must be amputated. The resulting limitations on mobility may become severe enough to prevent an individual with PAD from engaging in substantial gainful activity.
An intensive literature search found neither research on the participation of persons with PAD in the workforce generally, nor more detailed analyses of workforce participation by ABI score or by any other objective laboratory test result or medical finding. This lack of research on the employment effects of PAD may be explained by its relatively low prevalence in the working-age population. Furthermore, most people who have PAD are asymptomatic, and many people with ischemic symptoms think these are due to aging or other medical conditions and do not report them.
An article on the impact of surgery for PAD on returning to work examined a retrospective follow-up study in Finland of 67 middle-aged patients mean equals 53 years. Of those, 63 had a positive outcome based on vascular criteria. Of the 50 patients not yet retired at the time of the surgery, 41 returned to work. After 10 years, only 9 of the 41 who had returned to work were still working. Of the rest, 13 had retired most due to the progression of PAD , and 19 had died. A preoperative ABI less than or equal to 0.
In the absence of research on the predictors of employment of those with PAD, its impact on functions that are plausibly related to work, such as exercise tolerance or ability to walk a certain distance or speed, must serve as proxies for work disability. A number of studies have examined the association between ABI and various measures of functional ability Eberhardt et al. A few studies have looked at the association of PAD with measures of peak exercise capacity on a treadmill Hiatt et al.
These studies consistently found that patients with PAD are functionally impaired and that the degree of functional limitation increased as clinical measures of impairment worsened. The studies found, for example, that:. Less than 40 percent of the participants with an ABI lower than 0. Patients with abnormal less than 0. The hazard ratios for losing the ability to walk one-quarter mile or walk up and down one flight of stairs without assistance more than 5 years from diagnosis were 4.
Studies have also found that the impact of PAD on health-related quality of life is substantial. In one study, the impact was comparable to that of other cardiovascular conditions, although PAD patients were most affected by calf pain while other cardiovascular patients were most affected by chest pain, shortness of breath, and palpitations Regensteiner et al. Although ABI and other measures of hemodynamic severity are clearly associated with functional capacity, especially at the very low and high ends of the scale, they are not strong predictors of functional limitations.
Contemporary management of peripheral arterial disease: III. Endovascular and surgical management.
For example, the correlation of ABI at rest with walking ability on a treadmill of a given individual is low Hiatt et al. This is probably due to a number of factors, including individual differences in comorbidities, muscle pathology, leg blood flow, and conditioning Brass et al.
As a result, some patients with a low ABI will have little walking impairment, while others with a higher ABI will have marked walking impairment Hirsch et al. In this situation, ABI or other blood pressure measure is not sufficient to sharply differentiate claimants who are unable to work from those who are able to work without additional evidence of functional limitations consistent with incapacity to work. The listing for PAD requires the existence of intermittent claudication plus specified test results based on ankle or toe blood pressure readings Box This results in four sublistings for PAD.
The first, 4. The second,. Decrease in systolic blood pressure at the ankle on exercise see 4. Sublisting 4. The third and fourth sublistings were added when the PAD listing was revised in The inclusion of toe pressures addressed the fact that the ankle blood pressure readings are not a valid measure of PAD in individuals with abnormally stiff ankle arteries because of medial arterial calcification or other causes.
The PAD listing must also be read in conjunction with part 4. The serious effects of PAD are delineated in 4. SSA will pay for an exercise Doppler study if one has not been done or if it is needed to determine if the claimant meets sublisting 4. SSA requires the exercise test to be performed on a treadmill at 2 mph on a 12 percent grade for up to 5 minutes. Blood pressures at the ankle are measured after exercise and the time required for the systolic blood pressure to return to or near to the preexercise level is determined.
The fundamental conclusion regarding evaluation of PAD disability is that hemodynamic measures such as the ABI do not adequately distinguish between individuals able to work and individuals unable to work. Individuals with an ABI less than 0. Some individuals will be able to work despite intermittent clau-. Adopting more severe values, that is, an ABI less than 0.
Alternatively, adopting an ABI greater than 0. The basic recommendation for improving the PAD listing as an early screening tool is to supplement the medical diagnostic and severity requirements with evidence of severe functional limitations.
The committee also recommends some clarifications in and medical updates of listing 4. Listing 4. In practice, however, a diagnosis of PAD is usually based on the ABI, and the other diagnostic methods are reserved for cases in which further evaluation is needed to make the diagnosis and determine appropriate medical management or to help guide decisions to intervene invasively. Technically, the Doppler techniques used to determine ankle and toe blood pressures do not produce images. Similarly, the techniques used to record waveforms do not produce images.
Also, although duplex ultrasonography images the leg arteries with B-mode ultrasound, it also measures flow velocity with pulsed Doppler, and the latter technique—which is not imaging—is often the main basis for a diagnosis of PAD.
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The committee was informed that SSA considers Doppler studies to be appropriate medically acceptable imaging. Current listing 4. Intermittent claudication is considered to be the classic symptom of PAD. It is an appropriate listing requirement because it is usually associated with severe functional limitations on ability to walk and climb stairs. However, other symptoms in the absence of intermittent claudication can also indicate inability to engage in any gainful activity. For example, some individuals with an ABI less than 0.
In addition, individuals may apply to SSA for disability benefits with advanced-stage symptoms that have succeeded an earlier period of intermittent claudication. These include rest pain i. These are appropriately mentioned in the introductory section to the cardiovascular system listings, but they are not in the PAD listing as an alternative to intermittent claudication. The committee understands that if a claimant has atypical leg pain attributable to PAD that limits walking, but meets the other requirements of 4.
The committee recommends that, rather than rely on equivalence, a broader set of symptoms be permitted to meet the listing than intermittent claudication alone see Recommendation b. Treatments for PAD exist described above that reduce symptoms and increase mobility and quality of life. These include supervised physical rehabilitation, medications, and, if indicated, angioplasty or bypass surgery. The committee recommends that a requirement that the applicant be on a regimen of prescribed treatment be added to the listing see Recommendation c.
For evaluating disability, SSA strongly prefers clinical tests that are very sensitive which would screen in the highest percentage of claimants unable to work as possible and very specific which would screen out as many individuals who can work as possible. As with all clinical screening tests, however, there is a trade-off between sensitivity and specificity.
In this case, the higher the ABI, the more claimants unable to work will meet the Listings and be allowed, but also the more claimants who can work will be allowed. For example, if an ABI less than or equal to 0. This gain would come at the cost of specificity, however, because many individuals with PAD who could work would be included.
Similarly, if the listing required an ABI less than or equal to 0. There would be no false positives, but this would make the listing ineffective as an administrative device for speeding decisions on obvious allowances. Because some individuals with an ABI less than 0. An ABI less than 0. Virtually everyone with this ABI score has severe leg pain and substantial muscle weakness, severely limiting mobility and stamina.
Although this test result requirement would be very specific, the decrease in sensitivity would mean that more individuals who actually met. This would defeat the purpose of the Listings, which is to reduce the percentage of claimants going through Steps 4 and 5 who ultimately will be allowed. The committee also discussed setting a higher ABI cut-off value, such as 0.
This would make the listing very sensitive, probably allowing most claimants truly unable to work because of PAD, and it would require fewer Step 4 and 5 determinations. However, it would also reduce specificity and allow more false positives, which would undermine the credibility of the disability program.
Unfortunately, the literature search found no studies of the sensitivity and specificity of an ABI less than 0. However, based on personal clinical observations by some committee members and logical extrapolation from studies of functional status of individuals with various ABI values, the committee recommends retaining the current ABI value of less than 0. Also, the PAD listing could be simplified by folding Criteria B, C, and D into a new, broader criterion, in which tests other than the ABI can be used to establish listing-level severity.
The basis for this change is the relative lack of evidence that toe pressures or changes in ankle pressure during exercise are predictive of functional status. The current introductory section to the cardiovascular system, which dates from , notes that medical standards for evaluating exercise toe pressures do not exist, which is still the case. Given that TBI and toe systolic pressure results require interpretation by DDS medical consultants and consultative examiners, SSA might broaden as well the range of tests that can be used to establish listing-level severity see Recommendation e.
This criterion would apply to claimants with an ABI of 0. The committee concludes that an ABI less than 0. Although an ABI less than 0. At the same time, some claimants with ABIs of 0. Therefore, an ABI less than 0. The committee concludes that, to increase sensitivity without significantly decreasing specificity, the ABI and other clinical signs should be augmented with an assessment of function.
However, several studies have indicated that patients with PAD have an increased risk for all-cause mortality and for death from coronary heart disease than those without PAD. Currently, the presence of subclinical vascular damage represents a topic of great interest; examples include the pivotal role of carotid intima—media thickness in stratifying patients who are candidates for therapy initiation and the role of arterial stiffness in predicting future CV events in patients with coronary artery disease.
The lack of an adequate evaluation of early atherosclerotic lesions of the lower limbs is a serious shortcoming, especially when considering the possible association of PAD with known CV risk factors and the possible predictive role of PAD and its involvement in global CV risk stratification. To overcome these limits, in this study, we introduced a new ultrasonographic score, the ULLA score, which facilitates the categorization of atherosclerotic lesions of the lower limbs in all stages of PAD and associating these ultrasonographic categories with CV risk profiles.
The main finding of our study is that the total severity index of the proposed ultrasonographic score is associated with age and male gender and with the other main traditional CV risk factors, that is, smoking, hypertension, diabetes, dyslipidemia, sedentary lifestyle and previous CV events, even after adjustment for age, gender and BMI. Moreover, our data confirm that specific CV risk factors are selectively associated with the proximal or distal districts; in particular, smoking status and dyslipidemia are selectively associated with the proximal district score, whereas CV family history and sedentary lifestyle are selectively associated with the distal district score.
Packs per year of smoking, hypertension and diabetes are significantly associated with both the proximal and distal district scores.
Contemporary evaluation and management of lower extremity peripheral artery disease.
However, for hypertension, the magnitude of the association is larger for the proximal district score, whereas for diabetes it is larger for the distal district score. Numerous hypotheses have been proposed to explain the site selectivity of atherosclerotic lesions, including hemodynamic stress related to arterial geometry and anatomic, cellular or biochemical variations in the arterial wall.
These findings confirm what is already known about the correlation between PAD and CV risk factors and with regard to specific districts and single CV risk factors. The findings extend the relationships established in previous studies to all stages of PAD, including early, asymptomatic stages.
The current data, in fact, generally have been obtained from studies of patients undergoing endovascular treatment for advanced stages of PAD generally Fontaine stages III—IV , which correspond to the detection of hemodynamically significant lesions through instrumental imaging. Moreover, the diagnostic tool used in most studies has been angiography, which is considered the gold standard for grading atherosclerotic lesions of the lower extremities.
First, angiography only allows the specific study of the proximal arteries, with segments distal to the popliteal artery often not considered because of their relatively poor visualization. Moreover, in many angiographic studies, disease severity was based on the number of occlusions, and the atherosclerotic pattern was defined only by the endovascular target lesions treated.
Other studies have used noninvasive techniques to assess PAD by detecting perfusion effects rather than the degree or site of stenosis within single arteries. Most of these include ABI evaluation, a measurement comparing the ankle systolic blood pressure to the brachial artery systolic blood pressure. As mentioned above, the proposed ULLA score overcomes these limitations, allowing a complete evaluation of the entire lower limb atherosclerotic burden and extending the results to all stages of PAD, including early stages. Moreover, after excluding patients with altered ABI or with symptoms suggestive of PAD, our results remained substantially unchanged, confirming the robustness of the proposed score even in the early, preclinical stages of PAD.
It is plausible that this result reflects the reduced systemic involvement of vascular damage in these patients. Considering PAD at all stages of the disease can have a role also in the recent research revealing the role of PAD involvement in CV risk stratification. Risk stratification in CV disease prevention represents a major goal for twenty-first century medicine.
Assessment of traditional CV risk factors, such as blood pressure and low-density lipoprotein cholesterol levels, remains the cornerstone of risk estimation; however, a residual risk may remain even after controlling for traditional CV risk factors. Therefore, new markers, mainly those related to inflammation and genetic profiles, have recently been added to scoring systems to better assess the risk of CV disease, together with instrumental techniques for measuring asymptomatic organ damage.
In particular, the independent prognostic value of carotid ultrasonography with evaluation of carotid intima—media thickness and plaques in predicting CV events has been widely demonstrated. In particular, our findings could improve the identification of individuals with a low-moderate year risk for CV disease based on classical scoring systems but a moderate-high lifetime risk, allowing these individuals to benefit from early interventions designed to prevent progression to the high-risk group in later life.
Moreover, exploring the possible presence of subclinical atherosclerosis in the lower limb districts could be of interest because multiple organ damage carries a worse prognosis than single organ involvement. Another important implication of the ULLA score is the ability to compare the real association of CV risk factors with the atherosclerotic lesion distribution in different districts.
This association is often deduced through instrumental methods with different sensitivities. Certainly, the most interesting future research on the proposed ULLA score will be studying its predictive properties with respect to the risk of CV event development. In fact, it is well known that only a small percentage of patients with PAD require lower extremity intervention; thus, screening for PAD should be not beneficial as much in reducing the risk of symptomatic PAD or ischemic limb event, rather than it should be help identify those who need aggressive preventive measures for CV and cerebrovascular risk reduction.
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