Peripheral Arterial Disease

2. Definition of Peripheral Arterial Disease (PAD) The presence of a stenosis or occlusion in the aorta or arteries of the limbs

3. Prevalence of PAD Increases With Age The population-based Rotterdam Study of 7715 subjects at least 55 years old found a high prevalence of PAD (19.1%) but a rather low prevalence of IC (1.6%). The prevalence PAD increased dramatically with increasing age from less than 10% in those 55 through 59 years old to nearly 60% in those 85 years old or older.1 In 613 patients whose average age was 66 years and who were recruited from the population-based San Diego Study, the prevalence of large-vessel PAD on noninvasive testing was 11.7 %, and an additional 16% had isolated small-vessel PAD. In contrast, IC rates were 2.2% in men and 1.7% in women.2 In the San Diego Study group, large-vessel PAD also increased dramatically with age and was slightly more common in men and in those with hyperlipidemia.2 Keywords: prevalence, PAD, IC, women The population-based Rotterdam Study of 7715 subjects at least 55 years old found a high prevalence of PAD (19.1%) but a rather low prevalence of IC (1.6%). The prevalence PAD increased dramatically with increasing age from less than 10% in those 55 through 59 years old to nearly 60% in those 85 years old or older.1 In 613 patients whose average age was 66 years and who were recruited from the population-based San Diego Study, the prevalence of large-vessel PAD on noninvasive testing was 11.7 %, and an additional 16% had isolated small-vessel PAD. In contrast, IC rates were 2.2% in men and 1.7% in women.2 In the San Diego Study group, large-vessel PAD also increased dramatically with age and was slightly more common in men and in those with hyperlipidemia.2 Keywords: prevalence, PAD, IC, women

4. Independent Risk Factors for PAD* When attempting to identify a patient�s risk for PAD, it is essential for the clinician to identify and assess the risk factors involved. In order to help identify the risk factors associated with PAD, 5,084 individuals of age 65 or over, as part of a larger study by Newman et al exploring the relationship between ABI and CVD, were grouped according to baseline clinical CVD status and ABI (< 0.8, = 0.8 to < 0.9, = 0.9 to < 1.0, and = 1.0 to < 1.5). An ABI cutoff point of 0.9 was used as the maximum threshold to identify those individuals having PAD. Risk factors associated with an ABI of < 1.0 were investigated and assessed using a stepwise multiple logistic regression analysis in order to determine the relative risk. Newman and colleagues revealed four important age-adjusted factors that should be considered in addition to age when assessing a patient�s risk for PAD: 1. Diabetes Relative risk: 4.05 2. Smoking (currently) Relative risk: 2.55 3. Hypertension Relative risk: 1.51 4. Total cholesterol (10 mg/dL) Relative risk: 1.10 When used in conjunction with the ankle-brachial index (ABI), accurate risk factor assessment can further enhance the physician�s ability to calculate the risk for PAD. Newman and colleagues have shown that, in addition to age, diabetes, smoking, hypertension, and total cholesterol are factors that clinicians should consider when determining a patient�s risk for PAD. Newman AB, Siscovick DS, Monolio TA, et al. Ankle-arm index as a marker of atherosclerosis in the cardiovascular health study. Circulation. 1993;88:837-845When attempting to identify a patient�s risk for PAD, it is essential for the clinician to identify and assess the risk factors involved. In order to help identify the risk factors associated with PAD, 5,084 individuals of age 65 or over, as part of a larger study by Newman et al exploring the relationship between ABI and CVD, were grouped according to baseline clinical CVD status and ABI (< 0.8, = 0.8 to < 0.9, = 0.9 to < 1.0, and = 1.0 to < 1.5). An ABI cutoff point of 0.9 was used as the maximum threshold to identify those individuals having PAD. Risk factors associated with an ABI of < 1.0 were investigated and assessed using a stepwise multiple logistic regression analysis in order to determine the relative risk. Newman and colleagues revealed four important age-adjusted factors that should be considered in addition to age when assessing a patient�s risk for PAD: 1. Diabetes Relative risk: 4.05 2. Smoking (currently) Relative risk: 2.55 3. Hypertension Relative risk: 1.51 4. Total cholesterol (10 mg/dL) Relative risk: 1.10 When used in conjunction with the ankle-brachial index (ABI), accurate risk factor assessment can further enhance the physician�s ability to calculate the risk for PAD. Newman and colleagues have shown that, in addition to age, diabetes, smoking, hypertension, and total cholesterol are factors that clinicians should consider when determining a patient�s risk for PAD. Newman AB, Siscovick DS, Monolio TA, et al. Ankle-arm index as a marker of atherosclerosis in the cardiovascular health study. Circulation. 1993;88:837-845

5. Diabetes Increases Risk of PAD Using baseline clinical data from the population-based Edinburgh Artery Study of 1592 subjects between the ages of 55 and 74 years, Lee and colleagues found that the 288 subjects with diabetes or IGT had a higher prevalence of PAD than the 1304 with normal glucose tolerance. PAD was present in 22.4% of the diabetic subjects and 19.9% of the IGT subjects, compared with 12.5% of those with normal glucose tolerance. PAD occurred at a significantly increased rate in subjects with diabetes or IGT, compared with those with normal glucose tolerance. This finding was significant at a P value less than or equal to 0.005. The odds ratio for the prevalence of PAD in those with diabetes/IGT compared with that for those with normal glucose tolerance was 1.64 (95% CI, 1.17-2.31). Keywords: diabetes, prevalence, PADUsing baseline clinical data from the population-based Edinburgh Artery Study of 1592 subjects between the ages of 55 and 74 years, Lee and colleagues found that the 288 subjects with diabetes or IGT had a higher prevalence of PAD than the 1304 with normal glucose tolerance. PAD was present in 22.4% of the diabetic subjects and 19.9% of the IGT subjects, compared with 12.5% of those with normal glucose tolerance. PAD occurred at a significantly increased rate in subjects with diabetes or IGT, compared with those with normal glucose tolerance. This finding was significant at a P value less than or equal to 0.005. The odds ratio for the prevalence of PAD in those with diabetes/IGT compared with that for those with normal glucose tolerance was 1.64 (95% CI, 1.17-2.31). Keywords: diabetes, prevalence, PAD

6. Manitoba Vascular Health Service (Diabetes) Known Diabetes 29% (252 / 869) New Dx. Diabetes 40% (205 / 512) New Dx. IGT 27% (138 /512) Overall 68% DM or IGT

7. PAD Risk Factors are Synergistic In a study of the 295 subjects who developed occlusive PAD during the 26-year Framingham Study of 5209 subjects, cigarette smoking, hypertension, and IGT were found to be strong risk factors for PAD, as manifested by IC, whereas serum cholesterol was a weak risk factor for PAD. Overall, hypertension alone increased the risk of IC 2.5-fold in men and four-fold in women. In those with normal blood pressure, total cholesterol level, and glucose tolerance, smoking increased the relative risk of IC to 3.5. The effects of smoking were even greater in those with a higher blood pressure and cholesterol level, in whom smoking increased the relative risk of IC to 10 compared with 3.1 for that of nonsmokers. A particularly strong synergistic effect was found between smoking, very elevated systolic blood pressure and total cholesterol level, and IGT in increasing the risk of IC. In patients with this combination of risk factors, the relative risk of IC was 43, whereas it was 18 in those who had very elevated systolic blood pressure and total cholesterol and IGT but did not smoke Keywords: PAD, smoking, hypertension, IC, women, relative risk In a study of the 295 subjects who developed occlusive PAD during the 26-year Framingham Study of 5209 subjects, cigarette smoking, hypertension, and IGT were found to be strong risk factors for PAD, as manifested by IC, whereas serum cholesterol was a weak risk factor for PAD. Overall, hypertension alone increased the risk of IC 2.5-fold in men and four-fold in women. In those with normal blood pressure, total cholesterol level, and glucose tolerance, smoking increased the relative risk of IC to 3.5. The effects of smoking were even greater in those with a higher blood pressure and cholesterol level, in whom smoking increased the relative risk of IC to 10 compared with 3.1 for that of nonsmokers. A particularly strong synergistic effect was found between smoking, very elevated systolic blood pressure and total cholesterol level, and IGT in increasing the risk of IC. In patients with this combination of risk factors, the relative risk of IC was 43, whereas it was 18 in those who had very elevated systolic blood pressure and total cholesterol and IGT but did not smoke Keywords: PAD, smoking, hypertension, IC, women, relative risk

8. Clinical Manifestations of PAD Asymptomatic Intermittent claudication Discomfort, ache, cramping in leg with exercise�resolves with rest Functional impairment Slow walking speed, gait disorder Rest pain Pain or paresthesias in foot or toes, worsened by leg elevation and improved by dependency Ischemic ulceration and gangrene PAD can be asymptomatic or include IC symptoms, functional impairment, rest pain, and ischemic ulceration and gangrene. IC symptoms include discomfort, aching, and leg cramps during exercise that resolve with rest. Functional impairment includes slow walking speed and gait disorder. Rest pain includes pain or paresthesias in the foot or toes that are worsened by leg elevation and improved by dependency. Keywords: PAD, asymptomatic, IC, functional impairment, rest pain, gangrene, gait disorder, paresthesiasPAD can be asymptomatic or include IC symptoms, functional impairment, rest pain, and ischemic ulceration and gangrene. IC symptoms include discomfort, aching, and leg cramps during exercise that resolve with rest. Functional impairment includes slow walking speed and gait disorder. Rest pain includes pain or paresthesias in the foot or toes that are worsened by leg elevation and improved by dependency. Keywords: PAD, asymptomatic, IC, functional impairment, rest pain, gangrene, gait disorder, paresthesias

9. Clinical Presentation of PAD In half of all cases, the clinical presentation of PAD is asymptomatic. PAD has a typical clinical presentation in only approximately 15% of all cases. In approximately one-third of all cases, PAD has an atypical clinical presentation. In 1% to 2% of all cases, PAD presents as CLI. Keywords: PAD, asymptomatic, typical, atypical, CLI In half of all cases, the clinical presentation of PAD is asymptomatic. PAD has a typical clinical presentation in only approximately 15% of all cases. In approximately one-third of all cases, PAD has an atypical clinical presentation. In 1% to 2% of all cases, PAD presents as CLI. Keywords: PAD, asymptomatic, typical, atypical, CLI

10. Ankle Brachial Index In measuring the ABI, systolic blood pressure is measured in each arm and in the dorsalis pedis and posterior tibial arteries in each ankle by using Doppler ultrasonography. The higher of the two arm pressures is selected, as is the higher of the two pressures in each ankle. The right and the left ABIs are determined by dividing the higher ankle pressure in each leg by the higher arm pressure. In the example illustrated, to calculate the right ABI, the higher of the two right ankle pressures, in this case the dorsalis pedis pressure of 80 mmHg, is divided by the higher of the two arm pressures, which is the left arm pressure of 160 mmHg 80 divided by 160 is 0.5 To calculate the left ABI, the higher of the two left ankle pressures, in this case the posterior tibial pressure of 120 mmHg, is divided by the higher of the two arm pressures, which again is the left arm pressure of 160 mmHg 120 divided by 160 is 0.75 An ABI greater than 0.9 is considered normal. In this example, the right ABI is 0.5, and the left ABI is 0.75. Because both ABIs are less than 0.9, both are abnormal, which indicates the presence of IC in both legs Keywords: ABI, IC In measuring the ABI, systolic blood pressure is measured in each arm and in the dorsalis pedis and posterior tibial arteries in each ankle by using Doppler ultrasonography. The higher of the two arm pressures is selected, as is the higher of the two pressures in each ankle. The right and the left ABIs are determined by dividing the higher ankle pressure in each leg by the higher arm pressure. In the example illustrated, to calculate the right ABI, the higher of the two right ankle pressures, in this case the dorsalis pedis pressure of 80 mmHg, is divided by the higher of the two arm pressures, which is the left arm pressure of 160 mmHg 80 divided by 160 is 0.5 To calculate the left ABI, the higher of the two left ankle pressures, in this case the posterior tibial pressure of 120 mmHg, is divided by the higher of the two arm pressures, which again is the left arm pressure of 160 mmHg 120 divided by 160 is 0.75 An ABI greater than 0.9 is considered normal. In this example, the right ABI is 0.5, and the left ABI is 0.75. Because both ABIs are less than 0.9, both are abnormal, which indicates the presence of IC in both legs Keywords: ABI, IC

11. Indications for an ABI History of classic or suspected claudication History of CLI (rest pain, gangrene, nonhealing wound) Any diabetic patient >50 years old Any diabetic patient <50 yr old who has risk factors All patients with PAD symptoms All patients >70 years old All patients >50 years old who smoke or have diabetes Traditional indications for ABI measurement include history of classic of suspected claudication history of CLI as indicated by rest pain, gangrene, or a nonhealing wound The ADA recommends ABI measurement for any diabetic patient more than 50 years old any diabetic patient less than 50 years old with risk factors such as smoking, hypertension, hyperlipidemia, or a duration of diabetes of more than 10 years any patients with symptoms of PAD1 The AHA-ACC recommend ABI measurement for all patients with PAD symptoms all patients more than 70 years old all patients more than 50 years old but less than 69 years old who smoke or have diabetes2 Keywords: ABI, CLI, rest pain, gangrene, smoking, hypertension, diabetes, PAD Traditional indications for ABI measurement include history of classic of suspected claudication history of CLI as indicated by rest pain, gangrene, or a nonhealing wound The ADA recommends ABI measurement for any diabetic patient more than 50 years old any diabetic patient less than 50 years old with risk factors such as smoking, hypertension, hyperlipidemia, or a duration of diabetes of more than 10 years any patients with symptoms of PAD1 The AHA-ACC recommend ABI measurement for all patients with PAD symptoms all patients more than 70 years old all patients more than 50 years old but less than 69 years old who smoke or have diabetes2 Keywords: ABI, CLI, rest pain, gangrene, smoking, hypertension, diabetes, PAD

12. ABI Testing: Highly Sensitive and Specific ABI testing has been shown to be more effective in detecting PAD than Papanicolaou (Pap) testing is in detecting cervical cancer, fecal occult blood testing is in detecting colorectal carcinoma, and mammography is in detecting breast cancer. The ABI is up to 95% sensitive in detecting angiogram-positive IC and almost 100% specific in identifying apparently healthy persons.1 In contrast, a systematic review of 94 studies of the conventional Pap smear found that, in the 12 studies with the least biased estimates, the sensitivity of the test ranged from 30% to 87%, and its specificity ranged from 86% to 100%.2 In a study of 8104 California HMO patients screened for colorectal carcinoma, the sensitivity of fecal occult-blood testing ranged from 37% to 69%, and its specificity ranged from 87% to 98%, depending on the type of test used.3 In a study of the effectiveness of mammography in detecting breast cancer, its specificity ranged from 75% to 90%, and its specificity ranged from 90% to 95%.4 Keywords: ABI, PAD, ICABI testing has been shown to be more effective in detecting PAD than Papanicolaou (Pap) testing is in detecting cervical cancer, fecal occult blood testing is in detecting colorectal carcinoma, and mammography is in detecting breast cancer. The ABI is up to 95% sensitive in detecting angiogram-positive IC and almost 100% specific in identifying apparently healthy persons.1 In contrast, a systematic review of 94 studies of the conventional Pap smear found that, in the 12 studies with the least biased estimates, the sensitivity of the test ranged from 30% to 87%, and its specificity ranged from 86% to 100%.2 In a study of 8104 California HMO patients screened for colorectal carcinoma, the sensitivity of fecal occult-blood testing ranged from 37% to 69%, and its specificity ranged from 87% to 98%, depending on the type of test used.3 In a study of the effectiveness of mammography in detecting breast cancer, its specificity ranged from 75% to 90%, and its specificity ranged from 90% to 95%.4 Keywords: ABI, PAD, IC

13. ABI Limitations Incompressible arteries (elderly patients, patients with diabetes, renal failure, etc) Resting ABI may be insensitive for detecting mild aortoiliac occlusive disease Not designed to define degree of functional limitation Normal resting values in symptomatic patients may become abnormal after exercise Does not distinguish between stenosis and occlusion Although the ABI is highly sensitive and specific for detecting PAD, the ABI has a number of important limitations. For example, the ABI is ineffective in assessing PAD in patients with incompressible arteries, such as the elderly and patients with diabetes or renal failure. The resting ABI is insensitive for detecting mild aortoiliac occlusive disease. The ABI was not designed to define the degree of functional limitation. In symptomatic patients, normal resting ABI values may become abnormal after exercise. The ABI does not distinguish between stenosis and occlusion. Keywords: ABI, PAD, elderly, diabetes Although the ABI is highly sensitive and specific for detecting PAD, the ABI has a number of important limitations. For example, the ABI is ineffective in assessing PAD in patients with incompressible arteries, such as the elderly and patients with diabetes or renal failure. The resting ABI is insensitive for detecting mild aortoiliac occlusive disease. The ABI was not designed to define the degree of functional limitation. In symptomatic patients, normal resting ABI values may become abnormal after exercise. The ABI does not distinguish between stenosis and occlusion. Keywords: ABI, PAD, elderly, diabetes

14. PAD Survival Curve

15. Cause of Death in IC Patients In a study of the cause of death in patients with IC 55% died of cardiac causes 25% died of nonvascular causes 11% died of cerebral causes 9% died of other vascular causes Keywords: ICIn a study of the cause of death in patients with IC 55% died of cardiac causes 25% died of nonvascular causes 11% died of cerebral causes 9% died of other vascular causes Keywords: IC

16. Association Between ABI and All-Cause Mortality In 4393 American Indians in their mid- to late-50s who were enrolled in the population-based Strong Heart Study, high ABI (>1.40) and low ABI (<0.90) were both found to predict mortality. This finding suggests that both upper and lower thresholds for ABI exist Adjusted risk estimates for all-cause mortality were 1.69 (CI, 1.34 to 2.14) for low ABI 1.77 (CI, 1.48 to 2.13) for high ABI Estimates for CVD mortality were 2.52 (CI, 1.74 to 3.64) for low ABI 2.09 (CI, 1.49 to 2.94) for high ABI Almost twice as many individuals were categorized as having high ABI than as having low ABI, which indicates that High ABI is not rare The health impact of high ABI may be greater than that of low ABI High ABI may be particularly important in populations with a high diabetes prevalence, such as American Indians and the elderly The upper limit of normal ABI should not exceed 1.40 Keywords: Strong Heart Study, ABI, mortality, CVD, diabetes, prevalence, elderly In 4393 American Indians in their mid- to late-50s who were enrolled in the population-based Strong Heart Study, high ABI (>1.40) and low ABI (<0.90) were both found to predict mortality. This finding suggests that both upper and lower thresholds for ABI exist Adjusted risk estimates for all-cause mortality were 1.69 (CI, 1.34 to 2.14) for low ABI 1.77 (CI, 1.48 to 2.13) for high ABI Estimates for CVD mortality were 2.52 (CI, 1.74 to 3.64) for low ABI 2.09 (CI, 1.49 to 2.94) for high ABI Almost twice as many individuals were categorized as having high ABI than as having low ABI, which indicates that High ABI is not rare The health impact of high ABI may be greater than that of low ABI High ABI may be particularly important in populations with a high diabetes prevalence, such as American Indians and the elderly The upper limit of normal ABI should not exceed 1.40 Keywords: Strong Heart Study, ABI, mortality, CVD, diabetes, prevalence, elderly

17. Critical Limb Ischemia (CLI) This slide illustrates a typical pair of feet with CLI. Note the dark, gangrenous patches on the lateral aspect and heel of the upper right foot. Keywords: typical, CLIThis slide illustrates a typical pair of feet with CLI. Note the dark, gangrenous patches on the lateral aspect and heel of the upper right foot. Keywords: typical, CLI

18. Peripheral Arterial Disease Complication: Ischemic Ulcer This slide illustrates one of the chief complications of PAD: ischemic ulcer, which in this patient affects the tip of the large toe. Keywords: PADThis slide illustrates one of the chief complications of PAD: ischemic ulcer, which in this patient affects the tip of the large toe. Keywords: PAD

19. Amputation Complications such as CLE frequently result in limb amputation in patients with severe PAD. Keywords: amputation, PADComplications such as CLE frequently result in limb amputation in patients with severe PAD. Keywords: amputation, PAD

20. Critical Limb Ischemia (CLI) Dormandy summarized the results of 19 studies of the outcome of patients with critical limb ischemia (CLI) after initial treatment. Analysis of the combined results found that, after 6 months of follow up, 45% of those studied were alive without having had an amputation 35% were alive but had to have an amputation 20% had died. Keywords: CLI, amputationDormandy summarized the results of 19 studies of the outcome of patients with critical limb ischemia (CLI) after initial treatment. Analysis of the combined results found that, after 6 months of follow up, 45% of those studied were alive without having had an amputation 35% were alive but had to have an amputation 20% had died. Keywords: CLI, amputation

21. The results of below-knee amputation in patients with PAD can be summarized as follows In the early post-operative period 60% achieved first-degree healing 15% achieved second-degree healing 15% had to have an above-knee amputation 10% died perioperatively. Two years after below-knee amputation 40% achieved full mobility 15% had to have amputation of the contralateral side 15% had to have an above-knee amputation on the index side 30% had died. Keywords: amputation, PADThe results of below-knee amputation in patients with PAD can be summarized as follows In the early post-operative period 60% achieved first-degree healing 15% achieved second-degree healing 15% had to have an above-knee amputation 10% died perioperatively. Two years after below-knee amputation 40% achieved full mobility 15% had to have amputation of the contralateral side 15% had to have an above-knee amputation on the index side 30% had died. Keywords: amputation, PAD

22. Treatment of Peripheral Arterial Disease

23. Two Goals in Treating Patients With PAD Improve ability to walk Important increase in peak walking distance Improvement in quality of life indicators Prevent progression to critical limb ischemia and amputation Decrease mortality from MI, stroke, and cardiovascular death Decrease nonfatal MI and stroke The goals of PAD treatment are two-fold: to improve the affected limb and to decrease cardiovascular morbidity and mortality. Limb-related improvement encompasses improvement in walking ability and prevention of progression to CLI and amputation. Aspects of improved walking ability include achieving a clinically important increase in peak walking distance and an improvement in quality of life (QoL) indicators. Typical QoL indicators include scores on the Walking Impairment Questionnaire and the Medical Outcome Questionnaire Short Form-36, which indicates improvement in general well-being Decreases in cardiovascular morbidity and mortality include decreased mortality from MI, stroke, and cardiovascular death, as well as decreased risk of nonfatal MI and stroke. Keywords: PAD, cardiovascular morbidity, mortality, progression, CLI, amputation, walking distance, quality of life, QoL, typical, MI, cardiovascular death, stroke The goals of PAD treatment are two-fold: to improve the affected limb and to decrease cardiovascular morbidity and mortality. Limb-related improvement encompasses improvement in walking ability and prevention of progression to CLI and amputation. Aspects of improved walking ability include achieving a clinically important increase in peak walking distance and an improvement in quality of life (QoL) indicators. Typical QoL indicators include scores on the Walking Impairment Questionnaire and the Medical Outcome Questionnaire Short Form-36, which indicates improvement in general well-being Decreases in cardiovascular morbidity and mortality include decreased mortality from MI, stroke, and cardiovascular death, as well as decreased risk of nonfatal MI and stroke. Keywords: PAD, cardiovascular morbidity, mortality, progression, CLI, amputation, walking distance, quality of life, QoL, typical, MI, cardiovascular death, stroke

24. Peripheral Arterial Disease Management of Cardiovascular Risks

25. Risk Reduction of Clopidogrel vs Aspirin in Patients With Atherosclerotic Vascular Disease Of the 19,185 patients studied in CAPRIE, 3867, or 20.2%, had diabetes. Approximately one-third of patients with PAD studied in CAPRIE had diabetes. In CAPRIE, clopidogrel�s superiority over aspirin at reducing the risk of reaching the composite end-point was greatest in the subgroup of patients who had PAD. Clopidogrel�s superiority over aspirin at reducing the risk of reaching the composite end-point was next greatest in all patients considered as a group. Clopidogrel produced roughly equal reductions in the risk of reaching the composite end-point in all patients considered as a group and in the subgroup who had experienced a stroke. However, in the subgroup of patients who had had an MI, aspirin was better than clopidogrel at reducing the risk of reaching the composite end-point. Keywords: CAPRIE, diabetes, PAD, aspirin, clopidogrel Of the 19,185 patients studied in CAPRIE, 3867, or 20.2%, had diabetes. Approximately one-third of patients with PAD studied in CAPRIE had diabetes. In CAPRIE, clopidogrel�s superiority over aspirin at reducing the risk of reaching the composite end-point was greatest in the subgroup of patients who had PAD. Clopidogrel�s superiority over aspirin at reducing the risk of reaching the composite end-point was next greatest in all patients considered as a group. Clopidogrel produced roughly equal reductions in the risk of reaching the composite end-point in all patients considered as a group and in the subgroup who had experienced a stroke. However, in the subgroup of patients who had had an MI, aspirin was better than clopidogrel at reducing the risk of reaching the composite end-point. Keywords: CAPRIE, diabetes, PAD, aspirin, clopidogrel

26. Intensive BP Therapy in Patients With Diabetes: Benefits in the PAD Group The Appropriate Blood Pressure Control in Diabetes Study (ABCD) followed 950 patients with type 2 diabetes for 5 years. Of the 950 subjects in ABCD, 480 were normotensive. Their baseline diastolic blood pressure was 80 to 89 mmHg. Of these, 447 were randomized to moderate vs intensive antihypertensive treatment to reduce diastolic blood pressure by 10 mmHg. Patients in the intensive blood pressure treatment group were randomized to receive enalapril or nisoldipine. PAD, defined as an ABI <0.9, was identified in 53 patients After adjustment for 9 risk factors, an inverse relation was found between ABI and cardiovascular events in the 227 patients who received moderate blood pressure treatment, as shown by the red line in the graph. This relation was significant at a level of P =.009. Moderate treatment resulted in a mean 4-year blood pressure of 137/81 mmHg. No relation was found between ABI and cardiovascular events in the 220 patients who received intensive treatment, as shown by the green line in the graph. Intensive treatment resulted in a mean 4-year blood pressure of 128/75 mmHg (P =.91). Twelve cardiovascular events occurred in PAD patients receiving moderate treatment (38.7%), and 3 cardiovascular events occurred in PAD patients receiving intensive blood pressure treatment (13.6%). With intensive control, the risk of an event was not increased even in those with the lowest ABI values and was the same as in patients without PAD In PAD patients with diabetes, intensive blood pressure control to a mean of 128/75 mmHg markedly reduced cardiovascular events. Keywords: Appropriate Blood Pressure Control in Diabetes Study, ABCD, diabetes, ABI, cardiovascular events, PAD Mehler PS, Coll JR, Estacio R, Esler A, Schrier RW, Hiatt WR. Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes. Circulation. 2003;107:753-756.The Appropriate Blood Pressure Control in Diabetes Study (ABCD) followed 950 patients with type 2 diabetes for 5 years. Of the 950 subjects in ABCD, 480 were normotensive. Their baseline diastolic blood pressure was 80 to 89 mmHg. Of these, 447 were randomized to moderate vs intensive antihypertensive treatment to reduce diastolic blood pressure by 10 mmHg. Patients in the intensive blood pressure treatment group were randomized to receive enalapril or nisoldipine. PAD, defined as an ABI <0.9, was identified in 53 patients After adjustment for 9 risk factors, an inverse relation was found between ABI and cardiovascular events in the 227 patients who received moderate blood pressure treatment, as shown by the red line in the graph. This relation was significant at a level of P =.009. Moderate treatment resulted in a mean 4-year blood pressure of 137/81 mmHg. No relation was found between ABI and cardiovascular events in the 220 patients who received intensive treatment, as shown by the green line in the graph. Intensive treatment resulted in a mean 4-year blood pressure of 128/75 mmHg (P =.91). Twelve cardiovascular events occurred in PAD patients receiving moderate treatment (38.7%), and 3 cardiovascular events occurred in PAD patients receiving intensive blood pressure treatment (13.6%). With intensive control, the risk of an event was not increased even in those with the lowest ABI values and was the same as in patients without PAD In PAD patients with diabetes, intensive blood pressure control to a mean of 128/75 mmHg markedly reduced cardiovascular events. Keywords: Appropriate Blood Pressure Control in Diabetes Study, ABCD, diabetes, ABI, cardiovascular events, PAD Mehler PS, Coll JR, Estacio R, Esler A, Schrier RW, Hiatt WR. Intensive blood pressure control reduces the risk of cardiovascular events in patients with peripheral arterial disease and type 2 diabetes. Circulation. 2003;107:753-756.

27. Heart Protection Study:Vascular Event by Prior Disease The Heart Protection Study compared the effects of taking 40 mg simvastatin or matching placebo daily for 5 years on mortality and vascular event rates in 20,536 adults age 40 to 80 years in the United Kingdom who had coronary disease, other occlusive arterial disease, or diabetes. Mean baseline LDL-C level was 2.4 mmol/L. Simvastatin therapy reduced the rate of first vascular events, defined as coronary death, MI, stroke, or revascularization, by about one-quarter in all patients as well as in all subgroups of patients, including the 3748 patients with PAD. This finding was highly statistically significant at a level of P < 0.0001. On the basis of these findings, the study authors concluded that using simvastatin, 40 mg daily, for 5 years would prevent about 100 people per 1000 from having at least one major vascular event. Keywords: mortality, diabetes, MI, stroke, revascularization, PAD Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22. The Heart Protection Study compared the effects of taking 40 mg simvastatin or matching placebo daily for 5 years on mortality and vascular event rates in 20,536 adults age 40 to 80 years in the United Kingdom who had coronary disease, other occlusive arterial disease, or diabetes. Mean baseline LDL-C level was 2.4 mmol/L. Simvastatin therapy reduced the rate of first vascular events, defined as coronary death, MI, stroke, or revascularization, by about one-quarter in all patients as well as in all subgroups of patients, including the 3748 patients with PAD. This finding was highly statistically significant at a level of P < 0.0001. On the basis of these findings, the study authors concluded that using simvastatin, 40 mg daily, for 5 years would prevent about 100 people per 1000 from having at least one major vascular event. Keywords: mortality, diabetes, MI, stroke, revascularization, PAD Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22.

28. Effects of Simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease(Am J Med 2003;114:359) Prospective randomized study Claudicants Placebo vs. Simvastatin 40 mg for 6 months N = 86 43 � placebo 43 - simvastatin

29. Effects of Simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease(Am J Med 2003;114:359)

31. Effects of Simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease(Am J Med 2003;114:359)

32. Effects of Simvastatin on walking performance and symptoms of intermittent claudication in hypercholesterolemic patients with peripheral vascular disease(Am J Med 2003;114:359) Conclusion High dose short term Rx with simvastatin improves Walking performance ABI�s Symptoms of claudication