Claudication as an ‘Orphan Disease’: Rationale and Goals of Drug Therapy for Peripheral Arterial Disease

Patients with peripheral arterial disease are often perceived to suffer from a disorder whose pathogenesis and symptoms are not amenable to drug therapies. This clinical misperception remains prevalent despite an abundance of data suggesting that diverse pharmacotherapies may modulate the natural history of this disease. Patients with chronic limb arterial occlusive disease suffer from a disease that is characterized by: (1) a prolonged asymptomatic state that can be identified by simple physical examination and confirmed by measurement of the ankle brachial index; (2) a multi-year period of symptomatic claudication; and (3) a variable rate of progression to critical limb ischemia or acute arterial occlusion. This stage-dependent disease progression is mediated via the dynamic, but as yet incompletely understood, interaction of factors that elicit endothelial dysfunction, atherogenesis, and thrombosis. Current data suggest that each of these contributory disease processes can be modulated by extant pharmacotherapies. Additionally, many novel pharmacotherapeutic agents that are currently under investigation may further improve the ability of clinicians to modulate these fundamental biologic processes. Pharmacologic therapies should be targeted to decrease the rate of limb arterial disease progression, to improve limiting symptoms, and to prolong life. Symptoms of claudication can be objectively assessed via both exercise testing and disease-specific questionnaires. The presence of lower extremity atherosclerotic disease is predictive of the presence of coronary heart disease and a foreshortened five-year survival. Current data suggest that clinical investigations should be able to effectively stratify this relative risk via use of both clinical variables (e.g., age, diabetes mellitus, tobacco use, etc.) or by measurement of the ankle brachial index (ABI). The role of the physician is to decrease suffering and to prolong life. Judicious administration of medical therapies can play a critical role in helping the vascular practitioner accomplish these goals.

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The Role of Tobacco Cessation, Antiplatelet and Lipid-Lowering Therapies in the Treatment of Peripheral Arterial Disease

Vascular Medicine ◽

10.1177/1358863x9700200314 ◽

1997 ◽

Vol 2 (3) ◽

pp. 243-251 ◽

Cited By ~ 81

Author(s):

Alan T Hirsch ◽

Diane Treat-Jacobson ◽

Harry A Lando ◽

Dorothy K Hatsukami

Keyword(s):

Peripheral Arterial Disease ◽

Arterial Disease ◽

Pharmacological Therapy ◽

Current Data ◽

Lipid Lowering ◽

History Of ◽

Medical Therapies ◽

Peripheral Arterial ◽

Interventional Therapies

Despite the widely held belief that there are no effective medical therapies for peripheral arterial disease (PAD), current data suggest that medical therapies can effectively modify the natural history of atherosclerotic lower extremity arterial occlusive disease. The ideal medical therapy would improve claudication, forestall the onset of limb-threatening events, decrease rates of invasive interventional therapies and improve long-term patient survival. These ideal outcomes might be achieved through the use of smoking cessation interventions, including behavioral and pharmacological therapy, and the administration of antiplatelet and lipid-lowering medications in patients with PAD.

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The arteriomobil project for peripheral arterial disease

VASA ◽

10.1024/0301-1526.37.4.345 ◽

2008 ◽

Vol 37 (4) ◽

pp. 345-352 ◽

Cited By ~ 5

Author(s):

Pfeiffer ◽

Bock ◽

Hohenberger ◽

Kröger

Keyword(s):

Peripheral Arterial Disease ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Computer Assisted ◽

German Population ◽

Co Morbidity ◽

History Of ◽

And Gender ◽

Peripheral Arterial ◽

Self Help Groups

Background: Peripheral Arterial Disease in Germany is underestimated with regard to incidence and the consequences. In 1997 the Federal Association of the Peripheral Arterial Disease Self Help Groups started the Arteriomobil Project to increase the awareness for venous and arterial diseases in the general population. We report peripheral arterial disease (PAD) prevalence rates and discuss the unique concept of this project. Patients and methods: The Arteriomobil is a mobile home modified to a simple investigation room with an examination couch, a Doppler equipment and a computer for data acquisition. From April 1997 to April 2007, a total of 14.785 volunteers aged 18 to 102 years (mean age ± SD: 64 ± 11 years, 63% females) were investigated. Patients were recruited as a result of their active visit to the Arteriomobil and their active participation in the investigation. In all participants the medical history was documented according to a standardized computer-assisted interview and a standardized Ankle Brachial Index (ABI) determined. Results: PAD prevalence in females (ABI < 0.9) increased from 2% in the 5th decade of life to 33% in 10th decade and in males from 4.8% to 41% accordingly. Age- and gender-adjusted odds ratios for PAD were highest in smoker: Odds ratio 2.85 (95% Confidence interval 2.5–3.2) and Diabetes mellitus 1.91 (95%CI 1.7–2.2). Hypertension and hypercholesterolemia had a lower impact. Family history of known PAD, CHD or CVD had no impact. Although 49.5% of all participants complained of "leg disorders during exercise" intermittent claudication turned out to be the most discriminating symptom for PAD 5.87 (95%IC 5.18–6.66). Previous myocardial infarction (MI) was the most frequently reported vascular co-morbidity in those with PAD (OR 2.23, 95%IC 1.9–2.7) followed by stroke (2.12, 1.7–2.7), angina pectoris (1.50, 1.3–1.8) and paresis (2.01, 1.6–2.6). The incidence of anti-platelet treatment was significantly higher in participants with coronary heart disease than in those with PAD or cerebrovascular disease. Conclusions: The Arteriomobil Project is the largest database regarding the prevalence of PAD in the German population. and the data underlines the high prevalence of PAD in Germany.

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Results of open vascular surgical therapy in chronic peripheral arterial disease

VASA ◽

10.1024/0301-1526/a000132 ◽

2011 ◽

Vol 40 (5) ◽

pp. 359-367 ◽

Cited By ~ 4

Author(s):

Balzer ◽

Weis-Müller

Keyword(s):

Peripheral Arterial Disease ◽

Surgical Therapy ◽

Critical Limb Ischemia ◽

Limb Ischemia ◽

Arterial Disease ◽

Current Data ◽

Operating Theatre ◽

Surgical Strategies ◽

Peripheral Arterial ◽

Aortoiliac Region

Surgery in chronic peripheral arterial disease (PAD) can alleviate symptoms in claudicants and may impede amputation in critical limb ischemia. The current data on different surgical strategies and techniques from the aortoiliac region to the pedal arteries as well as amputation as last resort are described and discussed. Treatment of PAD depends on the condition of the patient and his comorbidities. The question of optimal therapy for each patient cannot always be answered in the operating theatre or the angio-suite.

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Prevalence of peripheral arterial disease among patients with acute coronary syndrome, a sample of Iraqi patients in Al-Yarmook Teaching Hospital 2016

Journal of the Faculty of Medicine Baghdad ◽

10.32007/jfacmedbagdad.6321824 ◽

2021 ◽

Vol 63 (2) ◽

pp. 50-56

Author(s):

Osama A. Altaei ◽

Abbass N. Al-Sharifi

Keyword(s):

Acute Coronary Syndrome ◽

Peripheral Arterial Disease ◽

Previous History ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Leg Pain ◽

P Value ◽

Coronary Syndrome ◽

History Of ◽

Peripheral Arterial

Abstract Background: A significant proportion of patients with ischemic heart disease have been associated with peripheral arterial disease, yet it is still underestimated by our health system as many of patients are asymptomatic and this condition remains under diagnosed and therefore undertreated. Objective: To study prevalence of peripheral arterial disease of the lower limbs in patient with acute coronary syndrome and its association with certain risk factors. Method: A cross sectional descriptive study was conducted in the coronary care unit at Al-Yarmouk Teaching Hospital from the 1st of January 2016 to the 1st of November 2016 where hundred and fifty (150) patients enrolled to the coronary care unit with approved acute coronary syndrome, had been evaluated for peripheral arterial disease by assessing Demographic, risk factors and clinical features of the patients, including age groups, gender, hypertension, diabetes mellitus, smoking, dyslipidemia, family history. of coronary artery disease, previous history of cerebrovascular accident, body mass index, leg pain, measurement of ankle brachial index using hand held continuous wave Doppler device. Results: in 150 acute coronary syndrome patients were included male were (70.7%) , peripheral arterial disease was found in 31.2% through measuring ankle brachial index, 51% of those patients were asymptomatic and 29.8% with atypical leg pain and 12.8% with intermittent leg pain and 6.4% had pain at rest. And ankle brachial index in the 150 patients with acute coronary syndrome were 68.8% normal (ankle brachial index =1.4-0.91) and 21.3% (ankle brachial index =0.9-0.71) and 7.3 %( ankle brachial index =0.69-0.41) and 2.6% (ankle brachial index ≤0.40). Factors independently related to peripheral arterial disease were old age (>60 years) which constitutes 51% and p value was 0.013, and smoking which constitutes 46.8% and P value was 0.04, and dyslipidemia which constitutes 74% and P value was 0.03, and finally previous history of cerebrovascular accident which constitutes 21.2% and P value was 0.0018. Conclusion: The prevalence of peripheral arterial disease in patients presenting with acute coronary syndrome is considerable and significant, the majority of patients were asymptomatic, it is associated with increased cardiovascular risk. Factors like aging, hypertension, diabetes mellitus, smoking, previous history of cerebrovascular accident, and dyslipidemia were strong predictors of peripheral arterial disease. Key word: peripheral arterial disease , acute coronary syndrome, hypertension, diabetes mellitus.

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The prevalence of peripheral arterial disease in diabetic subjects in south-west Nigeria

African Journal of Primary Health Care & Family Medicine ◽

10.4102/phcfm.v4i1.354 ◽

2012 ◽

Vol 4 (1) ◽

Cited By ~ 5

Author(s):

Bolaji O. Oyelade ◽

Akintayo D. OlaOlorun ◽

Louis O. Odeigah ◽

Isaac O. Amole ◽

Olufemi S. Adediran

Keyword(s):

Peripheral Arterial Disease ◽

Intermittent Claudication ◽

Objective Assessment ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Cross Sectional ◽

Index Measurement ◽

Clinical Methods ◽

History Of ◽

Peripheral Arterial

Background: Peripheral arterial disease (PAD) is rarely sought for and generally underdiagnosed even in diabetics in developing countries like Nigeria. PAD is easily detected and diagnosed by the ankle-brachial index, a simple and reliable test. Objectives: To determine the prevalence of PAD in diabetic subjects aged 50–89 years and the value of ankle-brachial index measurement in the detection of PAD.Method: A cross-sectional descriptive study of 219 diabetic subjects aged 50–89 years was carried out. The participants were administered a pre-tested questionnaire and measurement of ankle-brachial index (ABI) was done. The ankle-brachial index < 0.90 was considered equivalent to peripheral arterial disease.Results: The overall prevalence of PAD was 52.5%. The prevalence of symptomatic PAD was 28.7% whilst that of asymptomatic PAD was 71.3%. There were a number of associations with PAD which included, age (p < 0.05), sex (p < 0.05), and marital status (p < 0.05). The use of the ankle-brachial index in the detection of PAD was clearly more reliable than the clinical methods like history of intermittent claudication and absence or presence of pedal pulses.Conclusion: The prevalence of PAD is relatively high in diabetic subjects in the southwestern region of Nigeria. Notable is the fact that a higher proportion was asymptomatic. Also the use of ABI is of great value in the detection of PAD as evidenced by a clearly more objective assessment of PAD compared to both intermittent claudication and absent pedal pulses.

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Prevalence of Peripheral Arterial Disease and Associated Vascular Risk Factors in 65-Years-Old People of Northern Barcelona

Journal of Clinical Medicine ◽

10.3390/jcm10194467 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4467

Author(s):

Gabriela Gonçalves-Martins ◽

Daniel Gil-Sala ◽

Cristina Tello-Díaz ◽

Xavier Tenezaca-Sari ◽

Carlos Marrero ◽

...

Keyword(s):

Risk Factors ◽

Peripheral Arterial Disease ◽

Strong Association ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Cross Sectional ◽

Screening Programs ◽

History Of ◽

Peripheral Arterial ◽

Male Subjects

Objective: To determine the prevalence and risk factors associated with peripheral arterial disease (PAD) in Northern Barcelona at 65 years of age. Methods: A single-center, cross-sectional study, including males and females 65 years of age, health care cardholders of Barcelona Nord. PAD was defined as an ankle–brachial index (ABI) < 0.9. Attending subjects were evaluated for a history of common cardiovascular risk factors. A REGICOR score was obtained, as well as a physical examination and anthropometric measurements. Results: From November 2017 to December 2018, 1174 subjects were included: 479 (40.8%) female and 695 (59.2%) male. Overall prevalence of PAD was 6.2% (95% CI: 4.8–7.6%), being 7.9% (95% CI: 5.9–9.9%) in males and 3.8% (95% CI: 2.1–5.5%) in females. An independent strong association was seen in male smokers and diabetes, with ORs pf 7.2 (95% CI: 2.8–18.6) and 1.8 (95% CI: 1.0–3.3), respectively, and in female smokers and hypertension, with ORs of 5.2 (95% CI: 1.6–17.3) and 3.3 (95% CI: 1.2–9.0). Male subjects presented with higher REGICOR scores (p < 0.001). Conclusion: Higher-risk groups are seen in male subjects with a history of smoking and diabetes and female smokers and arterial hypertension, becoming important subgroups for our primary healthcare centers and should be considered for ABI screening programs.

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Clinical study of peripheral arterial occlusive disease of lower extremities

International Surgery Journal ◽

10.18203/2349-2902.isj20181116 ◽

2018 ◽

Vol 5 (4) ◽

pp. 1388

Author(s):

Prasad C. ◽

Santosh Nayak K.

Keyword(s):

Peripheral Arterial Disease ◽

Peripheral Arterial Occlusive Disease ◽

Lower Extremities ◽

Limb Ischemia ◽

Arterial Disease ◽

Arterial Occlusive Disease ◽

Occlusive Disease ◽

Age Group ◽

History Of ◽

Peripheral Arterial

Background: Peripheral arterial occlusive disease or commonly known as peripheral arterial disease (PAD) comprises those entities which result in obstruction to blood flow in the arteries, exclusive of the coronary and intracranial vessels and the term is usually applied to disease involving the arteries of lower extremity. Peripheral arterial disease is an important manifestation of atherosclerosis involving the arteries of legs. Vascular surgeons continue to encounter complications of atherosclerosis as their most common clinical challenge. Objective of this study was to know the various etiologies and different clinical presentation of Peripheral arterial occlusive disease.Methods: This was a cross sectional observational study of 50 cases diagnosed with Peripheral Arterial disease of the lower extremities, done during the period from January 2013 to June 2014 among the Patients with Peripheral Arterial disease of the lower extremities admitted to surgical wards of SCBMCH, Cuttack.Results: All the cases in the present study fall under the category of chronic lower limb ischemia and no cases of acute limb ischemia. Majority of the cases in atherosclerosis were above the age of 50 years, while in the TAO group majority belong to the age group between 31 to 50 years. TAO was usually limited to the distal part of the limb. All patients with TAO had a history of smoking and 61% of atherosclerotic patients gave history of smoking.Conclusions: TAO and Atherosclerosis are the etiologies for ischemia in these cases, with atherosclerosis being more common of the two. TAO presented at a younger age group whereas atherosclerosis presented in the older age group.

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Hallucal thenar index: A new index to detect peripheral arterial disease using laser speckle flowgraphy

Vascular ◽

10.1177/1708538120938935 ◽

2020 ◽

pp. 170853812093893

Author(s):

Kazuhiro Tsunekawa ◽

Fumio Nagai ◽

Tamon Kato ◽

Ikkei Takashimizu ◽

Daisuke Yanagisawa ◽

...

Keyword(s):

Blood Flow ◽

Peripheral Arterial Disease ◽

Operating Characteristic ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Laser Speckle ◽

Laser Speckle Flowgraphy ◽

Skin Perfusion ◽

Peripheral Arterial ◽

Cutaneous Blood

Objectives Laser speckle flowgraphy is a technology using reflected scattered light for visualization of blood distribution, which can be used to measure relative velocity of blood flow easily without contact with the skin within a short time. It was hypothesized that laser speckle flowgraphy may be able to identify foot ischemia. This study was performed to determine whether laser speckle flowgraphy could distinguish between subjects with and without peripheral arterial disease. Materials and methods All subjects were classified based on clinical observations using the Rutherford classification: non-peripheral arterial disease, class 0; peripheral arterial disease group, class 2–5. Rutherford class 6 was one of the exclusion criteria. Laser speckle flowgraphy measured the beat strength of skin perfusion as an indicator of average dynamic cutaneous blood flow change synchronized with the heartbeat. The beat strength of skin perfusion indicates the strength of the heartbeat on the skin, and the heartbeat strength calculator in laser speckle flowgraphy uses the blood flow data to perform a Fourier transform to convert the temporal changes in blood flow to a power spectrum. A total of 33 subjects with peripheral arterial disease and 40 subjects without peripheral arterial disease at a single center were prospectively examined. Laser speckle flowgraphy was used to measure hallucal and thenar cutaneous blood flow, and the measurements were repeated three times. The hallucal and thenar index was defined as the ratio of beat strength of skin perfusion value on hallux/beat strength of skin perfusion value on ipsilateral thenar eminence. The Mann–Whitney U-test was used to compare the median values of hallucal and thenar index and ankle brachial index between the two groups. A receiver operating characteristic curve for hallucal and thenar index of beat strength of skin perfusion was plotted, and a cutoff point was set. The correlation between hallucal and thenar index of beat strength of skin perfusion and ankle brachial index was explored in all subjects, the hemodialysis group, and the non-hemodialysis (non-hemodialysis) group. Results The median value of the hallucal and thenar index of beat strength of skin perfusion was significantly different between subjects with and without peripheral arterial disease (0.27 vs. 0.87, respectively; P < 0.001). The median value of ankle brachial index was significantly different between subjects with and without peripheral arterial disease (0.8 vs. 1.1, respectively; P < 0.001). Based on the receiver operating characteristic of hallucal and thenar index, the cutoff was 0.4416 and the sensitivity, specificity, positive predictive value, and negative predictive value were 68.7%, 95%, 91.7%, and 77.6%, respectively. The correlation coefficients of all subjects, the hemodialysis group, and the non-hemodialysis group were 0.486, 0.102, and 0.743, respectively. Conclusions Laser speckle flowgraphy is a noninvasive, rapid, and widely applicable method. Laser speckle flowgraphy using hallucal and thenar index would be helpful to determine the differences between subjects with and without peripheral arterial disease. The correlation between hallucal and thenar index of beat strength of skin perfusion and ankle brachial index indicated that this index was especially useful in the non-hemodialysis group.

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