Peripheral Arterial Diseases

Download this issue Back to summary

Peripheral arterial diseases

Peripheral arterial disease in Europe
Dan Olinic (Romania)

Peripheral arterial disease begins as an asymptomatic disease, which is often associated with a high risk of cardiovascular disease. Of the 17 million people diagnosed with peripheral arterial disease in the European Union, the estimated prevalence in people ≥65 years is 17.1%. In a study that analyzed 460 patients with known peripheral arterial disease, atypical pain symptoms occurred in 60% of the patients (JAMA. 2001;206:1599-1606). These symptoms include (i) pain that is different from typical exertional claudication pain; (ii) pain not requiring cessation of physical activity; (iii) pain lasting longer than 10 min after cessation of physical activity; and (iv) pain that occurs both at rest and upon exertion. The prevalence of peripheral arterial disease is higher in men aged 50 to 59 (3.1% to 2.7%) and aged 70 to 79 (11.6% to 11.5%) than in women, and its distribution across ethnic origins is as follows: non–Hispanic whites (43.5%), African-Americans (20%), Hispanics (20.7%), and Chinese-Americans (15.6%). Peripheral arterial disease risk factors include behavioral factors (eg, tobacco use, physical inactivity, harmful use of alcohol, and a diet rich in salt, fat, and calories), metabolic factors (eg, hypertension, diabetes, high cholesterol levels, and obesity), and other factors (eg, poverty, low education status, advancing age, sex, genetic disposition, stress, and depression). In European populations, there are 500 to 1000 cases of critical limb ischemia every year per million, with a prevalence of 1% to 3% in patients with peripheral arterial disease and 1% to 2% in patients with critical limb ischemia requiring lower limb amputation. Future trends are difficult to predict, especially with the changing risks in the population (eg, tobacco smoking and diabetes) and the limited evidence on trends during the past few decades that have suggested a decline in the incidence of intermittent claudication. Active screening/ankle brachial index vs a “passive” symptomatic diagnosis needs to be conducted to decrease the impact of peripheral arterial disease.

Cost of peripheral arterial disease and trends in complications
Mariella Catalano (Italy)

The frequency of peripheral arterial disease is expected to increase by about 35% by the year 2030, considering that there is the marked increase in peripheral arterial disease burden with advancing age. From 2005 to 2009, total peripheral arterial disease cases increased by 20.7%, critical limb ischemia by 2.9%, major amputations decreased by 1.1%, and minor amputations slightly increased by 0.13%. The crude overall in-hospital mortality remained unchanged in patients with a limp (2.2%), while it decreased by 1.4% in patients with critical limb ischemia; however, the mortality rate increased significantly in patients with a limp (P<0.001). Total endovascular revascularizations increased by 46%, thromboembolectomy by 67%, endarterectomy by 42%, and patch plastic by 21%, whereas, peripheral bypasses decreased by 2%. The total reimbursement costs for peripheral arterial disease for inpatient care increased by 21%, with an average per-case reimbursement cost in 2009 of 4506 euros for patients with a limp and 6791 euros for patients with criticallimb ischemia. The focus should be turned to prevention, early diagnosis, cooperation and networking, patient endorsement, awareness education, and specific target populations to reduce the impact of peripheral arterial disease on health care costs and outcomes.

The concept of prevention
Jean-Claude Wautrecht (Belgium)

What are the differences between prevention and health promotion? Health promotion refers to a set of strategies and methods implemented at different social levels in an attempt to increase people’s health resources and potentials. Health promotion interventions are often designed and conducted by public health specialists, without a specific problem, risk factor, or disease in mind; they usually promote general health. Prevention, unlike health promotion, involves activities aimed at avoiding and reducing the likelihood of or delaying harm to a person’s health. Prevention activities can take place on three levels (primary, secondary, and tertiary) depending on the time, objective, and target of preventive intervention. Preventive interventions are performed by medical experts to fight specific diseases (eg, cardiovascular diseases). Specifically, health promotion is resource oriented, nonspecific, related to health science, requires an active participation from patients/citizens, and focuses on health; whereas, prevention is burden oriented, specific, related to medicine, requires passive participation from patients/citizens, and focused on disease. Prevention has many faces; therefore, it needs more than one approach because the results depend on how early the interventions are planned. In the future, simple and inexpensive interventions will produce significant results. Education, at all levels (specialists, family doctors, health professionals, patients, and the whole population), is the key to success.

European biobanks
Bahare Fazeli (Iran)

According to Time Magazine, the creation of biobanks is one of ten ideas that are changing the world. A biobank is a safe house for biological samples that could be used to research new treatments for diseases. A biobank contains biological material, and it is connected to information and legal issues, such as consent and patient data safety and protection. Biobanks enable a shift from “one-size-fits-all” to more targeted therapies with respect to age, sex, demography, and relevant costs (personalized medicine). Biobanks promote a personalized genetic study with genome information (demographic, social, and environmental data) to help predict and identify risk factors for the development of better prevention methods. One limitation for vascular disease researchers is low sample sizes. In light of the large sample size of biological specimens and clinical data on vascular diseases, personalized medicine can be developed with the main goal being to avoid amputation. The VAS Biobank is a biorepository that accepts, processes, and stores biospecimens and associated data for use in research and clinical care on peripheral diseases. It is possible to contact VAS Biobank at

Best papers of the ESVM 2016 meeting

Residual cardiovascular risk in peripheral artery disease: exploring the role of albumin-creatinine excretion rate (ACR) in a prospective study
Sandra Mastroianno (Italy)

This study assessed whether a marker of microvascular dysfunction, such as the albumin-creatinine excretion rate (ACR), might be useful for evaluating residual cardiovascular risk in patients affected by advanced peripheral arterial disease. A total of 264 patients with a diagnosis of advanced peripheral arterial disease were followed for approximately 33}11 months. According to the overall median ACR value, the investigators divided their population into lower and higher ACR groups. Of the 64 major cardiovascular events, defined as myocardial infarction, cerebral ischemia, myocardial and/or peripheral revascularization, or death, observed, 23 occurred in the lower ACR group and 41 in the higher ACR group. Thus, in this prospective study, high ACR levels were predictive of cardiovascular events in patients affected by advanced peripheral arterial disease.

Effects of supervised exercise on reticulated reactive platelets and erythrocyte fragments in patients with peripheral atherosclerosis
Sergio De Marchi (Italy)

Platelet activation plays an important role in atherosclerosis progression. The immature platelet fraction reflects the degree of reticulated platelets, which are highly reactive young platelets associated with cardiovascular complications. Furthermore, the presence of a wide red blood cell distribution, mostly due to fragmented red blood cells, is considered a negative prognostic factor for coronary artery disease. The effects of a 15-day aerobic training period on the immature platelet fraction and fragmented red blood cells were evaluated at rest and after a maximal walking exercise in 12 patients with intermittent claudication (stage II of Leriche-Fontaine classification). Exercise training can reduce the immature platelet fraction and the fragmented red cells in patients with peripheral arterial disease. The immature platelet fraction increases after maximal exercise testing, which is attenuated during the training period. Marchi hypothesized that training, which probably improves oxidation, inflammation, and endothelial function, is effective in reducing both the platelet activation (immature platelet fraction) and fragmented red blood cell count.

Undernutrition, a novel marker of peripheral arterial disease: the EPIDEMCA study
Ileana Desormais (France)

There is an ongoing debate regarding the association between obesity and peripheral arterial disease. However, the association between undernutrition and prevalent peripheral arterial disease has been poorly assessed. This study evaluated the association between undernutrition and peripheral arterial disease in elderly patients in an African population. Patients ≥65 years from two urban and two rural areas of the Republic of Congo and the Central Africa Republic (n=1815) were enrolled in the study. The existence of peripheral arterial disease was defined by an ankle-brachial index value >0.90. The patients were categorized into four groups according to the World Health Organization criteria and their BMI: (i) undernutrition (<18.5 kg/m2); (ii) normal (18.5 to 24.9 kg/m2); and (iii) overweight (25 to 29.9 kg/m2); and (iv) obese (≥30 kg/m2). The prevalence of undernutrition was higher in patients with peripheral arterial disease than in those without the disease (37.1% vs 33.5%, P=0.0333). Undernutrition remained significantly associated with peripheral arterial disease after adjustment for all potential confounding factors, such as the general population (OR, 2.09; P=0.0009) and sex (males: OR, 2.82; P=0.0038 and females: OR, 1.75; P=0.0492). In the multivariate analysis, there was no association between the overweight (OR, 1.10; 95% CI, 0.62-1.96) or obesity (OR, 1.55; 95% CI, 0.74-3.23) groups and peripheral arterial disease in the overall cohort and per country. Therefore, undernutrition seems to be associated with peripheral arterial disease in elderly communities in central Africa. Pending further confirmation, this potentially novel risk factor should be taken into account as a target to improve global cardiovascular health.

Symptomatic lower-limb giant-cell arteritis: characteristics, management and long-term outcomes
Claire Le Hello (France)

The characteristics, evolution, and long-term outcomes of symptomatic lower-limb giant-cell arteritis are rarely reported. In a retrospective analysis of 8 patients (6 women; mean age 63.6±10.9 years; follow-up, 137.3±57.3 months), the classic signs of giant-cell arteritis, such as headaches, polymyalgia rheumatic, and inflammatory syndrome, were less frequently observed. Conversely, a bilateral and rapidly progressive lower limb claudication was documented in all patients, which appeared as the first sign in 5 patients. Inflammatory lesions were localized more frequently in the superficial femoral and popliteal arteries. All patients received corticosteroids for 132±76.2 months; 2 subjects were treated with an immunosuppressive agent. Only 3 patients required a revascularization. In this group, thromboendarterectomy and endovascular procedures were not effective, whereas bypasses were successful. Lower limb claudication regressed slower than cephalic signs in 7 patients (10.5±12.1 months) and disappeared in 5 (16.8±9.8 months). Every patient had one relapse (23.9±26.7 months; mean corticosteroid dose, 0.28±0.30 mg/kg/day). Lower-limb giant-cell arteritis caused only one of the 4 deaths observed during the follow-up. In conclusion, long-term mortality that is attributable to symptomatic lower-limb giant-cell arteritis seems low despite frequent relapses and corticosteroid dependence.

Vascular diseases: particularities for women

Peripheral arterial diseases
Alessandra Bura-Riviere (France)

Little is known about sex-specific differences in peripheral arterial disease. Although the age-dependent prevalence of peripheral arterial disease in adult women is lower than that for men, the total population burden of peripheral arterial disease appears to be higher in women. The women included in most of the studies were older, were less frequently smokers, and presented at more advanced stages of the disease. Although women were less likely than men to undergo lower extremity revascularization (eg, fewer bypasses in the COPART registry), procedural complications and stent or bypass occlusion are more frequent, and the long-term mortality is higher (72% vs 54% at 3 years). In conclusion, the prevalence of peripheral arterial disease is high in women, the symptoms are often absent or underestimated, and the diagnosis is often made at more advanced stages.

Aortic and peripheral arterial vascular surgery
Nellie Della Schiava and Antoine Millon (France)

Estrogens often protect women from aortic aneurysms. Although the screening and indications are the same between women and men, there are many controversies about earlier surgery because of smaller body sizes. In comparison with men, the evolution of aortic aneurysms is more aggressive with faster growth, higher rupture rates (4 times), higher mortality in case of rupture (3 times), and lower repair rates in women with the same comorbidities. For elective or emergency surgery, female sex is an independent risk factor. In the long term after an operation or endovascular aneurysm repair, women have lower survival rates, which may be due to older age and the advanced disease state at the time of repair due to the delay in diagnosis and hormonal differences. Compared with men, women have an anatomy that is often less suitable for endovascular aneurysm repair due to a shorter neck length, increased neck angulation, and smaller iliac vessel diameters. For carotid stenosis, women have poorer short-term outcomes after surgery compared with men, which may be due to older age at the time of the surgery, smaller vessel diameter, hormonal differences, lower sensitivity to antiplatelet therapy, different plaque morphology, higher occurrence of microembolic signals, and higher stenosis rates. Compared with men, women with lower extremity arterial occlusive disease are older, with a more advanced disease at presentation, smaller vessel diameters, and have poorer outcomes, including higher bypass failure and amputation rates. The small aorta syndrome especially affects young women, and it is associated with coronary artery disease (88%) and diabetes (42%). Endovascular treatment is feasible for this group of patients. In conclusion, earlier screening and better medical management of cardiovascular risk factors are important for women. Biomedical research will help solve these issues. Specific recommendations with better scientific evidence from studies including only women are necessary.

Vascular acrosyndromes
Pavel Poredos (Slovenia)

Acrosyndromes are acral circulatory disorders caused by vasomotor deterioration or occlusion of distal arteries that involve the distal part of the toes or fingers.
• Primary Raynaud’s phenomenon predominantly affects young women, where the treatment consists of lifestyle modifications and, in advanced cases, vasodilating drugs. The secondary form has the symptoms and signs of an underlying disease, such as systemic lupus erythematosus.
• Acrosyanosis is a symmetric, painless, and bluish discoloration of distal parts of the body, where the diagnosis is based on the clinical description. Constriction of venules and capillaries of unknown causes are responsible for the disease. The secondary form is associated with hypoxemia, neoplasms, hematological diseases, and toxicities.
• Chilblains are caused by an abnormal skin reaction to cold, and the symptoms fade with warmer temperatures.
• Paroxysmal finger hematomas occur spontaneously with recurring episodes, and they are characterized by ecchymosis on the volar side of the proximal phalanx, with an associated risk of brain and gastrointestinal bleeding. Treatment only involves treating the symptoms.
• Blue-toe syndrome is caused by the release of cholesterol crystals from atheromatous plaques.
• Acral necrosis is frequently accompanied by renal failure. Treatment involves treating the symptoms with antiplatelet drugs.
• Cryoglobulinemia is a medical condition in which the blood contains large amount of cryoglobulins that become insoluble at low temperatures.
• Cryoglobulinemia can be associated with multiple myeloma, hepatitis C, and systemic lupus erythematosus.
• Primary antiphospholipid antibody syndrome is related to antibodies (anticardiolipins), but there is no clinical manifestation of systemic lupus erythematosus or Sjögren’s syndrome.
• Primary systemic vasculitis is caused by inflammation and the destruction of blood vessel walls. Treatment consists of cytostatic drugs and corticosteroids.

In conclusion, the primary forms of these diseases are usually benign, periodic, and provoked by a cold environment; however, the secondary forms are related to other systemic diseases. Clinical symptoms are constant, more serious, and often accompanied by necrosis and ulcers. Diagnosis is based on clinical presentation of the tips of the fingers and toes. These conditions are more frequent in women than in men. Treatment of primary (benign) acrosyndromes consists of treating the symptoms and making lifestyle modifications. For secondary acrosyndromes, treatment of the underlying disease and the symptoms with drugs is necessary.

Vascular diseases in the Middle East

Study of clinical course and natural history of thromboangeitis obliterans (Buerger’s disease)
Hadi Modaghegh (Iran)

Thromboangeitis obliterans (Buerger’s disease), a nonatherosclerotic, segmental, occlusive, inflammatory condition of small- and medium-sized arteries (affecting adjacent veins and nerves), is characterized by highly cellular vessels (continued by recanalization or fibrosis) in young smokers. Thromboangeitis obliterans is a common vascular disease in South and Southeast Asia, the Middle East, Far East, and Eastern European countries. In Iran, the prevalence rate is 3.3 per 100 000 people. The etiology is unknown with many hypotheses: autoimmune, genetic, hypercoagulable state, oral infection (poor oral hygiene), and inflammatory. Smoking (even passive) is the most important risk factor for the pathogenesis, initiation, and progression of thromboangeitis obliterans. In Iran, patients with thromboangeitis obliterans are usually addicted to opium in addition to tobacco. In Modaghegh’s clinical experience, there is a 46% amputation rate. Among the therapeutic options, only prostaglandin IV and sympathectomy shorten the exacerbation episode. In some cases, prostaglandin therapy induces prolonged remission.

Middle East vascular entities, what is special?
Louy Altarazi (Syria)

Altarazi emphasized the high prevalence of inflammatory vascular diseases in the Middle East. In Syria, more than 56% of males and 18% of females are smokers. Teenagers start smoking around age 16 (1 Nargleh = 20 to 50 cigarettes), and the high prevalence of smoking causes early atherosclerosis and Buerger’s disease. About 15% to 35% of the population is diabetic with a high amputation rate due to a lack of a consensus for the management of the diabetic foot. Therefore, proper prevention and management of vascular diseases are crucial public health concerns in the Middle East.