Peripheral Arterial Vascular Disease Research Articles

Invited commentary

Dr Vouyouka and colleagues are to be commended for their important contribution to the literature entitled: “Lessons learned from the analysis of gender effect on risk factors and procedural outcomes of lower extremity peripheral arterial disease”. The influence of gender on peripheral arterial disease (PAD) is not well studied and is not well defined in the current literature. Unfortunately, women have been excluded from clinical trials due to the confounding factors such as hormonal influences, and Dr Vouyouka's analysis of a large administrative data set emphasizes gender-related disparities that exist in the care of patients with atherosclerotic vascular disease. This is truly a tragedy, as it is well known that PAD is a surrogate marker for systemic vascular disease. Besides having an elevated risk of severe atherothrombotic vascular events such as stroke, heart disease, and limb loss, patients with PAD also experience a resultant decrease in quality of life and increased cardiovascular morbidity and mortality.1Gerhard M. Baum P. Raby K.E. Peripheral arterial-vascular disease in women: prevalence, prognosis, and treatment.Cardiology. 1995; 86: 349-355Crossref PubMed Scopus (26) Google Scholar, 2Diehm C. Schuster A. Allenberg J.R. et al.High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: cross-sectional study.Atherosclerosis. 2004; 172: 95-105Abstract Full Text Full Text PDF PubMed Scopus (652) Google Scholar, 3Higgins J.P. Higgins J.A. Epidemiology of peripheral arterial disease in women.J Epidemiol. 2003; 13: 1-14Crossref PubMed Google Scholar Despite the magnitude of this health problem, screening and treatment rates in high-risk populations are inappropriately low, particularly for women. Aggressive screening programs to detect atherosclerosis have been advocated as well as aggressive risk factor management in women with asymptomatic disease.4Gen Teh L. Sieunarine K. Eikelboom J. Prendergast F.J. Goodman M.A. Joesbury K. et al.Suboptimal preventive practices in patients with carotid and peripheral vascular occlusive disease in a tertiary referral setting.ANZ J Surg. 2003; 73: 932-937Crossref PubMed Scopus (7) Google Scholar Primary prevention measures can be instituted once an estimate of absolute cardiovascular risk is known. Furthermore, as Dr Vouyouka indicates in the discussion section, many health care providers do not address cardiovascular disease or risk factors with their female patients, and sometimes are not aware of gender differences in symptoms, symptom reporting, and differing patient beliefs and attitudes. The authors clearly conclude from this data analysis that “aggressive modification of risk factors … may improve gender-related disparity in the outcomes of vascular disease”. However, in order for this to take place, the risk factor must be recognized through thorough history taking or evaluation. The burden is upon the medical profession to identify women and men prior to the onset of symptoms or limb-threatening disease, or even the onset of coronary or cerebrovascular symptoms. We must recognize women as having equivalent risks of atherosclerotic disease as men and proceed with testing women to avoid misdiagnosis. We also need to identify societal obstacles that promote isolation and prevent women from seeking evaluation and work to circumvent these obstacles. This article is an important one that should be read by physicians of numerous specialties.

Fatores de risco para lesão renal aguda após cirurgia cardíaca

The aim of the present study was to identify risk factors for acute renal failure in patients with normal levels of serum creatinine who had undergone coronary artery bypass graft (CABG) surgery and/or valve surgery. Data from a cohort of 769 patients were assessed using bivariate analyses and binary logistic regression modeling. Three hundred eighty one patients underwent CABG, 339 valve surgery and 49 had undergone both simultaneously. Forty six percent of the patients were female and the mean age was 57 +/- 14 years (13 to 89 years). Seventy eight (10%) patients presented renal dysfunction postoperatively, of these 23% needed hemodialysis (2.4% of all patients). The mortality for the whole cohort was 10%. The overall mortality for patients experiencing postoperative renal dysfunction was 40% (versus 7%, P < 0.001), 29% for those who did not need dialysis and 67% for those who needed dialysis (P = 0.004). The independent risk factors found were: age (P < 0.000, OR: 1.056), congestive heart failure (P = 0.091, OR: 2.238), COPD (P = 0.003, OR: 4.111), endocarditis (P = 0.001, OR: 12.140), myocardial infarction < 30 days (P = 0.015, OR: 4.205), valve surgery (P = 0.016, OR: 2.137), cardiopulmonary bypass time > 120 min (P = 0.001, OR: 7.040), peripheral arterial vascular disease (P = 0.107, 2.296). Renal dysfunction was the most frequent postoperative organ dysfunction in patients undergone CABG and/or valve surgery and age, congestive heart failure, COPD, endocarditis, myocardial infarction < 30 days, valve surgery, cardiopulmonary bypass time >120 min, and peripheral arterial vascular disease were the risk factors independently associated with acute renal failure (ARF).

Phlebotomy (bloodletting) in patients with metabolic syndrome: A randomized controlled trial

Question Metabolic syndrome has an increasing prevalence worldwide and there is an urgent need for improvement of medical treatment. In traditional medical systems bloodletting is a frequently recommended therapy in subjects with obesity and vascular disease. Recent randomized studies showed that bloodletting improves insulin sensitivity in patients with diabetes mellitus and increased ferritin concentration and might be beneficial in younger patients with peripheral arterial vascular disease. We aimed to test if traditional bloodletting has beneficial effects in patients with metabolic syndrome. Methods A randomized controlled study with a study period of 3 months was conducted in 64 self-referred subjects that had a confirmed diagnosis of metabolic syndrome as defined by recent guidelines. Thirty-three subjects (60±7 yr; BMI 32.8±5.5 kg/m 2 ) were allocated to the bloodletting intervention group and 31 subjects (57±10 yr; BMI 32.5±5.6 kg/m 2 ) to the control group (waiting list). In the intervention group two phlebotomies with removal of 300–400 ml of venous blood were performed at day 1 and after 4 weeks. Primary outcomes were the course of seated systolic blood pressure and of insulin sensitivity as measured by HOMA-Index. Secondary endpoints included diastolic blood pressure, ferritin, serum iron, hematocrit, HbA1c, LDL/HDL-quotient and blood glucose. Results Baseline characteristics were balanced between groups. Seated systolic blood pressure dropped from 148.5±12.3 to 130.5±11.8 mmHg in the intervention group and from 144.7±14.4 to 143.8±11.9 mmHg in the control group (group difference −16.6 mmHg, 95% CI:−20.7 to −12.5; p p =0.251). Diastolic blood pressure, heart rate, blood glucose, HbA1c and LDL/HDL were significantly decreased by bloodletting. Bloodletting led to reductions of serum iron concentration, plasma ferritin and a slight decrease in hematocrit with no serious adverse events. Conclusions Phlebotomy (bloodletting) effectively decreases blood pressure and improves metabolic parameters in patients with metabolic syndrome. Larger studies should test the longer-term efficacy of bloodletting in metabolic syndrome, hypertension and lipid disorders.

Clindamycin vasculitis in patients with peripheral arterial vascular disease

Clindamycin was first synthesized in 1966. It is a chemical derivative of lincomycin with activity against aerobic gram-positive and gram-negative bacteria. The side effects include diarrhea, pseudomembranous colitis, metallic taste in the mouth, transient elevation of transaminases, granulocytopenia, thrombocytopenia, and rash. The incidence of maculopapular rashes has been reported to be approximately 10%. Leukocytoclastic angitis or vasculitis induced by clindamycin has been reported (Lambert et al., Cutis 30:615–619, 1982) and this is a very serious complication in patients with peripheral arterial vascular diseases which may leads to severe and deep necrotizing vasculitis. We report two cases of necrotizing vasculitis due to clindamycin which was used for the treatment of chronic wounds in patients suffering of peripheral vascular disease.

Interventional radiology in the elderly

Interventional radiological percutaneous procedures are becoming all the more important in the curative or palliative management of elderly frail patients with multiple underlying comorbidities. They may serve either as alternative primary minimally invasive therapies or adjuncts to traditional surgical treatments. The present report provides a concise review of the most important interventional radiological procedures with a special focus on the treatment of the primary debilitating pathologies of the elderly population. The authors elaborate on the scientific evidence and latest developments of thermoablation of solid organ malignancies, palliative stent placement for gastrointestinal tract cancer, airway stenting for tracheobronchial strictures, endovascular management of aortic and peripheral arterial vascular disease, and cement stabilization of osteoporotic vertebral fractures. The added benefits of high technical and clinical success coupled with lower procedural mortality and morbidity are highlighted.

MODELLING OF THE RISK FACTORS AND CHRONIC DISEASESTHAT INFLUENCE THE DEVELOPMENT OF SERIOUS HEALTHCOMPLICATIONS

BACKGROUND Some chronic diseases, like diabetes type 2 and hypertension, and risk factors, such asobesity, hypercholesterolemia, and smoking, are strongly correlated with the potentialdevelopment of serious health complications that can threaten a patient’s life or significantly influence the quality of life, while at the same time representing an enormous economic burden. Such complications include, for example, stroke, coronary heart disease,peripheral arterial vascular disease, end-stage renal disease and congestive heart failure. METHODS For a quantitative evaluation of the mentioned patient groups, the age distribution andan estimation of the treatment expenses a dynamic mathematical model was developed,where special attention was devoted to its structure, as it should enable the sequentialconstruction and representation of different forms of data information. The model wasrealized in the Matlab program package with the Simulink Toolbox.

Modeling the influence of risk factors and chronic diseases on the development of strokes and peripheral arterial-vascular disease

Several chronic diseases and risky lifestyles have become an important social burden in many countries around the world, a problem which should not be underestimated. The situation is even more worrying when we take into account their influence on serious health complications that can threaten patients’ lives or significantly reduce their quality of life. The presented modeling-and-simulation study enables us to estimate the number of patients with type-2 diabetes, hypercholesterolemia and hypertension, obese and smoking people and the influence of these conditions on the development of strokes and peripheral arterial-vascular diseases. In addition, an estimate of treatment costs makes it possible to evaluate the social burden and provide information about the potential savings resulting from treating intensive chronic diseases.

Dipyridamole for Preventing Stroke and Other Vascular Events in Patients With Vascular Disease

Graeme J. Hankey MD, FRCP Section Editor: Patients with limited cerebral ischemia of arterial origin are at risk of serious vascular events (4% to 11% annually). Aspirin reduces that risk by 13%. In one trial, adding dipyridamole to aspirin was associated with a 22% risk reduction compared with aspirin alone. However, a systematic review of all trials of antiplatelet agents by the Antithrombotic Trialists’ Collaboration showed that, in high-risk patients, there was virtually no difference between the aspirin-dipyridamole combination and aspirin alone. To assess the efficacy and safety of dipyridamole versus control in the secondary prevention of vascular events in patients with vascular disease. We searched the Cochrane Stroke Group trials register (searched June 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library Issue 2, 2006), MEDLINE (1966 to May 2006) …

Reference data for distal blood pressure in healthy elderly and middle‐aged individuals measured with the strain gauge technique. Part I: Resting distal blood pressure

Objective. Most patients referred to our department for distal blood pressure (DBP) determination on suspicion of arterial peripheral vascular disease (apvd) are more than 60 years of age, whereas the only available reference data for resting pressure are based on data from healthy individuals aged between 43 and 57 years. Our aim was to investigate whether newly collected reference data for DBP measured using the strain‐gauge technique in healthy subjects older than 60 years and in others between 45 and 58 years were significantly different from the old reference data used in daily practice. Material and methods. Group I comprised 31 healthy persons aged between 61 and 87 years and group II 14 healthy middle‐aged hospital staff members aged between 45 and 58 years. Strict rules of inclusion were followed. Results. For group I, significantly greater gradients (DBPtoe – systolic arm blood pressure and DBPtoe – DBPankle) were found in the new reference data compared to the old. No significant difference between the mean values of the gradient (DBPankle – systolic arm blood pressure) was found between the old and new reference data, although the variation was significantly wider in the new reference data; the lower level of normality was therefore −15 mmHg compared to 0 mmHg in the old reference data. For group II, no significant differences between the gradients were found comparing the new and old reference data. Conclusion. These new data indicate that reference data gathered from middle‐aged subjects should be changed when DBP measurements are used in patients older than 60 years of age.

Reference data for distal blood pressure in healthy elderly and middle‐aged individuals measured with the strain gauge technique. Part II: Distal blood pressure after exercise

Objective. Distal blood pressure (DBP) determination after an exercise test is used on suspicion of arterial peripheral vascular disease (apvd). In our department. the average age of these patients is about 60 years. The usual reference values for pressures after exercise were based on data collected in the early 1970s from healthy individuals in the age range 21–26 years. Our aims were to collect new reference data for DBP at ankle level after exercise based on older populations, and to compare between reference data for different age groups to find out whether the normal values are dependent on age. Material and methods. DBP after exercise was measured using the strain‐gauge technique on individuals in two groups: group I comprising 25 healthy persons aged between 61 and 82 years, and group II 14 healthy persons aged between 45 and 58 years. Strict rules of inclusion were followed. Results. Normal values are dependent on age. The average differences (ankle DBPafter−ankle DBPbefore) immediately after walking were 25 mmHg, 12 mmHg and −8 mmHg in group I, group II and the old data, respectively. Comparison among groups showed significant differences (p⩽0.01). Conclusion. Normal values for elderly and middle‐aged persons are presented. Use of normal values based on young people may result in underestimation of DBP response and hence underestimation of the degree of possible apvd, especially in elderly individuals.

Local thrombolysis in the treatment of peripheral arterial vascular diseases

While atherosclerosis develops in a progressive manner, acute arterial thrombosis and embolism are characterized by fulminant occlusion of vessels. Special localisation of atherosclerotic plaques might result in severe and life threatening clinical symptoms. Multidisciplinary consultations of angiologist, radiologist and surgeon are necessary to identify the most proper diagnosis, and urgent intervention should be taken which nowadays involves local thrombolysis, too. The essence of this method is a prolonged, intravenous infusion of tissue plasminogen activator administered locally into the thrombus via an intraarterial catheter. Revascularisation can be controlled by angiography. The authors present the indications and contraindications of local thrombolysis in peripheral arterial disease and also demonstrate two cases which support the importance of this question. Data of some recent publications are also discussed. This emphasizes that local thrombolysis is equivalent to surgical possibilities. In specific cases, with complex clinical situations this method might be the first choice of treatment. Finally the most important conclusions and future prospects are presented.

Association of vitamin B12, folate and homocysteine with functional and pathological characteristics of the elderly in a mountainous village in Sicily

Homocysteine is associated with age, folate and vitamin B(12). Our study investigated the functional and clinical characteristics of the elderly (aged 60-85 years) of San Teodoro, a village in Central Sicily, and evaluated associations with vitamin B(12), folate and homocysteine. Subjects (n=280) were examined after door-to-door recruitment using interview, physician examination and laboratory tests. A total of 19.3% of the population had a low blood level of folate (<7 nmol/L) and 3.2% had low vitamin B(12) concentration (<100 pmol/L). The level of dependency, determined by the Barthel index, influenced homocysteine blood levels (p<0.0001), independent of age (p<0.0001), folate (p=0.0028) and vitamin B(12) (p=0.0165). Homocysteine was significantly associated with stroke (p=0.0027) and peripheral arterial vascular disease (p=0.0001), but not with myocardial infarction, angina pectoris, venous thrombosis or cancer. Vitamin B(12) was lower in myocardial infarction and higher in diabetes and venous thrombosis compared to the other diseases. The prevalence of deficits in folate and vitamin B(12) was paradoxically high in the mountainous northeastern area of Sicily. Our study also underlines the association of homocysteine with dependency of the elderly and with stroke and peripheral arteriopathy.

Risk of coronary surgery for hospital and early morbidity and mortality after initially successful percutaneous intervention

This study examines the influence of a successful PCI upon preoperative patient profile, peroperative management and postoperative, including one-year follow-up, results. From January 1999 through December 2001, 1141 patients (91%) underwent coronary artery bypass grafting (CABG) as the primary intervention for myocardial revascularization (group A) and 113 patients (9%) underwent primary CABG after an initially successful PCI (group B). Patients undergoing CABG after a failed PCI were not included. Patients in group B were statistically significant younger (P=0.010), with more peripheral arterial vascular (P=0.015) and renal disease (P=0.036). Left main coronary artery stenosis was significantly lower in group B (P=0.004). The number of diseased vessels did not differ between the two groups. However, less distal anastomoses were performed in group B (P=0.001). Postoperatively there was no statistically significant differences, in the percentages of myocardial infarction, arrhythmias, reinterventions, neurological, renal and pulmonary complications, and hospital mortality. One-year follow-up did not show any statistically significant differences in cardiac related mortality (P=0.25) or recurrent ischemic events (P=0.27). Multivariate analysis did not identify a successful PCI as a risk factor for early and late adverse outcomes. Previous PCI does not seem to result in a higher postoperative mortality or morbidity after CABG.

Donor-specific sensitization by cadaveric venous allografts used for arterial reconstruction in peripheral arterial occlusive vascular disease.

The use of allogeneic venous grafts from postmortal organ donors allows for the reconstruction of critically affected arteries in patients with peripheral occlusive vascular disease. We were interested to determine the prevalence and specificity of anti-HLA antibodies in patients after allogeneic vein transplantation. Anti-HLA class I and II alloantibodies were analyzed by flowcytometric analysis using color-coded microbeads coated with HLA antigens including recombinant single antigens. Nine out of 10 patients involving 12 venous allografts were positive for anti-HLA alloantibodies. All antibody-positive patients carried both anti-HLA class I and II alloantibodies. Anti-donor HLA specificity of the anti-HLA alloantibodies was seen in seven out of nine patients for anti-class I antibodies and in eight out of nine patients for anti-HLA class II antibodies. A high rate of donor-specific allosensitization was seen after allogeneic venous transplantation. In conclusion, allosensitization not only includes a humoral response against the constitutively expressed class I antigens but also extends to class II antigens.

A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients

Cardiovascular morbidity and mortality are highly prevalent in haemodialysis (HD) patients and have been recently associated with vascular calcifications. The objective of our study was to assess the value of a simple vascular calcification score for the prediction of cardiovascular death, cardiovascular hospitalizations and fatal and non-fatal cardiovascular events in HD patients, and to correlate this score with cardiovascular disease and with other known predictors of vascular disease. In this observational, prospective study 123 chronic HD patients (75 males and 48 females; 20% diabetic) were included, who were on low-flux HD treatment for 46.6+/-52 months (mean+/-SD). We set up a simple vascular calcification score based on plain radiographic films of pelvis and hands. Brachial pulse pressure and mean arterial pressure (MAP) were measured and cardiovascular events and hospitalization episodes were assessed. During an observational period of 37 months there were 17 cardiovascular deaths; 28 patients needed cardiovascular hospitalizations and 32 patients suffered fatal and non-fatal cardiovascular events. Coronary artery disease was diagnosed in 43 patients (35%), peripheral arterial disease in 33 patients (26.8%), cerebrovascular disease in 16 patients (13%) and vascular disease (coronary artery disease or peripheral arterial disease or cerebral vascular disease) in 61 patients (49.6%). By binary logistic regression, diabetes (P = 0.01), male sex (P<0.001), age (P = 0.02), HD duration (P = 0.02) and MAP (P = 0.03) were independently associated with a vascular score > or =3. This score > or =3 was independently associated with coronary artery disease (P = 0.008), peripheral arterial disease (P<0.001) and vascular disease (P = 0.001). Patients with a vascular calcification score > or =3 had a 3.9-fold higher risk of cardiovascular mortality (P = 0.03), a 2.8-fold higher risk of cardiovascular hospitalizations (P = 0.02) and a 2.3-fold higher risk of fatal or non-fatal cardiovascular events (P = 0.04). The present vascular calcification scoring represents a simple tool for the assessment of cardiovascular risk related with vascular calcifications in chronic HD patients.

Two Italian kindreds carrying the Arg136→Ser mutation of the Apo E gene: development of premature and severe atherosclerosis in the presence of epsilon 2 as second allele

Background and Aims: Type III hyperlipoproteinemia, or dysbetalipoproteinemia, is commonly associated with apolipoprotein E2 homozygosity (Cy Background and Aims:12, Cy Background and Aims:58). Apo E2-Christchurch (Arg136→Ser), a rare mutation of the Apo E gene, located in the receptor-binding domain of the protein, has been found to be associated in the vast majority of cases of dysbetalipoproteinemia. Methods and Results: This is the first report of two Italian kindreds carrying the Arg136→Ser mutation. One family is a four-generation kindred from Genoa (Liguria, Italy) with a high rate of mortality due to coronary artery disease: the proband was a 51-year-old woman with previous myocardial infarction and residual angina, severe carotid atherosclerosis, peripheral arterial vascular disease and arterial hypertension. The other family was identified in Palermo (Sicily, Italy): the proband was an overweight 62-year-old man with a mixed form of hyperlipidemia. The mutation, which was identified by means of Apo E genotyping followed by direct sequencing, co-segregated with the same haplotype in the two families. Conclusions: The family histories and clinical examinations of these subjects clearly show that the Apo E Arg136→Ser variant fully expresses a type III phenotype in association with a second allele coding for Apo E2, and only partially in association with a second allele coding for Apo E4.

Logistic-based patient grouping for multi-disciplinary treatment

Present-day healthcare witnesses a growing demand for coordination of patient care. Coordination is needed especially in those cases in which hospitals have structured healthcare into specialty-oriented units, while a substantial portion of patient care is not limited to single units. From a logistic point of view, this multi-disciplinary patient care creates a tension between controlling the hospital’s units, and the need for a control of the patient flow between units. A possible solution is the creation of new units in which different specialties work together for specific groups of patients. A first step in this solution is to identify the salient patient groups in need of multi-disciplinary care. Grouping techniques seem to offer a solution. However, most grouping approaches in medicine are driven by a search for pathophysiological homogeneity. In this paper, we present an alternative logistic-driven grouping approach. The starting point of our approach is a database with medical cases for 3603 patients with peripheral arterial vascular (PAV) diseases. For these medical cases, six basic logistic variables (such as the number of visits to different specialist) are selected. Using these logistic variables, clustering techniques are used to group the medical cases in logistically homogeneous groups. In our approach, the quality of the resulting grouping is not measured by statistical significance, but by (i) the usefulness of the grouping for the creation of new multi-disciplinary units; (ii) how well patients can be selected for treatment in the new units. Given a priori knowledge of a patient (e.g. age, diagnosis), machine learning techniques are employed to induce rules that can be used for the selection of the patients eligible for treatment in the new units. In the paper, we describe the results of the above-proposed methodology for patients with PAV diseases. Two groupings and the accompanied classification rule sets are presented. One grouping is based on all the logistic variables, and another grouping is based on two latent factors found by applying factor analysis. On the basis of the experimental results, we can conclude that it is possible to search for medical logistic homogenous groups (i) that can be characterized by rules based on the aggregated logistic variables; (ii) for which we can formulate rules to predict to which cluster new patients belong.

Risk factors for early hospital readmission after cardiac operations

Objective: Early hospital readmissions after cardiac procedures are both costly and harmful to patients. We investigated the factors that predispose to readmission to develop strategies to minimize this problem. Methods: As part of a prospective data collection, patients having cardiac procedures at our institution are routinely tracked for 30 days after their discharge from the hospital. We reviewed 2650 patients in our cardiac database who underwent operations over the past 5 years. We used univariate and multivariate statistical techniques to identify risks for readmission. Results: Of 2574 discharged patients, 252 (9.8%) required readmission. The most common causes of readmission are cardiac (42%), pulmonary (19%), gastrointestinal (10%), extremity complications (6.7%; deep vein thrombophlebitis, peripheral arterial vascular disease, and saphenous vein harvest site problems), sternal wound problems (7.5%), and metabolic problems (4%). Of more than 70 variables studied, only 6 are significant multivariate predictors of readmission: female sex (P =.002); diabetes (P =.001); chronic lung problems (P =.011); increased distance between home and hospital (P >.001); preoperative atrial fibrillation (P =.002); and preoperative chronic renal insufficiency (P =.002). Type of operation, redo procedures, and other intraoperative and postoperative variables are not important multivariate predictors of readmission. Prolonged hospital length of stay for the initial procedure did not cause more frequent readmission. The costs of initial hospitalization (operating room costs combined with postoperative in-hospital costs) were not significantly increased in those patients who required readmission. Conclusions: The high-risk patient for readmission is a woman with diabetes, chronic lung disease, renal insufficiency, and preoperative atrial fibrillation who lives at a distance from the hospital. Readmission does not depend on periprocedural variables (eg, cardiopulmonary bypass time) or on postoperative complications. High procedural costs from the initial hospitalization do not predispose to readmission. These results suggest interventions that may reduce readmission.J Thorac Cardiovasc Surg 2001;122:278-86

Assessment of peripheral arterial vascular disease with radionuclide techniques

Various radioisotopic imaging techniques for noninvasive detection of vessel stenosis and for functional investigation of reduced blood flow and follow-up have been developed during the last decade in peripheral vascular disease (PVD), with the aim of replacing invasive techniques and complementing standardized methods. Radionuclide assessment of PVD is divided into 2 major groups: imaging of perfusion and metabolic investigations. The measurement of arterial blood flow and muscle perfusion is intended to show the morphology, to evaluate the functional consequences of PVD, and to quantify the latter. The application of radiolabeled tracers was developed as a noninvasive alternative to angiography in morphologic imaging. Treadmill testing has been used to assess the functional effects of reduced blood flow in PVD where the onset of pain indicates the stage of disease, but the results can be confused by other symptoms. Scintigraphic measurement of muscle perfusion should detect insufficient nutritional blood flow in peripheral muscle and thus have a higher specificity for PVD than treadmill testing alone. Although there are very promising theoretical and experimental data in animals, the clinical use of radionuclide investigations is limited by different technical problems, such as methodologic differentiation between skin and muscle perfusion, the lack of controlled and prospective studies, and incomplete correlation with other standardized routine techniques. Among the great number of radioisotopic metabolic imaging techniques, only radiolabeled platelets and lipoproteins, to some extent, have shown a limited potential clinical use. Some other approaches seem to have a high potential from a theoretical point of view. They are limited, however, by a great number of problems. Correlation with sonographic or magnetic resonance imaging (MRI) findings may identify a potential metabolic value. Correlation with angiography reflecting the extent of the disease makes no sense. So far with PVD, neither radioisotopic perfusion studies nor metabolic imaging techniques are able to achieve a level of routine application or wider meaningful interpretation of the clinical condition of a specific patient. Competing techniques are easier to perform, less expensive, faster, more widely available, and do not carry the radiation burden. Positron emission tomography is still in its early stages of application, with great theoretical potential but at a high price. A great deal of work is still required to transform in vitro and experimental experience into more meaningful routine radioisotopic investigations in patients with PVD.

Cellular adhesion molecules and atherogenesis

Atherosclerosis as manifested by coronary, cerebral, and peripheral arterial vascular disease is the leading cause of morbidity and mortality in the United States. Our understanding of the process of atherogenesis has evolved from the epidemiologic identification of cardiac risk factors to an increasing understanding of the molecular basis of vascular pathobiology. Evidence for the role of chronic inflammation in atherogenesis has been accumulating over the last decade and suggests that a generalized cellular and humoral inflammatory response promotes the formation of the atherosclerotic plaque. To target potential sites of intervention by which to inhibit or arrest the progression of atherosclerosis, an understanding of the molecular determinants of inflammation in the vasculature is critical. Localization of the cellular inflammatory response and regulation of the humoral inflammatory response are both mediated through the interactions of a group of specialized molecules, collectively referred to as cellular adhesion molecules. The cell-surface expression of these molecules in response to pathophysiological stimuli mediates the interaction between the endothelium and blood cells central to the development of atherosclerosis. As initially described, adhesion molecules serve as mediators of cell– cell and cell–matrix interactions. More recently, these molecules have been shown to participate in cell emigration, signaling functions, and other vascular physiological responses. The structure, function, and regulation of these specialized molecules in atherogenesis are the focus of this review.