bluuebunny/crossref_metadata_2025 huggingface dataset:
A contemporary approach to thrombolytic therapy for pulmonary embolism
Authors: Goldhaber Samuel Z
Published: January 2007

Successfully utilized contemporary pulmonary embolism thrombolysis reverses right heart failure rapidly and safely. This therapeutic approach may lower mortality from pulmonary embolism and reduce morbidity from chronic pulmonary hypertension. Unlike myocardial infarction thrombolysis, a 2-week `time window' is available, during which treatment can be initiated. A high concentration of the thrombolytic agent is administered in a brief infusion lasting several hours. No special laboratory testing is needed. Currently, the only contemporary thrombolytic regimen for pulmonary embolism that is approved by the Food and Drug Administration is tissue plasminogen activator, in a dose of 100 mg/2 h. New thrombolytic agents under development for pulmonary embolism include reteplase, saruplase, and recombinant staphylokinase. Future clinical trials will require multicenter collaboration and will focus on relevant endpoints such as the reduction of mortality and recurrent venous thromboembolism.
Surgical management of abdominal aortic aneurysm
Authors: Yeung Benson Kwok Fai , Pearce William H
Published: January 2007

Abdominal aortic aneurysms (AAA) are increasingly common in the aging population. While the etiology of abdominal aortic aneurysms is unknown, there is growing evidence that suggests an immune response. The majority of AAA are asymptomatic and when treated are standard open surgical procedures. The overall mortality rate is 5% or less. The current recommendations for the treatment of aneurysms are based on diameter: diameters exceeding 5 cm in good-risk younger patients should be treated. Aortic aneurysms tend to enlarge over time with a growth-rate between 0.2 and 0.4 mm per year. Once rupture occurs mortality is estimated to exceed 75%, with half of the patients dying prior to arriving at the hospital and the remaining one-half following surgical correction. Recently, minimally invasive techniques have been developed to treat AAA in high-risk patients. These techniques involve the use of covered stented grafts. Current clinical investigations are underway both in this country and in Europe, which have yielded promising results. However, long-term complications are unknown. Currently, aortic aneurysms are best treated with open surgical management.
Therapy of unstable angina with the low molecular weight heparins
Authors: Ageno Walter , Turpie Alexander GG
Published: January 2007

Unstable angina is in most cases caused by partial or complete coronary artery occlusion due to the disruption of an atherosclerotic plaque and to thrombus formation. An immediate antithrombotic approach is essential to prevent fatal and non-fatal myocardial infarction, and the combination of aspirin and unfractionated heparin has played a pivotal role in the past years. Low molecular weight heparins have improved pharmacokinetic and pharmaco-dynamic properties over unfractionated heparin that have resulted in greater efficacy and safety in the field of venous thromboembolism. Low molecular weight heparins can be administered by once or twice daily subcutaneous injections at fixed, weight-adjusted doses without the need for monitoring. Because of their potential, many recent clinical trials have evaluated their efficacy and safety in the management of patients with unstable angina. Three low molecular weight heparins have so far been tested: nadroparin, dalteparin and enoxaparin. The results of the published trials confirm that the newer compounds are at least as safe and effective as unfractionated heparin, and offer considerable therapeutic advantages. Nevertheless, the different properties of the three compounds and perhaps the different designs of the clinical trials have led to not entirely comparable findings.
The association between physical activity, cardiorespiratory fitness, and lipoprotein(a) concentrations in a tri-ethnic sample of women: The Cross-Cultural Activity Participation Study
Authors: Drowatzky Katrina L , Durstine J Larry , Irwin Melinda L , Moore Charity G , Davis Paul G , Hand Gregory A , Gonzalez M Francisco , Ainsworth Barbara E
Published: January 2007

The purpose of this cross-sectional study was threefold: (1) to examine ethnic differences in plasma lipoprotein(a) [Lp(a)] concentrations; (2) to examine the relationship between physical activity levels (moderate, moderate-vigorous, and total MET-min/day) and Lp(a) concentrations; and (3) to determine the relationship between maximal treadmill time and Lp(a) concentrations among African-American, Native American, and Caucasian women (n = 140, ages 40-70 years: 54.5610.7). Physical activity records were kept for two 4-day periods, scheduled 1 month apart, a total of 8 days, and each activity was assigned a code from the `Compendium of physical activity'. Subjects completed a graded exercise test to determine maximal treadmill time, and a fasted blood sample was collected to quantify Lp(a) concentration. Lp(a) concentrations were negatively skewed with a geometric mean of 28.3 mg/dl (25-75%: 10.4- 43.1 mg/dl) in African-Americans (n = 47), 2.9 mg/dl (25-75%: 1.2-7.4 mg/dl) in Native Americans (n = 45), and 9.4 mg/dl (25-75%: 2.6-22.4 mg/dl) in Caucasians (n = 48). African-American women had significantly higher (p,0.05) Lp(a) concentrations than either Native Americans or Caucasians. No relationships were observed among moderate, moderate-vigorous, and total MET-min/day of physical activity, maximal treadmill time, and Lp(a) concentrations. Significant ethnic differences in Lp(a) concentrations were found, with African-American women having higher Lp(a) concentrations than Native American and Caucasian women. Lp(a) concentrations were not associated with any physical activity variables. Therefore, physical activity and maximal treadmill time did not influence Lp(a) concentrations in this tri-ethnic population of women.
Secondary prevention of coronary artery disease in patients undergoing elective surgery for peripheral arterial disease
Authors: Nass Caitlin M , Allen Jerilyn K , Jermyn Roland M , Fleisher Lee A
Published: January 2007

The purpose of the study was to assess the implementation of secondary prevention guidelines of coronary artery disease (CAD) in patients undergoing peripheral revascularization surgery. The design was a descriptive study of the prevalence of cardiac risk factors and preventive pharmacological therapy in vascular surgical patients set in an academic medical center between July 1996 and February 1999. A total of 237 patients were recruited, 82 (35%) having carotid surgery and 155 (65%) having lower extremity bypass. Data were collected from an existing database of a study examining perioperative cardiac events in vascular surgery patients. The majority of patients were hypertensive and 58% of patients had a blood pressure.140/90 mmHg. Most patients (81%) reported a history of tobacco use and 23% were active smokers. Of the 41% of patients who were diabetic, 46% had a random glucose .140 mg/dl. Half of the patients took aspirin, 35% a lipid-lowering medication, 30% a beta-blocker. Patients with lower extremity disease were less likely than patients with carotid disease to be on aspirin (45% vs. 62%), a lipid-lowering agent (30% vs. 45%), or a beta-blocker (26% vs. 39%) (all p,0.05). Of patients with heart disease, more men than women were on aspirin (62% vs. 45%) (p,0.05). In conclusion, our findings suggest that patients presenting for vascular surgery have a high prevalence of modifiable CAD risk factors that are not being adequately managed. Preoperative examination of vascular patients is an important opportunity to assess and implement neglected secondary prevention measures.
Inpatient utilization of medical services associated with peripheral arterial disease-related inpatient procedures in the Department of Defense
Authors: Zachry Woodie M , Shepherd Marvin D , Wilson James P
Published: January 2007

The objective of this study was to describe the inpatient procedural medical care utilization the first 10 years after initial inpatient confirmation of peripheral arterial disease (PAD). A retrospective review was carried out of the computer records of all the army beneficiaries of the Department of Defense healthcare system since 1971. Over 8000 subjects with an initial inpatient confirmation of PAD between January 1, 1980 and December 31, 1985 were reviewed for 10 years following the initial visit. The utilization of PAD-related invasive procedures gradually increased over the first 8 years, and rose sharply in the ninth and tenth years after initial diagnosis, while the utilization of examination procedures was highest in the first, fifth to seventh, ninth and tenth years. Procedures involving bypass and amputation had the highest utilization among invasive procedures, while procedures involving arteriography and ultrasonography accounted for 88% of all examination procedures. Bypass and repair of vessel procedures gradually rose throughout the 10 years after initial diagnosis, while amputations and skin grafts remained relatively constant. Procedures involving arteriography rose until year 5 and then tapered off, while utilization of ultrasonography rose in year 7 and tapered off. These results suggest that PAD-related studies should consider the progression of the disease past the fifth year after the initial inpatient visit for PAD when measuring a change in outcomes.
Predictors of carotid endarterectomy in middle-aged individuals
Authors: Forsblad J , Gottsäter A , Mätzsch T , Lindgärde F
Published: January 2007

The objective was to investigate which screening variables in a population study predicted carotid endarterectomy. Among 793 carotid endarterectomies performed at Malmö University Hospital between 1991 and 1998, 85 patients (14 females) were identified that had participated in a population screening between 1974 and 1991. Median time from screening to operation was 16 years (range 6-26 years). Screening variables were compared with corresponding values from the background screening population ( n = 33261). As operated patients were older than the background population at screening (49 [37-60] vs. 46 [26-61] years; p < 0.0001), comparisons were age-adjusted. Operated patients had higher systolic blood pressure (SBP; 130 [126-133] vs. 125 [125-125] mmHg; p < 0.01), serum total cholesterol (6.1 [5.9-6.3] vs. 5.7 [5.7-5.7] mmol/l; p < 0.0001), serum triglyceride (1.4 [1.3-1.6] vs. 1.1 [1.1-1.1] mmol/l; p < 0.0001), serum glutamic acid transferase (0.46 [0.40-0.53] vs. 0.40 [0.40-0.41] μkat/l; p < 0.05), and plasma fibrinogen (3.77 [3.42-4.16] vs. 3.35 [3.30-3.41] mmol/l; p < 0.05) levels, a lower 120-min insulin/glucose ratio at an oral glucose tolerance test (OGTT; 0.48 [0.38-0.58] vs. 0.60 [0.59-0.61]; p < 0.05) and forced vital lung capacity (3.7 [3.6-3.9] vs. 3.9 [3.9-4.0] l/min; p < 0.05), and a higher prevalence of smoking at screening (68% vs. 45%; p < 0.0001). Smoking, SBP, serum total cholesterol, and the 120-min insulin/glucose ratio remained independent predictors for carotid surgery in multivariate analysis. No differences existed among patients operated on because of symptomatic and asymptomatic stenosis. In conclusion, increased SBP and total cholesterol, lower 2-h insulin/glucose ratio at an OGTT, and smoking predict carotid surgery at long-term follow-up.
The Minnesota Regional Peripheral Arterial Disease Screening Program: toward a definition of community standards of care
Authors: Hirsch Alan T , Halverson Sheri L , Treat-Jacobson Diane , Hotvedt Peter S , Lunzer Mary M , Krook Susan , Rajala Scott , Hunninghake Donald B
Published: January 2007

The Minnesota Regional Peripheral Arterial Disease Screening Program was designed to define the efficacy of community PAD detection efforts, to assess the disease-specific and health-related morbidity, to assess PAD awareness rates, and to determine the magnitude of atherosclerosis disease risk factors and the intensity of their management. The target population was recruited via mass media efforts directed at individuals over 50 years of age and those with leg pain with ambulation. Screening sessions included assessments of the ankle-brachial index, blood pressure, fasting lipid profile, and use of validated tools to detect symptomatic claudication (by the Modified WHO-Edinburgh Claudication Questionnaire), walking impairment (Walking Impairment Questionnaire -WIQ), quality of life (MOS SF-36), PAD awareness, and the intensity of PAD medical therapeutic interventions. PAD was defined as any ankle-brachial index ≤0.85 or a history of lower extremity revascularization. The program evaluated 347 individuals and identified 92 subjects with PAD and 255 subjects without PAD, yielding a detection rate of 26.5%. Individuals with PAD were older, tended to have higher blood pressures, and had a significant walking impairment and an impaired health-related quality of life compared with the non-PAD subjects. Current rates of tobacco use were low. Lipid-lowering, estrogen replacement, anti-platelet, and antihypertensive medications and exercise therapies were underutilized in the PAD cohort. Peripheral arterial disease awareness was low in these community-identified patients. This Program demonstrated that individuals with PAD can be efficiently identified within the community, but that current standards of medical care are low. These data can assist in the future development of PAD awareness, education, and treatment programs.
Transcatheter embolization of renal artery aneurysm in Behçet’s disease
Authors: Planer D , Verstandig A , Chajek-Shaul T
Published: January 2007

A 20-year-old man with Behç et’s disease presented with a ruptured renal artery aneurysm. This patient had previously had aneurysms of the coronary arteries and coronary vein thrombosis that were treated with immunosuppression. A selective transcatheter embolization of the renal artery branch was done successfully and treatment with corticosteroids and methotrexate was added. Presented here is a rare complication of Behçet’s disease, with discussion on the pathophysiology, differential diagnosis, and the advantages and disadvantages of the angiographic treatment. This paper is supplemented with a comprehensive review of the literature.
Vascular viewpoint
Authors: Anand Sonia S
Published: January 2007

Objectives: To determine the relative effectiveness of intra-arterial thrombolysis compared with surgery for the treatment of lower-limb ischemia.

Methods: MEDLINE and EMBASE were searched for randomized controlled trials related to thrombolysis. The search was limited to English-language articles or trials which provided a detailed English summary of trial design and results, and trials that were published after 1980. Hand searching and review of citations was used to identify other papers. Randomized controlled trials (RCTs) only were included in the analysis; a quality score was given to each trial using the CONSORT statement. Data extraction was performed independently by two reviewers. A random effects model was used.

Outcomes: Mortality, amputation, major bleeding.

Results: A total of 34 papers were retrieved: 10 were RCTs and the remaining 24 were review articles, case series, or cohort studies. Seven were RCTs that compared surgery to thrombolysis. No significant differences in the rates of death or amputation were observed between patients who were randomized to thrombolysis compared to surgery. The odds ratios comparing thrombolysis to surgery for death at 30 days, and 6 and 12 months were 1.07, p = 0.73; 1.11, p = 0.72; and 0.59, p = 0.49, respectively. The odds ratios comparing thrombolysis to surgery for amputation at 30 days, and 6 and 12 months were 1.08, p = 0.78; 1.18, p = 0.38; and 1.14, p = 0.49, respectively. A significant excess of major bleeding was observed in the thrombolysis group. The odds ratio comparing thrombolysis to surgery for major bleeding at 30 days was 2.95 (95% CI: 1.62-5.36, p = 0.001). The 6 and 12 months odds ratios for bleeding were not reported.

Conclusion: The authors conclude that there is insufficient evidence to justify the widespread use of thrombolytic therapy in patients with leg ischemia, although subgroup analyses suggest benefit of thrombolysis in patients who have synthetic graft occlusions, and in patients who receive therapy after a short duration of ischemic symptoms, i.e. less than 14 days.
Comorbidities and exercise capacity in older patients with intermittent claudication
Authors: Katzel Leslie I , Sorkin John D , Powell Claudia C , Gardner Andrew W
Published: January 2007

Patients with peripheral arterial disease (PAD) and intermittent claudication often have coronary artery disease (CAD) and other comorbid medical problems. There is a paucity of information on the impact of coexistent medical conditions on exercise capacity and functional status in patients with PAD. This study examined the impact of CAD, diabetes, cigarette smoking, prior peripheral surgical revascularization and other medical conditions on claudication pain times and peak oxygen capacity (VO2) during maximal effort treadmill testing in 119 male outpatient volunteers (ankle-brachial index (ABI) of 0.65 ± 0.2, mean ± SEM) with a history of Fontaine Stage II PAD. Smoking status was significantly related to ambulatory function. Current smokers had a lower peak VO2 expressed in l/min than either former or never smokers (ANCOVA adjusted for age, p = 0.003). However, after adjustment for body weight, there was only a trend for a difference in peak VO2 between current (13.2 ± 0.5 ml/kg per min), former (14.2 ± 0.4 ml/kg per min) and never (15.4 ± 1.0 ml/kg per min) smokers (ANCOVA, p= 0.10). Current smokers had a shorter time to onset of claudication pain ( p = 0.023) and shorter maximal claudication pain times ( p = 0.029) than former or never smokers ( p = 0.023). The ABI 1 min after cessation of exercise was also lower in smokers compared to former and never smokers ( p = 0.018). There were no significant differences in functional performance measures or time to recovery from maximal claudication pain when patients were categorized on the presence or absence of CAD, diabetes, peripheral revascularization, arthritis, hypertension or dyslipidemia. Therefore, smoking adversely affected exercise capacity in these PAD patients, whereas the presence of CAD, diabetes and other medical problems had a relatively minor impact on exercise capacity. In conclusion, the relatively minor impact of comorbid medical conditions on walking ability in patients with PAD reflects the overwhelming limitation in ambulatory function due to the claudication pain.
Therapeutic thrombin injection of pseudoaneurysms: a multicenter experience
Authors: Mohler Emile R , Mitchell Marc E , Carpenter Jeffrey P , Strandness D Eugene , Jaff Michael R , Beckman Joshua A , Gerhard-Herman Marie
Published: January 2007

The standard non-invasive treatment of pseudoaneurysms has been ultrasound-guided compression (UGC). Problems with UGC include pain at the site of compression, long compression times and incomplete closure. Each of these difficulties is exacerbated with large pseudoaneurysms. Recently, ultrasound-guided injection of pseudoaneurysms with thrombin has gained popularity. The goal of this study was to report a multicenter registry using this technique and in so doing detail the clinical utility and safety of this emerging procedure. The medical records of all patients diagnosed with pseudoaneurysm in the vascular laboratory who underwent thrombin injection over the past year were reviewed for patient characteristics and clinical outcome. There were 91 patients (55 male) with a mean age of 69 years. Three patients also had an arteriovenous fistula. The majority of patients were receiving one or more antiplatelet agents and/or anticoagulants. All patients underwent pseudoaneurysm injection with bovine thrombin. The mean aneurysm diameter was 3.3 cm, with a range of 1.5-6.3 cm. Successful thrombosis of the pseudoaneurysm was achieved in 89/91 (98%) of cases. Anticoagulation with heparin was used in one of the unsuccessful cases. In two cases, UGC was used to close a small active region that did not completely thrombose after thrombin injection. There were two patients who had recurrence of pseudoaneurysm the day after successful injection and thrombosis of the pseudoaneurysm. There were no local complications after injection; however, one patient suffered a pulmonary embolus that was thought to be unrelated to the procedure. In conclusion, thrombin injection for the treatment of pseudoaneurysms is safe and effective, even in patients receiving anticoagulation. This procedure should be considered as the initial therapeutic approach for peripheral pseudoaneurysms.
Vascular complications in diabetes and their prevention
Authors: Kassab E , McFarlane SI , Sowers JR
Published: January 2007

Diabetes mellitus is increasing throughout the world. Cardiovascular disease (CVD) accounts for up to 80% of excess mortality in this high-risk population. Patients with diabetes have the same CVD risk factors as those people without diabetes. However, these risk factors are much more powerful in diabetic patients. CVD risk is especially high for diabetic women, and premenopausal diabetic women lose all the protection normally afforded to them by female sex hormones. Controlled clinical trials have clearly demonstrated that rigorous treatment of blood pressure, dyslipidemia and platelet hyperaggrebility strikingly reduces CVD risk in diabetic patients. Strategies directed at interrupting the renin-angiotensin system (both tissue and systemic systems) and the use of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors have proven to be especially beneficial for this high-risk population.
Non-diabetic microalbuminuria, endothelial dysfunction and cardiovascular disease
Authors: Pedrinelli Roberto , Dell’Omo Giulia , Penno Giuseppe , Mariani Mario
Published: January 2007

Subclinical increases in albuminuria (microalbuminuria) predict morbid events, but the reasons for that are still not understood in full. This paper reviews the existing evidence regarding the relationships of non-diabetic microalbuminuria and cardiovascular disease, the underlying assumption being that endothelial dysfunction contributes both to atherosclerotic macrovascular disease and renal microvascular disease of which albuminuria is a marker. Much data support that concept, and suggest a preferential link with endothelial activation in response to acute and subclinical inflammatory stimulation, although further studies are needed to establish the exact cause-effect mechanisms. Epidemiological studies also show associations with cardiovascular events, and some recent prospective results also indicate the power of micro-albuminuria to predict risk independently from conventional atherogenic factors. Thus, micro-albuminuria might be considered as an integrated marker of cardiovascular risk sensitive to systemic vascular status in addition to other parameters such as blood pressure levels, glucose metabolism, smoking habits, a profile rather unique among the prognostic predictors available to stratify risk in hypertensive patients.
Peripheral arterial disease - epidemiological aspects
Authors: Criqui Michael H
Published: January 2007

As many as 10 million people in the USA have peripheral arterial disease (PAD) with a prevalence over 10% in people aged more than 60 years old. Generally, men have a higher prevalence of PAD than women. The risk factors for PAD are similar to those for coronary artery disease (CAD) and cerebrovascular disease (CBVD), but diabetes and cigarette smoking have a particularly strong association with PAD. Patients with PAD also have CAD and CBVD as comorbidities, although the extent of co-morbidity depends on the sensitivity of assessment. The risk of mortality is proportional to the severity of PAD, and the relative risk of all-cause mortality due to PAD is unaltered by the presence of CAD or CBVD. PAD is under-recognized and under-treated, even though it should be regarded as a severe disease leading to significant death and disability from stroke and myocardial infarction (MI). Thus, accurate diagnosis of PAD could provide an early indication of the need for intervention and help prevent future morbidity and mortality.
Whole-body exercise thallium imaging in smokers
Authors: Tellier Philippe , Lecouffe Pascal , Vasseur C
Published: January 2007

Whole-body exercise thallium imaging (WBEI) can show abnormalities of leg muscle perfusion in patients with symptomatic peripheral artery disease (PAD). This study compared the exercise distribution of thallium-201 at different levels of the legs in asymptomatic smokers and non-smokers who performed a maximal graded treadmill test. A group of 74 smokers (more than 20 pack-years) with (n = 51) or without coronary artery disease (CAD) (n = 23) were included in group 1 and 64 non-smokers with a low probability of PAD and CAD in group 2. Patients in group 1 were older than the patients in group 2 (58 6 9 versus 48 6 12 years, p <0.0001). Indexes of asymmetry were significantly higher in group 1, at each level of the legs, both in anterior and posterior views (0.001 < p < 0.05), except at thigh level in anterior view. Fractional uptake indexes of thallium-201 were significantly lower in group 1 than in group 2 at calf level (p = 0.0001 in anterior and posterior views) and buttocks (p = 0.006 and p = 0.009 in anterior view only). Interextremity asymmetry was four to six times more frequent at calf level in smokers than in non-smokers. These WBEI abnormalities in smokers are highly suggestive of silent PAD or at least decreased vascular reactivity in clinically uninvolved vessels.
Vascular damage from smoking: disease mechanisms at the arterial wall
Authors: Powell Janet T
Published: January 2007

The products of tobacco combustion are absorbed into the systemic circulation. Absorbed nicotine stimulates the release of catecholamines, whilst other products (perhaps including nicotine) injure the arterial endothelium and promote atherogenesis. Free radicals and aromatic compounds diminish the endothelial synthesis of nitric oxide, causing impaired endothelium-dependent relaxation of arteries, the earliest clinical sign of endothelial dysfunction. Smoking alters the shear forces and rheology at the endothelial surface and these changes enhance the effects of products of tobacco combustion to upregulate leucocyte adhesion molecules on the endothelial surface. The increased oxidation of low density lipoprotein (LDL) in smokers has synergistic effects to promote monocyte adhesion and monocyte migration into the subintimal space. Continued stimulation of intimal cells by oxidized LDL leads to the development of atherosclerosis. Many of these effects are ameliorated by high concentrations of vitamin C. Smoking also potentiates thrombosis at the dysfunctional endothelium by increasing the concentration of plasma fibrinogen and altering the activity of platelets. All these proatherogenic effects of smoking to injure the endothelium also are observed, albeit to lesser extent, in passive smokers.
Long-term outcomes after deep venous thrombosis of the lower extremities
Authors: Prandoni Paolo , Lensing Anthonie WA , Prins Martin R
Published: January 2007

Few natural history studies are available which describe long-term outcomes after venous thromboembolism. However, symptomatic deep-vein thrombosis (DVT) of the lower extremities carries a high risk for recurrent venous thromboembolism that persists for many years. This risk is higher among patients with permanent risk factors including inherited abnormalities of hemostasis than among patients who have suffered trauma or who are postoperative. The development of recurrent ipsilateral DVT carries a high risk for severe post-thrombotic syndrome, an otherwise rare problem in patients with a first episode of DVT adequately treated with anticoagulant drugs and wearing vascular compression stockings. Long-term survival following DVT is generally good in the absence of malignancy. Carefully designed randomized trials are needed to determine whether chronic anticoagulation can reduce further the risks of recurrent DVT and symptoms of post-thrombotic syndrome.
Long-term, low-dose warfarin among venous thrombosis patients with and without factor V Leiden mutation: rationale and design for the Prevention of Recurrent Venous Thromboembolism (PREVENT) trial
Authors: Ridker Paul M ,   PREVENT Investigators
Published: January 2007

Standard therapy for patients with deep venous thrombosis and pulmonary embolism typically includes anticoagulation for a 3-6-month period with full dose warfarin. However, patients following this regimen experience high rates of recurrent thrombosis, re-hospitalization and mortality in the years immediately following cessation of anticoagulation. This is true for patients at average risk of disease recurrence, and for patients at elevated risk due to the presence of inherited defects of anticoagulation such as factor V Leiden mutation. Unfortunately, no clinical regimen currently available has proven to have sufficient benefit to support long-term prophylaxis. In particular, full dose warfarin is associated with substantially increased risks of hemorrhage when used on a long term basis. In contrast, while targeted low-dose warfarin (INR 1.5-2.0) is safe for long-term therapy, the efficacy of this approach in the prevention of recurrent venous thromboembolic disease has remained untested.

The Prevention of Recurrent Venous Thromboembolism (PREVENT) trial will evaluate the efficacy of prolonged treatment with low-dose warfarin in the secondary prevention of venous thromboembolism (VTE). Patients with a history of documented idiopathic venous thrombosis who have completed a standard course of anticoagulation therapy will be enrolled in a randomized, double-blind, placebo-controlled trial comparing usual care plus targeted low-dose warfarin to usual care plus placebo for a period of up to 4 years. Trial endpoints will include recurrent VTE, major bleeding episodes and all-cause mortality in the total patient population and separately in those patients with factor V Leiden.

The potential clinical impact of the PREVENT trial is broad since a positive finding would strongly support chronic low-intensity anticoagulation among patients with venous thrombosis who are at risk for recurrence following cessation of standard outpatient anticoagulation.
An objective method to estimate the severity of Raynaud phenomenon: digital blood pressure response to cooling
Authors: Maricq Hildegard R , Valter Ivo , Maricq John G
Published: January 2007

The treatment efficacy of patients with Raynaud phenomenon (RP) is determined from the decrease in severity of this condition, usually based on a decrease in frequency of RP attacks as reported by patients in a diary. Although subjective, this method is still the main endpoint measure in clinical trials.

The results of patients' digital blood pressure responses to cooling were compared with the reported RP attack frequency to determine whether the former could be used to estimate the severity of RP. The effect of local finger cooling on the digital systolic blood pressure was tested at 30°C, 20°C, 15°C and 10°C on 136 subjects with RP. The RP attack frequency was dichotomized into daily versus less than daily attacks.

The frequency of attacks and the digital systolic pressure (DSP) showed a significant association at all cooling temperatures (those with daily attacks showed lower DSP than those with less frequent attacks). In addition, patients experiencing daily attacks of RP showed a zero reopening pressure at higher local temperatures than those with less frequent RP attacks.

These results demonstrate that the response of the digital systolic blood pressure to cooling is closely associated with the RP attack frequency and therefore can be considered as an objective estimate of RP severity. This physiological measurement should be most useful in evaluating the clinical course of RP and the effect of its treatment, provided it is measured under standardized conditions.
Venous bypass and valve reconstruction: long-term efficacy
Authors: Eklof Bo G , Kistner Robert L , Masuda Elna M
Published: January 2007

Palma and Esperon described the first femoro-femoral cross-over bypass for iliac vein obstruction in 1958, and Kistner performed the first valve reconstruction for deep vein reflux in 1968. Such surgical development has stimulated better diagnostic methods that now form the foundation for a classification of chronic venous disease, and surgery has been supported by, and sometimes replaced by, the rapid progress in endovascular procedures with angioplasty and stenting. The ability now exists to relieve obstruction and repair reflux in the deep veins, and the results in the successful cases demonstrate the improvement that follows correction of the physiologic abnormalities. The detail in workup required to achieve an accurate diagnosis that is adequate enough to guide surgical treatment in these cases has set a new standard for the diagnosis of chronic venous disease that incorporates the clinical state, etiology, pathophysiology and anatomic distribution of the venous problem, and is incorporated in the CEAP (clinical, etiologic, anatomic, pathophysiologic) classification. The challenge at this time is to produce a reliable set of data that demonstrate the results of treatment in patients with chronic venous disease by conventional methods of bandaging, rest and elevation as well as specific surgical correction of venous obstruction and reflux and to follow these cases over a significant period of time.
Endovascular manipulation to restrict restenosis
Authors: Gershlick AH
Published: January 2007

The processes that take place following damage to the vessel wall are well understood. Endovascular manipulation by its very nature induces such damage and the repair process can lead to a recurrence of symptoms. There have been many clinical trials of drugs chosen for their known impact on preventing excess vessel wall response. With one or two exceptions none of these trials has shown any benefit, partly because only low doses could be given systemically to avoid side effects. Local drug delivery allows high doses to be given where needed, at the site of the process, without inducing systemic complications. There are various drugs and agents that have been shown to be effective in models of vessel wall damage, including heparin, nitric oxide, inhibitors of platelet function and the antisense oligonucleotides. Some of these agents are now being tested in clinical trials. Methods of delivering the agent include devices that bathe the luminal layer, deliver the agent to the media or inject it into the adventitia where a reservoir can form.

Stents improve the outcome after angioplasty, but can also induce a proliferative vessel wall response. To overcome this, stents have recently been considered as local delivery devices with radiation being delivered and polymer coated stents, loaded with agents, being developed.While local drug delivery provides great promise as a way of reducing the adverse effect of response of the vessel wall to damage, the results of clinical trials in humans are awaited.
Role of inflammation and metalloproteinases in plaque disruption and thrombosis
Authors: Shah Prediman K
Published: January 2007

Numerous pathological, clinical, angiographic and angioscopic studies have demonstrated that acute coronary syndromes (unstable angina, acute myocardial infarction and ischemic sudden death) are most frequently the consequence of plaque disruption (plaque rupture or superficial plaque erosion) and consequent coronary thrombosis. Several serial angiographic studies have demonstrated that nearly 60-70% of acute coronary syndromes evolve from mildly to moderately obstructive atherosclerotic plaques. Coronary plaque disruption appears to be a function of both the composition of the plaque (plaque vulnerability) as well as extrinsic triggers that may precipitate plaque disruption in a vulnerable plaque. Vulnerability for plaque disruption appears to be largely determined by the size of the lipid-rich atheromatous core, the thickness of the fibrous cap covering the core, and the presence of ongoing inflammation within and underneath the cap. inflammatory cells may play a critical role in plaque disruption through the elaboration of matrix degrading metalloproteinases or MMPs (collagenases, gelatinases, stromelysins and matrilysin) and by inhibition of function and survival of matrix-synthesizing smooth muscle cells. inflammatory cells may also play a critical role in triggering thrombosis following plaque disruption through the tissue factor pathway. In addition, stresses resulting from hemodynamic and mechanical forces may precipitate plaque disruption, particularly at points where the fibrous cap is weakest, such as at its shoulders. The degree of thrombosis following plaque disruption is determined by the thrombogenicity of the disrupted plaque, disturbed local rheology and systemic thrombotic-thrombolytic milieu. Surges in sympathetic activity provoked by sudden vigorous exercise, emotional stress -including anger, or cold weather, may also trigger plaque disruption. These observations have led to the concept of plaque stabilization as a new clinical strategy for the prevention of acute coronary syndromes. Plaque stabilization can be achieved through pharmacologic and lifestyle-modifying interventions that reduce vulnerability to plaque disruption by altering plaque composition and/or inflammatory activity within the plaque.
The generalized nature of atherosclerosis: how peripheral arterial disease may predict adverse events from coronary artery disease
Authors: Criqui Michael H , Denenberg Julie O
Published: January 2007

Non-invasive measurements, especially segmental pressure ratios and flow measurements, are useful for gauging the severity of peripheral arterial disease (PAD). Although the incidence of PAD is similar for men and women, men are more likely to have severe disease, while women usually have more moderate or asymptomatic disease. Published reports confirm the clinical impression that patients with PAD are more likely to have both coronary artery disease and cerebrovascular disease than those without PAD. However, the degree of overlap is a function of the sensitivity of the diagnostic assessments for the three conditions. A San Diego population study found that the incidence of PAD may be underestimated, with many patients being asymptomatic. Based on blood flow measurements, the study found that 11.9% of the study population had large vessel PAD. Morbidity from both coronary heart disease and stroke was increased in people with PAD, who were 2.5 times more likely to present with morbidity from cardiovascular disease (CVD) than those who did not have PAD. Several studies have now confirmed the strong predictive value of PAD for subsequent CVD mortality and that the risk of CVD mortality increases with the severity of PAD.
Non-invasive assessment of brachial artery endothelial vasomotor function: the effect of cuff position on level of discomfort and vasomotor responses
Authors: Mannion Timi C , Vita Joseph A , Keaney John F , Benjamin Emelia J , Hunter Liza , Polak Joseph F
Published: January 2007

Non-invasive assessment of brachial artery flow-mediated dilation using cuff occlusion of the arm above or below the elbow to stimulate flow is emerging as a highly useful technique to examine endothelial vasomotor function in human subjects. In anticipation of a large-scale investigation, an important issue is the acceptability of the technique to participants. The purpose of this study was to determine the level of discomfort associated with the technique and compare it to the commonly used procedure of venipuncture. Flow-mediated dilation was determined using cuff occlusion of the arm above the elbow and a blood sample was obtained by standard venipuncture from 54 subjects. The level of discomfort for each procedure was assessed and compared using a visual analogue scale and was found to be extremely low. When the occlusion cuff was positioned above the elbow, the discomfort was slightly more severe (1.9 6 1.9 cm) than venipuncture (1.0 6 1.3 cm, p = 0.003). In 27 subjects, the effect of cuff position (above or below the elbow) was compared: the below the elbow position was associated with a reduction in the percentage increase in flow (570 6 280% versus 900 6 560%, p = 0.005), flow-mediated dilation (6.8 6 3.8% versus 9.8 6 5.7%, p = 0.008) and discomfort (1.6 6 0.8 versus 3.7 6 2.2 cm, p = 0.008). When the cuff was located below the elbow, the level of discomfort was equivalent to that associated with venipuncture. Thus, non-invasive assessment of flow-mediated brachial artery dilation is well tolerated and appears to be suitable for a large-scale study of endothelial function.
Diagnosis and treatment of chronic lower extremity ischemia
Authors: Sanchez Luis A , Veith Frank J
Published: January 2007

Chronic lower extremity ischemia is due to progressive atherosclerosis of the aortoiliac and/or infrainguinal arteries. This disease process is of great importance as millions of patients are affected by lower extremity arterial occlusive disease. Most of these patients are asymptomatic but a growing number of them are symptomatic, with complaints ranging from mild claudication to gangrene. The increasing number of patients affected by lower extremity atherosclerosis is, in part, due to the `graying' of the general population and to the medical improvements of the past three decades that have allowed patients with generalized atherosclerosis to survive longer. Fortunately, the diagnosis and management of peripheral arterial occlusive disease has also significantly progressed leading to improved graft patency, limb salvage rates, and quality of life for patients.
Medical costs of treating venous stasis ulcers: evidence from a retrospective cohort study
Authors: Olin Jeffrey W , Beusterien Kathleen M , Childs Mary Beth , Seavey Caroline , McHugh Linda , Griffiths Robert I
Published: January 2007

Venous stasis ulcers (VSU) account for approximately 80-90% of lower extremity ulcerations. Given their prevalence and chronic nature, VSU are thought to impose a significant economic burden on Medicare (the USA's largest health insurance program) and other third party payers. However, comprehensive studies on the costs of VSU treatment are lacking. The objective of this study therefore was to examine comprehensively the direct medical costs of treating patients with a VSU in routine clinical practice.

A cohort of 78 patients who presented with a VSU to the Cleveland Clinic Foundation (CCF), a large primary and tertiary referral center, was studied retrospectively. All inpatient and out-patient costs related to VSU treatment that were incurred during the year following VSU presentation or until the ulcer healed, whichever occurred first, were quantified. A total of 71 (91%) patients healed during the study. The average duration of follow-up was 119 days (median: 84 days). The average number of visits per patient was seven (range: 2 to 57). A total of 14 (18%) patients underwent 18 hospitalizations for VSU care. The average total medical cost per patient was $9685 (median: $3036). Home health care, hospitalizations and home dressing changes accounted for 48%, 25% and 21% of total costs, respectively. Total costs were related to duration of active therapy, ulcer size and the presence of at least one comorbidity (p,0.05).

VSU are costly to manage, especially when time to healing is prolonged. The present findings reflect an underestimate of VSU costs since indirect costs were not examined. Time absent from work, forced early retirement, loss of functional independence and unquantifiable suffering may be additional factors that contribute to the overall burden of VSU.
Venous thrombus stability during acute phase of therapy
Authors: Caps Michael T , Meissner Mark H , Tullis Michael J , Polissar Nayak L , Manzo Richard A , Zierler Brenda K , Chandler Wayne L , Strandness D Eugene
Published: January 2007

The purpose of this study was to use serial venous duplex scans to document the status of deep venous thrombi during the early phase of therapy for acute, deep-vein thrombosis (DVT). A total of 71 consecutive participants treated for a first episode of acute DVT were monitored for new venous thrombosis using serial venous duplex scans. An average of 4.6 duplex scans were performed per patient (range, three to seven) during the 3-week study period. The cumulative incidence of contiguous/non-contiguous extension of the DVT at 3 weeks was 26% (95% CI = 14% to 38%). Nine of the 15 (60%) occurrences were asymptomatic. None of the classical risk factors for DVT was significantly associated with the development of new thrombi. The fraction of time during which the level of anticoagulation was considered `adequate' (international normalized ratio >2.0 and/or heparin concentration >0.2 IU/ml) was inversely associated with the risk of extension/new thrombi (p = 0.01, Cox proportional hazards analysis).

It was concluded that: (1) the frequency of contiguous/non-contiguous extension of venous thrombosis detectable during the first 3 weeks of therapy was higher than previously reported; (2) the majority of the occurrences were asymptomatic; and (3) the risk of developing this complication was inversely associated with the level of anticoagulation achieved.
Decrease in P-selectin levels in patients with hypercholesterolaemia and peripheral arterial occlusive disease after lipid-lowering treatment
Authors: Kirk Gwen , McLaren Margaret , Muir Andrew H , Stonebridge Peter A , Belch Jill JF
Published: January 2007

At sites of thrombosis and vascular injury, interactions occur among platelets, leucocytes and endothelial cells. Patients with peripheral arterial occlusive disease (PAOD) have been shown to have raised total serum cholesterol and serum triglycerides and increased sP-selectin levels when compared with controls. A total of 31 patients with PAOD and hypercholesterolaemia took part in this three-staged study. Soluble P-selectin (sP-selectin) levels were significantly lowered after 12 weeks of fluvastatin treatment (157.0 ng/ml versus 113.77 ng/ml, p = 0.01), whereas 12 weeks of placebo treatment had no statistically significant effect on sP-selectin levels (150.0 ng/ml versus 139.4 ng/ml). An unpaired t-test almost reached statistical significance (p = 0.051) when the levels by which sP-selectin fell after 12 weeks of active or placebo treatment were compared. The placebo group was then put onto long-term, active treatment and sP-selectin levels were significantly lowered by fluvastatin when compared to pre-treatment levels (150.0 ng/ml versus 110.0 ng/ml, p = 0.03). By lowering the levels of P-selectin, fluvastatin may not only attenuate atherosclerotic progression but may also decrease the platelet activation associated with PAOD.
Relief of sleep apnea after intravascular stenting for superior vena cava syndrome
Authors: Fernandez Bernardo , Smolley Laurence A , Swirsky Stephen M , Kaye Mark D
Published: January 2007

A rarely reported association of sleep apnea and superior vena cava stenosis from mediastinal fibrosis is described. A case is presented where substantial improvement in the sleep parameters and the symptoms of sleep apnea occurred subsequent to superior vena cava thrombolysis and stent angioplasty.