Vascular Medicine

Thromboangiitis obliterans (TAO) and antiphospholipid syndrome (APS) share the clinical characteristics of arterial thrombosis and recurrent thrombophlebitis. Although the association of anticardiolipin antibodies (aCLa) and TAO has been previously recognized, the prevalence and the clinical impact of this association remains unclear.

aCLa were measured by double ELISA in patients with TAO (n=47), premature atherosclerosis (pASO) (n=48) and otherwise healthy individuals (n=48). Antibody status was then compared to clinical presentation and outcomes in patients meeting the diagnostic criteria for TAO. The prevalence of aCLa was significantly higher in patients with TAO (36%) compared to either pASO (8%; p=0.01) or healthy individuals (2%; p,0.001). Patients with TAO and a high antibody titer tended to be younger and suffer a significantly higher rate of major amputations compared to those without the antibody (100% versus 17%; p=0.003). Clinical features of TAO not significantly altered by the presence of aCLa included upper limb involvement, digital necrosis, superficial thrombophlebitis (or deep venous thrombosis). Protein C, protein S, and anti-thrombin III were normal in all individuals.

TAO is associated with an increased prevalence of aCLa. The presence of a high antibody titer in these patients is associated with increased morbidity, including major limb amputation. In patients meeting the diagnostic criteria for TAO, screening for aCLa should be considered. Although attractive, the efficacy of chronic anticoagulation in this setting remains to be proven.

Raynaud’s phenomenon (RP) is a common and painful condition characterized by episodic digital ischaemia produced by emotion and cold. Treatment of RP is notoriously difficult because of the high incidence of side effects. The aim of our study was to investigate the clinical efficacy of a standardized Ginkgo biloba extract (Seredrin) in the treatment of RP in patients with no apparent, associated condition such as systemic sclerosis.

A two-week assessment period was done during which patients were asked to record frequency, severity and duration of attacks in diaries. Subjects were then randomized independently of the study centre to receive either active or placebo treatment for 10 weeks, during which time the same data were recorded in their diaries. Patients were seen after two and four weeks of treatment and at the end of the 10-week treatment phase. Blood samples pre- and post-treatment were taken for haemorrheology.

Only in the number of attacks per day was there a significant effect of treatment over placebo. The number of attacks per week prior to treatment with Seredrin was 13.2 6 16.5 reducing to 5.8 6 8.3, a reduction of 56%, whereas placebo reduced the number by only 27% (p < 0.00001). There were no significant differences in haemorrheology between the two groups.

Ginkgo biloba phytosome may be effective in reducing the number of Raynaud’s attacks per week in patients suffering from Raynaud’s disease.

The utility of low-molecular-weight heparin (LMWH) in the prophylaxis of venous thromboembolic disease has been examined using the surrogate endpoint of venographically identified thrombi. The largest portion of these thrombi were asymptomatic calf-vein thrombi. The clinical relevance of this observation is a matter of debate. The present study is designed to evaluate the impact of an LMWH on clinically important endpoints.

The current study is a randomized, prospective, double-blinded, multicenter, multinational, controlled clinical trial comparing dalteparin with placebo in moderately high-risk hospitalized medical patients. A total of 3300 patients will be randomized to receive either 5000 IU per day of dalteparin or placebo for 14 days. Patients will undergo appropriate evaluation for any symptomatic episodes and all patients will undergo a bilateral compression ultrasound (CUS) on day 21 to search for asymptomatic proximal thrombi.

The primary endpoint is the combination of objectively confirmed symptomatic deep vein thrombi (DVT), fatal or non-fatal pulmonary emboli, all proximal DVT, and sudden death.

This study will be the first study to examine clinically important endpoints in evaluating the effect of a LMWH in hospitalized medical patients. This study also is the first study to use CUS rather than venography in concordance with contemporary medical practice. This trial is thus designed to address this important question in a clinically relevant manner.

Renal artery stenosis (RAS) may cause hypertension, azotemia, episodes of flash pulmonary edema and congestive heart failure. Renal artery angioplasty and stenting was performed in 207 patients from 1991 to 1997. Thirty-nine of these patients (19%) underwent renal artery stenting for the control of recurrent episodes of congestive heart failure and flash pulmonary edema. All patients had angiographic evidence of severe (>70%) bilateral RAS (n = 18) or severe RAS to a solitary functioning kidney (n = 21).

Sixteen patients (41%) were male and 23 (59%) were female, mean age 69.9 years (range 50- 85 years). Of the 18 patients with bilateral RAS, 12 (66.6%) underwent bilateral stenting. Mean blood pressure decreased from 174/85 6 32/23 mmHg to 148/72 6 24/14 mmHg (p < 0.001). Mean number of blood pressure medications decreased from 3 6 1 to 2.5 6 1 (p = 0.006). Twenty-eight patients (71.8%) had improvement in blood pressure control. The mean serum creatinine decreased from 3.16 6 1.61 to 2.65 6 1.87 (p = 0.06). Six of 39 patients (15.4%) used angiotensin converting enzyme (ACE) inhibitors prior to stenting whereas 19 of 39 patients (48.7%) used ACE inhibitors poststenting (p = 0.004). Twenty of 39 patients (51.4%) demonstrated improvement in serum creatinine, 10 of 39 patients (25.6%) had stabilization of serum creatinine and nine of 39 patients (23%) demonstrated worsening. The number of hospitalizations due to congestive heart failure in the year preceding renal artery stenting was 2.4 6 1.4 and poststenting was 0.3 6 0.7 (p < 0.001). The New York Heart Association Functional Class decreased from 2.9 6 0.9 prestenting to 1.6 6 0.9 poststenting (p < 0.001). Thirty of 39 patients (77%) had no hospitalizations for congestive heart failure during a mean follow-up period of 21.3 months. Nine patients expired during the course of follow up; eight of the nine patients died within the first year after renal artery stenting.

Renal artery stenting decreased the frequency of congestive heart failure, flash pulmonary edema, and the need for hospitalization in most patients. Blood pressure was markedly improved in the majority of patients with improved or stabilized renal function. Evaluation for RAS is important in hypertensive patients who present with recurrent congestive heart failure or flash pulmonary edema.

Aortic disease can present as an acute chest pain syndrome. Although aortic dissection is the most common etiology, other processes such as intramural hematoma (IMH) and penetrating atherosclerotic ulcers are being increasingly recognized. They can all be accurately identified by computed tomography (CT) imaging or transesophageal echocardiography. The overlap between these processes regarding definition and mechanism is controversial. Treatment for all three conditions has thus far been dictated by location, wherein ascending or arch involvement (Stanford type A) necessitates surgery and descending disease (type B) is treated medically. Small studies suggest that subgroups of type A IMH may be treated medically with good outcomes.

An acute coronary syndrome (ACS) is the clinical manifestation of a thrombotic event occurring within a coronary artery narrowed by atherosclerosis. This atherothrombotic event is thought to occur following destabilizing changes within the atherosclerotic plaque, rendering it a surface on which thrombus can develop. The development and progression of this thrombus are determined by deleterious perturbations in the hemostatic equilibrium within the local environment of the plaque that favor thrombosis. Major risk factors for the development of atherosclerotic disease have been clearly established and are targets of aggressive modification in an effort to impede the development or slow the progression of disease. While conferring an increased risk for plaque development, these and other risk factors also establish a prothrombotic milieu within the microenvironment of the atherosclerotic plaque that favors thrombosis. This review seeks to address these traditional and emerging risk factors from the context of their pathologic effects on local hemostatic balance. Aggressive risk factor modification not only reduces atherosclerotic disease development and progression, but also ameliorates the prothrombotic state, and ultimately serves to reduce atherothrombotic events.

In contradistinction to chronic critical limb ischemia, the peripheral arterial disease patient with intermittent claudication is at relatively low risk for limb loss. As a result, initial claudication management should employ non-interventional therapies rather than immediate catheter-based or surgical revascularization. Although exercise therapy is the most efficacious conservative treatment for claudication, supervised exercise programs are not widely available at present. Consequently, a pharmacologic agent can be utilized to lessen the symptoms and improve the function of the claudicant. This manuscript provides a comprehensive review of the various pharmacotherapies that have been investigated for improving walking distance in the setting of intermittent claudication. Cilostazol, a phosphodiesterase III inhibitor, appears to provide the greatest benefit, significantly improving not only walking distance but quality of life as well. Early trials indicate that propionyl-l-carnitine, oral prostaglandins, l-arginine, and therapeutic angiogenesis may eventually yield significant benefit in lessening the symptoms of intermittent claudication.

Ischaemia of the bowel may arise from a number of causes affecting the arterial and venous compartments of the vascular tree. This article addresses the causes and consequences of arterial obstruction, which may compromise the supply of oxygenated blood to the bowel. These events may occur as an acute phenomenon, or they may present in a chronic fashion. The therapeutic options available to treat this condition are largely dependent on the mode of presentation and the amount of time that is available before irreversible damage occurs to the bowel integrity. In the acute phase, the viability of the bowel is in doubt, and this necessitates an open operative approach to assess the amount of bowel infarction which has already occurred. A variety of operative procedures are then available to limit this bowel loss and to secure the viability of the remaining bowel. In the more chronic phase there are alternative, less invasive procedures that may be appropriate for the patient, who may have suffered a prolonged period of undernourishment and dehydration. In such cases the immediate bowel viability is not in doubt, but the medium/long-term survival is compromised. Treatment options appropriate to each clinical scenario are discussed, along with the major technical issues associated with these treatments. A team approach to the most appropriate management plan is stressed, and the published outcomes reviewed.

Atherosclerosis is a form of arterial disease that manifests in the coronary circulation as coronary artery disease (CAD), in the carotid arteries as cerebrovascular disease, and in the aorta and lower extremity arteries as peripheral arterial disease (PAD). The systemic nature of the disease is reflected in the fact that individuals with PAD or carotid artery disease are more likely to have CAD than those without. Since individuals with PAD are at markedly increased risk of cardiovascular ischemic events, early Identification of this population and more aggressive medical interventions could substantially improve both morbidity and survival. The incidence of PAD in the general population is high, and currently affects 8-10 million Americans. The risk of developing PAD is predicted by both age and common atherosclerosis risk factors(e.g., smoking and diabetes). efficient office-based PAD detection depends on the application of objective techniques to establish this diagnosis. Objective noninvasive tests, such as measurement of the ankle-brachial index (ABI), are known to be more sensitive than traditional clinical assessments. Since the major threat to patients with PAD is from secondary cardiovascular ischemic events, a primary therapeutic goal is to modify atherosclerotic risk factors. While national recommendations mandate aggressive lowering of serum low-density lipoprotein cholesterol (LDL-C) levels as a primary treatment goal in all patients with overt atherosclerosis, as ‘coronary heart disease risk equivalent’ syndromes, individuals with PAD are less intensively treated than those with CAD. Statins are the most effective of current treatments in lowering LDL-C, and have proven efficacy in secondary prevention among patients with established CAD. The use of statin medications in high-risk groups such as PAD patients could prove particularly beneficial in reducing cardiovascular morbidity and mortality and therefore merits prospective clinical investigation.

Question: Does oral acetylcysteine prevent acute contrast nephropathy in patients with moderate renal impairment who undergo elective coronary angiography?

Population: Patients with moderate stable renal insufficiency (creatinine clearance,60 ml/min or serum creatinine .1.2 mg/dl [106 mmol/l]) who were scheduled to undergo elective coronary angiography with or without intervention.

Design and methods: Randomized placebo-controlled trial. A total of 200 patients were randomized to either oral acetylcysteine 600 mg BID (n = 102) or matching placebo (n = 98). Treatment was given for a total of four doses, starting the day before angiography and continuing on the day of the procedure. All patients received intravenous normal saline for 12 hours before and 6 hours after contrast exposure, and low osmolality contrast agents. Primary outcome was the occurrence of more than a 25% increase in serum creatinine level within 48 hours after contrast exposure. Coprimary outcomes were a change in creatinine clearance and serum creatinine level. Secondary outcomes were major adverse cardiac events, need for dialysis, and length of hospitalization. Patients, caregivers, and outcome assessors were blinded to group assignment. Analysis was by intention-to-treat.

Results: Within 48 hours after contrast administration 12/98 (12%) control patients and 4/102 (4%) acetylcysteine patients developed a more than 25% increase in serum creatinine level. Relative risk = 0.32 (95% CI: 0.10--0.96; p = 0.03). Serum creatinine was lower in the acetylcysteine group than in the control group during the first 48 hours after angiography (1.22 mg/dl [108 mmol/l] vs 1.38 mg/dl [122.9 mmol/l]; p = 0.006), but this difference was no longer significant at seven days. Creatinine clearance increased significantly more in the acetylcysteine group than in the placebo group at day two [+30% vs +5%; p < 0.001] and at day seven [+23% vs +15%; p = 0.045]. The average length of stay was half a day shorter in the group receiving acetylcysteine(p = 0.02). No patients in either group required dialysis. There were no treatment-related adverse events.

Conclusions: Acetylcysteine safely and effectively reduces the incidence of contrast-induced nephropathy in patients with moderate renal insufficiency undergoing coronary angiography.