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Endothelium-derived factors and peripheral vascular disease.

The endothelium plays a major role in modulating vascular tone, vascular growth, and interactions of the vessel wall with blood constituents. Therefore, abnormalities in endothelial function may play a primary or contributory role to a variety of vasculopathies that are characterized by thrombosis, excessive vasoconstriction, or vascular smooth muscle proliferation. Our increasing understanding of the complexity of endothelial functions will permit us to understand the mechanisms of vascular disease and to design new therapies directed at these mechanisms of disease.

Arterial Occlusive Diseases↗

The Legs for Life screening for peripheral vascular disease: compliance with physician recommendations in moderate- and high-risk assessed patients.

PURPOSE: To determine compliance within a community with recommendations made by physicians during the 1999 Legs for Life National Screening for Peripheral Vascular Disease (PVD) and Leg Pain. MATERIALS AND METHODS: Patients were initially screened for PVD by completion of the Legs for Life risk factor questionnaire and determination of bilateral ankle/brachial indexes (ABIs). Each patient subsequently met with an interventional radiologist or vascular surgeon. Patients with normal ABIs (>1.0 bilaterally) or mildly abnormal ABI(s) (<1.0 but >0.90) were classified at no and low risk for PVD, respectively; patients with ABI(s) of 0.70-0.89 were classified at moderate risk for PVD; and patients with ABI(s) <0.69 were classified at high risk for PVD. Risk factors for PVD were assessed by the consulting physician and discussed with all patients. Recommendations were made for additional evaluation and/or follow-up care, if necessary. Seven months after screening, patients who were assessed at moderate and high risk for PVD were contacted by telephone to determine if they had pursued additional care or testing. RESULTS: A total of 205 patients were screened for PVD, 48 (23%) of whom were determined to be at moderate to high risk. Forty-four (92%) patients were available for follow-up. At 7 months after screening, 31 (70%) patients had received no further medical advice or treatment. Thirteen (30%) of these patients had completed a follow-up appointment, but only three with a physician specializing in peripheral vascular disease. None of the patients had clinical follow-up with an interventional radiologist. Five (11%) patients had undergone noninvasive Doppler evaluation and one (2%) had undergone diagnostic arteriography. No patient had undergone any form of percutaneous or surgical intervention. CONCLUSION: Patient compliance with physician recommendations after outpatient screening for PVD is low. The Legs for Life screening program could be considered successful in that it provides for patient education and the identification of moderate to high-risk patients. Physicians participating in this program may have to modify their approach to patient screening and follow-up if a concomitant goal is to deliver specialty care.

Adult↗

Long-term results of arterial bypass surgery for impotence secondary to segmental vascular disease.

PURPOSE: We evaluated the long-term results of arterial bypass surgery in impotent men carefully selected for nonatherosclerotic arterial vascular disease. MATERIALS AND METHODS: During a 7-year period only 11 of 1,352 impotent men (0.8%) were selected as ideal candidates for arterial vascular surgery. Initial evaluation included history, physical examination and a screening pharmacological erection test. Duplex ultrasonography was performed in patients who failed to respond adequately to pharmacological stimulation and were believed to be potential candidates for vascular surgery. Further evaluation included formal nocturnal sleep laboratory testing, dynamic infusion cavernosometry and arteriography. Dorsal artery bypass was performed in 9 patients and arterialization of the deep dorsal vein was done in 2. RESULTS: Average followup was 50 months (range 12 to 84). Initial followup duplex ultrasonography revealed a significant increase in cavernous artery peak systolic blood flow velocity (p < 0.001) and patent arterial anastomoses in all but 1 patient. The initial success rate without supplemental injection therapy was 82% and the final success rate was 64%. Even with long-term followup, 91% of the patients were improved from baseline, and were sexually active with (27%) or without (64%) injection therapy. CONCLUSIONS: Arterial bypass surgery can be successful in select impotent patients without generalized atherosclerosis or other risk factors for impotence. Further refinement of screening parameters may improve patient selection and long-term results of vascular surgery.

Adult↗

Gene therapy for vascular disease.

Highly efficient methods that are now available allow for the genetic modification of cells that compose the vessel wall. The application of these gene transfer systems are already providing information that has enhanced our understanding of a variety of cellular processes relating to vascular biology. Recent experimental results using this technology also hold promise for more powerful therapeutic options in the treatment of vascular disease. This review discusses the most commonly used methods of gene transfer and details some current applications of these methodologies in animal models of vascular disease.

Animals↗

Renal artery stenosis in patients with peripheral vascular disease and its correlation to hypertension. A retrospective study.

To estimate the frequency of renal artery stenosis, and to detect the correlation between renal artery stenosis and hypertension, 450 consecutive patients with peripheral vascular disease (PVD) were selected. All subjects had undergone aorto-femoral conventional angiography. For a possible association with renal artery stenosis, risk factors, clinical and angiographical variables were evaluated e.g.: age, sex, diabetes mellitus, smoking habits, use of antihypertensive drugs, serum creatinine, serum cholesterol, ECG pathology, side of the renal artery lesion, bilateral stenoses, post-stenotic dilatation, number of renal arteries, aortic atherosclerosis, size of the kidneys and angiography induced renal dysfunction. Renal artery stenosis (RAS) was found in 49.1%, 117 patients had a moderate and 104 had a severe stenosis. Of the 221 patients with a renal artery lesion, 44 were normotensive, 177 hypertensive. Hypertension was significantly correlated to RAS. An association was also found for age over 70 years, smoking and pathologic ECG. It is concluded that renal artery stenosis is very common in a population with peripheral vascular disease, and the results achieved from this study makes it worthwhile to identify possible functional markers in a prospective study.

Adult↗

Validity of telephone interview data for vascular disease risk factors in a racially mixed urban community: the Northern Manhattan Stroke Study.

The aims of our study were to assess the validity and reliability of a telephone survey instrument designed to measure vascular disease risk factors and to assess whether these measurements were influenced by age, gender, race/ethnicity, or other sociodemographic variables. Subjects were sampled and interviewed using random digit dialing methodology from the multiethnic community of northern Manhattan. For the validity study, 261 consecutive subjects were clinically assessed in-person within 60 days of the telephone interview. A retest reliability study of the telephone interview was conducted in 92 randomly selected subjects within 30 days of the initial interview. The telephone interview instrument had a sensitivity of more than 55% and a specificity of 74% or greater for various vascular disease risk factors. Sensitivity, specificity, and positive predictive value did not vary significantly or systematically among whites, blacks, and Hispanics, but subjects with access to health care were more likely to provide valid data. The reliability substudy indicated a good reliability for the telephone interview. These results support the validity of telephone interviews for estimating the prevalence of vascular risk factors in urban populations.

Age Factors↗

Beneficial effects of a serine protease inhibitor in peripheral vascular disease.

Kallikrein, a serine protease known to generate bradykinin (a vasodilating peptide) in alkaline conditions, also generates angiotensin II (a vasoconstricting peptide) in weak acidic conditions. Based on this previous observation, the present study was performed to determine whether ischemic muscle tissue, in which the regional pH must decrease, produces angiotensin II by kallikrein or a similar enzyme, and whether nafamostat (NAF), a serine protease inhibitor, improves local hemodynamics under ischemic conditions caused by exercise in patients with ischemic peripheral vascular disease. NAF was administered intravenously to 20 patients with peripheral vascular disease. Lower-limb thermograms and blood flow were measured before and after exercise. Femoral venous blood of affected limbs was obtained to measure viscosity and humoral variables (i.e., pH, lactate, angiotensin II and bradykinin). Walking distance and subjective symptoms were also recorded. As a control, the same patients repeated this test with saline infusion on a separate day. NAF significantly increased maximal walking distance, improved subjective symptoms during exercise, and attenuated exercise-induced venous lactate and blood viscosity increases, and pH reduction. The blood viscosity increase correlated with the lactate increase. Pretreatment with NAF also resulted in a higher lower-limb skin temperature, and a greater increase of blood flow in the lower limbs after exercise than did pretreatment with saline. The results suggest that kallikrein-like serine protease may exacerbate ischemic symptoms. Changes in plasma bradykinin and angiotensin II in the femoral vein were not detectable, probably because of the lower levels of these peptides in the peripheral circulation.

Aged↗

Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials.

BACKGROUND AND PURPOSE: Aspirin is the most widely studied and prescribed antiplatelet drug for patients at high risk of vascular disease. We aimed to establish how the thienopyridines (ticlopidine and clopidogrel) compare with aspirin in terms of effectiveness and safety. METHODS: We did a systematic review of all unconfounded randomized trials comparing either ticlopidine or clopidogrel with aspirin for patients at high risk of vascular disease. The primary outcome was vascular events (stroke, myocardial infarction, or vascular death). Adverse outcomes were intracranial and extracranial hemorrhage, upper and lower gastrointestinal disturbances, neutropenia, thrombocytopenia, and skin rash. RESULTS: In 4 trials among 22 656 patients (including 9840 presenting with a transient ischemic attack/ischemic stroke), the thienopyridines reduced the odds of a vascular event by 9% (odds ratio 0.91, 95% CI 0.84 to 0. 98; 2P=0.01), preventing 11 (95% CI 2 to 19) events per 1000 patients treated for approximately 2 years. The thienopyridines produced significantly less gastrointestinal hemorrhage and upper gastrointestinal upset (indigestion/nausea/vomiting) than did aspirin. Both thienopyridines increased the odds of skin rash and of diarrhea (ticlopidine by approximately 2-fold and clopidogrel by approximately one third). Only ticlopidine increased the odds of neutropenia. CONCLUSIONS: The thienopyridines appear modestly more effective than aspirin in preventing serious vascular events in high-risk patients. Clopidogrel appears to be safer than ticlopidine and as safe as aspirin, making it an appropriate, but more expensive, alternative antiplatelet drug for patients unable to tolerate aspirin. However, there is insufficient information to determine which particular types of patients would benefit most, and which least, from clopidogrel instead of aspirin.

Aspirin↗