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PubMed1995

Vascular holism: the epidemiology of vascular disease.

This article reviews the distinguishing features of epidemiology and clinical medicine and their interdependence in clinical epidemiology as applied to vascular disease. Selected literature is reviewed to emphasize the principles of clinical epidemiology for five vascular disorders: abdominal aortic aneurysms, lower extremity peripheral arterial occlusive disease, cerebrovascular disease, deep vein thrombosis and pulmonary embolism, and varicose veins. These vascular disorders are prevalent and pose significant risks for death and disability. Many have risk factors that can be controlled. All can be treated by vascular surgery, but outcomes including functional health and well-being may fall short of that which is implied in our traditional surgical literature. Appropriate allocation of resources to detect and treat vascular disease demands that clinicians not only assume responsibility for the care of individual patients but also develop a working knowledge of the clinical epidemiology of vascular health and disease and its management within populations.

Cross-Sectional Studies↗
PubMed1992

Plasma lipid levels and platelet and neutrophil function in patients with vascular disease following fish oil and olive oil supplementation.

This double-blind study was designed to examine and compare the effects of supplementing the existing diet with fish oil or olive oil on lipids and cell function in patients with peripheral vascular disease. Thirty-two patients with symptomatic and angiographically demonstrated peripheral vascular disease were screened, matched, and randomly allocated to take either 15 g/d fish oil or olive oil for 4 weeks. Fish oil reduced serum triglyceride levels by 26%, but increased total cholesterol levels due to a significant increase in both low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein-2 cholesterol (HDL2-C). There was a nonsignificant decrease in HDL3-C levels. Olive oil reduced total cholesterol levels, accountable to a significantly decrease in LDL-C levels. Serum thromboxane B2 (TXB2) levels remained unchanged following fish oil, but were significantly increased by olive oil. Urinary excretion of TXB2 and 6-keto-PGF1 alpha was unaffected by either oil supplement. Platelet aggregation, which was measured in platelet-rich plasma in response to two doses of collagen or platelet-activating factor (PAF), was significantly reduced after fish oil, but was increased by olive oil. Following fish oil, there was a significant increase in eicosapentaenoic acid (EPA, 20:5) and docosahexaenoic acid (DHA, 22:6) levels and a decrease in arachidonic acid content of platelet phospholipids. The platelet fatty acid composition after olive oil was unchanged. Fish oil decreased neutrophil leukotriene B4 (LTB4) generation following calcium ionophore stimulation by 33%, while leukotriene B5 levels increased significantly. Neutrophil PAF production and plasma lyso-PAF were unaffected by either oil.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1975

[Nonocclusive mesenteric vascular disease following atrio-ventricular block and pacemaker treatment. Gangrene of small and large bowel with occlusion of inferieor mesenteric artery (author's transl)].

A case of nonocclusive mesenteric vascular disease consequential to a low cardiac output syndrome in a patient with a temporary pacemaker is reported. Preexisting occlusion of the inferior mesenteric artery resulted in a total gangrene of small and large bowel. Experimental findings suggest that this occlusion could have resulted in a compensatory increase of blood flow in the superior mesenteric artery. The possibility is discussed that the preexisting necessary increase of superior mesenteric blood flow could be followed by equally increased sensitivity of regional organic systems in non-occlusive mesenteric vascular disease.

Abdomen, Acute↗
PubMed2000

Prevention of coronary vascular disease by transplantation of T-cell-depleted bone marrow and hematopoietic stem cell preparation in autoimmune-prone w/BF(1) mice.

This project was designed to investigate the application of bone marrow transplantation to a progressive and ultimately fatal systemic autoimmune disease. Male (NZW x BXSB)F1 (W/BF1) mice develop acute systemic autoimmune disease characterized by degenerative coronary vascular disease (CVD) with myocardial infarctions, hypertension, thrombocytopenia, glomerulonephritis, and persistently elevated levels of circulating immune complexes. After preliminary studies established the onset of disease between 10 and 12 weeks of age, 6- to 8-week-old male W/BF1 mice were targeted for transplantation with either T-cell-depleted bone marrow or purified hematopoietic stem cells from haploidentical B6C3/F1 mice. Posttransplantation flow cytometric analysis of splenocytes demonstrated donor phenotypes in W/BF1 recipient mice that had received T-cell-depleted marrow or hematopoietic stem cell preparations (lineage negative, CD71 negative) from B6C3/F1 donors. Survival of W/BF1 mice transplanted with bone marrow from normal B6C3/F1 donors was very high, and assessment at 100 days after transplantation revealed reduction in onset and severity of disease. Autoantibodies to cardiolipin and double-stranded DNA were markedly reduced to levels present in normal mice. Immunohistochemistry of heart and kidney tissue revealed significant amelioration of degenerative CVD and glomerulonephritis in the majority of W/BF1 recipients of marrow transplants from B6C3/F1 donors. All engrafted W/BF1 mice displayed normal immunologic competence 100 days posttransplantation.

Animals↗
PubMed2006

Diabetic vascular disease: an experimental objective.

It is well known that humans with diabetes have more atherosclerosis and its complications. The causes of this relationship are, however, unclear. Although recent data show that improved glycemic control reduces arterial disease in type 1 diabetes, other studies have shown that subjects with "prediabetes" have more cardiovascular disease before the development of hyperglycemia. Thus, either hyperglycemia and/or lack of insulin actions are toxic to arteries, or metabolic derangements exclusive of hyperglycemia are atherogenic. For >50 years animal models of diabetes and atherosclerosis have been used to uncover potential mechanisms underlying diabetes associated cardiovascular disease. Surprisingly, diabetes alone increases vascular disease in only a few select animal models. Increased atherosclerosis has been found in several animals and lines of genetically modified mice; however, diabetes often also leads to greater hyperlipidemia. This makes it difficult to separate the toxic effects of insulin lack and/or hyperglycemia from those caused by the lipids. These studies are reviewed, as well as more recent investigations using new methods to create diabetic-atherosclerotic models.

Animals↗
PubMed2006

Brain volume changes in CADASIL: a serial MRI study in pure subcortical ischemic vascular disease.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease causing stroke and subcortical vascular dementia. Recent studies in sporadic subcortical ischemic vascular disease have drawn attention to brain atrophy as a clinically important marker of disease progression. However, little is known about the role of brain atrophy and its clinical correlates in CADASIL. METHOD: The authors determined the normalized brain volume (NBV) and percent brain volume change (PBVC) over 2 years in 76 CADASIL subjects (45.1 +/- 9.7 years) using the SIENA (structural image evaluation using normalization of atrophy) software and its adaptation for cross-sectional measurements (SIENAX). Baseline assessments included systolic blood pressure (SBP), homocysteine levels, BMI, and APOE genotyping. T2-lesion volumes and clinical scales were assessed at both time points. RESULTS: The NBV significantly correlated with all clinical scores (Rankin, NIH Stroke Scale, Barthel, structured interview for the diagnosis of Alzheimer dementia and multi-infarct dementia, Mattis dementia rating scale) at both time points independently of age and sex. PBVC correlated with changes of all clinical scores (all p < 0.01) except for the Mattis dementia rating scale (p = 0.10). In a linear regression model, age (p < 0.001), male sex (p < 0.01), and SBP (p = 0.07) were the main risk factors for a lower NBV at baseline. Age (p < 0.001) and SBP (p = 0.01) were risk factors for brain volume loss during follow-up. Sample size estimates showed that the number of individuals needed to demonstrate a treatment effect in a trial can be reduced when PBVC is used as an endpoint. CONCLUSIONS: This study identifies brain atrophy as an important aspect of the disease process in CADASIL and establishes significant correlations with multiple clinical aspects including cognition. Age and systolic blood pressure are risk factors for brain volume loss during follow-up. Percent brain volume change seems promising as an adjunct outcome measure in future interventional trials.

Adult↗
PubMed1990

Do pre-operative antibiotics reach the operative field in amputation surgery for peripheral vascular disease? A pilot study.

Amputation surgery in patients with peripheral vascular disease is associated with high revision and mortality rates. A prospective pilot study examined the intra-operative delivery of cefoxitin sodium to the amputation site, and used pre-operative transcutaneous oxygen pressure measurement to try to predict the tissue antibiotic levels at the amputation site. Antibiotic concentrations were measured in plasma and muscle from the amputation site at the time of amputation, and a significant difference in antibiotic distribution was found between healed and failed amputations. Transcutaneous oxygen pressures correlated with the antibiotic distribution.

Adult↗
PubMed1997

Donor-specific cytokine production by graft-infiltrating lymphocytes induces and maintains graft vascular disease in human cardiac allografts.

BACKGROUND: The development of graft vascular disease (GVD) in the allograft is a major impediment for long-term survival of heart transplant recipients. GVD may be mediated by cellular processes, in response to the transplanted heart, and regulated by cytokines. METHODS: We studied donor-specific cytokine production patterns in graft-infiltrating lymphocyte cultures propagated from endomyocardial biopsies. The biopsies were derived from patients with and without signs of GVD, as diagnosed by angiography at 1 year after heart transplantation. RESULTS: In the first year after transplantation, significantly more T-helper (Th) 1 cytokines (interleukin [IL]-2: P=0.04; interferon-gamma: P=0.01), but not Th2 (IL-4 and IL-6) cytokines, were produced by cultures of patients with GVD compared with patients without GVD. Thereafter, the Th1 cytokine levels in patients with GVD normalized to the levels of patients without GVD. Detectable levels of IL-6 were produced significantly more often (P=0.009) by cultures obtained more than 1 year after transplantation from patients with GVD. CONCLUSIONS: The results suggest that high levels of Th1 cytokines produced by graft-infiltrating lymphocytes early after transplantation may be responsible for activation of vascular endothelium, leading to the migration and proliferation of smooth muscle cells that is characteristic of GVD. IL-6, produced later after transplantation, continues this process by promoting smooth muscle cell proliferation.

Cells, Cultured↗
PubMed2005

ADVANCE: action in diabetes and vascular disease.

The burden of Type II diabetes is growing rapidly worldwide, across high-, middle- and low-income countries. This burden is associated primarily with increased risks of macrovascular and microvascular diseases, and it is agreed that multifactorial treatment regimens are required to reduce it. ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron-MR Controlled Evaluation) is a large-scale, 2 x 2 factorial, randomised clinical trial. It will investigate the potential benefits of blood pressure lowering, using a fixed low-dose combination of perindopril and indapamide vs placebo, and of tighter glucose control, using an intensive gliclazide-MR-based glucose control regimen vs a standard guidelines-based regimen, separately and together. The two primary outcomes are a composite macrovascular end point of nonfatal stroke, nonfatal myocardial infarction and cardiovascular death; and a composite microvascular end point of new or worsening nephropathy or microvascular eye disease. Following successful recruitment and randomisation of 11,140 participants by March 2003, the study is currently half way through its planned follow-up of 4.5 years. Adherence to randomised study treatment is good; and loss to follow-up is minimal. It is hoped that the study will answer a number of unresolved issues. The blood pressure lowering arm will investigate the possible reduction in major vascular disease in patients with Type II diabetes whether or not they have hypertension, and the possible benefits of blood pressure lowering in such patients already receiving background therapy with the ACE inhibitor perindopril. The glucose control arm will investigate the possible reduction in both macrovascular and microvascular disease achieved with tighter glucose control, targeting an HbA1c of 6.5% and a fasting blood glucose of 6.0 mmol/l. Finally, the factorial design will enable investigation of the combined effects of more intensive glucose control and tighter control of blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Impaired carotid and femoral viscoelastic properties and elevated intima-media thickness in peripheral vascular disease.

BACKGROUND: We undertook a study to determine whether peripheral vascular disease of the lower extremity (PVD) per se affects the arterial viscoelastic properties and intima-media thickness (IMT) of the carotid and femoral arteries. METHODS: Thirty-five patients with PVD, 35 age- and gender-matched control subjects were examined with ultrasound scan wall tracking system, with the simultaneous measurement of blood pressure for carotid and femoral IMT and viscoelastic properties. RESULTS: Subjects with PVD have significantly impaired carotid elastic properties including compliance (mean (SD): 6.50 (2.39) vs 9.93 (4.07) %mmHg(-1)x10(-2), P<0.001), Petersen's elastic modulus (1.77 (0.69) vs 1.19 (0.63) mmHg x 10(3), P=0.001) and stiffness index (17.92 (7.21) vs 12.10 (6.17), P=0.001) when compared to non-PVD controls. They also have significantly altered femoral elastic properties including Petersen's elastic modulus (5.94 (4.98) vs 3.64 (3.27) mmHg x 10(3), P=0.025) and stiffness index (58.42 (47.76) vs 36.96 (33.43), P=0.033). The carotid (0.85 (0.35) vs 0.59 (0.23) mm, P<0.001) and femoral (1.05 (0.39) vs 0.69 (0.31) mm, P<0.001) IMTs are also significantly elevated in PVD patients. After adjustment for the presumed cardiovascular load assessed on the basis of a cumulative total vascular risk score, as well as age, systolic and diastolic pressure, the carotid viscoelastic indices and the carotid and femoral IMTs remained highly significant. However, the difference in femoral elastic variables was no longer evident. CONCLUSION: PVD per se affects the femoral and carotid wall mechanics and morphology similarly to other cardiovascular risk factors and events. These parameters may provide further information for cardiovascular risk assessment in addition to the classical risk factors and the Framingham equation. Indeed, some guidelines have suggested that additional factors such as the carotid scan may influence the clinician's decision to intervene with therapy.

Aged↗
PubMed1991

Bacterial infection and peripheral vascular disease.

Whole blood filterability was monitored in 16 nondiabetic peripheral vascular disease (PVD) patients within forty-eight hours of onset of bacterial infection, after ten to seventeen days antibiotic therapy and again, ten days later, after convalescence. The whole blood filterability rate was constantly disturbed before infection in these patients; the impairment worsened significantly (as was expected during infection), but after convalescence the whole blood filterability rate did not return to preinfection levels. This further significant impairment in whole blood filterability was inversely correlated with a reduction in the patients' pain-free walking time as determined by a standard treadmell test performed after convalescence and compared with their average times before infection.

Bacterial Infections↗
PubMed1979

Energy cost of walking of below-knee amputees having no vascular disease.

Fifteen unilateral below-knee amputees with no preexisting vascular disease were studied during free velocity walking to determine energy expenditure with and without a prosthesis. Expired air was collected, and heart rate and respiratory rate data were telemetered. Mean velocity for the unrestrained walking was 71 m/min, both during ambulation with a prosthesis and during crutch walking (without a prosthesis). Heart rates were within normal ranges during prosthetic walking (106 beats/min), but rose significantly to 135 beats/min for crutch walking. Energy cost also rose significantly from a mean of 15.5 ml O2/kg/min with a prosthesis of 22.3 ml O2/kg/min with crutches. The oxygen uptake measured in units of ml O2/kg/m increased when the subjects walked faster or slower than their free cadence. We concluded that the use of the prosthesis should be encouraged and that the amputee should be allowed to choose his natural velocity of walking.

Adult↗
PubMedDate not supplied

Risk factors for vascular disease and dementia.

There is increasing evidence that risk factors for vascular disease and stroke are associated with cognitive impairment and Alzheimer's disease. This paper reviews current knowledge on the relationship between risk factors for stroke and Alzheimer's disease. The focus will be on 'classical' risk factors, including age and gender, socioeconomic status, diabetes, cholesterol, prior cardiovascular disease, atrial fibrillation, cigarette smoking and alcohol use; as well as on factors that more recently have been recognized as putative risk factors, including APOE genotype, serum homocysteine concentration, relative abnormalities in the hemostatic and thrombotic systems, and inflammation.

Alzheimer Disease↗
PubMed1987

Predicting stump healing following amputation for peripheral vascular disease using the transcutaneous oxygen monitor.

In patients with peripheral vascular disease requiring amputation, a below-knee stump is likely to result in improved function compared to above-knee. Unfortunately, clinical assessment of skin circulation is inaccurate, making the decision of amputation level difficult. The transcutaneous oxygen monitor has been investigated as a method of assessing skin circulation. A prospective study using the monitor in 51 amputations based on clinical assessment has shown that a transcutaneous oxygen tension (tcPO2) greater than 40 mm Hg is associated with stump healing, while measurements below that level lead to an unpredictable outcome. Half of the patients undergoing above-knee amputation had a tcPO2 level greater than 40 mm Hg at the below-knee site, suggesting that a successful distal amputation might have been performed. A further prospective study of 50 patients requiring amputation for peripheral gangrene showed that when amputations were performed at the lowest level in the limb with a tcPO2 greater than 40 mm Hg there was a higher rate of below-knee amputations (72%) and a higher rate of successful stump healing. Review of the literature confirms the potential of the monitor as a non-invasive, simple and accurate method of predicting stump healing.

Amputation, Surgical↗
PubMed2004

Effects of R-102444, an orally active 5-HT2A receptor antagonist, in rat models of peripheral vascular disease.

R-102444 is a prodrug that is metabolized into R-96544, a potent and selective 5-hydroxytryptamine2A (5-HT2A) receptor antagonist. The effects of R-102444 on peripheral vascular disease were examined using two different rat models: one induced by lauric acid and the other by ergotamine plus epinephrine. R-96544 (0.3-30 nM) relaxed the 5-HT (3 microM)-precontracted rat caudal artery in a concentration-dependent manner. The intravenous administration of R-96544 (0.3-3 microg/kg) to anesthetized rats inhibited the pressor response to 5-HT (50 microg/kg i.v.) dose dependently. The oral administration of R-102444 (1 mg/kg) to rats resulted in a marked inhibition of platelet aggregation induced by 5-HT plus ADP, and statistically significant inhibition was still evident 8 h after the dosing. In contrast, sarpogrelate, at a dose of 100 mg/kg p.o., produced only a moderate antiplatelet effect. Oral administration of R-102444 (1 mg/kg/day, o.d.) significantly prevented the progression of peripheral vascular lesion induced by the injection of lauric acid into a rat femoral artery, whereas sarpogrelate (100 mg/kg/day) showed only a minimal effect. Both 5-day treatments with R-102444 (1-30 mg/kg/day p.o., o.d.), one commenced 1 h before the injection of epinephrine plus ergotamine and one just after injection, resulted in the prevention of rat tail gangrene in a dose-dependent manner, whereas sarpogrelate (100 mg/kg) produced a minimal protection in this model. Based on these results, we conclude that 5-HT2A receptor activation is involved in peripheral vascular disease in the rat and that R-102444 is a useful oral agent for the investigation of diseases involving 5-HT2A receptor activation.

Administration, Oral↗
PubMed2000

A comparison of bolus chasing and static digital subtraction arteriography in peripheral vascular disease.

The purpose of this study was to compare the techniques of bolus chasing angiography (BCA) and digital subtraction angiography (DSA). 75 patients with symptomatic atherosclerotic peripheral vascular disease were randomly assigned to have their lower limbs examined by BCA or DSA. Dose-area product (DAP), time of examination and dose of contrast medium were measured. Staff doses were measured with personal electronic dosemeters. Image quality was assessed from the laser printed images. DSA produced better images of vessels below the inguinal ligament, particularly the crural vessels (1/76 vs 17/74 non-diagnostic examinations, p < 0.00001) but at a higher DAP (median 53.8 Gy cm2 vs 18.9 Gy cm2, p < 0.01). Contrast medium dose was higher with BCA (29.8 gI2 vs 25.3 gI2, p < 0.01). Staff doses per unit patient dose were 2.3-3.3 times higher with BCA than DSA. Because of the poor long-term prognosis of patients with peripheral vascular disease, the improved image quality obtained by DSA justifies the increased radiation dose.

Aged↗