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PubMed1999

In vivo microscopic study of microcirculatory perfusion of the skin of the foot in peripheral vascular disease.

OBJECTIVES: the aim of this study was to determine the proportion of perfused capillaries in the skin of the foot in patients with peripheral vascular disease, and compare it with that in normal subjects. DESIGN: experimental study comparing capillary perfusion in nine patients with severe peripheral vascular disease (group 2) with seven age- and sex-matched control subjects (group 1). MATERIALS AND METHODS: using in vivo video microscopy, a method was developed to measure the ratio of perfused to total capillaries, by comparing the numbers of corresponding capillaries before and after intravenous injection of sodium fluorescein. RESULTS: the mean percentage ratio of perfused to total capillaries was 54.7% (range 41-87%, standard deviation 16.5) in group 1, and 86.0% (range 62-100%, standard deviation 13.2) in group 2 (p<0.001, t-test). CONCLUSION: a significantly higher proportion of capillaries is perfused in the skin of the foot of patients with severe peripheral vascular disease than in that of normal subjects. This is of important pathophysiological significance and may have clinical implications with regard to the role of pharmacological intervention in severe limb ischaemia.

Adult↗
PubMed2004

Daily physical activity and heart rate response in people with a unilateral transtibial amputation for vascular disease.

OBJECTIVE: To study the activity level and heart rate response, objectively measured during normal daily life, of persons with a unilateral transtibial amputation for vascular disease. DESIGN: Case comparison. SETTING: General community, daily life in the Netherlands. PARTICIPANTS: Nine subjects with a unilateral transtibial amputation for vascular disease (convenience sample) and 9 control subjects without known impairments (matched for sex, age, social situation, employment). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Duration of dynamic activities, body motility (the intensity of body movement, measured with accelerometry), and heart rate (on 2 consecutive days). RESULTS: Persons with an amputation were less active than the comparison subjects (4.3% vs 11.4% of a 48-h period, P=.007). Body motility during walking was lower in the amputee group (.111 g vs.147 g, P=.003). No differences between groups were found in normalized heart rate during walking. In the amputee group, a strong relationship was found between body motility during walking and the percentage of the day that the subject walked (r=.88, P=.002). No relationship was found between the percentage of the day that persons with an amputation were active and data from disability questionnaires. CONCLUSION: Persons with a unilateral transtibial amputation for vascular disease were considerably less active than persons without known impairments. Heart rate response during walking of the amputee group did not differ from the response in the comparison group.

Activities of Daily Living↗
PubMed2001

Peripheral vascular disease and hypertension: a forgotten association?

Peripheral vascular disease (PVD) is associated with a high cardiovascular morbidity and mortality. Intermittent claudication is the most common symptomatic manifestation of PVD, but is also an important predictor of cardiovascular death, increasing it by three-fold, and increasing all-cause mortality by two to five-fold. Hypertension is a common and important risk factor for vascular disorders, including PVD. Of hypertensives at presentation, about 2-5% have intermittent claudication, with this prevalence increasing with age. Similarly, 35-55% of patients with PVD at presentation also have hypertension. Patients who suffer from hypertension with PVD have a greatly increased risk of myocardial infarction and stroke. Apart from the epidemiological associations, hypertension contributes to the pathogenesis of atherosclerosis, the basic underlying pathological process underlying PVD. Hypertension, in common with PVD, is associated with abnormalities of haemostasis and lipids, leading to an increased atherothrombotic state. Nevertheless, none of the large antihypertensive treatment trials have adequately addressed whether a reduction in blood pressure causes a decrease in PVD incidence. There is therefore an obvious need for such outcome studies, especially since the two conditions are commonly encountered together.

Antihypertensive Agents↗
PubMed1991

Albuminuria--a marker of renal and generalized vascular disease in insulin-dependent diabetes mellitus.

Atherosclerotic vascular disease is a major cause of morbidity and mortality in insulin-dependent diabetes mellitus. The frequent coexistence in these patients of microangiopathy and coronary artery disease was observed more than 30 years ago and later verified in large epidemiological studies. Thus, the subgroup (30-40%) of patients who develop clinical nephropathy, also are at extremely high risk of early cardiovascular death. A number of established cardiovascular risk factors are present not only in advanced clinical nephropathy but also in its earliest stages. These include elevated blood pressure, atherogenic changes in the plasma concentrations of lipids and lipoproteins, elevated plasma levels of fibrinogen and probably hyperreactivity of platelets. However, it seems unlikely that these risk factors fully explain the excess cardiovascular morbidity and mortality in insulin-dependent diabetic patients with clinical nephropathy. Patients with slightly elevated urinary albumin excretion are at increased risk of developing not only clinical nephropathy and coronary heart disease but also proliferative retinopathy and cardiomyopathy. We have, therefore, hypothesised that elevated urinary albumin excretion is a marker of generalized disease in the vascular wall of small and large blood vessels. Findings of elevated transcapillary escape rate of albumin, elevated plasma concentration of von Willebrand factor and impaired fibrinolytic capacity in early diabetic nephropathy have supported this hypothesis. However, the initial pathophysiological mechanisms involved are still hypothetical and largely unknown. During recent years the incidence of clinical nephropathy has declined and the prognosis of insulin-dependent diabetic patients has improved. Whether intervention directed against the often clustered cardiovascular risk factors will further improve the prognosis in proteinuric patients is suggested but still unknown. However, the key question is still, why is the vascular wall, in small and large blood vessels, vulnerable in some but not all diabetic patients? In the future more studies of the initial pathophysiological mechanisms involved in this vulnerability are needed.

Albuminuria↗
PubMed2004

Evidence of pulmonary vascular disease after heart transplantation for Fontan circulation failure.

OBJECTIVES: Elevated pulmonary vascular resistance may contribute to late Fontan circulation failure but is difficult to assess in such patients. Our aims were to assess outcomes of patients with failed Fontan circulation after heart transplantation and to determine whether elevated pulmonary vascular resistance might have contributed to the failure. METHODS: Fifteen patients (14 Fontan circulations, 1 Kawashima circulation) underwent transplantation. The most common indication was ventricular dysfunction (mean ventricular end-diastolic pressure 12.5 mm Hg). Patients with early failures (n = 4) required transplantation less than 1 year after the Fontan operation. Those with late failures (n = 11) underwent transplantation at least 1 year after the Fontan operation. Mean age at transplantation was 11.6 years. Mean Fontan-transplantation interval was 7.4 years. Mean pulmonary arterial pressure, transpulmonary gradient, and pulmonary vascular resistance before and after transplantation were assessed. Paired t tests of variable differences were used to compare variables. Survival was estimated by the Kaplan-Meier method. RESULTS: In-hospital mortality was 7%. There were 2 late events (1 death, 1 retransplantation) related to compliance or rejection issues. Graft survivals were 93%, 82%, and 82% at 3, 5, and 7 years, respectively. Posttransplantation pulmonary vascular resistance was elevated (>2.0 Wood units . m 2 ) in 11 of 14 survivors past initial hospitalization (mean 3.3 +/- 1.7 Wood units . m 2 ). Only patients with early Fontan failures (3 of 4) had normal posttransplantation pulmonary vascular resistance. In paired comparisons, posttransplantation transpulmonary gradient was increased by a mean of 6.8 mm Hg ( P < .0001) relative to pretransplantation value. CONCLUSIONS: Outcomes after heart transplantation for failed Fontan circulation were good. Mild-to-moderate pulmonary vascular disease was evident after heart transplantation for late failure. Elevated pulmonary vascular resistance is a likely contributor to Fontan circulation failure.

Adolescent↗
PubMed2002

Obesity, aerobic exercise, and vascular disease: the role of oxidant stress.

Oxidant formation in the vasculature contributes to vascular disease and dysfunction associated with obesity. In contrast, exercise-dependent production of oxidants may stimulate adaptive responses that protect against the development of such diseases. In this review, we discuss current concepts in the biology of reactive oxygen and nitrogen species and how their function is modulated in the context of vascular disease, obesity, and aerobic exercise.

Animals↗
PubMed1990

Vascular disease: the critical risk factor for mortality in older patients on CAPD.

Clinical course, complications and outcome were analyzed in 75 patients (14 women, 61 men) who started CAPD at age 55 years or older (55-81). These patients were separated in three groups. Group A patients had high risk for vascular disease (diabetes, hypertension, N = 45), group B patients had a presumed lower risk for vascular disease (primary renal disease, N = 22), and group C patients had miscellaneous conditions (N = 8). Group A was compared to group B. Patient and technique survival was statistically higher for group B than for group A. The rates of peritoneal dialysis related complications (peritonitis, tissue infections, catheter loss, hernias) were comparable between groups A and B. Hernias were seen frequently in all groups and had severe sequellae, including discontinuation of CAPD. Catastrophic vascular events were also seen in all groups, but the frequency of such events, particularly of catastrophic vascular events of the limbs, was statistically higher in group A than in group B. Vascular disease accounted for the majority of deaths in all groups. Four patients died from cardiovascular instability soon after changing from CAPD to hemodialysis. In conclusion, vascular disease is the major factor limiting survival in older CAPD patients. CAPD is superior to hemodialysis for a relatively small fraction of older patients with severe cardiovascular instability.

Aged↗
PubMed2004

Geriatric depression and vascular diseases: what are the links?

BACKGROUND: The term "vascular depression" has been proposed to describe a subset of depressive disorders that occurs in old age as a consequence of cerebrovascular disease. However, depression has been shown to result from other cardiovascular diseases such as coronary heart diseases, as well as to precipitate, worsen or precede vascular diseases. Depression also increases the likelihood of the incidence of vascular risk factors such as diabetes. AIMS: To review clinical and epidemiological evidence linking geriatric depression and vascular diseases, and to discuss the potential mechanisms that could underlie this association. METHOD: Systematic review of the literature of the last 5 years through Medline database search. RESULTS: Papers report the following potential ways of association: (1) there is a direct influence of vascular disease, in particular, arteriosclerosis, on the incidence of depression; (2) depressive disorders have a direct impact on the cardiovascular system; (3) depression and vascular disease share either a common pathophysiological process or genetic determinants. DISCUSSION: Depression can be understood as the direct consequence of brain damage in neurodegenerative disorders such as Parkinson's or Huntington's diseases. Similarly, vascular depression is mostly considered to be the consequence of microvascular lesions on prefrontal and subcortical regions. However, this functional neuroanatomical model offers no explanation for cases where depression has been shown to precede vascular diseases. Since cardiovascular diseases develop in a context of acquired environmental factors together with genetically determined disease, it may be postulated that geriatric depression could both result from brain lesions of vascular origin and also share some pathogenic or genetic determinants.

Aged↗
PubMed2001

C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: incidence and effect of combined genotypes on plasma fasting and post-methionine load homocysteine in vascular disease.

BACKGROUND: Moderately increased plasma concentrations of total homocysteine (tHcy) have been shown to be an important risk factor for vascular diseases. Two common polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, the thermolabile C677T and a more recently reported A1298C polymorphism, may contribute to hyperhomocysteinemia. METHODS: Using PCR and restriction fragment length polymorphism analysis, we studied the prevalence of the C677T and A1298C MTHFR genotypes and the combined effect of these polymorphisms on plasma tHcy concentrations, as measured by HPLC with fluorometric detection, both fasting and post-methionine load (PML), in 1238 individuals. RESULTS: The prevalences of the C677T and A1298C genotypes did not differ significantly in 772 individuals with documented coronary artery disease (CAD), 137 individuals with deep-vein thrombosis (DVT), and 329 individuals without documented vascular disease. Individuals homozygous for the 677T allele had significantly increased fasting tHcy, particularly in the presence of low folate, compared with individuals homozygous for the wild-type allele. Neither the 1298AC nor the 1298CC genotype was associated with significantly increased fasting or PML tHcy concentrations irrespective of serum folate. Of the nine combined MTHFR genotypes, six were present in >10% of the population. Of these, the difference in mean fasting tHcy reached statistical significance (P<0.005) only in individuals with the 677TT/1298AA genotype compared with individuals with the wild-type 677CC/1298AA genotype. Differences in mean fasting tHcy did not reach statistical significance in individuals heterozygous for both MTHFR variants. We detected two 677CT/1298CC and three 677TT/1298AC individuals; only one, an 677TT/1298AC individual, had increased tHcy (both fasting and PML). No individuals had the 677TT/1298CC genotype. CONCLUSIONS: The prevalences of the C677T and A1298C polymorphisms did not differ among individuals with CAD, DVT, or those without documented vascular disease. In contrast to the C677T polymorphism, the A1298C polymorphism is not associated with increased fasting tHcy. Although the two polymorphisms usually exist in trans configuration, crossover may occur rarely to form recombinant chromosomes.

Adult↗
PubMed1996

Carotid artery stenosis in peripheral vascular disease.

PURPOSE: The goal of the study was to assess the prevalence and severity of symptomatic and asymptomatic carotid artery disease in patients with peripheral vascular disease (PVD). METHODS: Consecutive patients with clinically and Doppler scanning-proven PVD (category 1 or greater) underwent prospective screening for the presence of carotid atherosclerosis with color-coded duplex ultrasonography. Preexisting risk factors were recorded with a standard questionnaire and included sex, age, diabetes mellitus, history of smoking, hypertension, prior stroke/transient ischemic attacks, and coronary artery disease. RESULTS: Three hundred seventy-three consecutive patients were studied over 2 years. The mean age of the patients was 70 +/- 10 years; there were 223 (60%) men and 150 (40%) women; 71% of the patients had a history of smoking, 47% had coronary artery disease, 43% had hypertension, and 21% had diabetes mellitus. Two hundred eleven (57%) patients had 30% or greater carotid artery stenosis detected by carotid artery duplex scanning. Sixty-seven (32%) of these had symptoms of ischemic cerebral events, of whom 22 had potentially operable carotid artery stenoses (70% to 99%), whereas 72 of the 144 symptom-free patients had 60% to 99% stenosis. An additional 34 patients would be eligible candidates for the ongoing carotid endarterectomy trials (North American Symptomatic Carotid Endarterectomy Trial and European Carotid Surgery Trial). Although all the risk factors were associated significantly with PVD and carotid artery disease (p < 0.002), male sex and prior stroke/transient ischemic attack were the strongest predictors. CONCLUSIONS: Routine carotid ultrasound screening of 373 consecutive patients with category I or greater PVD revealed that 22 patients with symptoms and 72 symptom-free patients were potential surgical candidates, representing 25% of the study cohort. An additional 34 patients were potential candidates for enrollment into the North American Symptomatic Carotid Endarterectomy Trial and European Carotid Surgery Trial.

Age Factors↗
PubMed1990

Perioperative and long-term prognostic value of intravenous dipyridamole thallium scintigraphy in patients with peripheral vascular disease.

The prognostic value of long-term risk stratification of patients with peripheral vascular disease who undergo intravenous dipyridamole thallium scintigraphy has not been well studied. We screened 131 patients with peripheral vascular disease who underwent intravenous dipyridamole thallium testing to determine cardiac event rates over an average follow-up of 18 +/- 10 months. Of the 131 patients, 111 subsequently had peripheral vascular surgery. The patients with abnormal thallium scans after dipyridamole had a significantly higher risk of death or myocardial infarction, both in the perioperative phase (7% versus 0%; p less than 0.001) and at late follow-up (17% versus 6%; p less than 0.01). The risk of a cardiac event was two-fold greater when a reversible as compared to a fixed thallium defect was present. Multivariate analysis selected the number of thallium segments with perfusion defects, prior history of angina pectoris, and chest pain during dipyridamole testing as perioperative predictors of a cardiac event. A reversible thallium defect was the only predictor of death or nonfatal myocardial infarction during late follow-up. Thus intravenous dipyridamole thallium scintigraphy is a useful noninvasive test for risk stratification of patients before peripheral vascular surgery and provides prognostic information as to the risk of a cardiac event in the 2-year period after the test. A reversible thallium defect is associated with a significant increased risk and would indicate that coronary angiography should be considered and preoperative coronary revascularization.

Aged↗
PubMed1998

Ex vivo gene therapy prevents chronic graft vascular disease in cardiac allografts.

OBJECTIVE: We hypothesized that ex vivo hyperbaric transfection of antisense oligodeoxynucleotides for blockade of intercellular adhesion molecule-1, an important mediator of cell adhesion and T-cell co-stimulation, would reduce chronic graft vascular disease in cardiac allografts. METHODS: PVG hearts underwent ex vivo transfection with antisense, reverse antisense intercellular adhesion molecule-1 oligodeoxynucleotide (80 micromol/L), or saline solution at 3 atm pressure for 45 minutes at 4 degrees C and were transplanted heterotopically into ACI recipients with or without treatment with intercellular adhesion molecule-1 (1A29) or leukocyte function associated antigen-1 (WT.1) monoclonal antibodies. Transfection efficiency was confirmed with fluorescein isothiocyanate-labeled oligodeoxynucleotides and fluorescent microscopy. Efficacy of intracellular adhesion molecule-1 blockade was assessed with the use of immunohistochemistry. Graft reperfusion injury was evaluated at 6 to 24 hours by neutrophil infiltration (myeloperoxidase [MPO]), cardiac edema (%wt/wt), and histologic injury (percent contraction band necrosis). Grafts from recipients treated with cyclosporine A (5 mg/kg per day, days 0 to 9) were scored for chronic graft vascular disease on postoperative day 90 ranging from 0 (no involvement) to 4 (>50% vascular occlusion). RESULTS: Transfection was highly efficient (fluorescein isothiocyanate-labeled oligodeoxynucleotides in 48%+/-5% of total myocardial nuclei) and effective at blocking intracellular adhesion molecule-1 expression (positive area in allografts taken on postoperative day 3 was reduced from 100%+/-0% to 52%+/-14%, n=4). Blockade with antisense oligodeoxynucleotides versus monoclonal antibodies was less effective at preventing reperfusion injury while more effective at reducing chronic graft vascular disease (score 0.98+/-0.48, p < 0.05). Reverse antisense oligodeoxynucleotides and vector control (antisense oligodeoxynucleotide infusion without pressure) groups failed to demonstrate this beneficial effect. CONCLUSION: Hyperbaric transfection of antisense oligodeoxynucleotides proved highly efficient, effective at blockade of intracellular adhesion molecule-1, and demonstrated a sequence-specific reduction in chronic graft vascular disease. This highly targeted alteration of donor organ immunogenicity may have an important future role in clinical immunosuppressive strategies.

Animals↗
PubMed1997

Association of hemostatic factors with peripheral vascular disease.

Hemostatic risk factors have been well established in coronary artery disease but less well studied in peripheral vascular disease. The relationship of coagulation and fibrinolytic proteins to lower limb arterial occlusive disease and other vascular risk factors remains poorly defined. Fibrinogen, factor VII coagulant activity, von Willebrand factor (vWf) antigen, and plasminogen activator inhibitor-1 (PAI-1) activity were measured in 46 adult participants in the Arterial Disease Multiple Intervention Trial (ADMIT) and in 76 control subjects and related to ankle-brachial systolic pressure index (ABI), a measure of lower limb arterial stenosis. The primary inclusion criterion for the ADMIT study population was an average of two ABIs <0.85. Fibrinogen and PAI-1 in ADMIT subjects were significantly higher than in control subjects (331 +/- 52 mg/dl vs 273 +/- 46 mg/dl, p < 0.0001; 18.7 +/- 10 units/ml vs 13.5 +/- 8.9 units/ml, p < 0.04). There were significant correlations of fibrinogen with ABI, factor VII coagulant activity, and systolic and diastolic blood pressures; PAI-1 with body mass index and age; and factor VII coagulant activity with cholesterol levels. Logistic regression analysis, considering hemostatic variables and several known nonhemostatic risk factors of peripheral arterial disease, showed that fibrinogen and systolic blood pressure were independently associated with ABI status in this population. The results demonstrate a strong independent correlation between fibrinogen levels and the presence of lower limb arterial stenosis. PAI-1 levels were elevated in ADMIT participants, but multivariate analysis did not demonstrate an independent relationship between PAI-1 and ABI.

Aged↗