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PubMed2005

Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and is projected to become the leading cause of mortality in the world. Atherosclerosis is the most important single factor contributing to this disease burden. In this study, we characterize relationships between endothelial dysfunction and vascular disease in an animal model of diet-induced, early-stage atherosclerotic vascular disease. We tested the hypothesis that hypercholesterolaemia induces vascular disease and impairs endothelium-dependent relaxation (EDR) in conduit arteries of adult male Yucatan pigs. Pigs were fed a normal fat (NF) or high fat cholesterol (HFC) diet for 20-24 weeks. Results indicate that, while the HFC diet did not alter EDR in femoral or brachial arteries, EDR was significantly decreased in both carotid and coronary arteries. Sudanophilic fatty streaks were significantly present in the abdominal aorta and common carotid artery. Histopathology revealed increased intima-media thickness (IMT) and foam cell accumulation in Stary Stage I-III lesions in the abdominal aorta, common carotid artery and femoral arteries. In the coronary arteries, the accumulation of foam cells in Stary Stage I and II lesions resulted in a trend for increased IMT. There was no evidence of vascular disease in the brachial arteries. These results indicate that early stages of CVD (Stary Stage I-III) precede decreases in EDR induced by HFC diet, because femoral arteries exhibited foam cell accumulation and an increased IMT but no change in endothelial function.

Acetylcholine↗
PubMed1989

A study of platelet fibronectin immunofluorescence in peripheral vascular disease and diabetes mellitus.

Platelets hyperaggregability and hypersecretion fibronectin (Fn) are known to occur in peripheral vascular disease (PVD) and diabetes mellitus (DM) with microangiopathy. To determine whether an increase in platelet membrane bound Fn constitutes to hyperaggregability of platelets, washed platelets from normal subjects and from patients with peripheral vascular disease and patients with diabetes mellitus were examined for the presence of fibronectin (Fn) by means of fluorescein linked antibody to Fn. Platelets from peripheral vascular disease and diabetes mellitus patients tended to aggregate during preparation and apparently exhibited greater fluorescence in platelet "smears" than was observed in smears from controls. In contrast, when washed platelet "smears" were prepared from platelet preparations containing iloprost, an analogue of prostacyclin, platelet aggregates did not form and the 'excess' of fluorescence disappeared from all the three groups. When platelets were stained for Fn fluorescence in suspensions, no fluorescence was observed on the surface of platelets from peripheral vascular disease and diabetes mellitus patients or controls. On stimulation with thrombin washed platelet suspension showed fluorescence for Fn. Platelet activation leads to Fn appearing on platelet surface but this effect cannot be quantified by optical fluorescence microscopy.

Adult↗
PubMed1999

Association of antiphospholipid antibodies with retinal vascular disease in systemic lupus erythematosus.

OBJECTIVES: To study the prevalence and characteristics of retinal vascular disease in patients with systemic lupus erythematosus (SLE) and to analyze their relationship with antiphospholipid antibodies (aPL) and other serological markers. PATIENTS AND METHODS: Eighty-two consecutive patients (77 women and 5 men; mean age, 36 years) were studied. All patients fulfilled the 1982 revised criteria of the American College of Rheumatology for the classification of SLE. Ophthalmologic examination included assessment of best corrected visual acuity, tonometry, slit-lamp biomicroscopy, and fundus examination. Serologic studies included determination of anticardiolipin antibodies (aCL) (ELISA), lupus anticoagulant (LA) (coagulation tests), antinuclear antibodies (indirect immunofluorescence), anti-DNA (Farr's test), and anti-ENA antibodies (counterimmunoelectrophoresis). RESULTS: Retinal vascular disease was detected in 13 (15%) of 82 SLE patients. The retinal lesions consisted of retinal vascular occlusions in six patients (five arterial and one venous), cotton-wool spots in three, optic disc edema in three, retinal hemorrhages in three, and ischemic optic neuropathy in one. Antiphospholipid antibodies were detected in 10 (77%) of these 13 patients: nine had aCL and two had the LA. When compared with patients without retinal vascular disease, patients with retinopathy had a higher prevalence of aPL (77% v. 29%, P = .005). CONCLUSIONS: Retinal vascular disease is frequent in patients with SLE. The presence of aPL is associated with a higher prevalence of retinal abnormalities in SLE patients.

Adolescent↗
PubMed1991

Risk factors for macrovascular disease in diabetes mellitus: the London follow-up to the WHO Multinational Study of Vascular Disease in Diabetics.

We have examined the relationship between baseline variables and the incidence of new macrovascular complications amongst the 497 members of the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics over a mean 8.33-year follow-up. In univariate logistic regression analysis the incidence of new ischaemic electrocardiographic abnormality was significantly associated with systolic and diastolic blood pressure, diabetes duration and hypertension in patients with insulin-dependent diabetes, and with smoking in patients with non-insulin-dependent diabetes. New myocardial infarction was associated with systolic blood pressure, plasma cholesterol, proteinuria and smoking in patient with non-insulin-dependent diabetes; there were no significant associations among patients with insulin-dependent diabetes. All new ischaemic heart disease was associated with hypertension in patients with insulin-dependent diabetes, and plasma cholesterol and smoking in patients with non-insulin-dependent diabetes. New cerebrovascular disease was associated with systolic and diastolic blood pressure, ECG abnormality and hypertension. New peripheral vascular disease was associated with smoking. Multivariate analysis showed the following significant associations 1) in patients with insulin-dependent diabetes: ECG abnormality; hypertension, myocardial infarction; smoking, ischaemic heart disease; hypertension, diabetes duration and smoking, 2) in patients with non-insulin-dependent diabetes: ECG abnormality; smoking, myocardial infarction; serum cholesterol, proteinuria and smoking ischaemic heart disease; smoking. For new cerebrovascular disease, proteinuria and ECG abnormality were significant predictors in multivariate analysis. Patients with diabetes share many of the established risk factors for nondiabetic subjects, in addition proteinuria may be of significance in the prediction of macrovascular disease in diabetes.

Adult↗
PubMed1999

Determinants of fasting and post-methionine homocysteine levels in families predisposed to hyperhomocysteinemia and premature vascular disease.

Elevated plasma total homocysteine (tHcy) levels, either measured in the fasting state or after oral methionine loading, are associated with an increased risk of atherothrombotic disease. Fasting and post-methionine hyperhomocysteinemia (HHC) overlap to a limited extent; both can occur as familial traits. We investigated determinants of fasting, postmethionine and delta (ie, post-methionine minus fasting levels) tHcy levels in 510 subjects of 192 HHC-prone families including 161 patients with clinical vascular disease and 349 without vascular disease. We focused on tHcy levels in relation to levels of vitamin B12, B6 and folate and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Multivariate linear analyses adjusted for the presence of vascular disease showed that fasting tHcy was significantly related to folate and vitamin B12, and the presence of the MTHFR TT genotype and the T allele, and to age, smoking habits, and serum levels of creatinine. Both post-methionine and delta tHcy levels were related to serum folate levels, and the presence of the MTHFR TT genotype and the T allele, and to postmenopausal status, and body mass index. An interaction was found between MTHFR TT genotype and serum folate levels for both fasting and post-methionine tHcy, ie, for a given decrease in serum folate, homocysteine levels increased more in subjects with the TT genotype than in those with the CC genotype. Fasting, post-methionine and delta tHcy were higher in patients with vascular disease than in their healthy siblings, but these levels were less dependent on serum folate levels (P<0.05), whereas the effect of MTHFR genotype was stronger (P=0.01). This study found evidence that post-methionine and delta tHcy levels are not only influenced by factors affecting homocysteine transsulfuration but also by factors that affect remethylation. The explained variances of fasting, post-methionine and delta tHcy were 49%, 62%, and 78%, respectively. We also found evidence, in patients with premature vascular disease but not in their healthy siblings, for a factor that increases tHcy levels but weakens the normal inverse relation between folate and tHcy and amplifies the effect of the MTHFR genotype.

Adult↗
PubMed2002

The effects of a low frequency acoustic waveform on peripheral vascular disease: a pilot study.

OBJECTIVE: To evaluate the effects of a low frequency acoustic waveform on peripheral vascular disease (PVD). DESIGN: Pilot study utilizing a one-group pre-intervention, post-intervention design. SETTING: Adults with peripheral vascular disease were recruited through local advertisements. The study was conducted at a local facility housing the electroacoustic transducer. INTERVENTION: A 25-min exposure to an electroacoustic transducer. OUTCOME MEASURES: Pre- and post-measurement of Doppler ultrasound blood-flow velocities in 10 arteries, ankle brachial index (RBI), foot assessment, and 1-week post telephone survey. RESULTS: A significant increase was noted in the right ankle brachial index (RABI) but not the left. Blood flow increased in all arteries, significantly in four. Thirteen participants reported improvement in symptom of peripheral vascular disease over the following week. CONCLUSIONS: While conclusions must be viewed cautiously, the significant differences noted warrant further study to examine effects of acoustic waveforms on peripheral vascular disease.

Acoustics↗
PubMed2004

Clinical utility of rapid prescreening magnetic resonance angiography of peripheral vascular disease prior to cardiac catheterization.

PURPOSE: The presence of peripheral vascular disease, in particular iliofemoral disease, is responsible in part for vascular complications from femoral artery cannulation. We investigated whether prescreening for vascular obstructions with magnetic resonance angiography (MRA) in high-risk patients with peripheral vascular disease (PVD) would provide useful information to angiographers seeking to improve the safety and efficiency of femoral artery access at cardiac catheterization. METHODS: Twelve consecutive patients with known or suspected PVD underwent contrast-enhanced, aorto-iliofemoral MRA using a real-time BolusTrak technique. Contrast-to-noise ratios for each patient were calculated. The cardiac angiographer reviewed the MRA prior to catheterization and selected an access site. The patients' subsequent clinical course was evaluated, and a postprocedure questionnaire was completed by the angiographer to define the value of the prescreening MRA. RESULTS: No significant vascular complications occurred in these patients as defined by failure of initially chosen access site, arterial dissection, limb ischemia, pseudoaneurysm formation, hemorrhage (including retroperitoneal hematoma), or need for blood transfusion or emergency vascular surgical repair. Statistical frequency analysis of the responses in the postprocedure questionnaire demonstrated that the MR data were clinically valuable in (1) influencing the initial choice of access site; (2) influencing technical alterations to the standard access; and, (3) enhancing confidence in the selection of access site. CONCLUSIONS: MRA prescreening in patients with PVD is an effective, novel adjunct to cardiac catheterization in selected patients that improves physician confidence and influences technical choices during coronary angiography from the femoral artery approach.

Adult↗
PubMed1977

Pulmonary vascular disease after systemic-pulmonary arterial shunt operations.

More than 1,100 patients underwent a systemic-pulmonary arterial shunt operation at the Children's Memorial Hospital, Chicago, from 1946 to 1974. Of these patients, 294 were studied to assess the presence of pulmonary vascular disease and the time of its occurrence after surgery. They were selected either because lung tissue was available for histologic grading of pulmonary vascular disease (114 patients) or because hemodynamic studies were performed after the shunt operation (180 patients). The shunts, all patent at the time of the study, ranged in duration from 1 month to 23 years. After a subclavan-pulmonary arterial shunt (75 patients) there was little evidence of advatients) pulmonary vascular disease in either histologic C2 of 25 patients) or hemodynamic (1 of 50 patients) studies. After an aortic-pulmonary arterial shunt (44 Waterston, 175 Potts) there was small likelikhood of advanced pulmonary vascular disease with a shunt duration of less than 5 years (1 of 35 histologic, 0 of 27 hemodynamic studies). With a shunt duration of more than 5 years the incidence of advanced pulmonary vascular disease increased significantly (15 of 54 histologic, 17 of 103 hemodynamic studies). A mean pulmonary arterial pressure of 50 mm Hg or greater strongly suggests the presence of advanced pulmonary vascular disease. When a systemic-pulmonary arterial shunt has provided effective palliation with decreased pulmonary pressure there is small likelihood that advanced pulmonary vascular disease will develop, even with a long shunt duration of 20 to 25 years.

Aorta↗
PubMed2004

Cellular microparticles: new players in the field of vascular disease?

Microparticles are small membrane vesicles that are released from cells upon activation or during apoptosis. Cellular microparticles in body fluids constitute a heterogeneous population, differing in cellular origin, numbers, size, antigenic composition and functional properties. Microparticles support coagulation by exposure of negatively charged phospholipids and sometimes tissue factor, the initiator of coagulation in vivo. Microparticles may transfer bioactive molecules to other cells or microparticles, thereby stimulating cells to produce cytokines, cell-adhesion molecules, growth factors and tissue factor, and modulate endothelial functions. Microparticles derived from various cells, most notably platelets but also leucocytes, lymphocytes, erythrocytes and endothelial cells, are present in the circulation of healthy subjects. Rare hereditary syndromes with disturbances in membrane vesiculation leading to a decreased numbers of microparticles clinically present with a bleeding tendency. In contrast, elevated numbers of microparticles are encountered in patients with a great variety of diseases with vascular involvement and hypercoagulability, including disseminated intravascular coagulation, acute coronary syndromes, peripheral arterial disease, diabetes mellitus and systemic inflammatory disease. Finally, microparticles are a major component of human atherosclerotic plaques. In view of their functional properties, cell-derived microparticles may be an important intermediate in the cascade of cellular and plasmatic dysfunctions underlying the process of atherogenesis.

Apoptosis↗
PubMed1999

Evidence that anticardiolipin antibodies are independent risk factors for atherosclerotic vascular disease.

Thrombophilic anticardiolipin antibodies (ACLAs) are independent risk factors for atherosclerotic vascular disease. We suggest that ACLAs IgG and IgM be routinely measured as ancillary atherothrombotic risk factors in all patients with atherosclerotic vascular disease events, in those at high risk for atherosclerotic vascular disease, and in those in whom thrombosis is a major pathoetiology.

Aged↗
PubMed2003

Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease.

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a key signaling molecule in vascular homeostasis. Loss of NO bioavailability due to reduced synthesis and increased scavenging by reactive oxygen species is a cardinal feature of endothelial dysfunction in vascular disease states. The pteridine cofactor tetrahydrobiopterin (BH4) has emerged as a critical determinant of eNOS activity: when BH4 availability is limiting, eNOS no longer produces NO but instead generates superoxide. In vascular disease states, there is oxidative degradation of BH4 by reactive oxygen species. However, augmentation of BH4 concentrations in vascular disease by pharmacological supplementation, by enhancement of its rate of de novo biosynthesis or by measures to reduce its oxidation, has been shown in experimental studies to enhance NO bioavailability. Thus, BH4 represents a potential therapeutic target in the regulation of eNOS function in vascular disease.

Animals↗
PubMed1996

Cohort study of predictive value of urinary albumin excretion for atherosclerotic vascular disease in patients with insulin dependent diabetes.

OBJECTIVE: To examine whether slightly elevated urinary albumin excretion precedes development of atherosclerotic vascular disease in patients with insulin dependent diabetes independently of conventional atherogenic risk factors and of diabetic nephropathy. DESIGN: Cohort study with 11 year follow up. SETTING: Diabetes centre in Denmark. SUBJECTS: 259 patients aged 19-51 with insulin dependent diabetes of 6-34 years' duration and without atherosclerotic vascular disease or diabetic nephropathy at baseline. MAIN OUTCOME MEASURES: Baseline variables: urinary albumin excretion, blood pressure, smoking habits, and serum concentrations of total cholesterol, high density lipoprotein cholesterol, sialic acid, and von Willebrand factor. END POINT: atherosclerotic vascular disease assessed by death certificates, mailed questionnaires, and hospital records. RESULTS: Thirty patients developed atherosclerotic vascular disease during follow up of 2457 person year. Elevated urinary albumin excretion was significantly predictive of atherosclerotic vascular disease (hazard ratio 1.06 (95% confidence interval 1.02 to 1.18) per 5 mg increase in 24 hour urinary albumin excretion, P = 0.002). Predictive effect was independent of age; sex; blood pressure; smoking; serum concentrations of total cholesterol, high density lipoprotein cholesterol, sialic acid, and von Willebrand factor; level of haemoglobin A(lc); insulin dose, duration of diabetes, and diabetic nephropathy (hazard ratio 1.04 (1.01 to 1.08) per 5 mg increase

Adolescent↗
PubMed2000

Elevated circulating homocyst(e)ine levels in placental vascular disease and associated pre-eclampsia.

We examined the hypothesis that hyperhomocyst(e)inaemia in the maternal or fetal circulation is associated with placental vascular disease with either the maternal syndrome of pre-eclampsia and/or fetal syndrome of growth restriction. Maternal plasma homocyst(e)ine levels were significantly higher in pregnancies complicated by pre-eclampsia, pregnancies with evidence of umbilical placental vascular disease, and pregnancies with both complications compared with the normal pregnancy group. In the fetal circulation mean plasma homocyst(e)ine concentration was significantly higher in the pre-eclampsia group compared with the normal group. The results suggest that hyperhomocyst(e)inaemia may be a risk marker for placental vascular disease and maternal pre-eclampsia. The elevated fetal plasma homocyst(e)ine concentrations, found only in the group of pregnancies with pre-eclampsia in the absence of umbilical placental vascular disease, may be due to an effect of placental vascular disease on homocyst(e)ine transfer from the maternal to fetal circulation.

Adult↗
PubMed2003

The role of platelets in peripheral vascular disease.

Platelets play a major role in acute ischaemic syndromes and peripheral vascular disease. They are involved in the development and progression of atherosclerosis, native vessel and graft thrombosis. They have a central role in the development of restenosis and reocclusion after peripheral percutaneous transluminal angioplasty. Antiplatelet therapy has been shown to be beneficial in patients undergoing peripheral vascular surgery or radiological intervention. Yet current routine therapy, namely aspirin and dipyridamole are limited in their mode of action and efficacy. Recent developments in the understanding of platelet function has led to the development of new more potent drugs such as clopidogrel. Combination of drugs and more specific investigation of individual platelet function may well result in improved bypass and angioplasty patency rates. The results of proposed large randomised controlled trials on the role and safety of aspirin and clopidogrel are awaited with interest. Given the importance of platelets in peripheral vascular disease highlighted in this review, achieving an optimal safe anti-platelet effect for each patient with peripheral vascular disease should be the target of future research.

Angioplasty, Balloon↗
PubMed1990

Medical management of symptomatic peripheral vascular disease.

As our society becomes older, peripheral vascular disease assumes greater significance. Many patients are not surgical candidates and, therefore, must opt for medical management. The podiatrist often assumes the role of primary health care provider, and a knowledge of the disease process, its consequences, and treatment alternatives becomes paramount. The authors detail the events leading to and the treatment options for symptomatic peripheral vascular disease.

Age Factors↗
PubMed2002

[Experience with transluminal stent-assisted angioplasty for intracranial vascular diseases].

OBJECTIVE: To assess the value of stent-assistant angioplasty for intracranial vascular diseases. METHODS: Thirteen patients with intracranial vascular diseases were treated consecutively by stent-assistant angioplasty for different purposes. Of these patients 7 had symptomatic intracranial artery stenosis, 3 intracranial wide-neck aneurysms, 2 intracranial pseudoaneurysms, and 1 bilateral transverse sinus stenosis. Clinical procedures and technical data of the patients were retrospectively analyzed. RESULTS: In the 7 patients, the degree of intracranial artery stenosis reduced from 83% to 5%. Three months after the operation they exhibited good patency of stented lesions. Intracranial wide neck aneurysms (with 2 pseudoaneurysms) were successfully embolized with GDC in 5 patients. The patients with bilateral transverse sinus stenosis were implanted a self-expanded stent in the right transverse sinus. One patient failed because of the tortuous configuration of the left jugular bulb, but the patient's symptoms were improved quickly after the procedure. CONCLUSION: Stent-assistant angioplasty is a useful technique for selected intracranial vascular diseases, and it needs further investigation.

Adult↗
PubMed2002

The role of matrix metalloproteinases in vascular disease.

There is growing interest in the role of matrix metalloproteinases in vascular diseases. These conditions are often characterized by excessive tissue remodelling, and increased matrix metalloproteinase activity has been demonstrated in aneurysms, intimal hyperplasia and atherosclerotic plaque disruption. These enzymes represent a potential target for therapeutic intervention to modify vascular pathology. The core of this review is derived from a MEDLINE database literature search. The review found that there is convincing evidence of increased matrix metalloproteinase activity in a spectrum of vascular disease. Evidence for an imbalance promoting increased matrix degradation is less well documented. However, studies of matrix metalloproteinase inhibition in vascular disease models suggest potential therapeutic benefit. In conclusion, in vivo studies of matrix metalloproteinase inhibition are required to further study the potential for reversal or deceleration of the excessive tissue remodelling that accompanies vascular disorders.

Connective Tissue Diseases↗
PubMed2003

Relationship between periodontal disease, tooth loss, and carotid artery plaque: the Oral Infections and Vascular Disease Epidemiology Study (INVEST).

BACKGROUND AND PURPOSE: Chronic infections, including periodontal infections, may predispose to cardiovascular disease. The present study investigates the relationship of periodontal disease and tooth loss with subclinical atherosclerosis. METHODS: We enrolled 711 subjects with a mean age of 66+/-9 years and no history of stroke or myocardial infarction in the Oral Infections and Vascular Disease Epidemiology Study. Subjects received a comprehensive periodontal examination, extensive in-person cardiovascular disease risk factor measurements, and a carotid scan using high-resolution B-mode ultrasound. Regression models were adjusted for conventional risk factors (age, sex, smoking, diabetes, systolic blood pressure, low- and high-density lipoprotein cholesterol, race-ethnicity, education, physical activity) and markers of cultural background, healthy lifestyle, and psychosocial health. RESULTS: Measures of both current and cumulative periodontitis became more severe as tooth loss increased. A significant association was observed between tooth loss levels and carotid artery plaque prevalence. Among those with 0 to 9 missing teeth, 46% had carotid artery plaque, whereas among those with >or=10 missing teeth, carotid artery plaque prevalence was approximately 60% (P<0.05). CONCLUSIONS: Our data suggest that tooth loss is a marker of past periodontal disease in this population and is related to subclinical atherosclerosis, thereby providing a potential pathway for a relationship with clinical events.

Age Distribution↗