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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes is associated with endothelial dysfunction, which in part may be related to uncoupling of the endothelial nitric oxide (NO) synthase enzyme, thus reducing the availability of NO. As folates may potentially reverse the uncoupling of NO synthase, we wanted to determine whether folic acid supplementation could modulate endothelial function and markers of inflammation in patients with type 2 diabetes without vascular disease. Nineteen patients with type 2 diabetes were treated with folic acid (10mg/day for 2 weeks) versus placebo in a randomized, placebo-controlled, cross-over study with an 8-week washout period between treatments. Fasting endothelium-dependent flow-mediated dilatation (FMD) of the brachial artery, endothelium-independent nitroglycerin-mediated dilatation (NMD), plasma homocysteine, serum lipids, folate, and inflammatory markers (high-sensitivity C-reactive protein, soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, interleukin-18, tumor necrosis factor-alpha) were assessed after each 2-week treatment period. Folic acid supplementation significantly increased folate levels and lowered plasma homocysteine levels. Folic acid significantly improved FMD compared to placebo (5.8 +/- 4.8% vs 3.2 +/- 2.7%, p = 0.02). There were no significant effects of folic acid supplementation on lipids, NMD, or the inflammatory markers. There was no relationship between the change in homocysteine and the improvement in FMD. Thus, 2 weeks of folic acid supplementation can improve endothelial dysfunction in type 2 diabetics independent of homocysteine-lowering, but does not modulate markers of inflammation.
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PMID:Folic acid improves endothelial dysfunction in type 2 diabetes--an effect independent of homocysteine-lowering. 1688 40

Diabetes incidence is increasing rapidly in the United States. Diabetes increases the risk for cardiovascular disease, the major cause of death in diabetic individuals. The conventional cardiovascular risk factors of hyperlipidemia and hypertension worsen diabetic vascular disease. Treatment targets for low-density lipoprotein cholesterol (LDL-C) and blood pressure in diabetic individuals are being debated. The SANDS is a randomized, open-label, 3-year trial to examine the effects of aggressive LDL-C (goal <70 mg/dL) and blood pressure (BP) (goal <115/75 mm Hg) reduction versus the standard goals of <100 mg/dL for LDL-C and <130/85 mm Hg for BP. Five hundred forty-nine American-Indian men and women >40 years old with type 2 diabetes were randomized to 1 of 2 groups. Lipids and BP are managed using Food and Drug Administration-approved medications in an algorithmic approach. The presence and progression of atherosclerosis are evaluated by carotid ultrasonography; echocardiography assesses cardiac function. The primary end point is the composite outcome of change in carotid artery intimal medial thickness and fatal/nonfatal cardiovascular events. These outcomes are combined by using a ranked analysis for carotid thickness and assigning a "worst rank" for a cardiovascular event. Secondary end points include carotid plaque score, left ventricular geometry and function, serum C-reactive protein, and safety measures. Unique aspects of the study design and analysis plan involve the use of a composite outcome and changes during the trial of LDL-C treatment goals for participants with baseline or incident cardiovascular disease in the conventional group because of changes in the standard of care. Study results will further understanding of the effects of aggressive risk factor reduction on atherosclerosis burden and cardiac function in diabetic individuals in US populations and will help determine optimal LDL-C and BP treatment goals for diabetic patients.
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PMID:Examination of lower targets for low-density lipoprotein cholesterol and blood pressure in diabetes--the Stop Atherosclerosis in Native Diabetics Study (SANDS). 1707 Jan 47

Coronary artery ectasia (CAE) is well-recognized, angiographic finding of abnormal coronary dilatation, and detected in 0.3-5.3% of angiographic studies. The gold standard for diagnosis this type of aneurysm is coronary angiography, which provides information about the size, sample, location and number of aneurysms. Despite growing prevalence in recent years, controversy still exists as to the pathogenetic mechanisms that underlie this entity. An increased incidence of CAE has been reported in several disorders. Examples include atherosclerotic vascular disease, heterozygous familial hypercholesterolemia, usage of substances including herbicide spray, acetylcholinesterase inhibitors and nitrates, previous arterial balloon angioplasty, polyarteritis nodosa and Kawasaki syndrome. In addition, possible factors contributing to CAE are imbalance between matrix metalloproteinase and tissue inhibitor of metalloproteinase, angiotensin converting enzyme genotype, elevated homocysteine levels, cocaine user, smoking, vascular trauma, nitrate use and diabetes. Emerging investigations have pinpointed inflammation as a central process in all stages of atherosclerosis. This inflammatory process culminates in acute thrombotic complications and clinical events, which is involved in different clinical settings of atherosclerotic diseases. Recent data have also showed that CAE is associated with inflammatory response presented as elevated inflammatory cytokines and C-reactive protein. Accordingly, more complete understanding of the pro- and anti-inflammatory circuits that operate during CAE in particular may foster the development of novel therapeutic approaches.
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PMID:Is any link between inflammation and coronary artery ectasia? 1722 19

Atherothrombotic vascular disease is a complex disorder in which inflammation and coagulation play a pivotal role. Rupture of high-risk, vulnerable plaques with the subsequent tissue factor (TF) exposure is responsible for coronary thrombosis, the main cause of unstable angina, acute myocardial infarction, and sudden cardiac death. Tissue factor (TF), the key initiator of coagulation is an important modulator of inflammation. TF is widely expressed in atherosclerotic plaques and found in macrophages, smooth muscle cells, extracellular matrix and acellular lipid-rich core. TF expression can be induced by various stimulants such as C-reactive protein, oxLDL, hyperglycemia and adipocytokines. The blood-born TF encrypted on the circulating microparticles derived from vascular cells is a marker of vascular injury and a source of procoagulant activity. Another form of TF, called alternatively spliced has been recently identified in human and murine. It is soluble, circulates in plasma and initiates coagulation and thrombus propagation. Evidence indicates that elevated levels of blood-borne or circulating TF has been associated with metabolic syndrome, type 2 diabetes and cardiovascular risk factors and is a candidate biomarker for future cardiovascular events. Therapeutic strategies have been developed to specifically interfere with TF activity in the treatment of cardiovascular disease.
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PMID:Atherothrombosis: role of tissue factor; link between diabetes, obesity and inflammation. 1724 34

C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta2-glycoprotein I (beta2GPI), implicating oxLDL/beta2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/beta2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of atherosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta2GPI complexes correlated with total cholesterol and hemoglobin A1c. Thus, the generation of CRP/oxLDL/beta2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/beta2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis.
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PMID:The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis. 1726 75

In patients with stable coronary artery disease, elevated levels of biomarkers of inflammation, including high-sensitivity C-reactive protein (hs-CRP) > or = 2.0 mg/L, are predictors of future vascular events. Because long-term low-dose colchicine is a safe and effective means of dampening inflammation, we conducted an open-label pilot study to determine whether it could significantly lower hs-CRP in patients with stable coronary artery disease in whom hs-CRP was > or = 2.0 mg/L despite taking both aspirin and high-dose atorvastatin therapy. Plasma hs-CRP was measured in 200 patients with clinically stable coronary artery disease who were taking aspirin and atorvastatin. In 64 patients, hs-CRP was > or = 2.0 mg/L. In 20 of these patients, hs-CRP was measured again at 2 weeks (no treatment group), and in 44 patients, hs-CRP was measured again after 4 weeks of open-label colchicine 0.5 mg twice daily (treatment group). In the no treatment group, mean baseline hs-CRP did not decrease significantly, measuring 4.28 +/- 2.03 mg/L at baseline and 3.70 +/- 2.30 mg/L after repeated measurement (mean change 11.0%, 95% confidence interval [CI] -30% to +9%, p = NS). In contrast, hs-CRP decreased in all patients administered colchicine, with mean baseline hs-CRP decreasing from 4.58 +/- 2.05 to 1.78 +/- 1.38 mg/L (p <0.001), an absolute decrease of 2.80 mg/L (95% CI 2.40 to 3.65 mg/L) and a relative decrease of 60% (95% CI 54% to 67%). In 28 patients (64%) in this group, the decrease in hs-CRP was >50% from baseline, and in 31 patients (70%), hs-CRP decreased to <2.0 mg/L. No significant side effects were reported. In conclusion, low-dose colchicine (0.5 mg twice daily) can effectively decrease hs-CRP in patients with clinically stable coronary artery disease and increased hs-CRP independent of aspirin and atorvastatin use. Additional controlled studies are warranted to confirm this observation and determine whether long-term use of low-dose colchicine can improve clinical outcomes in patients with advanced vascular disease.
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PMID:Effect of colchicine (0.5 mg twice daily) on high-sensitivity C-reactive protein independent of aspirin and atorvastatin in patients with stable coronary artery disease. 1735 Mar 70

C-reactive protein (CRP) is a risk marker and a potential modulator of vascular disease. Whether CRP modulates nitric oxide (NO) synthase (NOS) activity and NO metabolism remains unclear. We studied the effect of CRP on NO metabolism in transgenic mice that express human CRP (CRPtg). CRPtg and wild-type mice were subjected to controlled femoral artery wire injury. CRP serum levels at baseline and 6 and 24 h after injury were 12.4 +/- 9, 18.6 +/- 6.9, and 58.4 +/- 13 mg/l, respectively, in CRPtg mice but were undetectable at all time points in wild-type mice. Endothelial NOS protein and mRNA expression were significantly suppressed in the injured arteries of CRPtg mice (n = 5, P < 0.05). A similar reduction in eNOS expression was observed in the distant lung and heart. NO release after injury was significantly lower in CRPtg mice, as measured by nitrate and nitrite breakdown products, with a concomitant suppression of cGMP NO signaling after injury. Endothelial NOS and NO expression after vascular injury are locally and systemically suppressed in mice that express human CRP. These in vivo observations support the hypothesis that CRP modulates NO metabolism and may have implications regarding the mechanisms by which CRP modulates vascular disease.
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PMID:Transgenic expression of human C-reactive protein suppresses endothelial nitric oxide synthase expression and bioactivity after vascular injury. 1736 52

High sensitivity C-reactive protein (hsCRP) is an independent risk factor for cardiovascular disease, such as stroke or coronary artery disease. Genetic factors influence significantly the inter-individual variability of hsCRP. The aim of this study was to identify genomic regions influencing hsCRP levels. A genome scan was performed in two independent studies of Caucasian populations, namely 513 Western-European families ascertained for myocardial infarction (n = 1,406) and 120 French-Canadian families diagnosed with hypertension (n = 758). In the myocardial infarction families, 31% of the inter-individual variation of hsCRP levels was explained by genetic factors (P = 0.0000015) and loci influencing hsCRP were identified on chromosomes 10 (at 141 cM) and 5 (at 150 cM) with multipoint LOD scores of 3.15 and 2.23, respectively. An additional suggestive signal was detected on chromosome 2 in subset analyses. A similar degree of heritability has been observed in a second independent population of French-Canadian hypertensive families for hsCRP (30%) and linkage results for chromosome 10 were confirmed with maximum LOD score of 2.7. We identified a chromosomal region in two independent populations which influences hsCRP in addition to several unique regions. This provides targets for the identification of genes involved in the regulation of hsCRP and the development and progression of vascular disease, including stroke.
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PMID:A locus on chromosome 10 influences C-reactive protein levels in two independent populations. 1753 Feb 89

The complexity of the several pathogenic pathways that cause hypertension and vascular disease and the prolonged interval that appears to predate clinical morbidity have hindered inquiry into the association between GDM and vascular disorders. As a forme fruste of later type 2 diabetes, GDM-affected gravidas are identified as at risk of diabetes-related atherosclerosis, glomerular disruption, and pathogenic retinal angio-genesis. That GDM is evidence for underlying chronic conditions such as dysregulation of innate immune response that, independent of the diabetic state, produces vascular disease is difficult state, produces vascular disease is difficult to assert with the present published literature. Cross-sectional studies of patients with established gestational hypertension or preeclampsia are ambiguous as to the possible pathogenic effect of insulin resistance. Cohort studies initiated in early and mid-pregnancy show evidence that both gestational hypertension and preeclampsia may be more prevalent in gravidas with greater insulin resistance. The association of gestational glucose intolerance with gestational hypertension appears to be independent of obesity and ambient glycemia but explained in part by insulin resistance. Late pregnancy preeclampsia is associated with elevated mid-pregnancy BMI, blood pressure, fasting glucose and insulin, urate, and C-reactive protein, suggestive of metabolic and immune dysregulation. GDM appears to be associated with overexpressed innate immune response, which, in turn, is associated with vascular dysfunction and vascular disease. Among women with GDM, markers of insulin resistance do not appear to correlate with hypertension in short-term cohort studies. However, when non-GDM subjects are compared with subjects with GDM, postpregnancy studies do show an associated with vascular dysfunction and vascular disease. Among women with GDM, markers of insulin resistance do not appear to correlate with hypertension in short-term cohort studies. However, when non-GDM subjects are compared with subjects with GDM, postpregnancy studies do show an association of insulin resistance with both inflammatory dysregulation and vascular dysfunction. Cohort studies that have used population-based pregnancy databases consistently identify a clinically significant association of both gestational hypertension and preeclampsia with later hypertensive disorders. Associations with coronary artery disease or stroke are less consistent, requiring further investigation. Preventing the evolution of diabetes and lipid and immune dysregulation of the metabolic syndrome has become a silent public health issue because of the epidemic of childhood and early adulthood obesity and the opportunity at hand to treat insulin resistance by behavioral and pharmacological interventions. However, limited available literature highlights the need for long-term cohort studies of women with well-characterized metabolic and vascular profiles during pregnancy and decades later. Our present knowledge suggests that screening for GDM provides an opportunity of pregnancy outcome improvement. Limited studies of diabetes prevention in at-risk patient groups suggest that we may have the opportunity to reduce the risk of later diabetes. Additional investigation is required to determine if interventions that prevent or postpone diabetes also delay the onset of vascular disease.
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PMID:Gestational diabetes, pregnancy hypertension, and late vascular disease. 1759 80

C-reactive protein (CRP) is becoming more frequently measured in patients with vascular disease. Awareness of why CRP levels are measured, knowledge of normal versus elevated levels, ability to obtain accuracy in measurement, and teaching appropriate for patients with vascular disease may enhance the care given by vascular nurses. The purpose of this article is to provide a guide for vascular nurses in understanding the role of the serum marker CRP for patients with vascular disease.
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PMID:C-reactive protein measurement in the patient with vascular disease. 1772 10


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