Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerotic renal artery stenosis (RAS) is a recognized cause of renal impairment. RAS is often overlooked in unexplained chronic kidney disease (CKD). A retrospective analysis of renal angiograms was performed to determine the prevalence of occult renovascular disease in 64 (M:F, 46:18; ages 21-81 years [median 60 years]) patients with unexplained CKD. Twelve patients had diabetes mellitus (type II: 11) and 43 were smokers. Median serum creatinine was 5.2 mg/dl (range 1.5-10.6 mg/dl). Group A included patients with unexplained CKD and with no risk factors for RAS and Group B had patients with increased risk for RAS. A narrowing of the renal vessel, main artery or branch, by >50% on renal arteriography was used as diagnostic criteria for RAS. 31/64 patients had positive angiographic findings. Thirteen patients had unilateral RAS, 9 had bilateral RAS, 5 had unilateral stenosis with occlusion on the opposite side, 3 had unilateral occlusion and 1 had a solitary kidney with RAS. 19/34 (54%) in Group A and 12/30 (40%) in Group B had a positive renal angiogram. In 10 patients with a rise in serum creatinine on recent introduction of ACE inhibition, 2 had evidence of RAS on renal arteriography. Eleven patients underwent angioplasty and 2 reconstructive surgeries. In 4 patients, blood pressure control improved and anti-hypertensive drug requirements were reduced, whilst renal replacement therapy was postponed in 4, by 2-24 months. In 18 patients, the lesions were not amenable to angioplasty or reconstructive surgery. Four patients did not benefit in any form with intervention. Occult atheromatous renal vascular disease is a common, not readily predictable and potentially correctable etiology of unexplained CKD.
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PMID:Detection of occult renovascular disease in unexplained chronic kidney disease. 1636 2

For the best understanding of aging, we must consider a genetic pool in which genes with negative effects (deleterious genes that shorten the life span) interact with genes with positive effects (helpful genes that promote longevity) in a constant epistatic relationship that results in a modulation of the final expression under particular environmental influences. Examples of deleterious genes affecting aging (predisposition to early-life pathology and disease) are those that confer risk for developing vascular disease in the heart, brain, or peripheral vessels (APOE, ACE, MTFHR, and mutation at factor II and factor V genes), a gene associated with sporadic late-onset Alzheimer's disease (APOE E4), a polymorphism (COLIA1 Sp1) associated with an increased fracture risk, and several genetic polymorphisms involved in hormonal metabolism that affect adverse reactions to estrogen replacement in postmenopausal women. In summary, the process of aging can be regarded as a multifactorial trait that results from an interaction between stochastic events and sets of epistatic alleles that have pleiotropic age-dependent effects. Lacking those alleles that predispose to disease and having the longevity-enabling genes (those beneficial genetic variants that confer disease resistance) are probably both important to such a remarkable survival advantage.
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PMID:Genetic contribution to aging: deleterious and helpful genes define life expectancy. 1639 87

The risk factors for hypertension are only partly known, and accounts for the some of the deficiencies in current primary prevention strategies and in the design of new drugs for the management of this common condition. Recently, chronic low grade low-grade inflammation has been identified as an integral part in the pathogenesis of vascular disease. Of note, inflammation may also be implicated in the development of hypertension, either as a primary or secondary event. Indeed, several clinical studies have demonstrated increased numbers of well recognised pro-inflammatory markers, such as high sensitive C-reactive protein (hsCRP), in patients with hypertension, even after adjustment for potential confounding factors. Furthermore, elevated hsCRP levels have also been shown to be predictive for the development of hypertension in prehypertensive and normotensive patients. Pathophysiologically, inflammation has been implicated in both endothelial (dys)function and arterial stiffness in hypertension, with reduced availability of nitric oxide (NO) being integral to this process. Oxidative stress also appears to be a key feature in the reduced availability of NO and is aggravated by increased circulating angiotensin II (Ang II). Importantly, there is some evidence that drugs commonly used in the management of hypertension, such as statins, angiotensin converting enzyme inhibitors and Ang II receptor blockers have anti-inflammatory properties that can positively influence outcomes in patients with hypertension. The inflammatory state in hypertension may pose a new therapeutic target for future drug design.
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PMID:Is hypertension an inflammatory process? 1672 74

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
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PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62

Cardiovascular diseases are the major cause of death and a significant cause of disability in the Western world and more recently threaten to pose an increasing health burden on developing nations. People with pre-existent vascular disease are those at highest risk for adverse cardiovascular outcomes and require aggressive secondary preventive therapies. Large strides have been made in the development of pharmacologic agents that intervene on various pathways implicated in atherogenesis, thus offering the ability to greatly impact on disease progression and to prevent events. Compelling data derived primarily from randomized controlled trials have shown the benefits of aspirin (or antiplatelet agents) and angiotensin converting enzyme (ACE) inhibitors (A), beta-blockers and blood pressure (B) and cholesterol-lowering drugs (C), particularly statins, in preventing recurrent events and improving survival. Taken together these data are the foundation for the simple, but important advice for secondary prevention - the ABCs. In addition, the evidence for the central role of lifestyle factors as determinants of risk has lead to increased efforts towards developing interventions aimed at modifying lifestyle patterns. Today, the biggest challenge remains in the implementation of proven effective therapies. Our focus should turn to educating physicians and patients alike regarding available therapies and their indications. In addition systematic, sustainable and globally applicable approaches to the secondary prevention of cardiovascular diseases need to be developed to truly realize the vast potential benefits of existing therapies.
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PMID:Drug therapies in the secondary prevention of cardiovascular diseases: Successes, shortcomings and future directions. 1684 43

A D/D (deletion/deletion) polymorphism within the ACE (angiotensin 1-converting enzyme) gene increases the risk of microalbuminuria, a predictor of atherosclerotic vascular disease, in essential hypertension. It is unknown, however, whether this genetic profile is accompanied by disturbed macromolecular permeability of systemic capillary endothelium, possibly in the context of generalized endothelial dysfunction. In the present study, the ACE gene polymorphism was determined by PCR in 79 never-treated uncomplicated hypertensive men and 16 normotensive men as controls. Evaluation variables were TERalb (transcapillary escape rate of albumin; the 1-h decline rate of intravenous (125)I-albumin, a measure of integrity of systemic capillary endothelium), albuminuria and forearm vasodilation to intra-arterial acetylcholine, an index of NO (nitric oxide)-mediated vasomotion, in addition to a series of sensitive parameters of albumin permeation (blood pressure, metabolic status and smoking habits). Analyses were done by comparing D/D homozygotes with grouped I/D (insertion/deletion) and I/I (insertion/insertion) subjects. TERalb was higher in D/D hypertensives, who had higher albuminuria, more frequent microalbuminuria and comparable forearm responsiveness to intra-arterial acetylcholine. Fasting glucose and insulin, insulin sensitivity, 24-h blood pressure, smoking habits and metabolic parameters did not differ between the two groups. TERalb and urine albumin values were positively associated in the hypertensive subjects. In conclusion, ACE D/D homozygosis, independently of several confounding factors, associates with higher TERalb in men with essential hypertension. This may reflect noxious genetic influences on systemic vascular permeability, a critical control mechanism for atherogenesis in the absence of grossly impaired NO-mediated arteriolar responsiveness. The parallel behaviour of TERalb and albuminuria suggests some shared genetically mediated determinant of renal and systemic microvascular abnormalities in hypertension.
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PMID:ACE gene insertion/deletion polymorphism modulates capillary permeability in hypertension. 1688 37

The ADVANCE Retinal Measurements (AdRem) Study is a large intervention study evaluating the effects of target driven intensive glucose control and placebo controlled blood pressure lowering on retinal vascular changes. AdRem is a sub-study of the ADVANCE Study (Action in Diabetes and Vascular disease), a 2x2 factorial randomized controlled trial with an ACE inhibitor-diuretic combination (perindopril-indapamide) and a gliclazide MR-based regimen in patients with type 2 diabetes mellitus. The AdRem study is based on seven-field stereoscopic retinal photographs of both eyes. These are taken within 3 months after randomization in ADVANCE (baseline), at the biennial and at the final visit. The primary outcome is progression of two or more steps in ETDRS classification. Secondary outcomes include progression of retinal vascular lesions and distortion of retinal vascular geometry. Retinal photographs are made on film and digitized at a central laboratory. The AdRem study uses fully digitized quality control and grading. Between August 2002 and January 2004 1978 patients were included in the AdRem study, from 39 centers in 14 countries. Approximately 85% comply with the strict AdRem quality requirements. Publication of the results is expected in early 2008. The AdRem study is designed to provide reliable evidence on the effects of intensive glucose control and blood pressure lowering on both diabetic retinopathy and abnormalities of retinal vasculature in patients with type 2 diabetes mellitus.
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PMID:Rationale and design of the AdRem study: evaluating the effects of blood pressure lowering and intensive glucose control on vascular retinal disorders in patients with type 2 diabetes mellitus. 1764 53

Diabetes represents as independent risk factor for coronary artery disease (CAD) and the prognosis in term of survival rates is worse for diabetic patients who have CAD with report to those with CAD but no diabetes. The coronary artery disease in diabetes has specificities and, in particular, more extensive atherosclerosis. Diabetic patients are also more frequently asymptomatic. Due to the extreme complexity of ischemic vascular disease in patients with diabetes, an optimal therapeutic strategy is based on the correction of elevated blood glucose and lipid levels, of blood pressure, of platelet and coagulation abnormalities. Diabetic patients benefit from secondary prevention by drug therapy(aspirin, lipid lowering with statines, beta blocker and ACE inhibitors) to the same extent as, or more than, non-diabetic patients. Both percutaneous and surgical myocardial revascularization have been proved equally effective for CAD treatment in diabetes. A recent randomized trial has shown a significantly improved outcome after surgical revascularization. But, the effects of drug-eluting stents, which dramatically decrease the incidence of re-stenosis, seem promising.
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PMID:[Screening and management of coronary artery disease in diabetic patients]. 1719 66

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

Several genes have been implicated as influencing the outcome following traumatic brain injury (TBI). Currently the most extensively studied gene has been APOE. APOE can influence overall and rehabilitation outcome, coma recovery, risk of posttraumatic seizures, as well as cognitive and behavioral functions following TBI. Pathologically, APOE is associated with increased amyloid deposition, amyloid angiopathy, larger intracranial hematomas and more severe contusional injury. The proposed mechanism by which APOE affects the clinicopathological consequences of TBI is multifactorial and includes amyloid deposition, disruption of cytoskeletal stability, cholinergic dysfunction, oxidative stress, neuroprotection and central nervous system plasticity in response to injury. Other putative genes have been less extensively studied and require replication of the clinical findings. The COMT and DRD2 genes may influence dopamine dependent cognitive processes such as executive/frontal lobe functions. Inflammation which is a prominent component in the pathophysiological cascade initiated by TBI, is in part is mediated by the interleukin genes, while apoptosis that occurs as a consequence of TBI may be modulated by polymorphisms of the p53 gene. The ACE gene may affect TBI outcome via mechanisms of cerebral blood flow and/or autoregulation and the CACNA1A gene may exert an influence via the calcium channel and its effect on delayed cerebral edema. Although several potential genes that may influence outcome following TBI have been identified, future investigations are needed to validate these genetic studies and identify new genes that might influence outcome following TBI.
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PMID:Genetic influences on outcome following traumatic brain injury. 1734 13


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