Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with a clinical manifestation of atherothrombosis such as a recent ischaemic cerebrovascular event are at high risk of subsequent events. Atherothrombosis often reflects disseminated disease; thus, further events may occur not only in the same arterial distribution but also in other vascular beds. To achieve adequate secondary prevention in these patients, long-term antiplatelet therapy with consistent benefit across the atherothrombosis spectrum is required. In the CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) Trial, clopidogrel (clopidogrel bisulphate) was superior to acetylsalicylic acid (ASA) in reducing the combined risk of ischaemic stroke (IS), myocardial infarction (MI) or vascular death in patients with symptomatic atherosclerosis. Post hoc analyses demonstrated that the benefit of clopidogrel was amplified in high-risk patients, including patients with a history of previous ischaemic events, diabetic patients and patients with hypercholesterolaemia. The synergistic antiplatelet effect produced by using clopidogrel on top of ASA may be beneficial in high-risk patients. The benefit of dual antiplatelet therapy was recently examined in the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) Study, which demonstrated that long-term treatment with clopidogrel on top of standard therapy including ASA was superior to standard therapy alone in the prevention of major vascular ischaemic events in patients with unstable angina or non-Q-wave MI. The ongoing MATCH (Management of Atherothrombosis with Clopidogrel in High-risk Patients with Recent Transient Ischaemic Attack or Ischaemic Stroke) trial will evaluate the efficacy and safety of clopidogrel plus ASA versus clopidogrel alone in patients with recent transient ischaemic attack (TIA) or IS and with at least one additional risk factor. Approximately 7,600 patients will be enroled, with treatment and follow-up for each patient lasting 18 months. The primary combined efficacy endpoint will be the first occurrence of an event in the composite of IS, MI, vascular death or rehospitalization for an acute ischaemic event during the follow-up period. MATCH will explore the potential benefit of clopidogrel in high-risk stroke/TIA patients and together with CAPRIE and CURE could provide further evidence of the long-term benefit of clopidogrel in patients with major atherothrombotic manifestations.
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PMID:From CURE to MATCH: ADP receptor antagonists as the treatment of choice for high-risk atherothrombotic patients. 1180 84

The association between clinical coronary artery disease, cerebrovascular disease, and aortic atherosclerosis has not been examined in the general population. Transesophageal echocardiography was performed in 581 subjects, a random sample of the Olmsted County (Minnesota) population aged >/=45 years, participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. The frequency and severity of atherosclerosis of the thoracic aorta were determined in the population and the association between clinical coronary artery disease, cerebrovascular disease, and aortic atherosclerosis was examined. Previous myocardial infarction, angina pectoris, and coronary artery bypass surgery were significantly associated with aortic atherosclerosis, adjusting for age and gender (p </=0.01). Among subjects with atherosclerosis, these manifestations were associated with complex atherosclerosis (plaques >4-mm thick, ulcerated plaques, or mobile debris), adjusting for age and gender (p <0.05). Age, smoking, pulse pressure, previous myocardial infarction (odds ratio [OR] 4.67; 95% confidence interval [CI] 1.42 to 15.40), and coronary artery bypass surgery (OR 5.12; 95% CI 1.01 to 26.01) were independently associated with aortic atherosclerosis. Among subjects with atherosclerosis, age, smoking, pulse pressure, hypertension treatment, and coronary artery disease (OR 2.50; 95% CI 1.18 to 5.30) were independently associated with complex atherosclerosis. Weak associations were observed between previous ischemic stroke, transient ischemic attack, and aortic atherosclerosis, associations that were not significant after age- and gender-adjustment (p >0.2). Thus, coronary artery disease is strongly associated with aortic atherosclerosis and complex atherosclerosis in the general population. Cerebrovascular disease is weakly associated with aortic atherosclerosis, thereby questioning the overall importance of aortic atherosclerosis in the pathogenesis of cerebrovascular events in the general population.
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PMID:Relation of coronary artery disease and cerebrovascular disease with atherosclerosis of the thoracic aorta in the general population. 1180 26

Although the incidence of overt sequelae has traditionally been higher in patients undergoing isolated intracardiac procedures such as valve replacement or repair, recent studies show that the incidence of stroke for intracardiac procedures now approximates that for isolated coronary artery bypass grafting (CABG), in the range of 1 to 4%. In both intracardiac and extracardiac surgery, macroemboli (>200 microm in diameter) and microemboli (<40 microm in diameter) seem to be responsible for most neurologic complications. The risk of overt stroke is clearly increased in patients who undergo more complicated, combined procedures such as CABG plus valve replacement or CABG plus carotid endarterectomy. For isolated CABG, preoperative risk factors include advanced patient age, proximal aortic atherosclerosis, hypertension, previous stroke or transient ischemic attack, diabetes, and female gender. One area of controversy and current research concerns whether hypothermia is better than normothermia during cardiopulmonary bypass (CPB). Another debatable issue is whether CPB itself results in neurologic damage, owing to nonpulsatile perfusion, complement activation and the "inflammatory response," or a greater propensity for platelet activation and aggregation into microemboli in this setting. Strategies for preventing adverse neurologic outcome (new paradigms for managing intra-aortic plaque and controlling the cerebral reperfusion temperature) and for acute intervention (using specific cerebral protective agents) are under investigation. Further research into techniques for preventing or mitigating cerebral injury, particularly in high-risk patients, is clearly mandated.
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PMID:A review of risk factors for adverse neurologic outcome after cardiac surgery. 1191 28

The present study was performed to clarify the relation between plasma homocysteine and ischemic stroke. We studied the relationship between ischemic stroke and the known risk factors for atherosclerosis including plasma homocysteine in 91 in-patients (80.3 +/- 6.8 years) in a medical ward. Those diagnosed with transient ischemic attack, cerebral infarction were placed in the disease group. Blood was drawn from in-patients in a fasting state for determination of plasma homocysteine. Plasma homocysteine concentrations were determined using a high-performance liquid chromatography assay. The odds ratio of ischemic stroke was higher in the second (10.0-13.9 micromol/l) and third highest plasma homocysteine concentration groups (> or = 14.0 micromol/l) than in the first group (< 10.0 micromol/l) by 5.18 and 4.42-fold, respectively. Logistic regression analysis using ischemic stroke as an object variable, adjusted by various risk factors including the plasma homocysteine concentration showed that the odds ratio on combining the second and third groups was 5.80 (95% confidence interval (Cl): 1.50-22.5) compared with the first group. The findings confirmed that the association between plasma homocysteine concentration and ischemic stroke in Western populations is also present among the elderly Japanese.
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PMID:An association between plasma homocysteine concentrations and ischemic stroke in elderly Japanese. 1223 16

Atherosclerotic plaque at the arch of the aorta has been identified as a potential source for atheroembolic stroke. Imaging of aortic arch plaque can be performed with transesophageal echocardiography (TEE), but TEE is an invasive procedure. A new noninvasive method has been developed to image aortic arch plaque employing transcutaneous real time B-mode ultrasonography with color flow duplex Doppler. B-mode imaging has an 86% accuracy for identifying complex aortic arch plaques as compared with TEE. Noninvasive imaging of the aortic arch can be employed in diagnosing the etiology of cerebrovascular disease in patients with stroke or transient ischemic attack in conjunction with duplex B-mode sonography of the extracranial carotid arteries. It also provides a noninvasive method for studying atherosclerotic plaque in the aortic arch which is applicable for investigational studies of the mechanisms of atherosclerosis and evaluation of pharmacological agents designed to treat atherosclerotic disease.
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PMID:Noninvasive imaging of atherosclerotic plaque in the arch of the aorta with transcutaneous B-mode ultrasonography. 1248 26

A 74-year-old patient was referred for a rapidly increasing pacing threshold 9 months after DDD pacemaker implantation because of symptomatic total atrioventricular (AV) block. She had a history of hypertension, diabetes with micro-angiopathy and a recent transient ischaemic attack. The paced electrocardiogram on admission had a right bundle branch block pattern and 3-dimensional transoesophageal echocardiography demonstrated passage of the lead through an atrial septal defect with a left ventricular position in addition to moderate atherosclerosis of the ascending aorta. No thrombus could be detected on the lead. Percutaneous extraction is usually not recommended because of the risk of mobilization of thrombus material. However, the risk of stroke during removal using cardiopulmonary bypass in this patient was considerably increased because of the presence of multiple independent risk factors. Therefore, percutaneous extraction using a locking device was selected and performed without complications: follow-up was uneventful.
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PMID:Successful percutaneous extraction of an inadvertently placed left ventricular pacing lead. 1263 46

During the first 30 days after a stroke, the case fatality is about 25% and the major cause of death is the index stroke and its sequelae. The most consistent predictor of 30-day mortality after stroke is stroke severity. Other predictors include increasing age, a history of previous stroke, cardiac failure, and a high blood glucose concentration and white blood cell count. Other less common, but important, causes of early mortality are recurrent ischaemic stroke and a coronary event. The risk of a recurrent cerebrovascular event is highest in the first month (4%) and year (12%) after a stroke and transient ischaemic attack (TIA), probably reflecting the presence of active, unstable atherosclerotic plaque. Thereafter, the risk of a recurrent cerebrovascular event falls to about 5% per year, similar to the risk of a coronary event. During years 1-5 after a TIA and ischaemic stroke, cardiovascular disease increasingly becomes the major cause of death, reflecting the generalized nature of atherothrombosis, the most common cause of the index stroke. The most robust predictor of death within 1-5 years after stroke is increasing age, closely followed by cardiac failure. Additional baseline predictors of longer-term mortality include a history of previous symptomatic atherothrombosis (TIA, ischaemic stroke, peripheral arterial disease, and early-onset ischaemic heart disease), risk factors for atherothrombosis (smoking), other heart diseases (cardiac failure, atrial fibrillation) and increasing stroke severity. Lacunar syndromes can be predictive of relative longevity. At 5 years after stroke, survival is about 40%, and about half of survivors are disabled and dependent. The most robust predictors of disability at 5 years after stroke are increasing age, stroke severity, and recurrent stroke. The most powerful predictor of early recurrent stroke (within 30 days after stroke) is an atherosclerotic ischaemic stroke caused by large-artery atherosclerosis with >50% stenosis, whereas the strongest predictor of stroke recurrence over 5 years is diabetes. Other predictors of recurrent stroke include increasing age, previous TIA, atrial fibrillation, high alcohol consumption, haemorrhagic index stroke, and hypertension at discharge. The clinical implication of these findings is that strategies for optimizing long-term outcome after TIA and stroke should be directed toward reducing the high risk of recurrent stroke and coronary events by removing/recanalizing the symptomatic atherosclerotic plaque, controlling the underlying causal vascular risk factors, and administering long-term, effective antiplatelet therapy.
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PMID:Long-term outcome after ischaemic stroke/transient ischaemic attack. 1269 14

Antiplatelet drugs have been shown to prevent a range of atherothrombotic events, including transient ischaemic attack (TIA) and ischaemic stroke. Clopidogrel and ticlopidine are adenosine diphosphate (ADP)-receptor antagonists that inhibit ADP-induced fibrinogen binding to platelets, a necessary step in the platelet aggregation process. The Antithrombotic Trialists' Collaboration recently published a major meta-analysis that assessed the effect of antiplatelet therapy in patients with various manifestations of atherosclerosis. In total, this analysis included 135,000 patients in comparisons of antiplatelet agents versus control and 77,000 patients in comparisons of different antiplatelet regimens. This meta-analysis found that overall, antiplatelet therapy reduces the combined odds of stroke, myocardial infarction (MI) or vascular death by 22%, and that antiplatelet agents reduce the odds of a non-fatal stroke by 25% over a wide range of patients with or without a history of cerebrovascular disease. In the CAPRIE trial of clopidogrel versus acetylsalicylic acid (ASA), there was a 10% odds reduction for stroke, MI or vascular death in favour of clopidogrel (p = 0.03). In a meta-analysis performed by the Cochrane Stroke Group, ADP-receptor antagonist therapy significantly reduced the odds of a serious vascular event (stroke, MI or vascular death) by 9% (2p = 0.01) and of any stroke by 12%. The safety/tolerability profile of clopidogrel was superior to that of ticlopidine, and at least as good as that of ASA. In CURE, a long-term benefit was observed with the use of clopidogrel on top of standard therapy (including ASA in all patients), with a 20% relative risk reduction for the primary endpoint of cardiovascular death, MI or stroke (p < 0.001) in patients with unstable angina and non-Q-wave MI. A consistent benefit was seen across all patient subgroups, including patients with a previous history of stroke. More recently, CREDO has demonstrated the incremental benefit of prolonged use of clopidogrel on top of ASA in patients undergoing elective PCI, with a 27% reduction in the combined risk of death, MI or stroke after 12 months of therapy (p = 0.02) and a 25% reduction in stroke over the same time period. The MATCH trial is currently being conducted to test the hypothesis that long-term administration of clopidogrel on top of ASA is superior to clopidogrel alone for the reduction of major ischaemic events in patients with recent TIA or ischaemic stroke who are at high risk of atherothrombotic recurrence. Further trials of clopidogrel on top of standard therapy (including ASA) are planned in neurology; these include SPS3, in patients with small subcortical strokes, and ATARI, in patients who have recently recovered from a TIA.
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PMID:Evidence with antiplatelet therapy and ADP-receptor antagonists. 1269 15

Periodontitis has been shown to increase the systemic inflammatory response, which has been implicated in atherosclerosis and cerebrovascular events. We hypothesized an association between periodontitis or edentulism and Stroke/TIA in the ARIC Study. Data on 9415 dentate and 1491 edentulous adults included demographics, cardiovascular outcomes, lifestyle, laboratory measures, and, for 6436 of the dentate, a dental examination. The dependent variable was Stroke/TIA, and the exposure was extent (%) of attachment level 3+ millimeters (AL). Quartiles of AL and edentulism were compared for Stroke/TIA using odds ratios (OR) and 95% confidence intervals (CI), and confounders were controlled by logistic regression. Stroke/TIA was prevalent in 13.5% of periodontal examinees, 15.6% of dentate non-examinees, and 22.5% of edentulous persons. The highest quartile of AL (OR 1.3, CI 1.02-1.7) and edentulism (OR 1.4, CI 1.5-2.0) were associated with Stroke/TIA.
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PMID:Relationship of periodontal disease and edentulism to stroke/TIA. 1463 Sep 2

Analysis was made of the results of 11 internal carotid reconstructions using polydioxanone (PDS) sutures 6 months after intervention performed in 10 patients. All operations on the carotid bifurcation were accomplished using 5/0 PDS continuous suture. Nine eversion carotid endarterectomies and 2 internal carotid reconstructions were performed for Kinkiking. There were no neurologic complications, thromboses, bleedings or repeated operations after interventions on the brachiocephalic arteries. Six months later the patients were examined under ambulatory conditions and were provided color duplex scanning (CDS) of the reconstructed area. Measurements were made of the diameter of the common carotid artery (CCA) right beneath the anastomosis between the CCA and the internal carotid artery (ICA), of the maximal diameter of the anastomosis between the CCA and the ICA, and of the size of the proximal ICA segment right the anastomosis. During the 6-month period following surgical intervention, all 10 patients did not demonstrate any ischemic attacks (TIA) or strokes. No cases of anastomotic aneurysms were recorded. After 9 reconstructions no ICA restenoses were marked. In one case, restenosis accounted for 40% because of atherosclerosis progression and after one operation there developed asymptomatic thrombosis of the ICA. The study has demonstrated that the use of PBS absorbable suture for autoarterial ICA reconstruction provides for anastomosis integrity minimally over the period as long as 6 months.
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PMID:The short-term results of internal carotid reconstructions by absorbable suture material. 1465 16


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