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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiovascular disease is a major cause of death. There is evidence that this disease is predicted and its progression influenced by various factors (e.g. hyperlipidaemia). In this review, we consider aspects of platelet structure and function which may explain how this cell type contributes to the pathogenesis of vascular disease. The platelet also contains bioamines (serotonin, 5-HT; histamine) which are potent vasoactive substances. Studies involving patients with peripheral vascular disease (PVD) where abnormalities in platelet function (platelet aggregation and platelet shape change) and in bioamine status (vascular, platelet and plasma bioamine concentrations) are reviewed. We also discuss how platelet activation (in vitro) and plasma lipids influence intraplatelet bioamine status. Finally, we report in vitro evidence of the effect of two drugs prescribed to PVD patients: aspirin and naftidrofuryl. Aspirin is an ineffective inhibitor of 5-HT-induced whole blood platelet aggregation whereas naftidrofuryl is effective in the presence or absence of aspirin. By identifying and altering the factors which contribute to the pathogenesis of atherosclerosis we will be better equipped to prevent, reverse or retard this process.
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PMID:Serotonin, histamine and platelets in vascular disease with special reference to peripheral vascular disease. 134 86

Diabetes mellitus is associated with a high incidence of cardiovascular diseases not directly attributable to hyperlipidemia, smoking, or hypertension, but which in part may be explained by an enhanced tendency to thrombosis due to increased platelet activity. The aim of this study was to evaluate platelet function and compare the effectiveness of the antiplatelet drug aspirin on platelet aggregation in diabetic and nondiabetic subjects. Platelet aggregation and composition were examined in 20 male insulin-dependent diabetes mellitus (IDDM) patients and 20 nondiabetic control subjects matched for age and body mass index. All were normotensive with serum total cholesterol less than 6.5 mM. Although within the clinically acceptable normal range, blood pressure was significantly higher in diabetic patients (130/75 mmHg) than in control subjects (123/70 mmHg) (P less than 0.05). Serum thromboxane B2 and ex vivo aggregation of platelets in response to two doses of the agonists collagen and platelet-activating factor (PAF) were similar to nondiabetic subjects. However, after taking 100 mg/day aspirin for 5 days, platelet aggregation to collagen was reduced by 76% in control subjects compared to 56% in IDDM patients (P less than 0.001). Aspirin treatment also reduced the slope of the aggregation curve and increased the lag time (the period between the addition of collagen and the start of irreversible aggregation) significantly more in control than in diabetic platelets. This difference in platelet aggregation could not be attributed to differences in platelet serotonin or thromboxane A2 secretion, the latter being almost completely suppressed by aspirin in each group. Platelet aggregation to PAF was similar in both groups and was not affected by aspirin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential effect of aspirin on platelet aggregation in IDDM. 155 86

More than a decade has passed since the introduction of the concept that inhibition of platelet function may be helpful in preventing the initiation of thrombus formation. Aspirin has been recognized as inhibiting normal platelet function and the mechanism has been clearly delineated. Legions of patients have been studied to answer the question of whether aspirin is efficacious in the primary prevention of acute myocardial infarction. At the present time, however, a solid, clear answer is not available and firm recommendations cannot be made. A large number of studies evaluating aspirin and other antiplatelet agents in the prevention or delay of recurrent myocardial infarction (secondary prevention) have been completed and those studies reporting a favorable beneficial effect are in the minority. In these secondary prevention studies reporting success, the doses of aspirin employed were large enough to inhibit both the cyclo-oxygenase system and thromboxane A2 production as well as the synthesis of prostacyclin. Thus, in these studies if aspirin is effective in reducing adverse cardiovascular events, its efficacy is being mediated by an unknown mechanism. If the reader of the few studies that report positive results is convinced of the benefit of aspirin, it must be emphasized that thoughtful, cautious patient selection based upon the individual's cardiovascular risk profile must be exercised. Individual variation may exist with respect to aspirin's beneficial effect. It must be absolutely recognized that aspirin or any antiplatelet agent does not in any way substitute for the removal or treatment of coexisting risk factors such as tobacco, obesity, hypercholesterolemia, hyperlipidemia, hypertension, and metabolic disease. In contrast to aspirin, control of the above risk factors has been established as beneficial. Aspirin is not free of undesirable side-effects; fatalities secondary to hemorrhage have been reported, and these must be known in detail and understood by both physician and patient before this agent is prescribed in the prophylactic treatment of cardiovascular disease.
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PMID:Aspirin in the prevention of thrombosis. 203 Jun 40

Male rats of the JCR:LA-corpulent strain spontaneously develop atherosclerosis and myocardial lesions if corpulent. The corpulent rats exhibit a marked very low density hyperlipidemia and insulin resistance. The incidence of both vascular and myocardial lesions correlates strongly with the hyperinsulinemia, but not with the hyperlipidemia. Corpulent male rats were chronically treated with nifedipine or acetylsalicylic acid to explore the roles of smooth muscle spasm and platelet activity in induction of the myocardial lesions. Acetylsalicylic acid treatment was associated with no significant changes in fasting glucose, insulin, or lipid concentrations. Nifedipine caused no significant changes in glucose concentration but was associated with mildly increased insulin levels. Treatment with nifedipine resulted in significant decreases in serum triglyceride concentrations. The decreases were confined to longer-chain triacylglycerol molecular species with no change in the concentration of molecular species with 48 or 50 acyl carbon atoms. There was no effect on myocardial lesion frequency with acetylsalicylic acid treatment. In contrast, nifedipine prevented the development of old organized scarred lesions. This effect is similar to that seen with treatments that markedly reduce the insulin resistance. These findings suggest that platelet-initiated thrombus formation is not an important factor in lesion formation in the JCR:LA-cp rat, but that smooth muscle spasm is probably important.
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PMID:Prevention of myocardial lesions in JCR:LA-corpulent rats by nifedipine. 219 41

In about 50% of the cases of spontaneous deep vein thrombosis a congenital deficiency of an inhibitor of coagulation or an insufficient fibrinolytic mechanism can be detected. In arterial thromboembolism a connection with hyperactive platelets or with a diminished availability of tissue plasminogen activator can be found in about 70%. However, in these cases the defect which provokes thrombosis is mostly acquired and is connected with hyperlipidemia and/or with atherosclerotic alterations of the vessel wall. A study on patients with thromboembolic tendency and detectable risk factors was carried out. A total of 470 patients could be observed for 2 years under an adequate antithrombotic prophylaxis. The occurrence of thromboembolic episodes 2 years prior to prophylaxis and 2 years under prophylaxis was compared. In venous cases thrombosis could be controlled almost completely by coumarins when the underlying cause was a deficient plasmatic inhibitor. In patients with diminished fibrinolysis there was only a partial effect of oral anticoagulants. A better result could be obtained when pentosan polysulfate was administered. In arterial thromboembolism the results of prophylaxis were less convincing. The efficacy of ASA in patients with an increased platelet function was only moderate. In addition, ASA hat to be discontinued in about 20% of the patients because of gastrointestinal problems. Pentosan polysulfate in patients with a diminished fibrinolytic capacity had a fairly good effect and resulted in a 60% reduction of thromboembolic manifestations. It is shown that an exact diagnosis of the underlying deficiency which is likely to cause thrombosis can also improve the efficacy and the specificity of prophylaxis.
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PMID:Antithrombotic therapy in patients with known risk factors for thromboembolism. 248 12

The acute effects of fatty meals (900 kcal) rich in saturated (cream) or n-3 polyunsaturated (cod liver oil, CLO) fatty acids on human umbilical vein endothelial cells (ECM) and platelet behavior were studied. The ECM were incubated for 24 hours at 37 degrees C with either plasma or chylomicrons (CM) obtained 3 hours after the meals. The ability of the ECM to inhibit platelet aggregation (PIA) and the release of prostaglandin I2 measured as 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were measured after 24 hours of incubation, after stimulation and after freezing and thawing. Similar studies were done with CM from a patient with type V hyperlipoproteinemia. The release of 6-keto-PGF1 alpha was increased by postprandial plasma and by CM obtained after both meals. Plasma collected after CLO, but not after cream, increased PIA, whereas CM derived from all sources studied stimulated the PIA of ECM. No consistent correlation could be established between the release of 6-keto-PGF1 alpha and PIA. Increased platelet aggregation in platelet-rich plasma was always observed during postprandial hyperlipidemia.
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PMID:Effects of postprandial plasma and chylomicrons on endothelial cells. Differences between dietary cream and cod liver oil. 375 2

Each year in the United Kingdom about 250,000 people die from acute myocardial infarction, other ischaemic heart disease or stroke. Many will already have evidence of established vascular disease that predisposes to such an event--such as angina, peripheral vascular disease, atrial fibrillation, transient ischaemic attacks or a previous myocardial infarction or stroke. Others will have risk factors such as hypertension, diabetes mellitus or hyperlipidaemia, but the stroke or heart attack is the first evidence of established vascular disease. Aspirin was first discovered to have antiplatelet properties 30 years ago and since then many randomised clinical trials have sought to determine whether it (or other antiplatelet agents) can protect patients from heart attack or stroke. In this article we review the evidence and update our earlier conclusions on stroke, myocardial infarction, and unstable angina, arguing that aspirin should be widely used to reduce cardiovascular morbidity and mortality in certain high-risk patients.
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PMID:Aspirin to prevent heart attack or stroke. 763 3

Lower extremity vascular grafts, either vein or synthetic, fail for diverse reasons. Technical defects or poor surgical judgment doom a graft beyond any benefit pharmacotherapy can offer. Graft failure due to spontaneous thrombosis particularly affects prosthetic conduits, and use of antiplatelet agents (dextran, ASA) or anticoagulants (heparin, warfarin) is probably useful in this setting. An effective way to inhibit vein graft or anastomotic intimal hyperplasia remains elusive. Perhaps the most permanent and longstanding influence on lower extremity graft survival can be made through risk factor intervention aimed at arresting the progression of atherosclerosis. Aggressive treatment of hyperlipidemia, hypertension, smoking, and other known risk factors should be routinely and aggressively pursued in patients with lower extremity grafts, either autogenous or prosthetic. Lower extremity graft patency is optimally ensured by technically adept insertion of a proper autologous conduit in a well-selected patient. Pharmacotherapy may have a significant adjunctive role in the maintenance of graft patency, especially in high-risk settings such as limb salvage with associated poor outflow, a marginal vein graft, or the obligatory use of prosthetic material.
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PMID:Pharmacologic intervention to prevent graft failure. 763 20

The risk factors predominating in patients with peripheral arterial occlusive disease are cigarette smoking and diabetes. Moreover, hypertension and hyperlipidemia play an important role. Especially younger patients profit from elimination or treatment (primary or secondary prevention), whereas in elderly patients these measures are no longer crucial. In patients with intermittent claudication, the quality of life may be improved by physical training, vasoactive medicaments, optimal management of concomitant diseases and the different modalities of catheter therapy. According to the special situation in critical ischemia, surgical or catheter revascularization is preferred. If these two techniques cannot be used, intra-arterial or intravenous prostanoids are still promising. Aspirin and in second priority ticlopidine are suited for secondary prevention of arteriosclerosis not only in the extracranial, but also in the peripheral vascular region. After endarterectomy and catheter therapy, aspirin improves the long-term outcome by reducing the incidence of restenoses. Better results are obtained by oral anticoagulation in patients with emboli and after local thrombolysis.
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PMID:[Treatment strategies in arterial occlusive diseases]. 827 1

Recurrent stenosis (> 50%) after carotid endarterectomy is reported with a frequency ranging from 7-20%. 232 patients undergoing carotid endarterectomy were randomised to low-dose acetylsalicylic acid (ASA, 75 mg daily) or placebo (identical tablets). The treatment was started the day before surgery and continued for 6 months. All patients were followed clinically for 1 year. Doppler examination was performed preoperatively (n = 230) and postoperatively (n = 228) and at follow-up at 2 (n = 220) and at 6 months (n = 174) after surgery. The degree of stenosis was estimated from the maximum Doppler frequency shift in the internal carotid artery. Recurrent stenosis of 30% or more was detected in 85 of the 220 patients (38.6%) at 2 months, and at 6 months in 73 of the 174 examined patients (42.0%). Stenosis > 50% was seen in 16 patients (9.2%) and occlusion was found in four patients (1.8%) at 6 months. No difference between the low-dose ASA-treated group (n = 112) compared to the placebo group (n = 108) was seen regarding recurrent stenosis. Women had an increased risk of recurrent stenosis (p < 0.001), whereas other factors such as age, hyperlipidaemia, diabetes and smoking were not associated with increased risk. Importantly, the number of neurological events did not differ between those with or without restenosis. Therefore, the indications for surgery of asymptomatic recurrent stenosis are questionable. The progress of arteriosclerosis in the contralateral carotid artery did not differ between the treatment groups.
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PMID:Can recurrent stenosis after carotid endarterectomy be prevented by low-dose acetylsalicylic acid? A double-blind, randomised and placebo-controlled study. 835 92


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