Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007222 (cardiovascular disease)
 65,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is a pathological process caused by vascular remodeling. It symbolizes one of the major causes for morbidity and mortality in the western world. The causes for these vascular problems are manifold and different etiologies have been discussed. Since the 1980s the role of chronic inflammation has been considered and is now confirmed by many studies and experimental data. Several inflammatory pathways have been shown to participate in the atherosclerotic process. Different markers for inflammation have been found to predict the future risk for developing cardiovascular disease. Among these, high sensitivity C-reactive protein has been the most extensively validated. Newer markers such as CD40 ligand appear also to provide important information regarding risk stratification. Medications have been found to lower levels of inflammatory markers and perhaps decrease the associated clinical risk. Statins particularly appear to have anti-inflammatory mediated benefits, though other classes of drugs are also being evaluated. Lipid-lowering therapy in general has been found to be associated with reductions in inflammatory markers. Antithrombotic therapy, such as intravenous glycoprotein lIb/IIIa inhibitors and clopidogrel, has also been demonstrated to reduce inflammatory marker release. Peroxisome proliferator-activated receptor agonists are being evaluated for possible roles in targeting arterial inflammation. Angiotensin-converting enzyme inhibitors may also have anti-inflammatory properties. In this article we review the existing data in the inflammatory model of atherosclerosis. Furthermore, we discuss the prognostic value of different inflammatory markers and the potential benefit of anti-inflammatory therapies in cardiovascular disease.
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PMID:The role of inflammation in atherothrombosis: current and future strategies of medical treatment. 1556 94

Although antiphospholipid antibodies (aPL) are associated with thrombosis, it is not known who with aPL is at higher risk for thrombosis. It was the aim of this cross-sectional study to investigate how thrombophilic factors contribute to venous or arterial thrombosis in aPL-positive individuals. In outpatient test centres at two tertiary care hospitals, two hundred and eight (208) persons requiring aPL testing were matched by age, gender and centre to 208 persons requiring a complete blood count. Persons were classified as aPL-positive (having anticardiolipin, lupus anticoagulant and/or anti-beta(2)-glycoprotein I antibodies) or aPL-negative. Several thrombophilic factors were studied using logistic regression modelling. Results showed that the aPL-positive group had three-fold more events (37%) than the aPL-negative group (12%). In unadjusted analyses, clinically important associations were observed between factor V Leiden and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00, 1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively). After adjusting for recruitment group, persons with both APCR and aPL had a three-fold greater risk (OR, 95% CI = 3.31, 1.30-8.41) for venous thrombosis than those with neither APCR nor aPL. Similarly, after adjusting for hypertension, family history of cardiovascular disease, gender and recruitment group, persons with both hyperhomocysteinemia and aPL had a five-fold increased risk (OR, 95% CI = 4.90, 1.37-17.37) for arterial thrombosis compared to those with neither risk factor. In conclusion, APCR phenotype and hyperhomocysteinemia are associated with a higher risk of venous and arterial thrombosis, respectively, in the presence of aPL.
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PMID:Antiphospholipid antibodies and thrombosis: association with acquired activated protein C resistance in venous thrombosis and with hyperhomocysteinemia in arterial thrombosis. 1558 39

Platelet-dependent thrombosis is an important part of the pathophysiology of both percutaneous coronary interventions (PCI) and acute coronary syndrome (ACS). Data support the use of acute therapies that interfere with platelets to provide clinical benefit to patients presenting with acute cardiovascular disease. The discovery of platelet glycoprotein (GP) IIb/IIIa receptor antagonists has been a major advance in the pharmacotherapy for patients undergoing PCI and those presenting with ACS without ST-segment elevation. This article will cover the role of platelets in acute cardiovascular disease, as well as the discovery and development of the platelet GPIIb/IIIa inhibitors. The major focus of this article will be on examining key lessons from the trials in each of these areas as well as presenting a series of questions that still require answers from either ongoing or future research.
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PMID:Controversies surrounding platelet glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention and acute coronary syndromes. 1563 Jun 70

Platelet activity and platelet-endothelial cell interactions are important in the acute development of thrombosis, as well as in the pathogenesis of cardiovascular disease. An increasing number of foods have been reported to have platelet-inhibitory actions, and research with a number of flavanol-rich foods, including, grape juice, cocoa and chocolate, suggests that these foods may provide some protection against thrombosis. In the present report, we review a series of in vivo studies on the effects of flavanol-rich cocoa and chocolate on platelet activation and platelet-dependent primary hemostasis. Consumption of flavanol-rich cocoa inhibited several measures of platelet activity including, epinephrine- and ADP-induced glycoprotein (GP) IIb/IIIa and P-Selectin expression, platelet microparticle formation, and epinephrine-collagen and ADP-collagen induced primary hemostasis. The epinephrine-induced inhibitory effects on GP IIb/IIIa and primary hemostasis were similar to, though less robust than those associated with the use of low dose (81 mg) aspirin. These data, coupled with information from other studies, support the concept that flavanols present in cocoa and chocolate can modulate platelet function through a multitude of pathways.
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PMID:Flavanols and platelet reactivity. 1571 93

Over the past number of years numerous data have been published regarding increased atherosclerosis in patients with systemic lupus erythematosus (SLE), and it has been shown that premature or accelerated atherosclerosis is an important cause of morbidity and mortality in these patients. Besides the traditional risk factors for cardiovascular disease, the association between SLE and atherosclerosis can be attributed to additional risk factors closely related to inflammation and autoimmunity. In particular, several autoantibodies and their respective autoantigens have been identified as possible factors in the development and progression of the atherosclerotic process in SLE. The understanding of SLE-related risk factors for enhanced atherosclerosis could shed more light on disease mechanisms, leading to new therapeutic strategies for the treatment of cardiovascular diseases in SLE patients. In the present paper, the biological characteristics and possible pathogenetic role of the oxidized low-density lipoprotein (oxLDL) and anti-oxLDL, beta(2)-glycoprotein I (beta(2)GPI) and anti-beta(2)GPI, and heat-shock protein 60/65 (HSP60/65) and anti-HSP60/65 autoantibody systems are summarized.
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PMID:Systemic lupus erythematosus, atherosclerosis, and autoantibodies. 1612 77

Walking-induced calf pain as well as levels of different inflammation-sensitive plasma proteins (ISPs) are related to cardiovascular disease (CVD). This prospective cohort study explored the relationship between ISPs and walking-related calf pain and the interrelationships between ISPs and calf pain in the prediction of death and incidence of coronary events (CE). In 5,725 apparently healthy men, 46 +/-3.0 years old, plasma concentrations of orosomucoid (alpha(1)-acid glycoprotein), alpha(1)-antitrypsin, haptoglobin, fibrinogen, and ceruloplasmin were measured. Walking-induced calf pain was assessed by questionnaire. Mortality and incidence of CE were monitored over a mean follow-up of 18 years in subjects defined by the presence of calf pain and ISP level (0 to 1 or 2 to 5 ISP(s) in the top quartile). The prevalence of calf pain (7.3%) was significantly related to age, lifestyle, and traditional risk factors of CVD and ISP levels. The risk factor-adjusted relative risks for CE, CVD- and all-cause mortality were 1.89 (CI: 1.27 to 2.82), 2.90 (CI: 1.82 to 4.62), and 2.67 (CI: 1.97 to 3.57), respectively, for men with calf pain and high ISP levels (reference: no calf pain and low ISP levels). The corresponding risk for those with calf pain and low ISP levels were 1.34 (CI: 0.91 to 1.97), 1.47 (CI: 0.90 to 2.41), and 1.31 (CI: 0.95 to 1.81), respectively. These results indicate, on the one hand, that walking-induced calf pain is associated with high ISP levels and, on the other, that the risk of CVD in men with calf pain is substantially higher in those with high ISP levels than in those with low levels.
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PMID:Incidence of myocardial infarction and death in relation to walking-induced calf pain and plasma levels of inflammation-sensitive proteins. 1619 89

Cardiovascular disease accounts for significant morbidity and mortality in the elderly. Despite several, large cardiovascular clinical trials, data to guide therapy in this growing population subset are relatively limited. This review focuses on treatment approaches and recommendations for the management of elderly patients with acute myocardial infarction (MI) obtained from subgroup analyses from major clinical trials.Treatment options for acute MI in the elderly have changed dramatically since the 1990s. Reperfusion therapy by primary percutaneous coronary intervention has superseded the use of thrombolytic therapy for the treatment of acute ST-elevation myocardial infarction (STEMI). Clinical trial data have demonstrated that even transferring patients to facilities that have primary angioplasty capabilities is better than thrombolytic therapy, if the anticipated transfer time is of acceptable duration. Additionally, adjunctive use of the intravenous glycoprotein (GP) receptor antagonist, abciximab, during primary angioplasty affords a reduction in the composite primary end point of death, reinfarction, and target vessel revascularization, with much of the benefit derived from the latter. Thrombolytic therapy, barring any contraindication, must be used when mechanical revascularization is not available; however, the risk for complications in the elderly is higher, especially for those 75 years and older. Studies investigating the use of thrombolytics plus GP receptor antagonists with and without percutaneous coronary intervention show questionable benefit in the elderly.
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PMID:Evidence-based management of acute myocardial infarction in the elderly--current perspectives. 1636 78

Cardiovascular disease accounts for significant morbidity and mortality in the elderly. The clinical trial data available to guide therapy in this growing population subset are relatively limited. This review will focus on treatment approaches and recommendations obtained from subgroup analyses of elderly patients from major clinical trials for the management of chronic stable angina, acute coronary syndromes (unstable angina and non-ST-segment elevation myocardial infarction), and coronary revascularization. Recent advances in the treatment of stable angina have shown that use of angiotensin-converting enzyme inhibitors and lipid-lowering therapy as adjunctive measures show benefit in the elderly by reducing the occurrence of death, nonfatal myocardial infarction, and unstable angina. However, if patients experience disabling or unstable anginal symptoms despite effective medical therapy, coronary revascularization must be considered. Several clinical trials have shown a significant reduction in major adverse cardiac events when using intravenous glycoprotein receptor antagonists periprocedurally during percutaneous revascularization approaches in elderly patients with unstable angina or non-ST-segment elevation myocardial infarction, especially when these measures are performed as soon as possible. However, the success of myocardial revascularization by a percutaneous or surgical approach is highly dependent on the patient's associated comorbidities, especially in patients over age 80 years.
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PMID:Evidence-based management of coronary artery disease in the elderly--current perspectives. 1636 53

Several studies demonstrated an inverse association between polyphenol intake and cardiovascular events. Platelet recruitment is an important phase of platelet activation at the site of vascular injury, but it has never been investigated whether polyphenols influence platelet recruitment. The aim of the study was to analyze in vitro whether two polyphenols, quercetin and catechin, were able to affect platelet recruitment. Platelet recruitment was reduced by NO donors and by NADPH oxidase inhibitors and was enhanced by L-NAME, an inhibitor of NO synthase. Quercetin and catechin, but not single polyphenol, significantly inhibited platelet recruitment in a concentration-dependent fashion. The formation of superoxide anion was significantly inhibited in platelets incubated with quercetin and catechin but was unaffected by a single polyphenol. Incubation of platelets with quercetin and catechin resulted in inhibition of PKC and NADPH oxidase activation. Treatment of platelets with quercetin and catechin resulted in an increase of NO and also down-regulated the expression of GpIIb/IIIa glycoprotein. This study shows that the polyphenols quercetin and catechin synergistically act in reducing platelet recruitment via inhibition of PKC-dependent NADPH oxidase activation. This effect, resulting in NO-mediated platelet glycoprotein GpIIb/IIIa down-regulation, could provide a novel mechanism through which polyphenols reduce cardiovascular disease.
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PMID:Polyphenols enhance platelet nitric oxide by inhibiting protein kinase C-dependent NADPH oxidase activation: effect on platelet recruitment. 1677 7

Cardiovascular disease is the major cause of mortality in Western countries. Platelets play a crucial role in the development of arterial thrombosis and other pathophysiologies leading to clinical ischemic events. In the damaged vessel wall, platelets adhere to the subendothelium through an interaction with von Willebrand factor (VWF), which forms a bridge between subendothelial collagen and the platelet receptor glycoprotein (GP) Ib/IX/V. This reversible adhesion allows platelets to roll over the damaged area, decreasing their velocity and resulting in strong platelet activation. This leads to the conformational activation of the platelet GPIIb/IIIa receptor, fibrinogen binding and finally to platelet aggregation. As each interaction (collagen-VWF, VWF-GPIb and GPIIb/IIIa-fibrinogen) plays an essential role in primary haemostasis, loss of either of these interactions results in a bleeding diathesis, implying that interfering with these interactions might result in an anti-thrombotic effect. Whereas GPIIb/IIIa antagonists indeed are effective anti-thrombotics, it has been suggested that drugs which block the initial steps of thrombus formation (collagen-VWF or VWF-GPIb interaction) might have advantages over the ones that merely inhibit platelet aggregation. In this review we will discuss and compare the development of monoclonal antibodies (moAbs) that inhibit platelet adhesion or platelet aggregation. The effect of the moAbs in in vitro experiments, in in vivo models and in clinical trials will be described. Benefits, limitations, current applications and the future perspectives in the development of antibodies for each target will be discussed.
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PMID:Development of monoclonal antibodies that inhibit platelet adhesion or aggregation as potential anti-thrombotic drugs. 1701 2


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