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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating lipoprotein-associated phospholipase A2 (Lp-PLA2) is a marker of inflammation that plays a critical role in atherogenesis; its inhibition may have antiatherogenic effects. Studies from the West of Scotland Coronary Prevention Study (WOSCOPS), Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) and Rotterdam cohorts have shown that Lp-PLA2 is an independent predictor of coronary heart disease (CHD), and the association is not attenuated upon multivariate analysis with traditional risk factors and other inflammatory markers. Studies in subjects with coronary artery disease (CAD) have also shown associations between Lp-PLA2 and cardiovascular risk. At least two recent studies have shown that Lp-PLA2 is a risk predictor for stroke. Overall, epidemiological studies suggest that measurement of Lp-PLA2 in plasma may be a useful in identifying individuals at high risk for cardiovascular events.
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PMID:Lipoprotein-associated phospholipase A2, vascular inflammation and cardiovascular risk prediction. 1731 59

Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that belongs to the superfamily of phospholipase A2 enzymes. Although initial studies showed that Lp-PLA2 might be protective against atherosclerosis, emerging data seem to suggest that Lp-PLA2 may be proatherogenic, which is an effect thought to be mediated by lysophosphatidylcholine and oxidized nonesterified fatty acids, two mediators generated by Lp-PLA2. This article reviews the potential mechanisms by which Lp-PLA2 may participate in the pathogenesis of atherosclerosis and its clinical manifestations, namely, coronary artery disease and stroke.
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PMID:The role of lipoprotein-associated phospholipase A2 as a marker for atherosclerosis. 1787 17

Few studies have investigated the role of elevated lipoprotein-associated phospholipase A2 (Lp-PLA(2)) with stroke risk, and those that have are based on small numbers of strokes. No study has evaluated the effect of hormone therapy use on the association of Lp-PLA(2) and stroke. We assessed the relationship between Lp-PLA(2) and the risk of incident ischemic stroke in 929 stroke patients and 935 control subjects in the Hormones and Biomarkers Predicting Stroke Study, a nested case-control study from the Women's Health Initiative Observational Study. Mean (SD) levels of Lp-PLA(2) were significantly higher among case subjects (309.0 [97.1]) than control subjects (296.3 [87.3]; P<0.01). Odds ratio for ischemic stroke for the highest quartile of Lp-PLA(2), compared with lowest, controlling for multiple covariates, was 1.08 (95% CI: 0.75 to 1.55). However, among 1137 nonusers of hormone therapy at baseline, the corresponding odds ratio was 1.55 (95% CI: 1.05 to 2.28),whereas there was no significant association among 737 hormone users (odds ratio: 0.70; 95% CI: 0.42 to 1.17; P for interaction=0.055). Moreover, among nonhormone users, women with high C-reactive protein and high Lp-PLA2 had more than twice the risk of stroke (odds ratio: 2.26; 95% CI: 1.55 to 3.35) compared with women low levels in both biomarkers. Furthermore, different stroke cases were identified as high risk by Lp-PLA(2) rather than by C-reactive protein. Lp-PLA(2) was associated with incident ischemic stroke independently of C-reactive protein and traditional cardiovascular risk factors among nonusers of hormone therapy with highest risk in those who had both high C-reactive protein and high Lp-PLA(2).
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PMID:Lipoprotein-associated phospholipase A2, hormone use, and the risk of ischemic stroke in postmenopausal women. 1825 35

Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice. Eicosapentaenoic acid supplementation provided improvement in schizophrenia patients, while the combination of (eicosapentaenoic acid + docosahexaenoic acid) provided benefit in bipolar disorders. The ketogenic diet where >90% of calories are derived from fat is an effective treatment for epilepsy. Understanding cytokine-induced changes in lipid metabolism will promote novel concepts and steer towards bench-to-bedside transition for therapies.
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PMID:Altered lipid metabolism in brain injury and disorders. 1875 14

Basic and animal research implicate inflammatory mechanisms in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Inflammatory biomarkers, particularly high-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2, have been identified as potential predictors of stroke risk and prognosis. Infections may also precipitate stroke. Medications, especially hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), reduce inflammatory marker levels independently of lipid effects, and the ability of statins to reduce coronary events and stroke correlates with their effect on inflammatory biomarkers. Vaccination against influenza may also reduce stroke risk. Determining whether reduction of biomarkers reduces risk of recurrent stroke, however, requires further study before inflammatory markers become a routine part of the evaluation of stroke patients.
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PMID:Inflammatory markers and stroke. 1909 Nov 70

Chondroitin sulphate (CS) is a natural glycosaminoglycan present in the extracellular matrix and is formed by the 1-3 linkage of D-glucuronic acid to N-acetylgalactosamine. In chondrocytes, CS diminishes interleukin-1 beta(IL-1beta)-induced increases in p38 mitogen-activated protein kinase (p38MAPK) and signal-regulated kinase 1/2 (Erk1/2) phosphorylation, and decreases nuclear factor-kappaB (NF-kappaB) nuclear translocation and as a consequence, reduces the formation of pro-inflammatory cytokines, IL-1beta and TNF-alpha, and pro-inflammatory enzymes, such as phospholipase A2 (PLA2), cyclooxygenase 2 (COX-2) and nitric oxide synthase-2 (NOS-2). The mechanism of action of CS explains its beneficial effect on the cartilage, synovial membrane and subchondral bone. On the other hand, in vivo, CS given orally prevents hepatic NF-kappaB nuclear translocation, suggesting that systemic CS may elicit an anti-inflammatory effect in many tissues besides the articulation. There is preliminary evidence showing that in human beings, CS may be of benefit in other diseases where inflammation is an essential marker, such as psoriasis and atherosclerosis. The review of the literature suggest that CS might also be of interest for the treatment of other diseases with an inflammatory and/or autoimmune character, such as inflammatory bowel disease, degenerative diseases of the central nervous system and stroke, multiple sclerosis and other autoimmune diseases.
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PMID:Immunomodulatory and anti-inflammatory effects of chondroitin sulphate. 1952 43

Cardiovascular disease (CVD) is the number one cause of death in both adult men and women. It is evident that active inflammation in the coronary arteries remains a key factor in plaque instability and subsequent cardiovascular events. The current clinical dilemma is that inflammation can occur even in patients who are on statin therapy, as well as in patients with "normal" cholesterol levels. Because fully half of all patients with cardiovascular events have normal cholesterol levels, there is a need to re-evaluate the role of inflammatory factors and biomarkers to better identify patients at risk. Current risk factors include C-reactive protein, fibrinogen, and platelet activator inhibitor-1. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is another emerging risk factor. The weight of evidence suggests that this biomarker also promotes vascular inflammation. Patients with higher levels of Lp-PLA2 have higher rates of CVD and stroke. Measurement of Lp-PLA2 can improve the identification of people at increased risk for CVD, independent of cholesterol, or C-reactive protein level. Lp-PLA2 has been an innovative target of immunomodulation therapy, and clinical studies with specific inhibitors are in progress evaluating this approach for both atherosclerosis development and clinical event reduction.
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PMID:Lipoprotein-associated phospholipase A2: an independent predictor of cardiovascular risk and a novel target for immunomodulation therapy. 1969 Apr 73

The inflammatory reaction is characterized by increased circulatory levels of various indicators of the severity of inflammation. The objective was to investigate the value of lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with noncardioembolic ischemic stroke and severe proinflammatory reaction. There were investigated prospectively Lp-PLA2 levels in sera from 47 patients with ischemic stroke and severe inflammatory reaction (32 men and 15 women, mean age 63 +/- 4.23 years) as compared to 38 patients with ischemic stroke without inflammatory reaction (21 men and 17 women, mean age 61 +/- 5.52 years) and 114 healthy elderly controls. Lp-PLA2 levels were assessed using the diaDexus PLAC test (a noncompetitive ELISA). Out of 47 patients with ischemic stroke and severe inflammatory reaction 36 presented Lp-PLA2 high levels (79%). Lp-PLA2 was detected with high levels in 17 out of 30 patients with ischemic stroke without inflammatory reaction (45%). Patients with ischemic stroke and severe inflammatory reaction presented Lp-PLA2 with high levels more frequently than the healthy controls (RR 12.1 [95% CI. 6.22 to 19.333], p<0.0001). Levels of Lp-PLA2 were higher in subjects who experienced a stroke as compared to controls. Lp-PLA2 is a strong predictor of recurrent stroke risk and of increased risk of dying. The determination of Lp-PLA2 should be used to predict patient risk of cardiovascular disease and stroke; it does provide additional risk of inflammation when used in conjunction with the traditional markers. Lp-PLA2 might be used not only for risk stratification of stroke patients, but also as target for treatment.
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PMID:Phospholipase A2 in patients with noncardioembolic ischemic stroke and severe inflammatory reaction. 1988 71

Innate inflammation plays an important role in the pathogenesis and progression of atherosclerosis, plaque rupture, thrombosis, and stroke. Inflammatory biomarkers related to innate inflammation, including acute phase proteins, may predict first stroke. The utility of high-sensitivity C-reactive protein and other related markers may diminish among populations with established vascular risk. Other biomarkers, including lipoprotein-associated phospholipase A2, may provide complementary information about prognosis after stroke or subclinical vascular disease. The innate immune system originally evolved to provide protection against bacterial infections. Moreover, infections may also contribute to stroke risk. Summary measures representing multiple chronic infections have been associated with risk of stroke and atherosclerosis. Acute infections, particularly respiratory infections, have also been found to serve as precipitants of stroke in recent epidemiological studies. These findings could have clinical implications. Further studies are needed to determine the role of innate inflammation and infection in stroke pathogenesis and prevention.
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PMID:Impact of innate inflammation in population studies. 2095 32

Secretory phospholipase A2 (sPLA2) is an enzyme that plays an important role in the pathogenesis of atherosclerosis and of adverse cardiovascular events. It is currently the target of emerging therapeutic agents. Our study was designed to investigate the effect of aggressive lowering of low-density lipoprotein (LDL) cholesterol with ezetimibe and atorvastatin on sPLA2 activity. We randomized 100 patients with stable coronary artery disease (CAD) or CAD equivalent (diabetes, stroke, or peripheral vascular disease) to receive ezetimibe 10 mg/day in association with atorvastatin 40 mg/day (combination therapy group) versus atorvastatin 40 mg/day and placebo (monotherapy group). Patients on statin therapy before inclusion were allowed to enter the study as long as the potency of the statin was lower than atorvastatin 40 mg/day. Lipid profile, high-sensitivity C-reactive protein (hs-CRP), and sPLA activity were measured at baseline and after 8 weeks of therapy. The decrease in LDL cholesterol was more significant in the combination therapy group, but the decrease in hs-CRP was similar. sPLA2 activity significantly decreased in the ezetimibe/atorvastatin group from 29 U/ml (interquartile range 23 to 35) to 26 U/ml (23 to 29, p = 0.001) but remained similar in the placebo/atorvastatin group (23 U/ml, 19 to 32, vs 22 U/ml, 19 to 28, p = NS). In a multivariate stepwise linear regression model, change in sPLA2 correlated with change in hs-CRP (p <0.001), baseline LDL cholesterol level (p = 0.001), body mass index (p = 0.003), diabetes mellitus (p = 0.04) and combination therapy with ezetimibe/atorvastatin (p = 0.05). In conclusion, this study demonstrates that coadministration of ezetimibe and atorvastatin decreases sPLA2 activity.
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PMID:Comparison of the effects of combination atorvastatin (40 mg) + ezetimibe (10 mg) versus atorvastatin (40 mg) alone on secretory phospholipase A2 activity in patients with stable coronary artery disease or coronary artery disease equivalent. 2143 29


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