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Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study.

ABSTRACT: inflammatory markers may be associated with recurrent vascular events after stroke. We aimed to determine the association between IL-6, C-reactive protein, fibrinogen and white cell count, with recurrent vascular events after stroke, and to compare the association between circulating inflammatory markers with the risk of death from vascular vs nonvascular causes.we prospectively recruited patients with acute stroke (n=817) and followed them for up to 4 years for the occurrence of fatal or nonfatal recurrent stroke, myocardial infarction or fatal vascular events, and death from any cause (n=159).the delay to assessment was a median of 10 days. The adjusted incidence of the outcome cluster recurrent stroke, myocardial infarction or vascular death after stroke was significantly higher with higher levels of IL-6 (75(th) to 25(th) percentile hazard ratio, 1.56; 95% CI, 1.37-1.77), C-reactive protein (75(th) to 25(th) percentile hazard ratio, 1.08; 95% CI, 1.04-1.11), and fibrinogen (75(th) to 25(th) percentile hazard ratio, 1.45; 95% CI, 1.24-1.72). The associations between inflammatory markers and death were stronger than with recurrent vascular events. The associations of inflammatory markers with vascular and nonvascular deaths were similar.although inflammatory markers were associated with an increased risk of recurrent vascular events and vascular death after stroke, they were also associated with nonvascular causes of death, suggesting that inflammatory markers do not play a causal role specifically in the generation of recurrent vascular events after stroke. Future studies of the prediction of recurrent vascular events after stroke should concentrate on clinical variables or different blood markers.

SUBMITTER: Whiteley W

PROVIDER: S-EPMC3016514 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study.

Whiteley William W Jackson Caroline C Lewis Steff S Lowe Gordon G Rumley Ann A Sandercock Peter P Wardlaw Joanna J Dennis Martin M Sudlow Cathie C

Stroke 20101202 1

<h4>Background and purpose</h4>inflammatory markers may be associated with recurrent vascular events after stroke. We aimed to determine the association between IL-6, C-reactive protein, fibrinogen and white cell count, with recurrent vascular events after stroke, and to compare the association between circulating inflammatory markers with the risk of death from vascular vs nonvascular causes.<h4>Methods</h4>we prospectively recruited patients with acute stroke (n=817) and followed them for up t ...[more]

PMID: 21127302

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Project description:BACKGROUND:Major adverse cardiovascular events are the main cause of morbidity and mortality over the long term in patients undergoing carotid endarterectomy. There are few reports assessing the prognostic value of markers of inflammation in relation to the risk of cardiovascular disease after carotid endarterectomy. Here, we aimed to determine whether matrix metalloproteinases (MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10), tissue inhibitor of MMPs (TIMP-1) and in vivo inflammation studied by 18F-FDG-PET/CT predict recurrent cardiovascular events in patients with carotid stenosis who underwent endarterectomy. METHODS:This prospective cohort study was carried out on 31 consecutive patients with symptomatic (23/31) or asymptomatic (8/31) severe (>?70%) carotid stenosis who were scheduled for carotid endarterectomy between July 2013 and March 2016. In addition, 26 healthy controls were included in the study. Plasma and serum samples were collected 2?days prior to surgery and tested for MMP-1, MMP-2, MMP-7, MMP-9, MMP-10, TIMP-1, high-density lipoprotein, low-density lipoprotein, high-sensitivity C-reactive protein and erythrocyte sedimentation rate. 18F-FDG-PET/CT focusing on several territories' vascular wall metabolism was performed on 29 of the patients because of no presurgical availability in 2 symptomatic patients. Histological and immunohistochemical studies were performed with antibodies targeting MMP-10, MMP-9, TIMP-1 and CD68. RESULTS:The patients with carotid stenosis had significantly more circulating MMP-1, MMP-7 and MMP-10 than the healthy controls. Intraplaque TIMP-1 was correlated with its plasma level (r?=?0.42 P?=?.02) and with 18F-FDG uptake (r?=?0.38 P?=?.05). We did not find any correlation between circulating MMPs and in vivo carotid plaque metabolism assessed by 18F-FDG-PET. After a median follow-up of 1077?days, 4 cerebrovascular, 7 cardiovascular and 11 peripheral vascular events requiring hospitalization were registered. Circulating MMP-7 was capable of predicting events over and above the traditional risk factors (HR?=?1.15 P?=?.006). When the model was associated with the variables of interest, the risk predicted by 18F-FDG-PET was not significant. CONCLUSIONS:Circulating MMP-7 may represent a novel marker for recurrent cardiovascular events in patients with moderate to severe carotid stenosis. MMP-7 may reflect the atherosclerotic burden but not plaque inflammation in this specific vascular territory.

Project description:BackgroundThe objective of this study was to determine whether: (a) markers of acute inflammation (white cell count, glucose, interleukin-6, C-reactive protein, and fibrinogen) are associated with poor outcome after stroke and (b) the addition of markers to previously validated prognostic models improves prediction of poor outcome.Methods and findingsWe prospectively recruited patients between 2002 and 2005. Clinicians assessed patients and drew blood for inflammatory markers. Patients were followed up by postal questionnaire for poor outcome (a score of>2 on the modified Rankin Scale) and death through the General Register Office (Scotland) at 6 mo. We performed a systematic review of the literature and meta-analysis of the association between interleukin-6 and poor outcome after stroke to place our study in the context of previous research. We recruited 844 patients; mortality data were available in 844 (100%) and functional outcome in 750 (89%). After appropriate adjustment, the odds ratios for the association of markers and poor outcome (comparing the upper and the lower third) were interleukin-6, 3.1 (95% CI: 1.9-5.0); C-reactive protein, 1.9 (95% CI: 1.2-3.1); fibrinogen, 1.5 (95% CI: 1.0-2.36); white cell count, 2.1 (95% CI: 1.3-3.4); and glucose 1.3 (95% CI: 0.8-2.1). The results for interleukin-6 were similar to other studies. However, the addition of inflammatory marker levels to validated prognostic models did not materially improve model discrimination, calibration, or reclassification for prediction of poor outcome after stroke.ConclusionsRaised levels of markers of the acute inflammatory response after stroke are associated with poor outcomes. However, the addition of these markers to a previously validated stroke prognostic model did not improve the prediction of poor outcome. Whether inflammatory markers are useful in prediction of recurrent stroke or other vascular events is a separate question, which requires further study. Please see later in the article for the Editors' Summary.

Project description:BackgroundLow-grade inflammation is associated with depression, but studies of specific symptoms are relatively scarce. Association between inflammatory markers and specific symptoms may provide insights into potential mechanism of inflammation-related depression. Using longitudinal data, we have tested whether childhood serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels are associated with specific depressive symptoms in early adulthood.MethodsIn the ALSPAC birth cohort, serum IL-6 and CRP levels were assessed at age 9 years and 19 depressive symptoms were assessed at age 18 years. We used modified Poisson generalised linear regression with robust error variance to estimate the risk ratio (RR) and 95% confidence interval (95% CI) for each depressive symptom. In addition, we used confirmatory factor analysis to create two continuous latent variables representing somatic/neurovegetative and psychological dimension scores. Structural equation modelling was used to test the associations between IL-6 and these dimension scores.ResultsBased on data from 2731 participants, IL-6 was associated with diurnal mood variation, concentration difficulties, fatigue and sleep disturbances. The adjusted RRs for these symptoms at age 18 years for participants in top, compared with bottom, third of IL-6 at age 9 years were 1.75 (95% CI, 1.13-2.69) for diurnal mood variation, 1.50 (95% CI, 1.11-2.02) for concentration difficulties, 1.31 (95% CI, 1.12-1.54) for fatigue, and 1.24 (95% CI, 1.01-1.52) for sleep disturbances. At dimension level, IL-6 was associated with both somatic/neurovegetative (β = 0.059, SE = 0.024, P = 0.013) and psychological (β = 0.056, SE = 0.023, P = 0.016) scores.ConclusionsInflammation is associated with specific symptoms of depression. Associations with so-called somatic/neurovegetative symptoms of depression such as fatigue, sleep disturbances and diurnal mood variation indicate that these symptoms could be useful treatment targets and markers of treatment response in clinical trials of anti-inflammatory treatment for depression.

Project description:OBJECTIVES:To evaluate whether the association between migraine with aura and increased risk of cardiovascular disease is modified by vascular risk groups as measured by the Framingham risk score for coronary heart disease. DESIGN:Prospective cohort study. SETTING:Women's health study, United States. PARTICIPANTS:27 519 women who were free from cardiovascular disease at baseline with available information on the Framingham risk score and migraine status. MAIN OUTCOME MEASURES:Time to major cardiovascular disease event (non-fatal myocardial infarction, non-fatal ischaemic stroke, death from ischaemic cardiovascular disease), myocardial infarction, and ischaemic stroke. RESULTS:At baseline, 3577 (13.0%) women reported active migraine, of whom 1418 (39.6%) reported migraine with aura. During 11.9 years of follow-up, there were 697 cardiovascular disease events. We stratified participants based on 10 year risk of coronary heart disease estimated from the Framingham risk score (<or=1%, 2-4%, 5-9%, and >or=10%). Compared with women without migraine, the age adjusted hazard ratios in women with active migraine with aura were 1.93 (95% confidence interval 1.45 to 2.56) for major cardiovascular disease, 1.80 (1.16 to 2.79) for ischaemic stroke, and 1.94 (1.27 to 2.95) for myocardial infarction. When stratified by Framingham risk score, the association between migraine with aura and major cardiovascular disease was strongest in the lowest risk score group. There was a diametric association pattern for ischaemic stroke and myocardial infarction. Compared with women without migraine, the age adjusted hazard ratios in women who reported migraine with aura in the lowest Framingham risk score group were 3.88 (1.87 to 8.08) for ischaemic stroke and 1.29 (0.40 to 4.21) for myocardial infarction. Hazard ratios in women with migraine with aura in the highest Framingham risk score group were 1.00 (0.24 to 4.14) for ischaemic stroke and 3.34 (1.50 to 7.46) for myocardial infarction. Women with migraine without aura were not at increased risk of ischaemic stroke or myocardial infarction in any of the Framingham risk score groups. CONCLUSION:The association between migraine with aura and cardiovascular disease varies by vascular risk status. Information on history of migraine and vascular risk status might help to identify women at increased risk for specific future cardiovascular disease events. TRIAL REGISTRATION:Clinical trials NCT00000479.

Project description:BackgroundAn increasing body of evidence suggests that inflammation plays a key role in stroke, in particular stroke of atherosclerotic origin. Anti-inflammatory medications are a widely heterogeneous group of drugs that are used to suppress the innate inflammatory pathway and thus prevent persistent or recurrent inflammation. Anti-inflammatory agents have the potential to stabilise atherosclerotic plaques by impeding the inflammatory pathway. By targeting specific cytokines, the inflammatory pathway may be interrupted at various stages.ObjectivesTo assess the benefits and harms of anti-inflammatory medications plus standard care versus standard care with or without placebo for prevention of vascular events (stroke, myocardial infarction (MI), non-fatal cardiac arrest, unstable angina requiring revascularisation, vascular death) and all-cause mortality in people with a prior history of ischaemic stroke or transient ischaemic attack (TIA).Search methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL; last searched 29 May 2019); MEDLINE (1948 to 29 May 2019); Embase (1980 to 29 May 2019); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 29 May 2019); and Scopus (1995 to 29 May 2019). In an effort to identify additional published, unpublished, and ongoing trials, we searched several grey literature sources (last searched 30 May 2019). We incorporated all identified studies into the results section. We applied no restrictions with respect to language, date of publication, or study setting.Selection criteriaWe considered randomised controlled trials (RCTs) and cluster-randomised controlled trials that evaluated anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA.Data collection and analysisTwo review authors independently assessed for inclusion titles and abstracts of studies identified by the search. Two review authors independently reviewed full-text articles for inclusion in this review. We planned to assess risk of bias and to apply the GRADE method.Main resultsWe identified no studies that met the inclusion criteria.Authors' conclusionsThere is currently a paucity of evidence on the use of anti-inflammatory medications for prevention of major cardiovascular events following ischaemic stroke or TIA. RCTs are needed to assess whether use of anti-inflammatory medications in this setting is beneficial.

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Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study.

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Association of circulating inflammatory markers with recurrent vascular events after stroke: a prospective cohort study.

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