scholarly journals Calprotectin predicts mortality after ischemic stroke and is present in the thrombus

2020 ◽  
Author(s):  
Juan Marta-Enguita ◽  
Manuel Navarro-Oviedo ◽  
Idoia Rubio-Baines ◽  
Nuria Aymerich ◽  
Maria Herrera ◽  
...  

Abstract Background- Inflammatory response plays an important role in many processes related to acute ischemic stroke (AIS). Calprotectin (S100A8/S100A9), released by monocytes and neutrophils, is a key protein in the regulation of inflammation and thrombosis. The purpose of this study is to evaluate the association of circulating calprotectin with other inflammatory biomarkers and AIS prognosis, as well as the calprotectin content in stroke thrombi.Methods- Among the 748 patients treated at a comprehensive stroke centre between 2015-2017, 413 patients with confirmed acute ischemic injury were evaluated. Patients with systemic inflammation or infection at onset were excluded. Plasma calprotectin was measured by ELISA in blood samples of AIS patients within the first 24h. Univariate and multivariate logistic regression models were performed to evaluate its association with mortality and functional independence (FI) at 3-months (defined as modified Rankin Scale<2), and intracranial haemorrhage (ICH) after stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n=44). Results- Higher calprotectin levels were associated with 3-month mortality and ICH, while lower calprotectin levels were documented in patients with 3-month FI. After adjusting for potential confounders, plasma calprotectin levels remained associated with 3-month mortality [OR (95%CI); 3.06, (1.67-5.61)]. Patients with calprotectin≥2.26 µg/mL were 4-times more likely to die [OR 3.98, (1.88-8.41)]. Likewise, Neutrophil-Lymphocyte Ratio (NLR) and C-Reactive Protein (CRP) were also associated with 3-month mortality [OR 1.98, (1.17-3.35); and 1.39, (1.02-1.89) respectively]. A multimarker approach demonstrated that patients with increased calprotectin, CRP and NLR had the poorest outcome with a mortality rate of 42.3% during follow-up. S100A9 protein, as part of the heterodimer calprotectin, was present in all thrombi retrieved from AIS patients. Mean S100A9 content was 3.5% and tended to be higher in patients who died (p=0.09). Moreover, it positively correlated with platelets (Pearson r 0.46, p<0.002); leukocytes (0.45, p<0.01) and neutrophil elastase (0.70, p<0.001) thrombi content. Conclusions- Plasma calprotectin is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with poor outcome after AIS. Presence of S100A9 in stroke thrombi suggests a possible inflammatory mechanism in clot formation and further studies are needed to determine its influence in resistance to reperfusion.

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Juan Marta-Enguita ◽  
Manuel Navarro-Oviedo ◽  
Idoia Rubio-Baines ◽  
Nuria Aymerich ◽  
Maria Herrera ◽  
...  

Abstract Background Inflammatory response plays an important role in many processes related to acute ischemic stroke (AIS). Calprotectin (S100A8/S100A9), released by monocytes and neutrophils, is a key protein in the regulation of inflammation and thrombosis. The purpose of this study is to evaluate the association of circulating calprotectin with other inflammatory biomarkers and AIS prognosis, as well as the calprotectin content in stroke thrombi. Methods Among the 748 patients treated at a comprehensive stroke center between 2015 and 2017, 413 patients with confirmed acute ischemic injury were prospectively evaluated. Patients with systemic inflammation or infection at onset were excluded. Plasma calprotectin was measured by ELISA in blood samples of AIS patients within the first 24 h. Univariate and multivariate logistic regression models were performed to evaluate its association with mortality and functional independence (FI) at 3 months (defined as modified Rankin Scale < 3) and hemorrhagic transformation (HT) after ischemic stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n = 44). Results Higher calprotectin levels were associated with 3-month mortality, HT, and lower 3-month FI. After adjusting for potential confounders, plasma calprotectin remained associated with 3-month mortality [OR (95% CI) 2.31 (1.13–4.73)]. Patients with calprotectin ≥ 2.26 μg/mL were 4 times more likely to die [OR 4.34 (1.95–9.67)]. Addition of calprotectin to clinical variables led to significant improvement in the discrimination capacity of the model [0.91 (0.87–0.95) vs 0.89 (0.85–0.93); p < 0.05]. A multimarker approach demonstrated that patients with increased calprotectin, CRP, and NLR had the poorest outcome with a mortality rate of 42.3% during follow-up. S100A9 protein, as part of the heterodimer calprotectin, was present in all thrombi retrieved from AIS patients. Mean S100A9 content was 3.5% and tended to be higher in patients who died (p = 0.09). Moreover, it positively correlated with platelets (Pearson r 0.46, p < 0.002), leukocytes (0.45, p < 0.01), and neutrophil elastase (0.70, p < 0.001) thrombus content. Conclusions Plasma calprotectin is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with poor outcome after AIS. The presence of S100A9 in stroke thrombi suggests a possible inflammatory mechanism in clot formation, and further studies are needed to determine its influence in resistance to reperfusion.


Author(s):  
Andriy Zhydkov ◽  
Mirjam Christ-Crain ◽  
Robert Thomann ◽  
Claus Hoess ◽  
Christoph Henzen ◽  
...  

AbstractThe added value of biomarkers, such as procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC), as adjuncts to clinical risk scores for predicting the outcome of patients with community-acquired pneumonia (CAP) is in question. We investigated the prognostic accuracy of initial and follow-up levels of inflammatory biomarkers in predicting death and adverse clinical outcomes in a large and well-defined cohort of CAP patients.We measured PCT, CRP and WBC on days 1, 3, 5, and 7 and followed the patients over 30 days. We applied multivariate regression models and area under the curve (AUC) to investigate associations between these biomarkers, the clinical risk score CURB-65, and clinical outcomes [i.e., death and intensive care unit (ICU) admission].Of 925 patients with CAP, 50 patients died and 118 patients had an adverse clinical outcome. None of the initial biomarker levels significantly improved the CURB-65 score for mortality prediction. Follow-up biomarker levels showed significant independent association with mortality at days 3, 5, and 7 and with improvements in AUC. Initial PCT and CRP levels were independent prognostic predictors of adverse clinical outcome, and levels of all biomarkers during the course of disease provided additional prognostic information.This study provides robust insights into the added prognostic value of inflammatory markers in CAP. Procalcitonin, CRP, and to a lesser degree WBC provided some prognostic information on CAP outcomes, particularly when considering their kinetics at days 5 and 7 and when looking at adverse clinical outcomes instead of mortality alone.


Author(s):  
Mahmoud Elbelkimy ◽  
Naglaa ELkhayat ◽  
Ahmed ElSadek ◽  
Alia Mansour ◽  
Mariam Aboutaleb

Abstract Background Elevated CRP and increased CCA-IMT are both associated with the occurrence of stroke. CRP and IMT are closely associated; the higher the CRP, the greater the carotid atherosclerosis as measured by carotid IMT. Objectives To study the relationship between elevated C-reactive protein as a blood biomarker and increased intimal media thickness of carotid artery, and its relation to infarct size and its impact on prognosis. Materials and methods This study is an analytical observational study, in which 73 patients who have recently suffered first-ever acute ischemic stroke in the anterior circulation within 72 h were recruited. Only 64 of them were able to continue the study with follow-up during the 1 month and 3 months durations. Magnetic resonance imaging for the brain was done and the infarct volume was measured. All patients had quantitative Serum CRP level within 72 h from stroke onset and carotid duplex with assessment of carotid intimal media thickness (IMT). Results The results showed there is a significant positive correlation between highly sensitive C-reactive protein (hs-CRP) and MRS after 1 month yet no significant correlation was found between hs-CRP and IMT. Conclusion Highly sensitive C-reactive protein (hs-CRP) could serve as prognostic blood biomarker in long-term follow-up of stroke patients. Non-significant correlation was found in our study between increased hs-CRP and increased intima-media thickness (CCA-IMT).


Author(s):  
Tissi Liskawini Putri ◽  
Ratna Akbari Ganie ◽  
Aldy S. Rambe

Proses inflamasi merupakan perjalanan penyakit dari strok iskemik akut, yang melibatkan penumpukan mediator inflamasi daninfiltrasi leukosit. Nilai Rasio Neutrofil-Limfosit (RNL) di beberapa penelitian dapat digunakan untuk meramalkan strok akibat iskemikakut yang caranya mudah dilakukan. High sensitivity C Reactive Protein (hs-CRP) merupakan reaktan tahap akut yang kadarnyameningkat di strok iskemik. Oleh karena itu bermanfaat sebagai petanda peramal hal terkait. Penelitian ini bertujuan untuk mengetahuiperbedaan nilai antara RNL dan hs-CRP dalam meramalkan hasilan pasien strok iskemik akut. Metode penelitian analitik observasionaldengan rancangan kohort prospektif. Hasil dinilai dengan modified Rankin Scale (mRS) (1–2=baik; 3–6=buruk) dan Barthel Index (BI)(0–20=ketergantungan jumlah keseluruhan, 21-60=berat; 1–90=sedang; 91–99=ringan dan 100=normal). Dari 43 sampel, didapatkanlaki-laki 24 orang (55,8%) dan perempuan 19 orang (44,2%) dengan rerata usia 57,12 ± 9,8 tahun. hubungan positif didapatkansedang dan bermakna antara RNL dengan hasilan mRS dan BI pasien strok iskemik akut (r=0,585; p=0,001 dan r=0,564; p=0,001).Hubungan positif didapatkan kuat dan bermakna antara hs-CRP dan hasilan mRS (r=0,614; p=0,001) serta didapatkan hubunganpositif dengan kekuatan sangat kuat dan bermakna antara hs-CRP dan hasilan n BI pasien strok iskemik akut (r=0,881; p=0,001).Dengan membandingkan ketepatan kedua data didapatkan RNL 86% dan hs-CRP 88% (p=0,6554). Perbedaan tidak bermakna terdapatantara nilai RNL dan hs-CRP sebagai peramal hasilan pasien strok iskemik akut.


2012 ◽  
Vol 82 (1) ◽  
pp. 41-52 ◽  
Author(s):  
P. Earnest ◽  
S. Kupper ◽  
M. Thompson ◽  
Guo ◽  
S. Church

Homocysteine (HCY), C-reactive protein (hsCRP), and triglycerides (TG) are risk factors for cardiovascular disease (CVD). While multivitamins (MVit) may reduce HCY and hsCRP, omega-3 fatty acids (N3) reduce TG; yet, they are seldom studied simultaneously. We randomly assigned 100 participants with baseline HCY (> 8.0 umol/L) to the daily ingestion of: (1) placebo, (2) MVit (VitC: 200 mg; VitE: 400 IU; VitB6: 25 mg; Folic Acid: 400 ug; VitB12: 400 ug) + placebo, (3) N3 (2 g N3, 760 mg EPA, 440 mg DHA)+placebo, or (4) MVit + N3 for 12 weeks. At follow-up, we observed significant reductions in HCY (umol/L) for the MVit (- 1.43, 95 %CI, - 2.39, - 0.47) and MVit + N3 groups (- 1.01, 95 %CI, - 1.98, - 0.04) groups, both being significant (p < 0.05) vs. placebo (- 0.57, 95 %CI, - 1.49, 0.35) and N3 (1.11, 95 % CI, 0.07, 2.17). hsCRP (nmol/L) was significantly reduced in the MVit (- 6.00, 95 %CI, - 1.04, - 0.15) and MVit + N3 (- 0.98, 95 %CI, - 1.51, - 0.46) groups, but not vs. placebo (- 0.15, 95 %CI, - 0.74, 0.43) or N3 (- 0.53, 95 %CI, - 1.18, 0.12). Lastly, we observed significant reductions in TG for the N3 (- 0.41, 95 %CI, - 0.69, - 0.13) and MVit + N3 (- 0.71, 95 %CI, - 0.93, - 0.46) groups, both significant vs. placebo (- 0.10, 95 %CI, - 0.36, 0.17) and MVit groups (0.15, 95 %CI, - 12, 0.42). The co-ingestion of MVit + N3 provides synergistic affects on HCY, hsCRP, and plasma TG.


VASA ◽  
2017 ◽  
Vol 46 (3) ◽  
pp. 187-192 ◽  
Author(s):  
Aleš Pleskovič ◽  
Marija Šantl Letonja ◽  
Andreja Cokan Vujkovac ◽  
Jovana Nikolajević Starčević ◽  
Katarina Gazdikova ◽  
...  

Abstract. Background: This prospective study was designed to evaluate the effect of inflammatory markers on the presence and progression of subclinical markers of carotid atherosclerosis in a 3.8-year follow-up period in patients with type 2 diabetes mellitus (T2DM). Patients and methods: A total of 595 subjects with T2DM were enrolled. Subclinical markers of carotid atherosclerosis (carotid intima media thickness (CIMT), plaque thickness, and plaques presence) were assessed with ultrasound at the time of recruitment and again after 3.8 years. Subjects with T2DM were divided into 2 groups according to the plasma high sensitive C-reactive protein (hs-CRP) levels (subjects with hs-CRP ≥ 2 mg/L and subjects with hs-CRP below 2 mg/L). Results: Subjects with T2DM and hs-CRP levels ≥ 2 mg/L had higher CIMT in comparison with subjects with T2DM and hs-CRP levels below 2 mg/L, and higher incidence of plaques/unstable plaques in comparison with subjects with T2DM and hs-CRP levels below 2 mg/L. Multivariate logistic regression analysis found the association between the HDL cholesterol level and presence of plaques, whereas the inflammatory marker hs-CRP was not associated with subclinical markers of progression of carotid atherosclerosis. Multiple linear regression analysis found the association between the hs-CRP levels and either CIMT progression rate or a change in the number of sites with plaques in a 3.8-year follow-up. Conclusions: We demonstrated an association between the inflammatory marker hs-CRP and either CIMT or incidence of plaques/unstable plaques at the time of recruitment in Caucasians with T2DM. Moreover, we found the association between hs-CRP levels and either CIMT progression rate or a change in the number of sites with plaques in a 3.8-year follow-up in subjects with T2DM.


2020 ◽  
Vol 17 ◽  
Author(s):  
Shiling Chen ◽  
Chao Pan ◽  
Ping Zhang ◽  
Yingxin Tang ◽  
Zhouping Tang

Abstract:: Acute Ischemic Stroke (AIS) is currently the most frequently reported neurological complication of Coronavirus disease 2019 (COVID-19). This article will elaborate on the clinical features of inpatients with COVID-19 and AIS and the pathophysiological mechanism of AIS under the background of COVID-19. Through a detailed search of relevant studies, we found that the incidence of AIS among COVID-19 patients varied from 0.9% to 4.6%, and AIS has been observed in many people without underlying diseases and cardiovascular risk factors as well as young people. The National Institute of Health Stroke Scale (NIHSS) score of COVID-19 patients with AIS was higher than historical AIS patients, and the proportion of large vessel occlusion (LVO) was about 64.2%. COVID-19 patients with AIS have commonly high levels of D-D dimer, fibrinogen, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR), suggesting systemic hyperinflammatory and hypercoagulable state. The pooled mortality of COVID-19 patients with AIS was 38% and the mortality of LVO patients is higher (45.9%). Compared with COVID-19-negative AIS patients in the same period in 2020 and 2019, COVID- 19 patients with AIS had a worse prognosis.


2021 ◽  
pp. 1-9
Author(s):  
Murat Yildirim ◽  
Bulent Koca

BACKGROUND: Lymphocyte-to-C-reactive protein ratio (LCR) has been used as a post-surgical prognostic biomarker in patients with gastric and colorectal cancer. However, its relationship with early postoperative complications in these patients is unknown. In this study, we aimed to reveal the relationship between LCR and postoperative complications. METHODS: Eighty-one patients operated for stomach and colorectal cancer between January 2020 and August 2020 were prospectively analyzed. On preoperative and postoperative days 1, 3 and 5, other inflammatory parameters, mainly LCR, neutrophil lymphocyte ratio (NLR), were recorded. The patients were divided into two groups according to Clavien-Dindo classification as stage III and higher complications major, stage I-II/non-complication minor. RESULTS: Fifty seven patients were operated for colorectal cancer, 24 patients for gastric cancer. The mean age of the patients was 65.6 ± 12.6, 34.6% of them was women. Age, operation time and hospital stay were significantly different between the groups (p= 0.004, p= 0.002, p< 0.001). Major complications developed in 18 patients. On postoperative day 5, LCR found superior diagnostic accuracy in predicting major postoperative complications compared to other inflammatory markers. On the postoperative 5th day, the cut-off value of LCR was 0.0034, 88.8% (71.9–94.8) sensitivity, and 85.7% (73.6–95.4) selectivity. CONCLUSION: Among different inflammatory markers, postoperative LCR is a safe and effective predictor of postoperative complications, especially after gastric and colorectal cancer surgery on day 5.


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