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Laboratory abnormalities in children with mild and severe coronavirus disease 2019 (COVID-19): A pooled analysis and review.
Henry, BM, Benoit, SW, de Oliveira, MHS, Hsieh, WC, Benoit, J, Ballout, RA, Plebani, M, Lippi, G
Clinical biochemistry. 2020;:1-8
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Abstract
Limited data exists to-date on the laboratory findings in children with COVID-19, warranting the conduction of this study, in which we pool the currently available literature data on the laboratory findings seen in children with mild and severe COVID-19. Following an extensive literature search, we identified 24 eligible studies, including a total of 624 pediatric cases with laboratory-confirmed COVID-19, which report data on 27 different biomarkers. We then performed a meta-analysis to calculate the pooled prevalence estimates (PPE) for these laboratory abnormalities in mild COVID-19. As data was too limited for children with severe COVID-19 to allow pooling, results were presented descriptively in a summary of findings table. Our data show an inconsistent pattern of change in the leukocyte index of mild and severe cases of COVID-19 in children. Specifically, changes in leukocyte counts were only observed in 32% of the mild pediatric cases (PPE: 13% increase, 19% decrease). In mild disease, creatine kinase-MB (CK-MB) was frequently elevated, with a PPE of 33%. In severe disease, c-reactive protein (CRP), procalcitonin (PCT), and lactate dehydrogenase (LDH) were frequently elevated. Based on data obtained from early COVID-19 studies, leukocyte indices in children appear inconsistent, differing from those reported in adults that highlight specific leukocyte trends. This brings into question the utility and reliability of such parameters in monitoring disease severity in the pediatric population. Instead, we suggest physicians to serially monitor CRP, PCT, and LDH to track the course of illness in hospitalized children. Finally, elevated CK-MB in mild pediatric COVID-19 cases is indicative of possible cardiac injury. This highlights the importance of monitoring cardiac biomarkers in hospitalized patients and the need for further investigation of markers such as cardiac troponin in future studies.
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Anti-inflammatory Therapies for Cardiovascular Disease: Signaling Pathways and Mechanisms.
Martínez-Hervás, S, González-Navarro, H
Revista espanola de cardiologia (English ed.). 2019;(9):767-773
Abstract
Cardiovascular diseases (CVD) are the clinical manifestation of atherosclerosis, a chronic inflammatory disease promoted by several risk factors such as dyslipidemia, type 2 diabetes mellitus, hypertension, and smoking. Acute CVD events are the result of an unresolved inflammatory chronic state that promotes the rupture of unstable plaque lesions. Of note, the existing intensive therapies modify risk factors but do not prevent life-threatening recurrent ischemic events in high-risk patients, who have a residual inflammatory risk displayed by increased C-reactive protein (CRP) levels. Better understanding of the role of innate and adaptive immunity in plaque development and rupture has led to intensive investigation of anti-inflammatory strategies for CVD. Some of them are being tested in specific clinical trials and use lower doses of existing medications originally developed for other inflammatory diseases such as rheumatoid arthritis and psoriasis, which have high CVD risk. Other investigations are retrospective and meta-analyses of existing clinical trials that evaluate the incidence of CVD in these inflammatory diseases. Others are based on preclinical testing such as vaccines. In this article, we summarize the main anti-inflammatory strategies and associated molecular mechanisms that are being evaluated in preclinical or clinical CVD studies.
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Markers of Atherosclerosis: Part 1 - Serological Markers.
Tibaut, M, Caprnda, M, Kubatka, P, Sinkovič, A, Valentova, V, Filipova, S, Gazdikova, K, Gaspar, L, Mozos, I, Egom, EE, et al
Heart, lung & circulation. 2019;(5):667-677
Abstract
Atherosclerosis is a major contributor to morbidity and mortality worldwide. With therapeutic consequences in mind, several risk scores are being used to differentiate individuals with low, intermediate or high cardiovascular (CV) event risk. The most appropriate management of intermediate risk individuals is still not known, therefore, novel biomarkers are being sought to help re-stratify them as low or high risk. This narrative review is presented in two parts. Here, in Part 1, we summarise current knowledge on serum (serological) biomarkers of atherosclerosis. Among novel biomarkers, high sensitivity C-reactive protein (hsCRP) has emerged as the most promising in chronic situations, others need further clinical studies. However, it seems that a combination of serum biomarkers offers more to risk stratification than either biomarker alone. In Part 2, we address genetic and imaging markers of atherosclerosis, as well as other developments relevant to risk prediction.
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Nontraditional Risk Factors in Cardiovascular Disease Risk Assessment: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.
Lin, JS, Evans, CV, Johnson, E, Redmond, N, Coppola, EL, Smith, N
JAMA. 2018;(3):281-297
Abstract
IMPORTANCE Incorporating nontraditional risk factors may improve the performance of traditional multivariable risk assessment for cardiovascular disease (CVD). OBJECTIVE To systematically review evidence for the US Preventive Services Task Force on the benefits and harms of 3 nontraditional risk factors in cardiovascular risk assessment: the ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) level, and coronary artery calcium (CAC) score. DATA SOURCES MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for studies published through May 22, 2017. Surveillance continued through February 7, 2018. STUDY SELECTION Studies of asymptomatic adults with no known cardiovascular disease. DATA EXTRACTION AND SYNTHESIS Independent critical appraisal and data abstraction by 2 reviewers. MAIN OUTCOMES AND MEASURES Cardiovascular events, mortality, risk assessment performance measures (calibration, discrimination, or risk reclassification), and serious adverse events. RESULTS Forty-three studies (N = 267 244) were included. No adequately powered trials have evaluated the clinical effect of risk assessment with nontraditional risk factors on patient health outcomes. The addition of the ABI (10 studies), hsCRP level (25 studies), or CAC score (19 studies) can improve both discrimination and reclassification; the magnitude and consistency of improvement varies by nontraditional risk factor. For the ABI, improvements in performance were the greatest for women, in whom traditional risk assessment has poor discrimination (C statistic change of 0.112 and net reclassification index [NRI] of 0.096). Results were inconsistent for hsCRP level, with the largest analysis (n = 166 596) showing a minimal effect on risk prediction (C statistic change of 0.0039, NRI of 0.0152). The largest improvements in discrimination (C statistic change ranging from 0.018 to 0.144) and reclassification (NRI ranging from 0.084 to 0.35) were seen for CAC score, although CAC score may inappropriately reclassify individuals not having cardiovascular events into higher-risk categories, as determined by negative nonevent NRI. Evidence for the harms of nontraditional risk factor assessment was limited to computed tomography imaging for CAC scoring (8 studies) and showed that radiation exposure is low but may result in additional testing. CONCLUSIONS AND RELEVANCE There are insufficient adequately powered clinical trials evaluating the incremental effect of the ABI, hsCRP level, or CAC score in risk assessment and initiation of preventive therapy. Furthermore, the clinical meaning of improvements in measures of calibration, discrimination, and reclassification risk prediction studies is uncertain.
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Effects of conjugated linoleic acid supplementation on serum C-reactive protein: A systematic review and meta-analysis of randomized controlled trials.
Mazidi, M, Karimi, E, Rezaie, P, Ferns, GA
Cardiovascular therapeutics. 2017;(6)
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Abstract
AIM: To undertake a systematic review and meta-analysis of prospective studies to determine the effect of conjugated linoleic acids (CLAs) supplementation on serum C-reactive protein (CRP). METHOD PubMed-Medline, Web of Science, Cochrane Database, and Google Scholar databases were searched (up until May 2016) to identify prospective studies evaluating the impact of CLAs supplementation on serum CRP. Random-effects models meta-analysis was used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Heterogeneity was quantitatively assessed using the I2 index. Systematic review registration: CRD42016038945. RESULTS From a total of 85 entries identified via searches, 14 studies were included in the final selection. The meta-analysis indicated a significant increase in serum CRP concentrations following supplementation with CLAs (weighted mean difference [WMD] 0.63 mg/dL, 95% confidence interval [95% CI] 0.13-1.13, N=21 arms, heterogeneity P=.026; I2 =52.3%). These findings were robust in sensitivity analyses. Random-effects meta-regression revealed that changes in serum CRP levels were independent of the dosage of CLAs supplementation (slope: -0.02; 95% CI: -0.10, 0.12; P=.889) or duration of follow-up (slope: 0.271; 95% CI: -0.05, 0.59; P=.098). CONCLUSIONS This meta-analysis suggests that CLA supplementation is associated with an increase in plasma CRP concentrations and a reduction in serum adiponectin concentrations, which indicates that CLA supplements have a proinflammatory effect. Randomized control trials with larger sample size and a longer follow-up period may be required for future investigations to provide an unequivocal answer.
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Effects of supplementation with quercetin on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials.
Mohammadi-Sartang, M, Mazloom, Z, Sherafatmanesh, S, Ghorbani, M, Firoozi, D
European journal of clinical nutrition. 2017;(9):1033-1039
Abstract
Promising experimental studies suggest that quercetin has potential anti-inflammatory effects. However, the results of current clinical trials on quercetin's effects on the C-reactive protein (CRP), a sensitive inflammatory biomarker, are ambiguous. We conducted a meta-analysis of available randomized controlled trials (RCTs) to resolve this inconsistency and quantify the net effect of quercetin on circulating CRP concentrations. A systematic search was performed in several databases including SCOPUS, PubMed-Medline and Google Scholar until 16 June 2016. We used a random-effects model in combination with weight mean difference (WMD) and 95% confidence intervals (CI) for data analysis. Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis and publication bias. The meta-analysis of seven RCTs (10 treatment arms) showed a significant reduction of circulating CRP levels (WMD: -0.33 mg/l; 95% CI: -0.50 to -0.15; P<0.001) following quercetin supplementation. In the subgroup analysis, a significant reducing effect was observed in trials with ⩾500 mg/day dosage (WMD: -0.34 mg/l; 95% CI: -0.52, -0.16; P⩽0.001) and in those with CRP <3 mg/l (WMD: -0.34 mg/l; 95% CI: -0.51, -0.18; P⩽0.001). In meta-regression, there was no association between changes in CRP concentrations, dose of supplementation and CRP baseline values. Our findings showed a significant effect of quercetin supplementation on the C-reactive protein-especially at doses above 500 mg/day and in patients with CRP <3 mg/l.
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The effects of red yeast rice dietary supplement on blood pressure, lipid profile, and C-reactive protein in hypertension: A systematic review.
Xiong, X, Wang, P, Li, X, Zhang, Y, Li, S
Critical reviews in food science and nutrition. 2017;(9):1831-1851
Abstract
Interest is increasing regarding the potential health effects of red yeast rice (RYR) consumption, which is described as a "natural statin" in China. This review aims to evaluate the efficacy of RYR on blood pressure (BP), lipid profile, and C-reactive protein (CRP) in treating hypertension. Seven electronic databases including the Cochrane Central Register of Controlled Trials, EMBASE, PubMed, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (VIP), the Chinese Biomedical Literature Database (CBM), and the Wanfang database were searched. To investigate the role of RYR for hypertension, randomized controlled trials for the use of RYR either as monotherapy or in combination with conventional medicine versus placebo, no intervention, or conventional medicine for hypertension were identified. A total of 21 trials containing 4558 patients were analyzed, the majority of which had low methodological quality. "RYR plus conventional therapy" exhibited significant lowering effects on serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and CRP but exhibited no significant effect on systolic BP, diastolic BP, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with "placebo plus conventional therapy." "RYR plus conventional therapy" showed significant lowering effects on systolic BP, TC, LDL-C, and CRP but no effect on diastolic BP, TG, and HDL-C compared with "placebo plus conventional therapy." No significant difference in BP and lipid profile between "RYR plus conventional therapy" and "statins plus conventional therapy" was observed. "RYR plus statins" appeared to be more effective in lowering BP, TC, TG, and LDL-C but without a significant difference in HDL-C compared to statins. No serious adverse events were reported. The results of this meta-analysis suggested some supportive but limited evidence regarding RYR for hypertension. Further rigorously designed trials are warranted before RYR could be recommended to hypertensive patients.
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Effects of Coenzyme Q10 on Markers of Inflammation: A Systematic Review and Meta-Analysis.
Zhai, J, Bo, Y, Lu, Y, Liu, C, Zhang, L
PloS one. 2017;(1):e0170172
Abstract
BACKGROUND/OBJECTIVE Chronic inflammation contributes to the onset and development of metabolic diseases. Clinical evidence has suggested that coenzyme Q10 (CoQ10) has some effects on inflammatory markers. However, these results are equivocal. The aim of this systematic review was to assess the effects of CoQ10 on serum levels of inflammatory markers in people with metabolic diseases. METHODS Electronic databases were searched up to February 2016 for randomized controlled trials (RCTs). The outcome parameters were related to inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C reactive protein (CRP). RevMan software was used for meta-analysis. Meta-regression analysis, Egger line regression test and Begg rank correlation test were performed by STATA software. RESULTS Nine trials involving 428 subjects were included in this meta-analysis. The results showed that compared with control group, CoQ10 supplementation has significantly improved the serum level of CoQ10 by 1.17μg/ml [MD = 1.17, 95% CI (0.47 to 1.87) μg/ml, I2 = 94%]. Meanwhile, it has significantly decreased TNF-α by 0.45 pg/ml [MD = -0.45, 95% CI (-0.67 to -0.24) pg/ml, I2 = 0%]. No significant difference was observed between CoQ10 and placebo with regard to CRP [MD = -0.21, 95% CI (-0.60 to 0.17) mg/L, I2 = 21%] and IL-6 [MD = -0.89, 95% CI (-1.95 to 0.16) pg/ml, I2 = 84%]. CONCLUSIONS CoQ10 supplementation may partly improve the process of inflammatory state. The effects of CoQ10 on inflammation should be further investigated by conducting larger sample size and well-defined trials of long enough duration.
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Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.
Mazidi, M, Karimi, E, Rezaie, P, Ferns, GA
Journal of diabetes and its complications. 2017;(7):1237-1242
Abstract
AIM: To undertake a systematic review and meta-analysis of randomized controlled trials of the effect of glucagon-like peptide-1 receptor agonist (GLP-1 RAs) therapy on serum C-reactive protein (CRP) concentrations. METHOD PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched for the period up until March 16, 2016. Prospective studies evaluating the impact of GLP-1 RAs on serum CRP were identified. A random effects model (using the DerSimonian-Laird method) and generic inverse variance methods were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Heterogeneity was quantitatively assessed using the I2 index. Random effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential moderator. International Prospective Register for Systematic Reviews (PROSPERO) number CRD42016036868. RESULTS Meta-analysis of the data from 7 treatment arms revealed a significant reduction in serum CRP concentrations following treatment with GLP-1 RAs (WMD -2.14 (mg/dL), 95% CI -3.51, -0.78, P=0.002; I2 96.1%). Removal of one study in the meta-analysis did not change the result in the sensitivity analysis (WMD -2.14 (mg/dL), 95% CI -3.51, -0.78, P=0.002; I2 96.1%), indicating that our results could not be solely attributed to the effect of a single study. Random effects meta-regression was performed to evaluate the impact of potential moderator on the estimated effect size. Changes in serum CRP concentration were associated with the duration of treatment (slope -0.097, 95% CI -0.158, -0.042, P<0.001). CONCLUSIONS This meta-analysis suggests that GLP-1 RAs therapy causes a significant reduction in CRP.
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C-reactive protein and cardiovascular risk in bipolar disorder patients: A systematic review.
Marshe, VS, Pira, S, Mantere, O, Bosche, B, Looper, KJ, Herrmann, N, Müller, DJ, Rej, S
Progress in neuro-psychopharmacology & biological psychiatry. 2017;(Pt B):442-451
Abstract
OBJECTIVES New research is revealing a strong association between inflammatory markers with bipolar disorder (BD), potentially due to the high prevalence of cardiovascular disease and cardiovascular risk factors in BD. We aimed to synthesize the literature examining the association between the clinically most relevant inflammatory marker, C-reactive protein (CRP) and cardiovascular disease and cardiovascular risk factors in patients with BD. METHODS MEDLINE, Embase and PsychInfo were systematically searched for all relevant English language articles published prior to April 2017. Articles were included if they examined the association between CRP and cardiovascular risk factors/disease in BD. RESULTS Fifteen relevant articles were retrieved. Studies were mostly cross-sectional and heterogeneous in the cardiovascular risk factors investigated. Overall, elevated CRP was associated with increased risk of metabolic syndrome, elevated body mass index, higher waist circumference, and obesity. CRP was inconsistently associated with elevated fasting glucose, insulin levels, serum triglycerides, total cholesterol levels, and low high density lipoprotein (HDL) levels. Atypical antipsychotic use may mediate some of these effects. No study examined CRP's association with actual cardiovascular disease (e.g. coronary artery disease) in BD. CONCLUSIONS In BD, CRP is associated with increases in several cardiovascular risk factors, suggesting that systemic inflammation could be a shared driving force for both outcomes of BD and cardiovascular risk. Further longitudinal research is needed in this area to verify causality, including an examination of actual cardiovascular disease. Non-pharmacological and pharmacological treatments with anti-inflammatory effects should also be investigated, particularly in patients with increased CRP, for their potential to reduce cardiovascular risk in BD.