Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and electrochemiluminescense-based multi-array platform

Background - In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. Methods - We measured, in a large ongoing cohort study (n = 574), by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD) and single-biomarker techniques (ELISA or immunoturbidimetric assay), the following biomarkers of low-grade inflammation: C-reactive protein (CRP), serum amyloid A (SAA), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects’ cardiovascular risk factors by ANOVA. Results - Despite that both methods ranked individuals’ levels of biomarkers very similarly (Pearson’s r all=0.755) absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP), 0.711 (SAA), 0.895 (sICAM-1) and 0.858 (sVCAM-1). Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method. Conclusions - Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies

Low-grade inflammation, but not endothelial dysfunction, is associated with greater carotid stiffness in the elderly: the Hoorn Study

OBJECTIVE:: Biomarkers of low-grade inflammation and endothelial dysfunction are associated with cardiovascular disease. Arterial stiffening may be a mechanism through which low-grade inflammation and (or) endothelial dysfunction lead to cardiovascular disease. Therefore, we investigated whether low-grade inflammation and endothelial dysfunction were associated with greater carotid stiffness in a population-based cohort of elderly individuals. METHODS:: We determined biomarkers of low-grade inflammation (C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumour necrosis factor alpha and soluble intercellular adhesion molecule 1), and of endothelial dysfunction (von Willebrand factor, soluble vascular cell adhesion molecule 1, soluble endothelial selectin, soluble thrombomodulin, soluble intercellular adhesion molecule 1 and flow-mediated dilation), and combined these into mean z-scores (n = 572; women = 286; age 67.5 +/- 6.6 years). Additionally, we determined by ultrasonography carotid diameter, distension, pulse pressure and intima-media thickness. Carotid stiffness indices were determined by calculation of the distensibility and compliance coefficient, Young's elastic modulus and beta stiffness index. RESULTS:: The study population was characterized by a high prevalence of cardiovascular disease (46%), hypertension (66%) and the use of lipid-lowering (16%) and antihypertensive (34%) medication. After adjustment for the above in addition to sex, age, glucose tolerance status and current smoking, the low-grade inflammation z-score was positively associated with Young's elastic modulus [beta (95% confidence interval) 0.080 (0.021-0.139), P = 0.008]. This association was primarily driven through greater diameter. After adjustment for the variables above, the endothelial dysfunction z-score was not associated with carotid stiffness. CONCLUSION:: These data suggest that low-grade inflammation, in the elderly, plays an important role in carotid artery remodelling and stiffening

Strategia di ricerca e sviluppo

Flow-mediated dilation is aimed at normalization of local wall shear stress under varying blood flow conditions. Blood flow velocity and vessel diameter are continuous and opposing influences that modulate wall shear stress. We derived an index FMDv to quantify wall shear stress normalization performance by flow-mediated dilation in the brachial artery. In 22 fasting presumed healthy men, we first assessed intra-and inter-session reproducibilities of two indices pFMD(v) and mFMD(v), which consider the relative peak and relative mean hyperemic change in flow velocity, respectively. Second, utilizing oral glucose loading, we evaluated the tracking performance of both FMDv indices, in comparison with existing indices [i.e., the relative peak diameter increase (%FMD), the peak to baseline diameter ratio (D-peak/D-base), and the relative peak diameter increase normalized to the full area under the curve of blood flow velocity with hyperemia (FMD/shear(AUC)) or with area integrated to peak hyperemia (FMD/shear(AUC_peak))]. Inter-session and intra-session reproducibilities for pFMD(v), mFMD(v) and %FMD were comparable (intra-class correlation coefficients within 0.521-0.677 range). Both pFMD(v) and mFMD(v) showed more clearly a reduction after glucose loading (reduction of similar to 45%, p = 0.074); D-peak/D-base (similar to 11%, p >= 0.074); FMD/shear(AUC_peak) (similar to 20%, p >= 0.016) and FMD/shear(AUC) (similar to 38%,

Regional peak flow as a novel approach to assess regional pulmonary mechanics by electrical impedance tomography: an observational validation study

Background: Spontaneous breathing efforts during mechanical ventilation are a widely accepted weaning approach for acute respiratory distress syndrome (ARDS) patients. These efforts can be too vigorous, possibly inflicting lung and diaphragm damage. Higher positive end expiratory pressure (PEEP) levels can be used to lower the magnitude of vigorous breathing efforts. Nevertheless, PEEP titrating tools are lacking in spontaneous mechanical ventilation (SMV). Therefore, the aim is to develop an electrical impedance tomography (EIT) algorithm for quantifying regional lung mechanics independent from a stable plateau pressure phase based on regional peak flow (RPF) by EIT, which is hypothetically applicable in SMV and to validate this algorithm in patients on controlled mechanical ventilation (CMV).Methods: The RPF algorithm quantifies a cumulative overdistension (ODRPF) and collapse (CLRPF) rate and is validated in a prospective cohort of mechanically ventilated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients on CMV. ODRPF and CLRPF are compared with compliance-based cumulative overdistension (ODP500) and collapse (CLP500) rates from the Pulmovista 500 EIT device at multiple PEEP levels (PEEP 10 cmH2O to PEEP 24 cmH2O) in EIT measurements from CMV patients by linear mixed models, Bland-Altman analysis and intraclass correlation coefficient (ICC).Results: Seventy-eight patients were included. Linear mixed models revealed an association between ODRPF and ODP500 of 1.02 (0.98-1.07, P<0.001) and between CLRPF and CLP500 of 0.93 (0.80-1.05, P<0.001). ICC values ranged from 0.78 to 0.86 (P<0.001) for ODRPF and ODP500 and from 0.70 to 0.85 (P<0.001) for CLRPF and CLP500 (PEEP 10 to PEEP 24). The mean bias between ODRPF and ODP500 in these PEEP levels ranged from 0.80% to 4.19% and from -1.31% to 0.13% between CLRPF and CLP500.Conclusions: A RPF approach for quantifying regional lung mechanics showed a moderate to good agreement in coronavirus disease 2019 (COVID-19) related ARDS patients on CMV compared to the compliance-based approach. This, in addition to being independent of a plateau pressure phase, indicates that the RPF approach is a valid method to explore for quantifying regional lung mechanics in SMV

A Healthy Diet Is Associated with Less Endothelial Dysfunction and Less Low-Grade Inflammation over a 7-Year Period in Adults at Risk of Cardiovascular Disease

Background: A healthy diet rich in fish, fruit, and vegetables, but moderate in alcohol and low in dairy products and meat, has been associated with a lower rate of incident cardiovascular disease (CVD). The underlying mechanisms, however, remain unclear. Endothelial dysfunction and low-grade inflammation play important roles in CVD. A healthy diet might modify these phenomena. Objective: We investigated the associations between the above food groups and overall biomarker scores of endothelial dysfunction and low-grade inflammation in a 7-y longitudinal study. Methods: Using longitudinal data from 557 participants at increased CVD risk from the CODAM (Cohort on Diabetes and Atherosclerosis Maastricht) Study, we assessed diet intake by food-frequency questionnaire and measured plasma biomarkers of endothelial dysfunction [von Willebrand factor, soluble vascular cell adhesion molecule 1, soluble endothelial selectin, soluble thrombomodulin, soluble intercellular adhesion molecule 1 (sICAM-1)] and low-grade inflammation [C-reactive protein, serum amyloid A, interleukin (IL)-6, IL-8, tumor necrosis factor a, and sICAM-1]. At baseline, participants were aged 59.6 ± 6.9 y. Measurements were performed then and after 7 y. Biomarkers were combined into overall scores (sum of z scores; higher scores indicating worse function). Longitudinal data were analyzed with generalized estimating equations and adjusted for sex, age, glucose metabolism, energy intake, body mass index, physical activity, alcohol consumption, and smoking. Results: Higher consumption of fish (per 100 g/wk), but not total consumption of vegetables, fruit, alcohol-containing beverages, dairy products, or meat, was associated with a lower overall endothelial dysfunction score over 7 y (β: -0.027; 95% CI: -0.051, -0.004). No associations were observed with the overall low-grade inflammation score. Further food component analyses indicated that consumption of more lean fish (per 100 g/wk) and raw vegetables (per 100 g/d), and fewer high-fat dairy products (per 100 g/d) was associated with less endothelial dysfunction [(β: -0.038; 95% CI: -0.072, -0.005), (β: -0.095; 95% CI: -0.191, 0.000), and (β: -0.070; 95% CI: -0.131, -0.009), respectively]. Consumption of more fresh fruit (per 100 g/d), wine (per 100 mL/wk), and poultry (per 100 g/d), and fewer high-fat dairy products (per 100 g/d) was associated with less low-grade inflammation [(β: -0.074; 95% CI: -0.133, -0.015), (β:-0.006; 95% CI: -0.013, 0.001), (β:-0.247; 95% CI: -0.479, -0.014), and (β:-0.100; 95% CI: -0.182, -0.019), respectively]. Conclusion: These data suggest that the dietary modification of endothelial dysfunction and low-grade inflammation, processes that are important in atherothrombosis, is possible

Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and an electrochemiluminescense-based multi-array platform.

Background: In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. Methods: We measured, in a large ongoing cohort study (n = 574), by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD) and single-biomarker techniques (ELISA or immunoturbidimetric assay), the following biomarkers of low-grade inflammation: C-reactive protein (CRP), serum amyloid A (SAA), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects' cardiovascular risk factors by ANOVA. Results: Despite that both methods ranked individuals' levels of biomarkers very similarly (Pearson's r all >= 0.755) absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP), 0.711 (SAA), 0.895 (sICAM-1) and 0.858 (sVCAM-1). Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method. Conclusions: Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies