Log-transformed C-reactive Protein Research Articles

Causal effect of C-reaction protein and endometrial cancer: Genetic evidence of the role of inflammation in endometrial cancer.

Consensus remains elusive regarding the relationship between C-reactive protein (CRP) levels and endometrial cancer (EC). Our study sought to elucidate the causal association between CRP and EC, aiming to contribute to the understanding of this complex interplay. We primarily utilized the random-effects inverse variance-weighted method. This approach served as the foundation for our analysis, complemented by 3 additional techniques, including Mendelian randomization-Egger, weighted-median, and weighted mode. A series of sensitivity analyses were also conducted to affirm the stability and reliability of our results. Employing the inverse variance-weighted method, our findings indicated that a one-unit increment in log-transformed CRP concentrations (mg/L) was associated with a relatively 9.7% increased risk of overall EC (odds ratio [OR] = 1.097, 95% confidence interval [CI]: 0.996-1.208, P = .061), an 11% higher risk of endometrioid endometrial cancer (OR = 1.110, 95% CI: 1.000-1.231, P = .049) and a 25% increased risk of non-endometrioid cancers (OR = 1.250, 95% CI: 1.005-1.555, P = .045). Sensitivity analyses did not reveal evidence of horizontal pleiotropy in the analysis of CRP and overall EC, endometrioid endometrial cancer, or non-endometrioid cancers (P > .05). In the reverse analysis, our data demonstrated that EC exert no reverse effect on CRP levels. Our study suggested causal relationships between CRP and an elevated risk of EC and its subtypes, which contribute to the ongoing discourse on the role of inflammation, as indicated by CRP levels, in the etiology of EC and its variants.

Do Time-Dependent Repeated Measures of Anthropometric and Body Composition Indices Improve the Prediction of Incident Diabetes in the Cohort Study? Findings from a Community-Based Korean Genome and Epidemiology Study.

Cumulative evidence consistently shows that anthropometric and body composition measurements are strongly linked to the risk of incident diabetes, typically based on baseline measurements. This study aims to assess whether repeated measurements enhance the prediction of diabetes risk beyond baseline assessments alone. We utilized data from a 16-year population-based follow-up cohort within the Korean Genome and Epidemiology Study, comprising 6,030 individuals aged 40 to 69 years at baseline. We included eight indices: a body shape index (ABSI), body adiposity index (BAI), waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), weight-adjusted skeletal muscle index (SMI), percent body fat, and fat-to-muscle ratio. The effect of these measurements for incident diabetes was estimated using Harrell's C-indexes and hazard ratios with 95% confidence intervals, employing time-dependent Cox proportional hazard models. Over the 16-year follow-up, 939 new diabetes cases were identified (cumulative incidence, 15.6%). The median number of indicator measurements per participant was eight. The basic model, including 10 features (sex, age, education levels, physical activity, alcohol intake, current smoking, total energy intake, dietary diversity score, and log-transformed C-reactive protein levels, and quartiles of unweighted genetic risk score at baseline), yielded a Harrell's C-index of 0.610. The highest C-index in repeated measurements was for WC (0.668) across the general population, weight-adjusted SMI in men, and WHR in women. However, except for ABSI and BAI, the diabetes predictive power of the other indicators was comparable. Additionally, repeated measurements of WC, BMI, and WHR in women were found to contribute to improved discrimination compared to baseline measurements, but not in men. Utilizing repeated measurements of general and central adiposity to predict diabetes may be helpful in predicting hidden risks, especially in women.

Chronic inflammation is associated with impaired cardiac structure and function in patients with inflammatory arthritis: the ARTCADIA Study

Abstract Background Inflammation as an underlying cause of cardiac dysfunction has been underscored in recent years. Patients with inflammatory arthritis (IA) are at risk of being exposed to a high degree of chronic and systemic inflammation. It is therefore important to investigate whether high inflammatory burden impacts cardiac structure and function in patients with IA. Purpose To examine the impact of long-term inflammation on measures of cardiac structure and function in individuals with rheumatoid arthritis (RA) and axial Spondyloarthritis (axSpA), collectively referred to as IA, in a large cohort. Methods In a prospective cohort study, outpatients with a diagnosis of IA were included over two years during their biannual rheumatological routine appointment. In total, 1,285 participants were included. Participants were evaluated at a cardiology research center where echocardiography was performed following a pre-defined protocol. To evaluate chronic inflammation, C-reactive protein (CRP) was averaged from clinical outpatient visits registered in a rheumatological database. Uni- and multivariable linear regressions were used to examine the relationship between echocardiographic measures and log-transformed CRP. Results Among the 1,285 participants, 903 (70%) were diagnosed with RA, 358 (28%) with axSpA, and 24 (2%) with other forms of IA. Mean age was 60 ± 13 years, 64% were female. The median number of outpatient visits was 30 (Interquartile range (IQR): 18 - 48), median disease duration was 12 (IQR: 6 - 20) years, and the median outpatient CRP was 5.7 (IQR: 3.7 – 9.8) mg/L. 519 (40%) patients had hypertension (HT), 113 (9%) diabetes mellitus (DM), 76 (5.9%) ischemic heart disease (IHD) and 35 (2.5%) heart failure (HF). Mean left ventricular (LV) ejection fraction was 54.6 ± 5.7%, mean numerical global longitudinal strain (GLS) was 17.8 ± 2.4%, mean LV mass index (LVMi) was 73 ± 18 g/m2 and mean tricuspid annular plane systolic excursion (TAPSE) was 2.5 ± 0.4 cm. In univariable analyses, higher levels of CRP were significantly associated with lower GLS, p < 0.001; higher E/e’, p = 0.001; higher LVMi, p < 0.001 and lower TAPSE, p = 0.005 (Figure). The associations remained significant after adjusting for clinical characteristics including disease duration, age, sex, blood pressure, body mass index, physical activity, pack-years of smoking, cholesterol, HT, DM, heart rate, atrial fibrillation, IHD and HF (p < 0.05 for all associations). We observed no significant interactions between the IA diagnosis and inflammation across the significant echocardiographic measures. Conclusion In a large cohort of patients with IA, increasing levels of chronic inflammation determined by outpatient CRP was associated with impaired measures of cardiac structure and function and remained significant after adjusting for clinical characteristics. The prognostic and clinical implication of these findings needs to be explored in future studies.Linear regression splines

Gut Dysbiosis in Patients With Fontan Circulation.

The process underlying Fontan pathophysiology is multifactorial and may include gut dysbiosis (GD). We investigated the presence of GD and elucidated its correlation with Fontan pathophysiology. Gut microbiomes of 155 consecutive patients with Fontan pathophysiology and 44 healthy individuals were analyzed using 16S rRNA sequencing of bacterial DNA extracted from fecal samples. GD was evaluated on the basis of α and ß diversities of the gut microbiome and was compared with natural log-transformed C-reactive protein, hemodynamics, von Willebrand factor antigen (a bacterial translocation marker), Mac-2 binding protein glycosylation isomer (a liver fibrosis indicator), peak oxygen uptake, and heart failure hospitalization. Patients with Fontan exhibited GD in terms of α and ß diversities as compared with controls (P<0.01). Reduced α diversity was associated with a failed hemodynamic phenotype, hypoxia, high natural log-transformed C-reactive protein levels, and elevated von Willebrand factor antigen and Mac-2 binding protein glycosylation isomer levels (P<0.05-0.01). In addition to elevated von Willebrand factor antigen and hypoxia, decreased α diversity was independently correlated with a high natural log-transformed C-reactive protein level (P<0.05), which was associated with liver imaging abnormalities and a heightened risk of heart failure hospitalization (P<0.01 for both). Patients with Fontan pathophysiology exhibited GD compared with healthy individuals, and GD was linked to failed hemodynamics and systemic inflammation with a poor prognosis. Therefore, GD may play a pivotal role in a failing Fontan status, including Fontan-associated liver disease, through GD-associated systemic inflammation.

Coffee consumption and C-reactive protein levels: A systematic review and meta-analysis

AimsConsiderable debate exists regarding the association between coffee consumption and C-reactive protein (CRP) levels and the shape of this association. We conducted a meta-analysis to assess the relationship between coffee consumption and CRP levels. Data synthesisWe searched PubMed and Web of Science databases and conducted a hand search as of June 27, 2023. Meta-analyses were conducted using standardized mean differences (SMDs) with random-effects models, based on the geometric mean of CRP from included studies. We identified 13 studies for our systematic review and included 11 cross-sectional studies, involving a total of 66,691 subjects, in our meta-analysis. We found a linear inverse association between coffee consumption and CRP levels (p-value = 0.002) and did not find evidence of a non-linear association (p for non-linearity = 0.13). Compared with the lowest category of coffee consumption (median, non-drinkers), the SMDs of log-transformed CRP levels were −0.02 (95% confidence interval [CI]: −0.05 to 0.00) for the third highest (median, 0.5 cup/day), −0.09 (95% CI: −0.15 to −0.04) for the second highest (median, 2.5 cups/day), and −0.14 (95% CI: −0.25 to −0.04) for the highest category (median, 4.5 cups/day). The inverse association tended to be stronger in women, but the difference by gender was not significant. Compared to the limited number of studies not adjusting for smoking, those that adjusted showed a strong linear inverse association, although the difference was not significant. ConclusionsOur findings indicate that coffee consumption is inversely associated with CRP levels. These associations may vary with potential modifiers, including gender and smoking adjustment. ProsperoCRD42023445986.

Multidimensional Religiousness and Spirituality Are Associated With Lower Interleukin-6 and C-Reactive Protein at Midlife: Findings From the Midlife in the United States Study.

Religiousness and spirituality (R/S) are associated with lower morbidity and mortality, yet the physiological mechanisms underlying these associations are under-studied. Chronic inflammation is a plausible biological mechanism linking R/S to downstream health given the sensitivity of the immune system to the social environment and the role of inflammation in many chronic diseases. The purpose of the present study was to examine associations between multiple R/S dimensions and two markers of chronic inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP). In this cross-sectional study, data came from biological subsamples of two cohorts from the Midlife in the United States (MIDUS) Study (combined N = 2,118). Predictors include six R/S measures (service attendance, spirituality, private religious practices, daily spiritual experiences, religious coping, and R/S-based mindfulness). Outcomes include log-transformed IL-6 and CRP. Covariates include age, gender, cohort, race, educational attainment, body mass index (BMI), smoking status, and physical activity. Older adults, women (vs. men), non-White (vs. White) adults, those with higher BMIs, current smokers, and those not meeting physical activity guidelines had significantly higher IL-6 and CRP. In fully adjusted models, greater spirituality, daily spiritual experiences, religious coping, and R/S-based mindfulness were associated with lower IL-6. Higher spirituality was also associated with lower CRP. Many dimensions of R/S may be health protective for adults given their associations with lower levels of chronic inflammation. Findings underscore the importance of examining multiple dimensions of R/S to understand mechanistic pathways.

High Serum Galectin-3 Level as a Potential Biomarker of Peripheral Artery Disease in Patients Undergoing Hemodialysis.

Galectin-3 is implicated in the pathogenesis of inflammation and atherosclerosis. Peripheral arterial disease (PAD), characterized by a reduced ankle-brachial index (ABI), is a prognostic marker for mortality in patients on hemodialysis. We investigated the relationship between serum galectin-3 levels and PAD in patients undergoing regular hemodialysis. We carried out a cross-sectional study at a medical center, involving 92 participants. Serum galectin-3 levels were assessed by a commercially available enzyme-linked immunosorbent assay. ABI measurement was done with an automatic device based on oscillometry. Participants were categorized into two groups, normal and low ABI, based on a 0.9 cut-off point. Eighteen patients (19.6%) exhibited a low ABI. In individuals with low ABIs, we observed a greater prevalence of diabetes mellitus, elevated serum C-reactive protein (CRP) levels, increased galectin-3 levels, and lower serum creatinine levels. Furthermore, serum galectin-3 levels (odds ratio [OR]: 1.056, 95% confidence interval [CI]: 1.003-1.112, p = 0.037) and CRP (per 0.1 mg/dL increment, OR: 1.195, 95% CI: 1.032-1.383, p = 0.017) were identified as independent predictors of PAD. Serum galectin-3 and log-transformed CRP levels were also independently and significantly negatively correlated with the left and right ABI values. Serum galectin-3 levels correlate with PAD in patients undergoing maintenance hemodialysis.

The effect of immunomodulatory drugs on aortic stenosis: a Mendelian randomisation analysis.

There are currently no approved pharmacological treatment options for aortic stenosis (AS), and there are limited identified drug targets for this chronic condition. It remains unclear whether inflammation plays a role in AS pathogenesis and whether immunomodulation could become a therapeutic target. We evaluated the potentially causal association between inflammation and AS by investigating the genetically proxied effects of tocilizumab (IL6 receptor, IL6R, inhibitor), canakinumab (IL1β inhibitor) and colchicine (β-tubulin inhibitor) through a Mendelian randomisation (MR) approach. Genetic proxies for these drugs were identified as single nucleotide polymorphisms (SNPs) in the gene, enhancer or promoter regions of IL6R, IL1β or β-tubulin gene isoforms, respectively, that were significantly associated with serum C-reactive protein (CRP) in a large European genome-wide association study (GWAS; 575,531 participants). These were paired with summary statistics from a large GWAS of AS in European patients (653,867 participants) to then perform primary inverse-variance weighted random effect and sensitivity MR analyses for each exposure. This analysis showed that genetically proxied tocilizumab was associated with reduced risk of AS (OR 0.56, 95% CI 0.45-0.70 per unit decrease in genetically predicted log-transformed CRP). Genetically proxied canakinumab was not associated with risk of AS (OR 0.80, 95% CI 0.51-1.26), and only one suitable SNP was identified to proxy the effect of colchicine (OR 34.37, 95% CI 1.99-592.89). The finding that genetically proxied tocilizumab was associated with reduced risk of AS is concordant with an inflammatory hypothesis of AS pathogenesis. Inhibition of IL6R may be a promising therapeutic target for AS management.

Association of extracellular water/total body water ratio with protein-energy wasting and mortality in patients on hemodialysis

Bioimpedance analysis-assessed extracellular water/total body water (ECW/TBW) ratio may be a marker for mortality and poor nutritional status in hemodialysis patients. In 193 maintenance hemodialysis patients, we retrospectively investigated the relationships among ECW/TBW ratio, mortality, and protein-energy wasting (PEW). Four components—body mass index, normalized protein catabolic rate, normalized serum creatinine level, and serum albumin level—constitute the simple PEW score; this score was calculated based on the positive number of items concerning malnutrition among these four components. A score ≥ 3 indicated PEW. Patients were stratified by an ECW/TBW ratio cut-off value (0.40) and by PEW versus non-PEW status. The simple PEW score, cardiothoracic ratio, and log-transformed C-reactive protein level were independently correlated with the ECW/TBW ratio. Eighty-four patients died during follow-up (median 4.3 years). After adjustments for sex, age, hemodialysis vintage, histories of cardiovascular events and diabetes, and C-reactive protein level, a higher ECW/TBW ratio and PEW were independently related to elevated risks of all-cause death. Adding the ECW/TBW ratio to a baseline risk model including PEW significantly increased C-statistics from 0.788 to 0.835. In conclusion, the ECW/TBW ratio may be an indicator of PEW and may be a predictor of death even accounting for PEW, in hemodialysis patients.

Systemic inflammation and subsequent risk of amyotrophic lateral sclerosis: Prospective cohort study

BackgroundWhile systemic inflammation has been implicated in the etiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS), a condition with high case-fatality, is untested. Accordingly, we quantified the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with subsequent ALS occurrence. MethodsWe used data from UK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centers between 2006 and 2010. Venous blood was collected at baseline in the full cohort and assayed for CRP, and repeat measurement was made 3–7 years later in a representative subgroup (N = 14,514) enabling correction for regression dilution. ALS was ascertained via national hospitalization and mortality registries until 2021. We computed multivariable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles. ResultsIn an analytical sample of 400,884 initially ALS-free individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalizations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviors, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalizations (1.20; 1.00, 1.39). There was evidence of dose–response effects across tertiles of CRP for both outcomes (p for trend ≤ 0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalizations (1.37; 1.05, 1.76). ConclusionsHigher levels of CRP, a blood-based biomarker widely captured in clinical practice, is associated with moderately increased future risk of amyotrophic lateral sclerosis.

Incident racial discrimination predicts elevated C-Reactive protein in the Black Women’s experiences Living with Lupus (BeWELL) study

IntroductionRacial discrimination is a distinct health threat that increases disease risk among Black Americans. Psychosocial stress may compromise health through inflammatory mechanisms. This study examines incident experiences of racial discrimination and changes in the inflammatory biomarker C-reactive protein (CRP) over a two-year period among Black women with systemic lupus erythematosus (SLE)—an inflammatory autoimmune disease sensitive to psychosocial stress and characterized by stark racial inequities in outcomes. MethodsData are from the Black Women’s Experiences Living with Lupus (BeWELL) Study. Participants (n = 380) from metropolitan Atlanta, Georgia were enrolled from April 2015 to May 2017. Incident racial discrimination was assessed bi-annually via self-report using the Experiences of Discrimination measure. CRP was assessed annually over a two-year period. Latent change score analyses modeled longitudinal within-person associations between incident racial discrimination and change in log-transformed CRP from baseline to Year 2. ResultsIncident experiences of racial discrimination were associated with elevated log-CRP across the two-year study period (b = 0.039, SE = 0.017, 95% CI: 0.006, 0.071). For each domain of incident racial discrimination experienced, CRP increased 3.98%. ConclusionThis study contributes to growing evidence on the biological consequences of racism and is the first to document an association between incident racial discrimination and changes in inflammation among Black women with SLE. Racial inequities in SLE outcomes and other diseases driven by inflammatory pathways may be explained in part through experiences of racial discrimination.

Synergistic effect of lipoprotein (a) and C-reactive protein on prognosis of familial hypercholesterolemia

ObjectiveThe synergistic effect of lipoprotein (a) [Lp(a)] and C-reactive protein (CRP) on major adverse cardiovascular events (MACE) among patients with familial hypercholesterolemia (FH) is unknown. This study aimed to investigate the relations between Lp(a) and CRP levels and MACE in patients with FH whose Lp(a) levels are elevated. MethodsWe retrospectively investigated associations between genotypes and phenotypes, including low-density lipoprotein (LDL) cholesterol level and the occurrence of MACE among patients with FH (N = 786, male/female: 374/412). A Cox proportional hazard model was used to identify factors associated with MACE, adjusting for traditional risk factors. Patients with FH were divided into four groups, based on their Lp(a) and CRP levels, and assessed using Kaplan–Meier curves. ResultsThe median follow-up was 12.6 years (interquartile range [IQR], 9.5–17.9 years). During follow-up, 129 MACE were observed. Median Lp(a) and CRP levels were 21.4 (10.9–38.3) mg/dL and 0.20 (0.11–0.29) mg/dL, respectively. Under these conditions, natural log-transformed Lp(a) and CRP were not associated with MACE (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.91–1.25; P = 0.220; and HR, 1.12; CI, 0.96–1.28; P = 0.190, respectively). However, in Group 4, Lp(a) and CRP were significantly associated with MACE (HR, 2.44; CI, 1.42–3.46; P = 1.8 × 10−7). ConclusionsIn patients with FH, Lp(a) was significantly associated with MACE only when the CRP level was elevated. Patients with FH whose Lp(a) and CRP levels are elevated should be treated aggressively.

Abstract 9590: Synergistic Effect of Lipoprotein (a) and C-reactive Protein on Prognosis of Familial Hypercholesterolemia

Background: The synergistic effect of lipoprotein (a) [Lp(a)] and C-reactive protein (CRP) on major adverse cardiovascular events (MACE) among patients with familial hypercholesterolemia (FH) is unknown. Objective: This study aimed to investigate the relations between Lp(a) and CRP levels and MACE in patients with FH whose Lp(a) levels are elevated. Methods: We retrospectively investigated associations between genotypes and phenotypes, including low-density lipoprotein (LDL) cholesterol level and the occurrence of MACE among patients with FH (N = 786, male/female: 374/412). A Cox proportional hazard model was used to identify factors associated with MACE, adjusting for traditional risk factors. Patients with FH were divided into four groups, based on their Lp(a) and CRP levels, and assessed using Kaplan-Meier curves. Results: The median follow-up was 12.6 years (interquartile range [IQR], 9.5-17.9 years). During follow-up, 129 MACE were observed. Median Lp(a) and CRP levels were 21.4 (10.9-38.3) mg/dL and 0.20 (0.11-0.29) mg/dL, respectively. Under these conditions, natural log-transformed Lp(a) and CRP were not associated with MACE (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.91-1.25; P = 0.220; and HR, 1.12; CI, 0.96-1.28; P = 0.190, respectively). However, in Group 4, Lp(a) and CRP were significantly associated with MACE (HR, 2.44; CI, 1.42-3.46; P = 1.8 х 10 –7 ). Conclusion: In patients with FH, Lp(a) was significantly associated with MACE only when the CRP level was elevated. Patients with FH whose Lp(a) and CRP levels are elevated should be treated aggressively.

First-Generation College Students, Emotional Support, and Systemic Inflammation Following the College Transition

PurposeTo examine whether emotional support moderates the association between college generation status and concurrent and prospective levels of systemic inflammation during the college transition among a sample of older U.S. adolescents. MethodsAt an undergraduate tertiary institution, 41 first-generation college students (first-gens) and 46 continuing-generation college students (continuing-gens) in their first semester of college reported on basic demographic information and perceived emotional support. They also had their blood drawn midway through both the first and second semester to measure C-reactive protein and interleukin-6. An inflammatory composite for each semester was created by averaging the standardized scores for log-transformed C-reactive protein and interleukin-6. ResultsCompared to continuing-gens, first-gens had greater systemic inflammation in the first semester regardless of their level of emotional support (B = 0.515, p = .003). However, emotional support moderated the association between college generation status and prospective systemic inflammation in the second semester (B = −0.525, p = .007) such that first-gens had greater systemic inflammation compared to continuing-gens, but only if they reported lower levels of emotional support (B = 0.826, p = .002). This moderation effect held after further adjusting for systemic inflammation in the first semester (B = −0.374, p = .022). Also discussed are results of secondary analyses examining sources of support. DiscussionCompared to continuing-gens, first-gens had greater systemic inflammation in the first semester irrespective of emotional support, suggesting all first-gens may stand to benefit from college resources provided early in the college transition. Furthermore, first-gens who reported lower levels of emotional support may benefit from additional college resources provided beyond the first semester.

Development and validation of longitudinal c-reactive protein as dynamic response predictor for PD-L1 blockade in advanced NSCLC: Findings from four atezolizumab clinical trials.

e21113 Background: Numerous studies suggested that pre-treatment C-reactive protein (CRP) is a survival predictive biomarker for cancer patients treated with anti-PD-(L)1 blockade. However, the application of longitudinal CRP levels as dynamic biomarker for advanced non-small cell lung cancer (NSCLC) patients treated with anti-PD-(L)1 remains unexplored. Methods: This study analyzed four international, multi-center clinical trials (OAK, BIRCH, POPLAR and FIR trials) to conduct post-hoc analyses of NSCLC patients undergoing atezolizumab (anti-PD-L1) single-agent treatment. CRP test was performed ≤ 96 hours before Day 1 of each cycle. 1438 patients with more than 2 times CRP results (a total of 11,253 records) in all 3 collection timepoints. The primary endpoint was overall survival (OS). First, multivariate survival analysis was conducted to include clinical factors such as gender, ECOG-PS, race and metastases as contributing risk factors. Then, multivariate joint modelling of longitudinal and time-to-event data was used to establish the relationship between longitudinal CRP and OS in the OAK study, whereas external validation was performed by time-dependent AUC analysis on the BIRCH, POPLAR and FIR studies. Results: Log-transformed longitudinal CRP levels (log(CRP)) in combination with clinical factors in absence of PD-L1 expression emerged as independent predictors of worse OS in the OAK study (HR of jointed model = 2.08, 95% CI: 1.84-2.35, p &lt; 0.001) with a high accuracy (AUC = 0.74) for predicting OS. The predictive value of longitudinal CRP was validated in the external validation cohorts with good performance in OS (BIRCH: HR = 2.77 (95% CI: 2.31-3.44), AUC = 0.76; POPLAR: HR = 1.95 (95% CI: 1.50-2.64), AUC = 0.76; and FIR: HR = 1.83 (95% CI: 1.46 -2.39), AUC = 0.72). Conclusions: The Bayesian multivariate joint model demonstrated that longitudinal CRP is a strong survival dynamic predictor for atezolizumab-treated NSCLC patients.

TV time, physical activity, sedentary behaviour and cardiometabolic biomarkers in pregnancy-NHANES 2003-2006.

This study examined the impacts of individual and combined associations between moderate-to-vigorous physical activity (MVPA) and sedentary time (ST) (accelerometer-derived), as well as MVPA and television (TV) time (self-reported) on cardiometabolic biomarkers during pregnancy. Participants were 332 pregnant women from the 2003-2006 cycles of the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression models were conducted to examine the relationships between individual and combinations of high/low MVPA, ST, and TV time with cardiometabolic biomarkers: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein cholesterol (HDL), and C-reactive protein (CRP). Women with high MVPA (≥ 17 min/day) compared to those with low MVPA (< 17 min/day) had significantly lower BMI. Women with low ST (< 503 min/day) compared to those with high ST (≥ 503 min/day) had significantly lower SBP and DBP. Women with low TV (< 3 h/day) compared to those with high TV (≥ 3 h/day) had significantly lower BMI and log-transformed CRP. Women with a combination of low ST/high MVPA had lower SBP and DBP (ptrend < 0.03). Women with a combination of low TV/high MVPA had lower BMI and log-transformed CRP (ptrend < 0.00). We need to consider both physical activity and sedentary time for improved cardiometabolic health during pregnancy.

Inflammation and Conception in a Prospective Time-to-Pregnancy Cohort.

Inflammation may contribute to subfertility but this has not been well-explored in large prospective cohort studies. We conducted a prospective 12-month cohort study of time to pregnancy in North Carolina, the Time to Conceive study (2010-2016). Participants were 30-44 years old, without a history of infertility (N = 727). We analyzed blood samples with a high sensitivity assay for C-reactive protein (CRP). Women reported their weight, height, and other covariates. We natural log-transformed CRP and examined it (1) linearly, after exploration using restricted cubic splines and (2) in categories based on American Heart Association criteria. We estimated fecundability ratios (FRs) with log-binomial discrete-time-to-pregnancy models. Separate models included an interaction term with body mass index (BMI). The adjusted estimated FR per natural log-unit increase in CRP level was 0.97 (confidence interval [CI] = 0.91, 1.0). The FR (CI) for high CRP (>10 mg/L) compared with low CRP (<1 mg/L) was 0.78 (0.52, 1.2). Compared with normal-weight women with low CRP, women with obesity and high CRP had lower estimated fecundability, but the confidence interval was wide (FR = 0.63; CI = 0.35, 1.1). There was no pattern in the estimated fecundability across levels of CRP within categories of BMI. There was no evidence of an association between CRP and fecundability either alone or within levels of BMI. Further studies of CRP and fecundability should include higher levels of CRP and additional markers of inflammation.

Impact of a Vancomycin-Induced Shift of the Gut Microbiome in a Gram-Negative Direction on Plasma Factor VIII:C Levels: Results from a Randomized Controlled Trial.

Inflammation is present in several conditions associated with risk of venous thromboembolism. The gut microbiome might be a source of systemic inflammation and activation of coagulation, by translocation of lipopolysaccharides from gram-negative bacteria to the systemic circulation. To investigate whether a vancomycin-induced shift of the gut microbiome in a gram-negative direction influences systemic inflammation and plasma factor (F) VIII procoagulant activity (FVIII:C). We performed a randomized controlled trial including 43 healthy volunteers aged 19 to 37 years. Twenty-one were randomized to 7 days of oral vancomycin intake and 22 served as controls. Feces and blood were sampled at baseline, the day after the end of intervention, and 3 weeks after intervention. Gut microbiome composition was assessed by amplicon sequencing. C was measured using an activated partial thromboplastin time-based assay, cytokines were measured using multiplex technology, complement activation was measured using the enzyme-linked immunosorbent assay, and high-sensitivity C-reactive protein (CRP) was measured by an immunoturbidimetric assay. Vancomycin intake reduced gut microbiome diversity and increased the abundance of gram-negative bacteria. Change in FVIII:C in the intervention group was +4 IU/dL versus -6 IU/dL (p = 0.01) in the control group. A similar change was observed for log-transformed CRP (+0.21 mg/dL vs. -0.25 mg/dL, p = 0.04). The cytokines and complement activation markers remained similar in the two groups. The found slight increases in FVIII:C and CRP levels might support the hypothesis that a vancomycin-induced gram-negative shift in the gut microbiome could induce increased systemic inflammation and thereby a procoagulant state.

Serum Galectin-3 Level Is Positively Associated with Endothelial Dysfunction in Patients with Chronic Kidney Disease Stage 3 to 5.

Galectin-3, which is a novel biomarker of cardiovascular stress and related to inflammation, could predict adverse cardiovascular events. However, its relationship with endothelial function in patients with chronic kidney disease (CKD) remains inconclusive. This study aimed to investigate the association between serum galectin-3 levels and endothelial function in patients with stages 3–5 CKD. Fasting blood samples were obtained from 130 patients. Serum galectin-3 levels were determined using the enzyme-linked immunosorbent assay. The endothelial function, demonstrated as a vascular reactivity index (VRI), was measured noninvasively through digital thermal monitoring test. Then, we sorted the patients into poor, intermediate, and good vascular reactivity (VRI < 1.0, 1.0 ≤ VRI < 2.0, and VRI ≥ 2.0), accounting for 24 (18.5%), 44 (33.8%), and 62 (47.7%) patients, respectively. As the VRI decreased, the serum galectin-3 and C-reactive protein (CRP) levels significantly increased. The galectin-3 value positively correlated with the CRP value but negatively correlated with estimated glomerular filtration rate. In multivariable stepwise linear regression analysis, serum log-transformed galectin-3 level and log-transformed CRP were significantly negatively associated with VRI values. Therefore, galectin-3 together with CRP is associated with VRI values and is a potential endothelial function modulator and a valuable biomarker of endothelial dysfunction in patients with CKD.

Investigating whether a combination of higher CRP and depression is differentially associated with worse executive functioning in a cohort of 43,896 adults

Many depressed individuals experience difficulties in executive functioning that contribute substantially to functional impairment. It is unknown whether a subtype of depression characterized by chronic inflammation is differentially associated with worse executive functioning. This study examined whether the combination of depression and higher C reactive protein (CRP) is differentially associated with worse executive functioning and whether this association is stronger in older adults. This cross-sectional study analyzed data collected from a population-representative sample of 43,896 adults aged 44.13 years (SD = 13.52) who participated in the baseline assessment of the Lifelines cohort study. Multivariate regression models tested whether depressed individuals (established via structured interview) exhibiting higher levels of inflammation (indexed via high-sensitivity CRP assay following an overnight fast) performed worse on a behavioral test of executive functioning. Depression (B = −3.66, 95% CI: −4.82, −2.49, p < .001) and higher log-transformed CRP (B = −0.67, 95% CI: −0.87,-0.47, p < .001) were associated with worse executive functioning, after adjustment for age, sex, educational attainment, body mass index, smoking status, exposure to stressful life events and chronic stressors, sedentary behavior, and number of chronic medical conditions. Depressed individuals with higher log-transformed CRP exhibited differentially poorer executive functioning (B = −1.09, 95% CI: −2.07,-0.11, p < .001). This association did not differ based on age (B = 0.01, 95% CI: −0.08, 0.10, p = .82). Executive functioning is poorer in depressed individuals with higher CRP, even in early adulthood. Interventions that reduce inflammation may improve cognitive functioning in depression.