scholarly journals 876Association of blood markers of inflammation, vitamin status and the kynurenine pathway with age and all-cause mortality

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Pierre-antoine Dugué ◽  
Allison Hodge ◽  
Per Ueland ◽  
Øivind Midttun ◽  
Arve Ulvik ◽  
...  

Abstract Background Inflammation is a key feature of aging and a cause of numerous diseases. We investigated the association of 35 blood markers involved in inflammatory processes with age and mortality and developed a signature of ‘inflammaging’. Methods Thirty-five blood markers relating to the kynurenine pathway, vitamin status, and inflammation were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (1990-1994, median age 59 years) and follow-up (2003-2007, median age 70 years). Associations of each marker with age and all-cause mortality were assessed using linear and Cox regression, respectively. A signature of inflammaging was obtained via Lasso regression of age on the markers and tested for association with mortality; we compared mortality associations for this signature and two weighted scores across all markers associated with age and mortality, respectively. Results Most markers (29/35) were associated with age, with strongest associations observed for cystatin C, neopterin, quinolinic acid, and the kynurenine/tryptophan ratio, PAr index, and 3-hydroxykynurenine/xanthurenic acid ratio. Many markers (14/35) showed strong associations with mortality in particular neopterin, quinolinic acid, HK/XA, PAr index, CRP, IL-6 and KTr. The inflammaging signature included six markers and showed strong association with mortality (HR = 1.5, 95%CI: 1.3-1.7), almost as strong as the association of weighted scores combining all measured markers. Conclusions Our study highlights the key role played by markers of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. Key messages A signature of ‘inflammaging’ based on 6 markers may be useful to better predict mortality.

Author(s):  
Pierre-Antoine Dugué ◽  
Allison M Hodge ◽  
Arve Ulvik ◽  
Per M Ueland ◽  
Øivind Midttun ◽  
...  

Abstract Background Inflammation is a key feature of aging. We aimed to i) investigate the association of 34 blood markers potentially involved in inflammatory processes with age and mortality, ii) develop a signature of ‘inflammaging’. Methods Thirty-four blood markers relating to inflammation, B vitamin status and the kynurenine pathway were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (median age=59 years) and follow-up (median age=70 years). Associations with age and mortality were assessed using linear and Cox regression, respectively. A parsimonious signature of inflammaging was developed and its association with mortality was compared with two marker scores calculated across all markers associated with age and mortality, respectively. Results The majority of markers (30/34) were associated with age, with stronger associations observed for neopterin, cystatin C, IL-6, TNF-α, several markers of the kynurenine pathway and derived indices KTR (kynurenine/tryptophan ratio), PAr index (ratio of 4-pyridoxic acid and the sum of pyridoxal 5´-phosphate and pyridoxal), and HK:XA (3-hydroxykynurenine/xanthurenic acid ratio). Many markers (17/34) showed an association with mortality, in particular IL-6, neopterin, CRP, quinolinic acid, PAr index, and KTR. The inflammaging signature included ten markers and was strongly associated of mortality (HR per SD=1.40, 95%CI:1.24-1.57, P=2x10 -8), similar to scores based on all age-associated (HR=1.38, 95%CI:1.23-1.55, P=4x10 -8) and mortality-associated markers (HR=1.43, 95%CI:1.28-1.60, P=1x10 -10), respectively. Strong evidence of replication of the inflammaging signature association with mortality was found in the Hordaland Health Study. Conclusion Our study highlights the key role of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. A signature of inflammaging based on ten markers was strongly associated with mortality.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xin Liu ◽  
Ye Ruan ◽  
Limei Huang ◽  
Yanfei Guo ◽  
Shuangyuan Sun ◽  
...  

Abstract Background Cognitive leisure activity, such as reading, playing mahjong or cards and computer use, is common among older adults in China. Previous studies suggest a negative correlation between cognitive leisure activity and cognitive impairment. However, the relationship between cognitive leisure activity and all-cause mortality has rarely been reported. Objectives This study aims to explore the relationships between cognitive leisure activity and all-cause mortality in a community-based older people cohort in China. Methods The current study sample comprised 4003 community residents aged ≥60 y who were enrolled in June 2015, and were followed up every year from 2015 to 2018. Reading, playing mahjong or cards and computer use were measured by questionnaires and summed into a cognitive leisure activity index (CLAI) score. Time-Dependent Cox Regression Model and Kaplan-Meier survival analysis were used to examine the association of cognitive leisure activity with all-cause mortality. Results During the 4-year follow-up of 4003 participants, 208 (5.2%) deaths were registered. Of all participants, 66.8, 26.7, 6.1 and 0.35% reported CLAI scores of 0, 1, 2 and 3, respectively. A strong association was noted between the CLA score and all-cause mortality (adjusted hazard ratio [HR] = 0.72, 95% confidence intervals [CI]: 0.54–0.97, P = 0.028). Stratified analysis suggested that a higher CLAI score was significantly associated with a decreased risk of all-cause mortality mainly among those who were male, aged ≥80 y, cognitively impaired, and not diagnosed with cancer (P < 0.05). Conclusion Cognitive leisure activity was positively associated with reduced risk of death from all cause among the older people in major city of China, which helped promote a comprehensive understanding of health characteristics at advanced ages.


Author(s):  
Sahrai Saeed ◽  
Anastasia Vamvakidou ◽  
Spyridon Zidros ◽  
George Papasozomenos ◽  
Vegard Lysne ◽  
...  

Abstract Aims It is not known whether transaortic flow rate (FR) in aortic stenosis (AS) differs between men and women, and whether the commonly used cut-off of 200 mL/s is prognostic in females. We aimed to explore sex differences in the determinants of FR, and determine the best sex-specific cut-offs for prediction of all-cause mortality. Methods and results Between 2010 and 2017, a total of 1564 symptomatic patients (mean age 76 ± 13 years, 51% men) with severe AS were prospectively included. Mean follow-up was 35 ± 22 months. The prevalence of cardiovascular disease was significantly higher in men than women (63% vs. 42%, P &lt; 0.001). Men had higher left ventricular mass and lower left ventricular ejection fraction compared to women (both P &lt; 0.001). Men were more likely to undergo an aortic valve intervention (AVI) (54% vs. 45%, P = 0.001), while the death rates were similar (42.0% in men and 40.6% in women, P = 0.580). A total of 779 (49.8%) patients underwent an AVI in which 145 (18.6%) died. In a multivariate Cox regression analysis, each 10 mL/s decrease in FR was associated with a 7% increase in hazard ratio (HR) for all-cause mortality (HR 1.07; 95% CI 1.03–1.11, P &lt; 0.001). The best cut-off value of FR for prediction of all-cause mortality was 179 mL/s in women and 209 mL/s in men. Conclusion Transaortic FR was lower in women than men. In the group undergoing AVI, lower FR was associated with increased risk of all-cause mortality, and the optimal cut-off for prediction of all-cause mortality was lower in women than men.


2021 ◽  
pp. 1-13
Author(s):  
Seema Khadirnaikar ◽  
Annesha Chatterjee ◽  
Sudhanshu Kumar Shukla

BACKGROUND: Leukocyte infiltration plays an critical role in outcome of various diseases including Lung adenocarcinoma (LUAD). OBJECTIVES: To understand the genetic and epigenetic factors affecting leukocyte infiltration and identification and validation of immune based biomarkers. METHOD: Correlation analysis was done to get the associations of the factors. CIBERSORT analysis was done for immune cell infiltration. Genetic and epigenetic analysis were performed. Cox regression was carried out for survival. RESULTS: We categorized the TCGA-LUAD patients based on Leukocyte fraction (LF) and performed extensive immunogenomic analysis. Interestingly, we showed that LF has a negative correlation with copy number variation (CNV) but not with mutational load. However, several individual genetic mutations, including KRAS and KEAP1, were significantly linked with LF. Also, as expected, patients with high LF showed significantly increased expression of genes involved in leukocyte migration and activation. DNA methylation changes also showed a strong association with LF and regulated a significant proportion of genes associated with LF. We also developed and validated an independent prognostic immune signature using the top six prognostic genes associated with LF. CONCLUSION: Together, we have identified clinical, genetic, and epigenetic variations associated with LUAD LF and developed an immune gene-based signature for disease prognostication.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Kartas ◽  
A Samaras ◽  
D Vasdeki ◽  
G Dividis ◽  
G Fotos ◽  
...  

Abstract Background The association of heart failure (HF) with the prognosis of atrial fibrillation (AF) remains unclear. OBJECTIVES To assess all-cause mortality in patients following hospitalization with comorbid AF in relation to the presence of HF. Methods We performed a cross-sectional analysis of data from 977 patients discharged from the cardiology ward of a single tertiary center between 2015 and 2018 and followed for a median of 2 years. The association between HF and the primary endpoint of death from any cause was assessed using multivariable Cox regression. Results HF was documented in 505 (51.7%) of AF cases at discharge, including HFrEF (17.9%), HFmrEF (16.5%) and HFpEF (25.2%). A primary endpoint event occurred in 212 patients (42%) in the AF-HF group and in 86 patients (18.2%) in the AF-no HF group (adjusted hazard ratio [aHR] 2.27; 95% confidence interval [CI], 1.65 to 3.13; P&lt;0.001). HF was associated with a higher risk of the composite secondary endpoint of death from any cause, AF or HF-specific hospitalization (aHR 1.69; 95% CI 1.32 to 2.16 p&lt;0.001). The associations of HF with the primary and secondary endpoints were significant and similar for AF-HFrEF, AF-HFmrEF, AF-HFpEF. Conclusions HF was present in half of the patients discharged from the hospital with comorbid AF. The presence of HF on top of AF was independently associated with a significantly higher risk of all-cause mortality than did absence of HF, irrespective of HF subtype. Funding Acknowledgement Type of funding source: None


2021 ◽  
pp. 1-11
Author(s):  
Sai Pan ◽  
De-Long Zhao ◽  
Ping Li ◽  
Xue-Feng Sun ◽  
Jian-Hui Zhou ◽  
...  

<b><i>Background:</i></b> Erythropoiesis-stimulating agents (ESAs) constitute an important treatment option for anemia in hemodialysis (HD) patients. We investigated the relationships among the dosage of ESA, erythropoietin resistance index (ERI) scores, and mortality in Chinese MHD patients. <b><i>Methods:</i></b> This multicenter observational retrospective study included MHD patients from 16 blood purification centers (<i>n</i> = 824) who underwent HD in 2011–2015 and were followed up until December 31, 2016. We collected demographic variables, HD parameters, laboratory values, and ESA dosages. Patients were grouped into quartiles according to ESA dosage to study the effect of ESA dosage on all-cause mortality. The ERI was calculated as follows: ESA (IU/week)/weight (kg)/hemoglobin levels (g/dL). We also compared outcomes among the patients stratified into quartiles according to ERI scores. We used the Cox proportional hazards model to measure the relationships between the ESA dosage, ERI scores, and all-cause mortality. Using propensity score matching, we compared mortality between groups according to ERI scores, classified as either &#x3e; or ≤12.80. <b><i>Results:</i></b> In total, 824 patients were enrolled in the study; 200 (24.3%) all-cause deaths occurred within the observation period. Kaplan-Meier analyses showed that patients administered high dosages of ESAs had significantly worse survival than those administered low dosages of ESAs. A multivariate Cox regression identified that high dosages of ESAs could significantly predict mortality (ESA dosage &#x3e;10,000.0 IU/week, HR = 1.59, 95% confidence intervals (CIs) (1.04, 2.42), and <i>p</i> = 0.031). Our analysis also indicated a significant increase in the risk of mortality in patients with high ERI scores. Propensity score matching-analyses confirmed that ERI &#x3e; 12.80 could significantly predict mortality (HR = 1.56, 95% CI [1.11, 2.18], and <i>p</i> = 0.010). <b><i>Conclusions:</i></b> Our data suggested that ESA dosages &#x3e;10,000.0 IU/week in the first 3 months constitute an independent predictor of all-cause mortality among Chinese MHD patients. A higher degree of resistance to ESA was related to a higher risk of all-cause mortality.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Zaleska-Kociecka ◽  
K Witczak ◽  
K Bartolik ◽  
D Was ◽  
A Kleinork ◽  
...  

Abstract Background High mortality risk in heart failure (HF) is related to repeat HF hospitalizations but also individual patient characteristics. Purpose To evaluate the impact of HF re-/hospitalizations and patient-related factors (sex, HF etiology, age, comorbidity) on all-cause mortality. Methods Our study represents one of the most extensive retrospective cohort analyses consisting of 1,686,861 adult Polish HF patients who presented into public health system in years 2013–2018. It is a part of a nationwide National Health Fund registry covering out- and in-patient data for the entire Polish population (38,495,659 in 2013) since 2009. HF hospitalizations were extracted using ICD-10 coding, whereas the comorbidity was evaluated by means of Charlson Comorbidity Index (CCI). Results In years 2013–2018 the absolute number of HF hospitalizations in Poland grew by 33% to 264,808 in 2018, whereas the number of rehospitalizations increased 1.5-fold to reach 137,708 in 2018. In fact, nearly half of HF patients (n=817,432; 48.5%) experienced at least one hospitalization, while 15.4% (n=259,868) were rehospitalized during the study period. After initial hospitalization the readmission rate due to HF/all circulatory diseases at 30, 60, 180, 360, and 720 days was 10.4%/15.1%, 21.2%/28.3%, 43.9%/52.8%, 62%/70.4%, and 81%/87%, respectively. As compared to patients who were hospitalized just once, those who underwent at least one rehospitalization were more often female (p&lt;0.001), slightly older (p&lt;0.001), and with higher burden of comorbidities based on CCI (p&lt;0.001). Patient survival was highly dependent on hospitalization frequency (Fig. 1). Mean survival rate at day 720 was 66.4%, 59.8%, 54.9%, 51%, and 43.9% for 1st, 2nd, 3rd, 4th, and ≥5th hospitalization, respectively. After adjusting for age, sex, etiology (ischemic/non-ischemic) and CCI using a multivariate stratified Cox regression model, the estimated hazard ratios (HR) for all-cause mortality amounted to 1.22 (95% CI: 1.21–1.23, p&lt;0.001) for 2nd, 1.4 (95% CI: 1.39–1.42, p&lt;0.001) for 3rd, 1.58 (95% CI: 1.56–1.6, p&lt;0.001) for 4th, and 1.97 (95% CI: 1.95–1.98 p&lt;0.001) for 5th and subsequent hospitalizations, as compared to the first hospitalization. Conclusions Hospitalization rate in Poland is alarmingly high. Repeat HF hospitalizations strongly predict mortality rate for HF patients even after adjustment for age, sex, etiology, and comorbidity burden. Figure 1. Kaplan-Meier for survival post hosp. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): The project is co-financed by the European Union from the European Social Fund under the Operational Programme Knowledge Education Development and it is being carried out by the Analyses and Strategies Department of the Polish Ministry of Health.


Author(s):  
Marcela R. Entwistle ◽  
Donald Schweizer ◽  
Ricardo Cisneros

Abstract Purpose This study investigated the association between dietary patterns, total mortality, and cancer mortality in the United States. Methods We identified the four major dietary patterns at baseline from 13,466 participants of the NHANES III cohort using principal component analysis (PCA). Dietary patterns were categorized into ‘prudent’ (fruits and vegetables), ‘western’ (red meat, sweets, pastries, oils), ‘traditional’ (red meat, legumes, potatoes, bread), and ‘fish and alcohol’. We estimated hazard ratios for total mortality, and cancer mortality using Cox regression models. Results A total of 4,963 deaths were documented after a mean follow-up of 19.59 years. Higher adherence to the ‘prudent’ pattern was associated with the lowest risk of total mortality (5th vs. 1st quintile HR 0.90, 95% CI 0.82–0.98), with evidence that all-cause mortality decreased as consumption of the pattern increased. No evidence was found that the ‘prudent’ pattern reduced cancer mortality. The ‘western’ and the ‘traditional’ patterns were associated with up to 22% and 16% increased risk for total mortality (5th vs. 1st quintile HR 1.22, 95% CI 1.11–1.34; and 5th vs. 1st quintile HR 1.16, 95% CI 1.06–1.27, respectively), and up to 33% and 15% increased risk for cancer mortality (5th vs. 1st quintile HR 1.33, 95% CI 1.10–1.62; and 5th vs. 1st quintile HR 1.15, 95% CI 1.06–1.24, respectively). The associations between adherence to the ‘fish and alcohol’ pattern and total mortality, and cancer mortality were not statistically significant. Conclusion Higher adherence to the ‘prudent’ diet decreased the risk of all-cause mortality but did not affect cancer mortality. Greater adherence to the ‘western’ and ‘traditional’ diet increased the risk of total mortality and mortality due to cancer.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 282.2-282
Author(s):  
S. Ruiz-Simón ◽  
I. Calabuig ◽  
M. Gomez-Garberi ◽  
M. Andrés

Background:We have recently revealed by active screening that about a third of gout cases in the cardiovascular population is not registered in records [1], highlighting the value of field studies.Objectives:To assess whether gout screening in patients hospitalized for cardiovascular events may also help identify patients at higher risk of mortality after discharge.Methods:A retrospective cohort field study, carried out in 266 patients admitted for cardiovascular events in the Cardiology, Neurology and Vascular Surgery units of a tertiary centre in Spain. The presence of gout was established by records review and face-to-face interview, according to the 2015 ACR/EULAR criteria. The occurrence of mortality during follow-up and its causes were obtained from electronic medical records. The association between gout and subsequent mortality was tested using Cox regression models. Whether covariates affect the gout-associated mortality was also studied.Results:Of 266 patients recruited at baseline, 17 were excluded due to loss to follow-up (>6mo), leaving a final sample of 249 patients (93.6%). Thirty-six cases (14.5% of the sample) were classified as having gout: twenty-three (63.9%) had a previously registered diagnosis, while 13 (36.1%) had not and was established by the interview.After discharge, the mean follow-up was 19.9 months (SD ±8.6), with a mortality incidence of 21.6 deaths per 100 patient-years, 34.2% by cardiovascular causes.Gout significantly increased the risk of subsequent all-cause mortality, with a hazard ratio (HR) of 2.01 (95%CI 1.13 to 3.58). When the analysis was restricted to gout patients with registered diagnosis, the association remained significant (HR 2.89; 95%CI 1.54 to 5.41).The adjusted HR for all-cause mortality associated with gout was 1.86 (95% CI 1.01-3.40). Regarding the causes of death, both cardiovascular and non-cardiovascular were numerically increased.Secondary variables rising the mortality risk in those with gout were age (HR 1.07; 1.01 to 1.13) and coexistent renal disease (HR 4.70; 1.31 to 16.84), while gender, gout characteristics and traditional risk factors showed no impact.Conclusion:Gout was confirmed an independent predictor of subsequent all-cause mortality in patients admitted for cardiovascular events. Active screening for gout allowed identifying a larger population at high mortality risk, which may help tailor optimal management to minimize the cardiovascular impact.References:[1]Calabuig I, et al. Front Med (Lausanne). 2020 Sep 29;7:560.Disclosure of Interests:Silvia Ruiz-Simón: None declared, Irene Calabuig: None declared, Miguel Gomez-Garberi: None declared, Mariano Andrés Speakers bureau: Grunenthal, Menarini, Consultant of: Grunenthal, Grant/research support from: Grunenthal


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