Associations between disease severity, coping and dimensions of health-related quality of life in patients admitted for elective coronary angiography – a cross sectional study

<p>Abstract</p> <p>Background</p> <p>In patients with suspected coronary artery disease (CAD), the overall aim was to analyse the relationships between disease severity and both mental and physical dimensions of health related quality of life (HRQOL) using a modified version of the Wilson and Cleary model.</p> <p>Methods</p> <p>Using a cross-sectional design, 753 patients (74% men), mean age 62 years, referred for elective cardiac catheterisation were included. The measures included 1) physiological factors 2) symptoms (disease severity, self-reported symptoms, anxiety and depression 3) self-reported functional status, 4) coping, 5) perceived disease burden, 6) general health perception and 7) overall quality of life. To analyse relationships, we performed linear and ordinal logistic regressions.</p> <p>Results</p> <p>CAD and left ventricular ejection fraction (LVEF) were significantly associated with symptoms of angina pectoris and dyspnea. CAD was not related to symptoms of anxiety and depression, but less depression was found in patients with low LVEF. Angina pectoris and dyspnea were both associated with impaired physical function, and dyspnea was also negatively related to social function. Overall, less perceived burden and better overall QOL were observed in patients using more confronting coping strategy.</p> <p>Conclusion</p> <p>The present study demonstrated that data from cardiac patients to a large extent support the suggested model by Wilson and Cleary.</p

Association of Markers of Inflammation, the Kynurenine Pathway and B Vitamins with Age and Mortality, and a Signature of Inflammaging

Under embargo until: 2022-06-12Background 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 and (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 2 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, interleukin (IL)-6, tumor necrosis factor alpha (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, C-reactive protein, quinolinic acid, PAr index, and KTR. The inflammaging signature included 10 markers and was strongly associated with mortality (hazard ratio [HR] per SD = 1.40, 95% CI: 1.24–1.57, p = 2 × 10−8), similar to scores based on all age-associated (HR = 1.38, 95% CI: 1.23–1.55, p = 4 × 10−8) and mortality-associated markers (HR = 1.43, 95% CI: 1.28–1.60, p = 1 × 10−10), 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 10 markers was strongly associated with mortality.acceptedVersio

Air ambulance services in the Arctic 1999-2009 : a Norwegian study.

Air ambulance services in the Arctic have to deal with remote locations, long distances, rough weather conditions and seasonable darkness. Despite these challenges, the people living in the area expect a high quality of specialist health care. The objective of this study was to analyse the air ambulance operations performed in the Norwegian Arctic and study variations in diagnoses and flight patterns around the year. A retrospective analysis. All air ambulance operations performed during the time 1999 – 2009 period were analysed. The subjects were patients transported and flights performed. The primary outcome measures were patients’ diagnoses and task patterns around the year. A total of 345 patients were transported and 321 flights performed. Coronary heart and vascular disease, bone fractures and infections were the most common diagnoses. Most patients (85%) had NACA score 3 or 4. Half of all fractures occurred in April and August. Most patients were males (66%), and one fourth was not Norwegian. The median flying time (one way) was 3 h 33 m. Ten percent of the flights were delayed, and only 14% were performed between midnight and 8.00 AM. The period April to August was the busiest one (58% of operations). Norway has run a safe air ambulance service in the Arctic for the last 11 years. In the future more shipping and polar adventure operations may influence the need for air ambulances, especially during summer and autumn

Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Previous studies have suggested that components of one-carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case-control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5'-phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these association were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared with high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development. This article is protected by copyright. All rights reserved

Human genetic selection on the MTHFR 677C>T polymorphism

<p>Abstract</p> <p>Background</p> <p>The prevalence of genotypes of the 677C>T polymorphism for the MTHFR gene varies among humans. In previous studies, we found changes in the genotypic frequencies of this polymorphism in populations of different ages, suggesting that this could be caused by an increase in the intake of folate and multivitamins by women during the periconceptional period. The aim was to analyze changes in the allelic frequencies of this polymorphism in a Spanish population, including samples from spontaneous abortions (SA).</p> <p>Methods</p> <p>A total of 1305 subjects born in the 20th century were genotyped for the 677C>T polymorphism using allele specific real-time PCR with Taqman^®probes. A section of our population (n = 276) born in 1980–1989 was compared with fetal samples (n = 344) from SA of unknown etiology from the same period.</p> <p>Results</p> <p>An increase in the frequency of the T allele (0.38 vs 0.47; p < 0.001) and of the TT genotype (0.14 vs 0.24; p < 0.001) in subjects born in the last quarter of the century was observed. In the 1980–1989 period, the results show that the frequency of the wild type genotype (CC) is about tenfold lower in the SA samples than in the controls (0.03 vs 0.33; p < 0.001) and that the frequency of the TT genotype increases in the controls (0.19 to 0.27) and in the SA samples (0.20 to 0.33 (p < 0.01)); r = 0.98.</p> <p>Conclusion</p> <p>Selection in favor of the T allele has been detected. This selection could be due to the increased fetal viability in early stages of embryonic development, as is deduced by the increase of mutants in both living and SA populations.</p

Vitamin B6 catabolism and lung cancer risk:Results from the Lung Cancer Cohort Consortium (LC3)

Background Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. Materials and methods For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. Results PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). Conclusion Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor

Circulating B-vitamin biomarkers and B-vitamin supplement use in relation to quality of life in patients with colorectal cancer: results from the FOCUS consortium

Background: B vitamins have been associated with the risk and progression of colorectal cancer (CRC), given their central roles in nucleotide synthesis and methylation, yet their association with quality of life in established CRC is unclear.Objectives: To investigate whether quality of life 6 months postdiagnosis is associated with: 1) circulating concentrations of B vitamins and related biomarkers 6 months postdiagnosis; 2) changes in these concentrations between diagnosis and 6 months postdiagnosis; 3) B-vitamin supplement use 6 months postdiagnosis; and 4) changes in B-vitamin supplement use between diagnosis and 6 months postdiagnosis.Methods: We included 1676 newly diagnosed stage I-III CRC patients from 3 prospective European cohorts. Circulating concentrations of 9 biomarkers related to the B vitamins folate, riboflavin, vitamin B6, and cobalamin were measured at diagnosis and 6 months postdiagnosis. Information on dietary supplement use was collected at both time points. Health-related quality of life (global quality of life, functioning scales, and fatigue) was assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 6 months postdiagnosis. Confounder-adjusted linear regression analyses were performed, adjusted for multiple testing.Results: Higher pyridoxal 5'-phosphate (PLP) was cross-sectionally associated with better physical, role, and social functioning, as well as reduced fatigue, 6 months postdiagnosis. Associations were observed for a doubling in the hydroxykynurenine ratio [3-hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3-hydroxyanthranilic acid + anthranilic acid); an inverse marker of vitamin B6] and both reduced global quality of life (beta = -3.62; 95% CI: -5.88, -1.36) and worse physical functioning (beta = -5.01; 95% CI: -7.09, -2.94). Dose-response relations were observed for PLP and quality of life. No associations were observed for changes in biomarker concentrations between diagnosis and 6 months. Participants who stopped using B-vitamin supplements after diagnosis reported higher fatigue than nonusers.Conclusions: Higher vitamin B6 status was associated with better quality of life, yet limited associations were observed for the use of B-vitamin supplements. Vitamin B6 needs further study to clarify its role in relation to quality of life

MTHFR polymorphisms in gastric cancer and in first-degree relatives of patients with gastric cancer

Two common mutations, 677 C→T and a1298 A→C, in the methylenetetrahydrofolate reductase gene (MTHFR) reduce the activity of MTHFR and folate metabolism. Familial aggregation in a variable but significant proportion of gastric cancer (GC) cases suggests the importance of genetic predisposition in determining risk. In this study, we evaluate MTHFR polymorphisms in 57 patients with a diagnosis of GC, in 37 with a history of GC in first-degree relatives (GC-relatives), and in 454 blood donors. Helicobacter pylori (HP) infection was also determined. An increased risk was found for 677TT in GC patients with respect to blood donors (odds ratio (OR) = 1.98), and statistical significance was sustained when we compared sex–age-matched GC patients and donors (OR = 2.37). The 677TT genotype association with GC was found in women (OR = 3.10), while a reduction in the 667C allele frequency was present in both the sex. No statistically significant association was detected when 677–1298 genotype was stratified by sex and age. Men of GC-relatives showed a higher 1298C allele frequency than donors (OR = 4.38). Between GC and GC-relatives, HP infection frequency was similar. In conclusion, overall findings support the hypothesis that folate plays a role in GC risk. GC-relatives evidence a similar 677TT frequency to that found in the general population

Influence of folate status on genomic DNA methylation in colonic mucosa of subjects without colorectal adenoma or cancer

DNA hypomethylation may increase the risk of colorectal cancer. The main aim of this study was to assess the influence of folate status (serum and erythrocyte folate and plasma homocysteine concentrations) on DNA methylation. Methylenetetrahydrofolate reductase (MTHFR 677C → T and 1298A → C), methionine synthase (MS 2756A → G) and cystathionine synthase (CBS 844ins68) polymorphisms were measured to account for potential confounding effects on folate status and DNA methylation. A total of 68 subjects (33 men and 35 women, 36–78 years) free from colorectal polyps or cancer were recruited in a cross-sectional study. Tissue biopsies were obtained at colonoscopy for the determination of DNA methylation in colonic mucosa using an in vitro radiolabelled methyl acceptance assay. Serum and erythrocyte folate were inversely correlated with plasma homocysteine (r=−0.573, P<0.001 and r=−0.307, P=0.01 respectively) and DNA hypomethylation in colonic mucosa (r=−0.311, P=0.01 and r=−0.356, P=0.03). After adjusting for gender, age, body mass index, smoking and genotype, there were weak negative associations between serum and erythrocyte folate and colonic DNA hypomethylation (P=0.07 and P=0.08, respectively)