Protective lifestyle behaviours and lipoprotein particle subclass profiles in a middle-to older-aged population

Background and aims: Lipoprotein particle size is associated with increased atherosclerosis and cardiovascular disease risk. Certain lifestyle behaviours may be cardioprotective. We examined lipoprotein particle size and concentration relationships with a protective lifestyle behaviour (PLB) score. Methods: This was a cross-sectional analysis of 2045 middle-to older-aged adults. Lipoprotein particle subclass size and concentrations were determined using nuclear magnetic resonance spectroscopy. Five protective behaviours included never smoking, moderate alcohol intake, moderate to vigorous physical activity, a high-quality diet (upper 40% Dietary Approaches to Stop Hypertension score) and a normal body mass index (BMI) (18.5–24.9 kg/m2). Linear and logistic regression analyses tested individual protective behaviour and PLB score associations with lipoprotein subclasses. Results: Individual behaviour associations varied according to lipoprotein subclass, with normal BMI showing the greatest number of significant relationships. Logistic regression analyses revealed that subjects with the fewest number of protective behaviours had 1.4–2.8 increased odds of having less favourable lipoprotein profiles defined as above or below median level lipoprotein particle subclass size or concentration. Following additional adjustment for BMI, significant trend relationships were observed between the PLB score and large and medium very low-density lipoprotein (p = 0.001 and p < 0.001), total and smaller low-density lipoprotein (LDL) concentrations (p = 0.008 and p < 0.001), LDL size (p = 0.003) and a lipoprotein insulin resistance score (p = 0.003). Conclusions: Results show a cumulative protective effect of healthy lifestyle behaviours against an unfavourable potentially pro-atherogenic lipoprotein profile in middle-to older-aged adults, highlighting the importance of lifestyle promotion in healthy ageing

Dietary quality determined by the Healthy Eating Index-2015 and biomarkers of chronic low-grade inflammation: a cross-sectional analysis in middle-to-older aged adults

Low-grade systemic inflammation is associated with a range of chronic diseases. Diet may modulate inflammation and represents a promising therapeutic target to reduce metabolic dysfunction. To date, no study has examined Healthy Eating Index-2015 (HEI-2015) diet score associations with biomarkers of inflammation. Thus, our objective was to assess relationships between the HEI-2015 score and a range of inflammatory biomarkers in a cross-sectional sample of 1989 men and women aged 46-73 years, to test the hypothesis that better dietary quality would be associated with more favourable circulating levels of inflammatory biomarkers. Pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, coagulation factors and white blood cell counts were determined. Correlation and linear regression analyses were used to test HEI-2015 diet score relationships with biomarker concentrations. Higher dietary quality as determined by the HEI-2015 was associated with lower c-reactive protein (CRP) and interleukin 6 concentrations, white blood cell (WBC) counts and its constituents, adjusting for sex and age. Associations with CRP concentrations and WBC counts persisted in the fully adjusted models. No associations with complement component 3, tumour necrosis factor alpha, adiponectin, leptin, resistin or plasminogen activator inhibitor-1 levels were identified. Our data suggest that dietary quality, determined by the HEI-2015 score, in middle-to-older aged adults is associated with inflammatory biomarkers related to cardiometabolic health

Associations between the nutrient profiling system underlying the nutri-score nutrition label and biomarkers of chronic low-grade inflammation: a cross-sectional analysis of a middle- to older-aged population

Low-grade systemic inflammation is associated with a range of conditions. Diet may modulate inflammation and public health strategies are needed to guide consumers' dietary choices and help prevent diet-related disease. The Food Standards Agency nutrient profiling system (FSAm-NPS) constitutes the basis of the five-colour front-of-pack Nutri-Score labelling system. No study to date has examined FSAm-NPS dietary index associations with biomarkers of inflammation. Therefore, our objective was to test relationships between the FSAm-NPS and a range of inflammatory biomarkers in a cross-sectional sample of 2006 men and women aged 46-73 years. Individual participant FSAm-NPS scores were derived from food frequency questionnaires. Pro-inflammatory cytokine, adipocytokine, acute-phase response protein, coagulation factor and white blood cell count concentrations were determined. Correlation and linear regression analyses were used to examine FSAm-NPS relationships with biomarker levels. In crude and adjusted analyses, higher FSAm-NPS scores, reflecting poorer nutritional quality, were consistently and positively associated with biomarkers. In fully adjusted models, significant associations with concentrations of complement component 3, c-reactive protein, interleukin 6, tumour necrosis factor alpha, resistin, white blood cell count, neutrophils, eosinophils and the neutrophil-to-lymphocyte ratio persisted. These results suggest that dietary quality, determined by Nutri-Score rating, is associated with inflammatory biomarkers related to health

Comparing dietary score associations with lipoprotein particle subclass profiles: a cross-sectional analysis of a middle-to older-aged population

Background and objectives: Lipoprotein particle concentrations and size are associated with increased risk for atherosclerosis and premature cardiovascular disease. Studies also suggest that certain dietary behaviours may be cardioprotective. Limited comparative data regarding any dietary score/index-lipoprotein particle subclass associations exist. Thus, our objective was to assess relationships between the Dietary Approaches to Stop Hypertension (DASH), Health Eating Index-2015 (HEI-2015), Mediterranean Diet (MD) and Energy-adjusted Dietary Inflammatory Index (E-DII™) scores and plasma lipids and lipoprotein profiles to test the hypothesis that healthier diet (better quality and more anti-inflammatory) would be associated with a more favourable lipoprotein profile. Materials and methods: This was a cross-sectional study of 1862 men and women aged 46–73 years, randomly selected from a large primary care centre in Ireland. DASH, HEI-2015, MD and E-DII scores were derived from food frequency questionnaires. Lipoprotein subclass particle concentrations and size were determined using nuclear magnetic resonance spectroscopy. Correlation and multivariate-adjusted linear regression analyses with correction for multiple testing were performed to examine dietary score relationships with lipoprotein particle subclasses. Results: In fully adjusted models, higher diet quality or a more anti-inflammatory diet was associated with less large and medium very low-density lipoprotein (VLDL) (DASH and HEI-2015), intermediate-density lipoprotein (IDL) (DASH, MD and E-DII) and small high-density lipoprotein (HDL) (DASH, HEI-2015 and E-DII) particles. After accounting for multiple testing, relationships with large VLDL (DASH: β = -0.102, p = .037), IDL (DASH: β = -0.089, p = .037) and small HDL (DASH: β = -0.551, p = .014 and E-DII: β = 0.483, p = .019) concentrations persisted. Conclusions: These findings provide evidence that better diet quality, determined by the DASH score, may be more closely associated with a more favourable lipoprotein particle subclass profile in middle-to older-aged adults than the HEI-2015, MD and E-DII scores. A less pro-atherogenic lipoprotein status may be a potential mechanism underlying the cardioprotective effects of higher dietary quality

Comparing Dietary Score Associations With Lipoprotein Particle Subclass Profiles: A Cross-Sectional Analysis of a Middle-to Older-Aged Population

Background and objectives: Lipoprotein particle concentrations and size are associated with increased risk for atherosclerosis and premature cardiovascular disease. Studies also suggest that certain dietary behaviours may be cardioprotective. Limited comparative data regarding any dietary score/index-lipoprotein particle subclass associations exist. Thus, our objective was to assess relationships between the Dietary Approaches to Stop Hypertension (DASH), Health Eating Index-2015 (HEI-2015), Mediterranean Diet (MD) and Energy-adjusted Dietary Inflammatory Index (E-DII™) scores and plasma lipids and lipoprotein profiles to test the hypothesis that healthier diet (better quality and more anti-inflammatory) would be associated with a more favourable lipoprotein profile. Materials and methods: This was a cross-sectional study of 1862 men and women aged 46–73 years, randomly selected from a large primary care centre in Ireland. DASH, HEI-2015, MD and E-DII scores were derived from food frequency questionnaires. Lipoprotein subclass particle concentrations and size were determined using nuclear magnetic resonance spectroscopy. Correlation and multivariate-adjusted linear regression analyses with correction for multiple testing were performed to examine dietary score relationships with lipoprotein particle subclasses. Results: In fully adjusted models, higher diet quality or a more anti-inflammatory diet was associated with less large and medium very low-density lipoprotein (VLDL) (DASH and HEI-2015), intermediate-density lipoprotein (IDL) (DASH, MD and E-DII) and small high-density lipoprotein (HDL) (DASH, HEI-2015 and E-DII) particles. After accounting for multiple testing, relationships with large VLDL (DASH: β = -0.102, p = .037), IDL (DASH: β = -0.089, p = .037) and small HDL (DASH: β = -0.551, p = .014 and E-DII: β = 0.483, p = .019) concentrations persisted. Conclusions: These findings provide evidence that better diet quality, determined by the DASH score, may be more closely associated with a more favourable lipoprotein particle subclass profile in middle-to older-aged adults than the HEI-2015, MD and E-DII scores. A less pro-atherogenic lipoprotein status may be a potential mechanism underlying the cardioprotective effects of higher dietary quality

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Clinical research nurse predictions of trial failure, recruitment and retention: a case for their early inclusion in trial design

Abstract Background Clinical research nurses are a key part of the clinical trial team but typically get involved later in the trial, usually during recruitment. The purpose of our study was to establish if CRNs who read the trial protocol can predict the performance of the trial. Methods We randomly selected 18 trial protocols with three statuses, terminated, withdrawn, and completed, from ClinicalTrials.gov, between 2014 and 2018 inclusive. We gave the protocols to five CRNs, asked them to make a judgement and provide a reason for that judgement (via a 12-item questionnaire) on the status of the trial (terminated, withdrawn or completed), if the trial met its recruitment target, if it recruited on time, and if it retained its participants. We also asked if it was likely a CRN was involved in the design of the trial. The CRNs were blinded to the study outcomes, did not receive any training on how to read a protocol and were prohibited from using/abstained from using the internet while completing the task. Results Twenty-three questionnaires on 23 trial protocols (18 different trials) were completed by 5 CRNs. The CRNs correctly predicted the trial status 48%, 95% CI: 29–67% (11/23) of the time; successful/unsuccessful recruitment 74%, 95% CI: 54–87% (17/23) of the time; on-time recruitment 70%, 95% CI: 49–84% (16/23) of the time; and participant retention 52%, 95% CI: 33–71% (12/23). CRNs identified 100% (sensitivity) of sites that hit their target and 63%, 95% CI: 36–84% (specificity) of sites that missed their target. Conclusions CRNs are very good judges of trial recruitment and site performance issues and are a vital part of the clinical trial team. Taken with the ESP (Estimating Site Performance) study, we have made a strong case for broadening the trial team at the trial design stage. Early engagement of a broad skillset can potentially offset problems of recruitment, retention and trial failure

RESEARCH ARTICLE HbA1c Alone Is a Poor Indicator of Cardiometabolic Risk in Middle-Aged Subjects with Pre-Diabetes but Is Suitable for Type 2 Diabetes Diagnosis: A Cross-Sectional Study

Objectives Glycated haemoglobin A1c (HbA1c) measurement is recommended as an alternative to fast-ing plasma glucose (FPG) for the diagnosis of pre-diabetes and type 2 diabetes. However, evidence suggests discordance between HbA1c and FPG. In this study we examine a range of metabolic risk features, pro-inflammatory cytokines, acute-phase response proteins, coagulation factors and white blood cell counts to determine which assay more accurately identifies individuals at increased cardiometabolic risk. Materials and Methods This was a cross-sectional study involving a random sample of 2,047 men and women aged 46-73 years. Binary and multinomial logistic regression were employed to examine risk feature associations with pre-diabetes [either HbA1c levels 5.7-6.4 % (39-46 mmol/mol) or impaired FPG levels 5.6-6.9 mmol/l] and type 2 diabetes [either HbA1c levels&gt;6.5 % (&gt;48 mmol/mol) or FPG levels&gt;7.0 mmol/l]. Receiver operating characteristic curve analysis was used to evaluate the ability of HbA1c to discriminate pre-diabetes and diabetes define

Descriptive characteristics of the study population according to depression and well-being score quartiles (n = 1821).

Descriptive characteristics of the study population according to depression and well-being score quartiles (n = 1821).</p