Hospital-treated prevalent infections, the plasma proteome and incident dementia among UK older adults.
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ABSTRACT:
SUBMITTER: Beydoun MA
PROVIDER: S-EPMC10755048 | biostudies-literature | 2023 Dec
REPOSITORIES: biostudies-literature
Publications
Hospital-treated prevalent infections, the plasma proteome and incident dementia among UK older adults.
Beydoun May A MA Beydoun Hind A HA Noren Hooten Nicole N Meirelles Osorio O Li Zhiguang Z El-Hajj Ziad W ZW Weiss Jordan J Maino Vieytes Christian A CA Launer Lenore J LJ Evans Michele K MK Zonderman Alan B AB
iScience 20231123 12
The plasma proteome can mediate the association of hospital-treated infections with dementia incidence. We screened up to 37,269 UK Biobank participants aged 50-74 years for the presence of a prevalent hospital-treated infection, subsequently tested as a predictor for ≤1,463 plasma proteins and dementia incidence. Four-way decomposition models decomposed infection-dementia total effect into pure mediation, pure interaction, neither or both through the plasma proteome. Hospital-treated infections ...[more]
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Project description:AimsThe role of ceramides in the pathogenesis of type 2 diabetes mellitus (T2DM) is incompletely characterized. Given that ceramides represent therapeutic targets to disrupt the euglycemia-T2DM transition, we aimed to characterize their association with prevalent and incident T2DM in a novel cohort.MethodsWe examined the cross-sectional and longitudinal association of baseline ceramides with prevalent and incident T2DM among 1423 adults (47% women; median (range) baseline age 72 (51-95) years) in the Mayo Clinic Study of Aging cohort. We examined the associations of ceramides with prevalent T2DM (adjusted odds ratio [95% confidence interval]) at baseline and incident T2DM (adjusted hazard ratio [95% confidence interval]) during median follow-up of 6.2 years, after adjusting for demographic and metabolic factors.ResultsAmong 1423 adults, there were 222 prevalent and 37 incident cases of T2DM. In cross-sectional analyses, higher levels of ceramide C16:0 were associated with lower odds of prevalent T2DM (aOR 0.84 [0.71-0.99];P = 0.03) whereas C18:0 (aOR 1.27 [1.06-1.42];P = 0.01), C18:0/16:0 (aOR 1.41 [1.22-1.62]; P < 0.001) and C18:0/24:0 (aOR 1.22 [1.05-1.41]; P = 0.01) were associated with higher odds. In Cox hazard regression models, C18:0/16:0 (aHR 1.63 [1.26-2.10];P < 0.001) and C18:0 (aHR 1.53 [1.12-2.08];P = 0.01) were associated with increased risk of incident T2DM.ConclusionsIn this prospective population-based cohort, ceramides were associated with prevalent T2DM (C16:0,C18:0, C18:0/C16:0 ratio, C18:0/C24:0 ratio) and incident T2DM (C18:0, C18:0/C16:0 ratio) and could suggest targets for the primary and secondary prevention of T2DM.
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Project description:Background and aimsFew population-based cohort studies, including both men and women, have explored circulating proteins associated with incident myocardial infarction (MI). This study investigated the relationships between circulating cardiometabolic-related proteins and MI risk using cohort-based and Mendelian randomization (MR) analyses and explored potential sex-specific differences.MethodsThe discovery cohort included 11 751 Swedish adults (55-93 years). Data on 259 proteins assessed with Olink proximity extension assays, biochemical, and questionnaire-based information were used. Participants were followed up for incident MI and death over 8 years through linkage to Swedish registers. Replication analyses were conducted on the UK Biobank sample (n = 51 613). In MR analyses, index cis-genetic variants strongly related to the proteins were used as instrumental variables. Genetic association summary statistic data for MI were obtained from the CARDIoGRAMplusC4D consortium and FinnGen.ResultsForty-five proteins were associated with incident MI in discovery and replication samples following adjustment for potential confounders and multiple testing. In the secondary analysis, 13 of the protein associations were sex-specific, with most associations identified among women. In MR analysis, genetically predicted higher levels of renin, follistatin, and retinoic acid receptor responder protein 2 were linked to an increased risk of MI. Tissue factor pathway inhibitor, tumor necrosis factor receptors 1 and 2, placenta growth factor had an inverse association with MI.ConclusionsThis study identified both new and confirmed previously established associations between circulating proteins and incident MI and, for the first time, suggested sex-specific patterns in multiple protein-MI associations.
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Project description:BackgroundAlthough loneliness and social isolation have been linked to an increased risk of non-communicable diseases such as cardiovascular disease and dementia, their association with the risk of severe infection is uncertain. We aimed to examine the associations between loneliness and social isolation and the risk of hospital-treated infections using data from two independent cohort studies.MethodsWe assessed the association between loneliness and social isolation and incident hospital-treated infections using data for participants from the UK Biobank study aged 38-73 years at baseline and participants from the nationwide population-based Finnish Health and Social Support (HeSSup) study aged 20-54 years at baseline. For inclusion in the study, participants had to be linked to national health registries, have no history of hospital-treated infections at or before baseline, and have complete data on loneliness or social isolation. Participants with missing data on hospital-treated infections, loneliness, and social isolation were excluded from both cohorts. The outcome was defined as a hospital admission with a primary diagnosis of infection, ascertained via linkage to electronic health records.FindingsAfter exclusion of 8·6 million participants for not responding or not providing appropriate consent, the UK Biobank cohort consisted of 456 905 participants (249 586 women and 207 319 men). 26 860 (6·2%) of 436 001 participants with available data were reported as being lonely and 40 428 (9·0%) of 448 114 participants with available data were socially isolated. During a median 8·9 years (IQR 8·0-9·6) of follow-up, 51 361 participants were admitted to hospital due to an infectious disease. After adjustment for age, sex, demographic and lifestyle factors, and morbidities, loneliness was associated with an increased risk of a hospital-treated infection (hazard ratio [HR] 1·12 [95% CI 1·07-1·16]), whereas social isolation was not (HR 1·01 [95% CI 0·97-1·04]). Of 64 797 individuals in the HeSSup cohort, 18 468 (11 367 women and 7101 men) were eligible for inclusion. 4466 (24·4%) of 18 296 were lonely and 1776 (9·7%) of 18 376 socially isolated. During a median follow-up of 10·0 years (IQR 10·0-10·1), 814 (4·4%) participants were admitted to hospital for an infectious disease. The HRs for the HeSSup study replicated those in the UK Biobank (multivariable-adjusted HR for loneliness 1·32 [95% CI 1·06-1·64]; 1·08 [0·87-1·35] for social isolation).InterpretationLoneliness might increase susceptibility to severe infections, although the magnitude of this effect appears modest and residual confounding cannot be excluded. Interventional studies are required before policy recommendations can advance.FundingAcademy of Finland, the UK Medical Research Council, and Wellcome Trust UK.
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Project description:ObjectivesUK Biobank is a UK-wide cohort of 502,655 people aged 40-69, recruited from National Health Service registrants between 2006-10, with healthcare data linkage. Type 2 diabetes is a key exposure and outcome. We developed algorithms to define prevalent and incident diabetes for UK Biobank. The algorithms will be implemented by UK Biobank and their results made available to researchers on request.MethodsWe used UK Biobank self-reported medical history and medication to assign prevalent diabetes and type, and tested this against linked primary and secondary care data in Welsh UK Biobank participants. Additionally, we derived and tested algorithms for incident diabetes using linked primary and secondary care data in the English Clinical Practice Research Datalink, and ran these on secondary care data in UK Biobank.Results and significanceFor prevalent diabetes, 0.001% and 0.002% of people classified as "diabetes unlikely" in UK Biobank had evidence of diabetes in their primary or secondary care record respectively. Of those classified as "probable" type 2 diabetes, 75% and 96% had specific type 2 diabetes codes in their primary and secondary care records. For incidence, 95% of people with the type 2 diabetes-specific C10F Read code in primary care had corroborative evidence of diabetes from medications, blood testing or diabetes specific process of care codes. Only 41% of people identified with type 2 diabetes in primary care had secondary care evidence of type 2 diabetes. In contrast, of incident cases using ICD-10 type 2 diabetes specific codes in secondary care, 77% had corroborative evidence of diabetes in primary care. We suggest our definition of prevalent diabetes from UK Biobank baseline data has external validity, and recommend that specific primary care Read codes should be used for incident diabetes to ensure precision. Secondary care data should be used for incident diabetes with caution, as around half of all cases are missed, and a quarter have no corroborative evidence of diabetes in primary care.
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