Population-based Prospective Cohort Research Articles

Longitudinal cardiac imaging for assessment of myocardial injury in non-hospitalised community-dwelling individuals after COVID-19 infection: the Rotterdam Study

BackgroundThe aim of this study was to assess the presence of myocardial injury after COVID-19 infection and to evaluate the relation between persistent cardiac symptoms after COVID-19 and myocardial function...

Association of weight change with cardiovascular events and all-cause mortality in obese participants with cardiovascular disease: a prospective cohort study

BackgroundStudies have examined the association between weight change and risk of cardiovascular (CV) outcomes in the general population. However, very few literature reported the association among obese people with established...

Smoking cessation is a protective factor for lung cancer onset and mortality: a population-based prospective cohort study

BackgroundSmoking is a pivotal modifiable risk factor for lung cancer (LC). Previous studies have indicated that a smoking cessation program might be incorporated into the LC screening program. However, the effects of smoking cessation and its duration with the age at onset (AAO) of LC, all-cause mortality, and LC-specific mortality remain unclear. We aimed to comprehensively investigate the association of smoking cessation-related behaviors on the AAO of LC, LC-specific and all-cause mortality.MethodsA total of 2671 smokers with LC as the primary site from the UK Biobank were included in this study, with a 7:3 ratio assigned randomly to a discovery set (n = 1872) and a validation set (n = 799). Generalized linear regression models were used for AAO of LC outcomes and Cox models for mortality outcomes.ResultsParticipants over 60 years old could still benefit from smoking cessation to prolong AAOs (β = 1.613 for men, P = 0.003; β = 1.533 for women, P = 0.018). A cessation duration of > 15 years was associated with a later AAO in men (P < 0.001). Moreover, smoking cessation before 60 years old, especially among those under 40 years, was significantly associated with a lower risk of all-cause mortality (men: hazard ratio (HR): 0.65 [95% confidence interval 0.51–0.83]; women: 0.62 [0.47–0.83]) and LC-specific mortality (men: 0.67 [0.51–0.87]; women: 0.68 [0.50–0.92]). Compared with continuous smokers, former smokers who quit smoking for more than 15 years had a lower risk of all-cause mortality (men: 0.70 [0.59–0.84]; women: 0.68 [0.56–0.84]) and LC-specific mortality (men: 0.71 [0.59–0.87]; women: 0.69 [0.56–0.86]).ConclusionsSmoking cessation after 60 years old may still be helpful for a later AAO of LC. Former smokers who quit smoking for more than 15 years have a reduced risk of developing LC and mortality.

Maternal seafood intake, dietary contaminant exposure, and risk of juvenile idiopathic arthritis: exploring gene-environment interactions

ObjectivesJuvenile idiopathic arthritis (JIA) originates from a complex interplay between genetic and environmental factors. We investigated the association between seafood intake and dietary contaminant exposure during pregnancy and JIA risk, to identify sex differences and gene-environment interactions.MethodsWe used the Norwegian Mother, Father, and Child Cohort Study (MoBa), a population-based prospective pregnancy cohort (1999–2008). JIA patients were identified through the Norwegian Patient Registry, with remaining mother-child pairs serving as controls. We assessed maternal seafood intake and dietary contaminants typically found in seafood using a food frequency questionnaire completed during pregnancy, mainly comparing high (≥90th percentile, P90) vs low (&amp;lt;P90) intake. Multivariable logistic regression calculated adjusted odds ratios (aOR), including sex-stratification analyses. A polygenic risk score (PRS) for JIA was used in a subsample to assess gene-environment interactions.ResultsWe identified 217 JIA patients and 71,884 controls. High vs low maternal intake of lean/semi-oily fish was associated with JIA (aOR 1.51, 95% CI 1.02-2.22), especially among boys (aOR 2.13, 95% CI 1.21-3.75). A significant gene-environment interaction was observed between total fish intake and PRS, with high fish intake associated with JIA primarily in those with low PRS (p&amp;lt;0.03). We found no associations between high vs low exposure to other types of seafood or environmental contaminants and JIA.ConclusionsWe found a modestly increased risk of JIA associated with high intake of lean/semi-oily fish during pregnancy, not explained by estimated exposure to dietary contaminants. Our data suggest a more pronounced association in children with a lower genetic predisposition for JIA.

Relationship between LE8 score and peripheral arterial disease from NHANES perspective.

Background: This study examined the link between the Life's Essential 8 (LE8) metric and peripheral artery disease (PAD) prevalence in the U.S. Patients and methods: This population-based prospective cohort study analyzed data from 6,076 participants aged 20 years and older from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. LE8 scores were categorized into low, moderate, and high cardiovascular health (CVH) levels. Multivariable weighted logistic regression and subgroup analyses were performed to examine the relationship between CVH and PAD, adjusting for demographic and clinical variables. Results: In final analysis, a total of 6,076 individuals were included, with a mean age of 59.41±12.80 years and 51.3% (n=3,115) being male. The prevalence of PAD was 6.9% (n=418). After adjusting for confounding factors, compared to participants with low CVH, those with moderate CVH had a 34% lower risk of PAD (OR: 0.66, 95% CI: 0.53-0.82), and those with high CVH had a 62% lower risk of PAD (OR: 0.38, 95% CI: 0.25-0.58). Conclusions: In conclusion, we report that lower CVH scores are associated with higher PAD risk among U.S. adults. These findings may contribute to the prevention strategies for PAD.

Occupation and 11-year lung function decline in the HUNT Study.

The association between occupational titles and lung function has mostly been examined through cross-sectional studies. Preventive measures are expected to mitigate adverse effects; hence, updated estimates are necessary. To study change in lung function measured by spirometry across occupations. This population-based prospective cohort study comprised 5618 working adult participants of the Trøndelag Health Study (HUNT3, 2005-07), Norway. Among these, 3800 individuals (43% men, mean age 42 years, range 20-55) also attended HUNT4 (2017-19). We analysed longitudinal decline in forced expiratory volume in 1 second (FEV1) z-score during the 11-year follow-up by occupation (white-collar workers as reference category), in mixed models, adjusting for age, sex and smoking. We assessed the prevalence of self-reported respiratory symptoms and disease in the working population in HUNT4 (n = 32 124) and HUNT3 (n = 32 070). Compared with white-collar workers, agricultural workers and 'drivers and mobile plant operators', had larger declines in FEV1 z-score during follow-up. In sex-stratified analyses, men defined as agricultural workers and 'drivers and mobile plant operators' had larger declines than white-collar workers. Among women, who were underrepresented in many blue-collar jobs, workers classified as 'machine operators and assemblers' experienced greater declines. In the working population in HUNT4, the prevalence of respiratory symptoms in connection with work was 8%, and lower among white-collar workers (6%) than blue-collar workers (14%). Although certain workers in Norway remain at risk for occupational lung function decline, there were modest differences between occupations. The findings encourage continuous efforts to implement preventive measures in high-risk jobs.

Incidence of childhood and youth epilepsy: A population-based prospective cohort study utilizing current International League Against Epilepsy classifications for seizures, syndromes, and etiologies.

This study was undertaken to describe incidence and distribution of seizures, etiologies, and epilepsy syndromes in the general child and youth population, using the current International League Against Epilepsy (ILAE) classifications. The study platform is the Norwegian Mother, Father, and Child Cohort Study (MoBa). Epilepsy cases were identified through registry linkages facilitated by Norway's universal health care system and mandatory reporting to the Norwegian Patient Registry. A standardized protocol guided medical record review, leading to validation of diagnoses and classification of seizures, epilepsy types, syndromes, and etiologies based on the latest ILAE criteria. MoBa included 111 365 participants aged 12-21 years by the end of follow-up on December 31, 2020. We identified 1053 children and youth with epilepsy (CYE). A defined epilepsy syndrome and/or identified etiology was found in 76% of CYE in this population-based study. Seizure types exhibited variation by age at onset. Focal epilepsies were predominant, occurring in 61% of CYE, whereas generalized epilepsies were identified in 24% of CYE. Standard clinical assessment identified etiology in 30% of CYE and in 55% with onset age < 2 years. Structural and identified genetic etiologies constituted 21% and 10%, respectively. Including presumed genetic and rare etiologies, 53% exhibited known etiology. A defined ILAE epilepsy syndrome was found in 53% of CYE. The cumulative incidence per 1000 children of the following ILAE epilepsy syndrome groups were as follows: self-limited epilepsies, 2.25; idiopathic generalized epilepsies, 1.75; and developmental and/or epileptic encephalopathies, 2.62. Using the new ILAE classifications, this population-based childhood study provides incidences of seizures, epilepsies, and epilepsy syndromes. Half of epilepsy cases are classified as an ILAE epilepsy syndrome with its prognostic and therapeutic implications, but a substantial proportion of cases still have unknown etiology.

Metabolic Syndrome and Risks of Breast Cancer Outcomes for Luminal, Triple-Negative, and HER2-Overexpressing Subtypes.

We evaluated the association between metabolic syndrome (MetS; obesity plus two metabolic risk factors) and breast cancer outcomes according to molecular subtype. This population-based prospective cohort consisted of 3,267 women ages 20 to 69 years diagnosed with a first primary invasive breast cancer from 2004 to 2015 in the Seattle-Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor, and HER2 expression: luminal (ER+), triple-negative (ER-/progesterone receptor negative/HER2-), and HER2-overexpressing (H2E; ER-/HER2+) subtypes. We used time-varying Cox models to assess the association of prevalent and incident MetS with risks of recurrence, breast cancer-specific mortality (BCSM), and all-cause mortality (ACM). MetS was associated with a greater risk of recurrence [HR, 3.24; 95% confidence interval (CI), 1.13-9.33] and BCSM (HR, 5.34; 95% CI, 2.32-12.31) only for the H2E subtype and greater risks of ACM for luminal (HR, 1.92; 95% CI, 1.37-2.68), H2E (HR, 5.09; 95% CI, 2.51-10.32), and all cases combined (HR, 1.90; 95% CI, 1.42-2.53). We also observed heterogeneity in recurrence and mortality outcomes across specific components of MetS and molecular subtypes. MetS is associated with ACM among women with breast cancer and with BCSM among women with the H2E subtype. These results highlight the importance of managing comorbidities to decrease the risk for adverse outcomes among breast cancer survivors.

Maintaining level of modifiable dementia risk scores is associated with better cognitive outcomes than increasing risk scores: A population-based prospective cohort study.

A brain healthy lifestyle, consisting of good cardiometabolic health and being cognitively and socially active in midlife, is associated with a lower risk of cognitive decline years later. However, it is unclear whether lifestyle changes over time also affect the risk for mild cognitive impairment (MCI)/dementia, and rate of cognitive decline. To investigate if lifestyle changes over time are associated with incident MCI/dementia risk and rate of cognitive decline. Population-based prospective cohort study SETTING: Personality and Total Health (PATH) Through Life Study cohort (Australia). 4,777 participants (50.4% women), recruited between 2000 and 2002, who were 40-44 and 60-64 years old at baseline, without a prevalent dementia diagnosis. Participants had to have cognitive outcome measures available after baseline. Various measurements (neurocognitive assessment, blood pressure) and survey responses (demographics, cognitive, social, and physical activity, smoking, alcohol consumption, body height and weight, depression, and previous diagnoses) were collected approximately every four years. A brain-healthy lifestyle was operationalized via two well-validated modifiable dementia risk scores, the LIfestyle for BRAin health (LIBRA) score and the modifiable part of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRImod). Their change over time was estimated using latent growth curve modelling, and their association with cognition and incidence of MCI/dementia was investigated using parallel process modelling and Cox regression analysis. Within those aged 60-64 years at baseline (n=2,409), 211 cases of incident MCI/dementia were recorded over a median follow-up time of 12.2 years. On average, individuals' LIBRA and ANU-ADRImod increased (i.e., worsened) over time, but individuals whose scores increased one standard deviation (SD) less had a 19.0-24.6% lower risk for MCI/dementia (hazard ratio (95% confidence interval): LIBRAchange over time=0.754 (0.664-0.857), ANU-ADRImod, change over time=0.810 (0.71-0.915)), while controlling for the risk score at baseline and multiple potential confounders. Various associations between dementia risk score trajectories and cognitive performance trajectories were observed. Efforts to maintain a brain healthy lifestyle could reduce the risk for MCI or dementia, and slow cognitive decline.

Development and external validation of the SMA2SH2ERS risk prediction model for aneurysmal subarachnoid haemorrhage in the general population: a population-based prospective cohort study

ObjectivesAneurysmal subarachnoid haemorrhage (ASAH) is a severe stroke type, preventable by screening for intracranial aneurysms followed by treatment in high-risk individuals. We aimed to develop and validate a risk prediction...

Gross Motor Development by Age and Functional Level in Children with Cerebral Palsy from 6 Months to 17 Years-A Norwegian Population-Based Registry Study.

Background: Cerebral palsy is a complex lifespan disability caused by a lesion to the immature brain. Evaluation of interventions for children with cerebral palsy requires valid and reliable outcome measures. Motor development curves and reference percentiles for The Gross Motor Function Measure (GMFM-66) are valuable tools for following, predicting, comparing, and evaluating changes in gross motor skills. The aims of this study were to create motor development curves with reference percentiles based on Norwegian data and compare them with published counterparts for Canadian children aged 2-21 years. Method: Prospective population-based cohort data from the Norwegian Quality and Surveillance Registry for Cerebral Palsy (NorCP) for 1206 children with 3612 GMFM-66 tests between 0.5 and 17.3 years of age. Median development by Gross Motor Function Classification System (GMFCS) levels was estimated using a generalized additive regression model with smoothed parameters for location, scale, and shape (based on the R GAMLSS library). To adjust for repeated individual measurements, we report the median curve of 100 random samples with only one observation per observed child. Results: The Norwegian motor development curves for GMFCS levels I-IV increase up to 7 years of age before flattening off, while GMFCS level V curves are relatively flat. Overall, both motor development curves and GMFM-66 percentiles are very similar to Canadian counterparts. Conclusions: The existing Canadian reference curves are valid also for Norway, working well for both clinical and research applications. However, Norwegian percentiles can be used from an earlier age.

Trajectories of antidepressant use and 6-year change in body weight: a prospective population-based cohort study.

Antidepressant drug treatment may be associated with weight gain, but long-term studies are lacking. We included 3,127 adults (1,701 women) from the REGICOR study, aged 55.6 (SD = 11.6) years on average in 2003-2006, living in the northeast of Spain. They had data at two time points (baseline and a median of 6.3 years later) on self-reported antidepressant use, body weight and height, and on baseline smoking, physical activity, diet quality, education, civil status, and depressive symptoms assessed with the Patient Health Questionnaire (PHQ-9) at follow-up. We defined four trajectories of antidepressant use as follows: never use, new use at follow-up, initial use discontinued, repeated use at both time points. We used multivariable linear models to estimate the association of these trajectories with the percentage of weight change. In people without obesity at baseline (n = 2,404), we also estimated the association with obesity incidence at follow-up. The average 6-year weight gain was 0.53kg (1.01% body weight), and 24.5% of the participants gained >5% of body weight. The majority (83.6%) of participants did not report any use of antidepressants, 6.2% initiated during follow-up, 5.1% discontinued it, and 5.1% reported their use at both time points. In multivariable analyses, compared to never users, all trajectories were associated with greater weight gain: +1.78% (0.57, 2.98) for initial use discontinued, +2.08% (0.97, 3.19) for new use at follow-up, and +1.98% (95% CI: 0.75, 3.20) for repeated use. In non-obese participants at baseline (n = 2,404), the odds ratio for becoming obese was 2.06 (1.03, 3.96) for repeated use and non-statistically significant for the other trajectories. In a population-based adult cohort, repeated use of antidepressants was strongly associated with weight gain. New and discontinued use was associated with weight gain, but non-significantly to obesity incidence. Given the global obesity epidemic and the widespread use of antidepressants, weight management and metabolic monitoring should be encouraged and integrated into depression follow-up guidelines alongside antidepressant prescriptions.

Socioeconomic position interacts with the genetic effect of a CRP gene common variant to influence C-reactive protein values.

C-Reactive Protein (CRP) values are partly determined by variation at the CRP gene locus, but also influenced by socioeconomic position (SEP) and related lifestyle factors. As gene-by-SEP interactions have been suggested for traits associated with CRP and SEP (e.g., BMI, coronary artery disease), the aim of this study was to investigate the strength of a possible interaction between a CRP gene common variant (rs4287174) and SEP in their joint influence on CRP levels in a population-based study sample. Single nucleotide polymorphism rs4287174 was genotyped in 4065 participants (aged 45-75 years) of the Heinz Nixdorf Recall study, a population-based prospective cohort. SEP indicators (education and income), risk factors (i.e., body mass index (BMI), total cholesterol, diabetes mellitus, coronary artery calcification, current smoking, hypertension, diet, no exercise) and blood serum CRP (mg/dl) were assessed at study baseline. Interaction analysis was based on linear regression and on stratified analyses (genetic effect stratified by SEP and vice versa) adjusted for age and sex using loge(CRP + 1) as dependent variable. Low SEP and rs4287174 T allele were both associated with higher CRP values. The strongest genetic effect was observed in the lowest educational group (≤ 10 years of education) with an exp(β) indicating 1.058-fold (95%-CI: 1.018; 1.100) average CRP values per additional T allele, while in the highest educational group (≥ 18 years) the association was considerably less strong (exp(β): 1.005 (95%-CI: 0.975; 1.037)). After including rs4287174-by-education interaction terms in the regression analysis, interaction was indicated suggesting stronger genetic effects on CRP in low SEP groups (exp(βinteraction): 1.056 (95%-CI: 1.005; 1.108); p = 0.029). The observed interaction did not seem to be substantially mediated by the risk factors included in the analysis. No indication for rs4287174-by-income interaction was observed. Results imply that genetic effects of the CRP locus are modified by education as an indicator of life course SEP.

The additive interaction of healthy lifestyles and genetic susceptibility on colorectal cancer risk in prediabetes: a large population-based prospective cohort study

ObjectiveWe aimed to investigate the interrelationships among polygenic risk scores (PRS), healthy lifestyle factors (HLFs), and colorectal cancer (CRC) risk in individuals with prediabetes. To investigate whether adherence to HLFs influence CRC risk in those with elevated PRS within this specific population.MethodsData from 22,408 prediabetes participants without CRC at baseline were analyzed from the UK Biobank. HLFs were graded using healthy lifestyle scores (HLSs) and classified as favorable, intermediate, or unfavorable, while the PRS for CRC was categorized as high, medium, or low. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for CRC risk.ResultsHigh PRS (HR: 2.36; 95% CI: 1.86–3.00) and medium PRS (HR: 1.42; 95% CI: 1.09–1.83) prediabetes were associated with increased CRC risk compared to those with low PRS. HLFs were linked to lower CRC risk in a dose–response manner, with never smoking (HR: 0.69; 95% CI: 0.57–0.84) and maintaining a healthy BMI (HR: 0.64; 95% CI: 0.49–0.82) associated with reduced CRC risk. Adherence to favorable HLFs may reduce the CRC risk in those with medium (HR: 0.51; 95% CI: 0.27–0.95) and high PRS (HR: 0.62; 95% CI: 0.39–0.99) over 15 years of follow-up. In participants with high PRS and unfavorable HLFs, the excess risk due to the additive interaction between PRS and HLFs was 1.41% (p < 0.01), especially for women (1.07%).ConclusionsThere is an additive interaction of PRS and HLFs on CRC risk in individuals with prediabetes. Adopting favorable HLFs should be integrated into the management of prediabetes individuals to reduce the risk of CRC.

Smoking-independent DNA methylation markers for lung cancer risk: External validation in a large population-based cohort study.

Smoking-associated epigenetic changes have been linked to lung cancer (LC) risk; however, the role of epigenetic alterations independent of smoking is yet to be fully understood. This study aimed to validate 16 previously reported CpG sites that are independent of smoking yet associated with LC risk within a population-based prospective cohort. Using the Infinium Methylation EPIC BeadChip kit or the Infinium HumanMethylation450K BeadChip Assay, DNA methylation (DNAm) in whole blood was assessed in four subsets (n = 736, 1027, 997, and 312) of a population-based cohort from Germany. The DNAm levels of the 16 smoking-independent CpG sites were analyzed. Hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated to assess associations of DNAm at the 16 CpG sites with LC risk, adjusting for multiple covariates, including smoking habits and a smoking-associated DNAm score. Over 17 years of follow-up, a total of 199 LCs were observed. Among the 16 CpGs, cg02211449 showed a negative association with LC risk (HR [95% CI] per SD increase, = 0.70 [0.63-0.78]), while cg11385536 (1.04 [1.01-1.07]), cg09736286 (1.64 [1.10-2.44]), cg19907023 (1.64 [1.01-2.66]), and cg22032485 (1.52 [1.04-2.21]) displayed positive associations with LC risk. Five of the 16 suggested smoking-independent CpGs could be externally validated as predictors of LC risk. Further research should address their potential contribution to enhanced LC risk stratification.

Third-grade school performance in children with special healthcare needs: a prospective cohort study

ObjectiveChildren with special healthcare needs (SHCN) due to a chronic health condition perform more poorly at school compared with their classmates. We aimed to estimate the effects of past, current,...

Normative Population-Derived Data for MRI Manifestations of Cerebral Small Vessel Disease.

Cerebral small vessel disease (SVD) is manifested on magnetic resonance imaging (MRI) by white matter hyperintensities, lacunes, microbleeds, and atrophy. While these manifestations can be part of normal aging, a high burden has been associated with cognitive impairment and vascular events. Distinguishing between normal versus abnormal SVD lesion burden in clinical practice remains complex. Our objective is to establish age- and sex-specific normative data for MRI manifestations of SVD, to support clinical assessment in individual patients. We used 11 465 MRI scans from 5402 participants of the Rotterdam Study, the Netherlands, an ongoing prospective population-based cohort since 1990, to develop percentile curves for white matter hyperintensities and brain parenchymal fraction and probability curves for the prevalence and count of lacunes and microbleeds, across ages 45 to 100 years, stratified by sex. Participants were primarily White (≈97%), with a mean age at first scan of 64.7 (range, 45.7-97.9) years, and 55.7% being female participants. For all SVD MRI manifestations, the curves demonstrated nonlinear trends, with accelerating burden with advancing age (eg, doubling of white matter hyperintensity fraction every 10 years). Regarding brain parenchymal fraction, a decline was seen earlier in male participants (≈45 years) than female participants (≈60 years) and was more pronounced in male participants over time. Female participants had slightly higher white matter hyperintensity fractions compared with male participants across all ages. Lacunes and microbleeds were more frequently found in male participants than in female participants, and microbleeds were more prevalent than lacunes. We provide comprehensive normative data for different MRI manifestations of SVD, presented as percentile and probability curves by age, stratified by sex. This can aid clinicians to actually quantify the SVD burden on an individual patient's MRI scans and detect patterns of abnormality.

Body size and occupational physical activity during the life course and gastrointestinal cancers.

Evidence on the associations of body size and occupational physical activity (PA) during the life course with gastrointestinal cancers is inconclusive. We analyzed data from the Golestan Cohort Study, a population-based prospective cohort study from Iran, with 50,045 individuals aged 40-75 years enrolled during 2004-2008 and followed through April 2023. Body size during adolescence, early adulthood, and at cohort baseline was assessed using validated pictograms. Large adolescent body size was associated with total gastrointestinal cancers (hazard ratio, HR: 1.09; 95% confidence interval, CI: 1.02-1.16) and liver cancer (HR: 1.49; 95% CI: 1.11-2.01). Large early-adulthood body size was associated with liver cancer (HR: 1.85; 95% CI: 1.35-2.52). Compared with normal weight during all stages, overweight or obesity during adolescence only or early adulthood only were associated with stomach cancer, esophageal squamous cell carcinoma, and liver cancer. Lower levels of adolescent occupational PA were associated with colon cancer (HR: 1.39; 95% CI: 1.10-1.75), while lower levels at cohort baseline were positively associated with colon cancer and inversely associated with rectal cancer. Our findings suggest that timing of obesity during the life course might differently affect risk of gastrointestinal cancers, while occupational PA was found to be associated with colon cancer only.

Association between the Life's essential 8 health behaviors score and all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease

BackgroundThe association between Life's Essential 8 (LE8) score and all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown. MethodsThis population-based prospective cohort study analyzed data of participants aged 20–79 years in the National Health and Nutrition Examination Survey from 2005 to 2018, with linked mortality information until 2019. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between different cardiovascular health (CVH) scores and all-cause mortality in participants with MASLD. ResultsAmong 11,988 participants, 4109 (34.3 %) were diagnosed with MASLD. During the median 7.8 years of follow-up, 912 deaths were recorded. Unexpectedly, the total LE8 CVH score was not associated with all-cause mortality in patients with MASLD (all P > .05). However, individuals with MASLD with moderate and poor LE8 health behaviors scores exhibited an increased risk of all-cause mortality (moderate: HR, 1.51; 95 % CI, 1.05–2.17; poor: HR, 2.32; 95 % CI, 1.64–3.30), particularly among patients with advanced fibrosis (moderate: HR, 1.77; 95 % CI, 1.07–2.92; poor: HR, 2.43; 95 % CI, 1.23–4.78). Population-attributable fraction estimates suggest that 35.0 % of all-cause mortality attributed to poor or moderate health behaviors scores could be avoided if ideal CVH metrics were achieved in all patients with MASLD. ConclusionThese findings demonstrate a significant association between the LE8 health behaviors score and all-cause mortality in patients with MASLD, highlighting the usefulness of this score in optimizing risk management strategies for MASLD in future clinical practice.

Association of early-life factors with biological age acceleration and the mediating effect of social environment risks in middle-aged and older adults.

Adverse early-life events influence the health with ageing throughout the life course. However, the effects of combined early-life risks on ageing acceleration in adults and the roles of social environment risks remain unknown. To investigate associations of maternal smoking, breastfeeding and birth weight with accelerated biological age (BA), and to explore genetic-predicted effect and mediating effect of social environment risks. Population-based prospective cohort. UK Biobank. 151773 participants. We used Klemera-Doubal BA (KDM-BA), PhenoAge and leukocyte telomere length (LTL) as BA biomarkers. Associations of early-life risk factors and score with BA acceleration were estimated using linear regression models. Genetic risk score (GRS) was calculated based on genetic variations for maternal smoking and birth weight. Polysocial risk scores (PsRS) for each BA were calculated by summing the number of dichotomised social environment factors significantly associated with each of the three BA biomarkers. Maternal smoking, non-breastfeeding and low birth weight were individually associated with BA acceleration. The early-life risk score was significantly associated with accelerated KDM-BA and PhenoAge and shorter LTL. The effects of GRS on accelerated BA were in the same direction. The BA-specific PsRS mediated the accelerated KDM-BA and PhenoAge and shorter LTL by 8.37%, 22.34% and 7.90%, respectively. Our findings demonstrated a dose-dependent association of combined early-life risks with accelerated BA in middle-aged and older adults, partially mediated by social environment risks. The findings highlight the importance of early identification and surveillance of high-risk individuals for ageing acceleration during adulthood.