Effect Of Modifiable Risk Factors Research Articles

Bidirectional Two-Sample Mendelian Randomization Analysis Reveals Causal Associations Between Modifiable Risk Factors and Fibromyalgia.

This study aims to investigate the potential causal effects of modifiable risk factors on Fibromyalgia (FM). Genetic variants associated with 34 exposure factors were obtained from Genome-wide association studies (GWAS). Summary statistics for FM were acquired from the FinnGen consortium. Bidirectional Mendelian randomization (MR) analysis was conducted between all exposures and outcomes. The inverse-variance weighted (IVW) method was employed as the primary estimation technique. Heterogeneity and pleiotropy were assessed using MR-PRESSO global test, the weighted median, Cochran's Q statistic and MR-Egger. Depression (OR=2.087, 95% CI: 1.466-2.971), alcohol consumption (OR=1.489, 95% CI: 1.094-2.028), body fat percentage (OR=1.524, 95% CI: 1.153-2.013) and body mass index (BMI) (OR=1.542, 95% CI: 1.271-1.872) were associated with an increased risk of FM among genetically susceptible individuals. Conversely, higher education level (OR=0.404, 95% CI: 0.297-0.549), longer years of education (OR=0.489, 95% CI: 0.290-0.825) and higher household income (OR=0.328, 95% CI: 0.215-0.502) were protective against FM. Additionally, rheumatoid arthritis (OR=1.138, 95% CI: 1.061-1.221) and ankylosing spondylitis (OR=1.079, 95% CI: 1.021-1.140) were identified as important risk factors for FM. This MR study unveiled a complex causal relationship between modifiable risk factors and FM. Psychosocial factors significantly increase the odds of FM, while obesity and some autoimmune diseases that frequently coexist with FM demonstrate causal associations. Additionally, lifestyle habits such as alcohol consumption are causally related to FM. Further investigation is needed to determine whether risk factors contribute to the pathogenesis of FM through mechanisms involving central sensitization, inflammatory, and hyperalgesia. This study enhances our understanding of the factors that drive FM onset and progression, offering valuable insights for future targeted prevention and treatment strategies.

Relationship between sleep, physical fitness, brain microstructure, and cognition in healthy older adults: A pilot study

BackgroundThere is a critical need for neuroimaging markers of brain integrity to monitor effects of modifiable lifestyle factors on brain health. This observational, cross-sectional study assessed relationships between brain microstructure and sleep, physical fitness, and cognition in healthy older adults. MethodsTwenty-three adults aged 60 and older underwent whole-brain multi-shell diffusion imaging, comprehensive cognitive testing, polysomnography, and exercise testing. Neurite Orientation Dispersion and Density Imaging (NODDI) was used to quantify neurite density (NDI) and orientation dispersion (ODI). Diffusion tensor imaging (DTI) was used to quantify axial diffusivity (AxD), fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD). Relationships between sleep efficiency (SE), time and percent in N3 sleep, cognitive function, physical fitness (VO2 peak) and the diffusion metrics in regions of interest and the whole brain were evaluated. ResultsHigher NDI in bilateral white and gray matter was associated with better executive functioning. NDI in the right anterior cingulate and adjacent white matter was positively associated with language skills. Higher NDI in the left posterior corona radiata was associated with faster processing speed. Physical fitness was positively associated with NDI in the left precentral gyrus and corticospinal tract. N3 % was positively associated with NDI in the left caudate and right pre- and postcentral gyri. Higher ODI in the left putamen and adjacent white matter was associated with better executive function. ConclusionNDI and ODI derived from NODDI are potential neuroimaging markers for associations between brain microstructure and modifiable risk factors in aging. If these associations are observable in clinical samples, NODDI could be incorporated into clinical trials assessing the effects of modifiable risk factors on brain integrity in aging and neurodegenerative diseases.

Systematic investigation of genetically determined plasma and urinary metabolites to discover potential interventional targets for colorectal cancer.

We aimed to identify plasma and urinary metabolites related to colorectal cancer (CRC) risk and elucidate their mediator role in the associations between modifiable risk factors and CRC. Metabolite quantitative trait loci were derived from 2 published metabolomics genome-wide association studies, and summary-level data were extracted for 651 plasma metabolites and 208 urinary metabolites. Genetic associations with CRC were obtained from a large-scale genome-wide association study meta-analysis (100 204 cases, 154 587 controls) and the FinnGen cohort (4957 cases, 304 197 controls). Mendelian randomization and colocalization analyses were performed to evaluate the causal roles of metabolites in CRC. Druggability evaluation was employed to prioritize potential therapeutic targets. Multivariable Mendelian randomization and mediation estimation were conducted to elucidate the mediating effects of metabolites on the associations between modifiable risk factors and CRC. The study identified 30 plasma metabolites and 4 urinary metabolites for CRC. Plasma sphingomyelin and urinary lactose, which were positively associated with CRC risk, could be modulated by drug interventions (ie, olipudase alfa, tilactase). Thirteen modifiable risk factors were associated with 9 metabolites, and 8 of these modifiable risk factors were associated with CRC risk. These 9 metabolites mediated the effect of modifiable risk factors (Actinobacteria, body mass index, waist to hip ratio, fasting insulin, smoking initiation) on CRC. This study identified key metabolite biomarkers associated with CRC and elucidated their mediator roles in the associations between modifiable risk factors and CRC. These findings provide new insights into the etiology and potential therapeutic targets for CRC and the etiological pathways of modifiable environmental factors with CRC.

The moderating effect of care time on care-related characteristics and caregiver burden: differences between formal and informal caregivers of dependent older adults.

This study examined differences in care burden between formal and informal caregivers of dependent older adults according to care-related characteristics, and whether care time had a moderating effect on the relationship between care-related characteristics and caregiver burden. Participants were formal (n = 520) and informal caregivers (n = 142) of dependent older adults in South Korea. Caregiver burden was measured using the Korean version of the Zarit Burden Interview. Data were analyzed using hierarchical regression with interaction terms and moderation analysis. Caregiver burden was higher for informal caregivers than formal caregivers. Factors associated with an increased risk of caregiver burden in both formal and informal caregiver of dependent older adults were caregivers' stress, physical strain, and care time. Care time significantly moderated the relationship between care attitude and care burden only among formal caregivers. When formal caregivers' care time was 1 standard deviation higher than the mean value, care attitude was significantly associated with care burden (bsimple = -0.903, SE = 0.106, p < 0.001). The caregiver burden of dependent older adults can be reduced by providing interventions to attenuate the effects of modifiable risk factors that were identified in this study. And to weaken the relationship between care attitude and burden of formal caregivers who have long care hours, a positive social atmosphere for care should be provided in addition to education. To realize sustainable care, policy considerations that reflect the results of this study will help solve the problem of formal and informal caregiver burden of dependent older adults.

The mediating role of neuroimaging-derived biological brain age in the association between risk factors for dementia and cognitive decline in middle-aged and older individuals without cognitive impairment: a cohort study

Neuroimaging-based brain-age delta has been shown to be a mediator linking cardiovascular risk factors to cognitive function. We aimed to assess the mediating role of brain-age delta in the association between modifiable risk factors of dementia and longitudinal cognitive decline in middle-aged and older individuals who are asymptomatic, stratified by Alzheimer's disease pathology. We also explored whether the mediation effect is specific to cognitive domain. In this cohort study, we included participants from the ALFA+ cohort aged between 45 years and 65 years who were cognitively unimpaired and who had available structural MRI, cerebrospinal fluid β-amyloid (Aβ)42 and Aβ40 measurements obtained within 1 year of each other, modifiable risk factors assessment, and cognitive evaluation over 3 years. Participants were recruited from the Barcelonaβeta Brain Research Center (Barcelona, Spain). Included individuals underwent a first assessment between Oct 25, 2016, and Jan 28, 2020, and a follow-up cognitive assessment 3·28 (SD 0·27) years later. We computed brain-age delta and composites of different cognitive function domains (preclinical Alzheimer's cognitive composite [PACC], attention, executive function, episodic memory, visual processing, and language). We used partial least squares path modelling to explore mediation effects in the associations between modifiable risk factors (including cardiovascular, mental health, mood, metabolic or endocrine history, and alcohol use) and changes in cognitive composites. To assess the role of Alzheimer's disease pathology, we computed separate models for Aβ-negative and Aβ-positive individuals. Of the 419 participants enrolled in ALFA+, 302 met our inclusion criteria, of which 108 participants were classified as Aβ-positive and 194 as Aβ-negative. In Aβ-positive individuals, brain-age delta partially mediated (percent mediation proportion 15·73% [95% CI 14·22-16·66]) the association between modifiable risk factors and decline in overall cognition (across cognitive domains). Brain-age delta fully mediated (mediation proportion 28·03% [26·25-29·21]) the effect of modifiable risk factors on the PACC, wherein increased values for risk factors correlated with an older brain-age delta, and, consequently, an older brain-age delta was linked to greater PACC decline. This effect appears to be primarily driven by memory decline. Mediation was not significant in Aβ-negative individuals (3·52% [0·072-4·17]) on PACC, although path coefficients were not significantly different from those in the Aβ-positive group. Our findings suggest that brain-age delta captures the association between modifiable risk factors and longitudinal cognitive decline in middle-aged and older people. In asymptomatic middle-aged and older individuals who are Aβ-positive, the pathology might be the strongest driver of cognitive decline, whereas the effect of risk factors is smaller. Our results highlight the potential of brain-age delta as an objective outcome measure for preventive lifestyle interventions targeting cognitive decline. La Caixa Foundation, the TriBEKa Imaging Platform, and the Universities and Research Secretariat of the Catalan Government. For the Spanish translation of the abstract see Supplementary Materials section.

Causal associations between leisure sedentary behaviors and sleep status with frailty: insight from Mendelian randomization study

BackgroundObservational studies have suggested that sedentary behaviors and sleep status are associated with frailty. However, it remains unclear whether these associations are causal.MethodsUsing summary statistics from genome-wide association studies, we evaluated the causal effect of modifiable risk factors, including leisure sedentary behaviors and sleep status on the frailty index (FI) using two-sample univariable and multivariable Mendelian randomization (MR) analyses. Genetic correlations were tested between the correlated traits.ResultsWe identified potential causal associations between the time spent watching television (β = 0.26, 95% confidence interval [CI]: 0.21–0.31, P = 3.98e-25), sleep duration (β = -0.18, 95%CI: -0.26, -0.10; P = 6.04e-06), and daytime napping (β = 0.29, 95%CI: 0.18–0.41, P = 2.68e-07) and the FI based on the inverse-variance-weighted method. The estimates were consistent across robust and multivariate MR analyses. Linkage disequilibrium score regression detected a genetic correlation between the time spent watching television (Rg = 0.43, P = 6.46e-48), sleep duration (Rg = -0.20, P = 5.29e-10), and daytime napping (Rg = 0.25, P = 3.34e-21) and the FI.ConclusionsGenetic predispositions to time spent watching television and daytime napping were positively associated with the FI, while sleep duration was negatively associated with the FI. Our findings offer key insights into factors influencing biological aging and suggest areas for interventions to promote healthy aging and slow down the aging process.

Causal Associations of Modifiable Risk Factors With Migraine: Evidence From Mendelian Randomization Analysis.

Background and objectives The exact etiology of migraine is unknown; however, it is likely a mixture of genetic and non-genetic factors including lifestyle variables like smoking and diet. This study aims to assess the causal effect of modifiable risk factors on the risk of migraine using two-sample Mendelian randomization. Materials and methods The study used publicly available genome-wide significant single nucleotide polymorphisms (SNPs). The study evaluated a diverse smoking exposure, encompassing age at smoking initiation, smoking intensity, and maternal smoking, alongside other pertinent risk factors, namely key dietary aspects, coffee consumption, BMI, and physical activity. Self-reported migraine was the outcome of the study. The genetic data for migraine were obtained from the FinnGen (Finland) and the UK Biobank (United Kingdom) cohorts. Results With sample sizes ranging from 64,949 to 632,802 for each risk factor collected from several consorts, the study included a total of 282 SNPs for all risk factors. The findings demonstrated that in the FinnGen consortium, genetically estimated dietary factors as well as BMI, were significantly associated with the risk of migraine (OR 0.765 per single unit of BMI, p = 0.011; OR 0.468 per one SD higher cheese intake, p = 0.012; OR 0.286 per one SD higher salad intake, p = 0.004, and 0.625 per one SD higher coffee consumption, p = 0.003, respectively). The results also showed that in the UK Biobankspecifically, a genetically estimated history of maternal smoking was significantly associated with an elevated risk of migraine (OR=1.02, p=0.004). Conclusions The latest study implies a connection between maternal smoking and a heightened risk of migraines, whereas cheese intake, salad intake, coffee consumption, BMI, and physical activity are associated with a lower risk of migraine development.

Ethnic Variation in Modifiable Risk Factors for Dementia

AbstractBackgroundWe aimed to estimate the population attributable fraction (PAF) of 12 modifiable risk factors (defined by the Lancet Commission 2020), for incident dementia cases in the UK Biobank (UKB), stratified by ethnicity. We considered if ethnic differences in dementia risk, were accounted for by modifiable risk factors. To identify appropriate priorities in dementia prevention, tailored to ethnicity.MethodThe UKB is a cohort study with 502,656 volunteer participants registered between 2006‐2010, aged 40‐60 years at baseline, and followed for up to 16.8 years. To estimate the PAF of 12 modifiable risk factors (diabetes, hypertension, depression, hearing loss, obesity, traumatic brain injury (TBI), less education, social isolation, physical inactivity, air pollution, and smoking), we first estimated hazard ratios (HRs)(adjusted for age, gender, and Townsend quintiles), or when ethnicity interacted with risk factors, then we estimated HRs stratified by ethnicity. HRs were then converted to relative risk for PAF calculation.Results6,624 incident cases of dementia developed in 1.3%(95%CI = 1.3‐1.3)(n = 6316/471297){of Whites}, in 1.3%(95%CI = 1.1‐1.5)(n = 104/8031){of Blacks}, and in 1.0%(95%CI = 0.8‐1.2)(n = 79/8001){of South Asians (S.Asian)}. The mean age at dementia diagnosis was 71.6 years(SD,6.1){in S.Asians}; 71.8 years(SD,6.8){in Blacks}; and 73.6 years(SD,5.5){in Whites}. The combined PAF(95%CI) for dementia were: 35.6%(35.5‐35.8){in Whites}, 33.9%(32.8‐34.9){in Blacks}, and 41.0%(39.9‐42.0){in S.Asians}. The highest individual PAFs in each ethnic group, compared to the rest, were as follow. Blacks and S.Asians, respectively, for midlife hypertension: 9.6%(9.0‐10.3) and 10.1%(9.5‐10.8) vs 6.5%(6.4‐6.5){in Whites}. S.Asians for (1)Depression: 8.5%(7.9‐9.1) vs 4.0%(3.6‐4.4){in Blacks}, and 5.8%(5.7‐5.9){in Whites}; (2)Diabetes: 6.0%(5.4‐6.5) vs 5.1%(4.6‐5.6){in Blacks}, and 3.5%(3.4‐3.5){in Whites}; (3)Excessive alcohol: 1.4%(1.2‐1.7) vs 0.0%{in Blacks and Whites}. Whites for (1)Hearing loss: 3.6%(3.6‐3.7) vs 2.4%(2.1‐1.8){in Blacks}, and 3.0%(2.6‐3.4){in S.Asians}; (2)TBI: 2.5%(2.4‐2.5) vs 1.3%(1.1‐1.6){in Blacks}, and 1.7%(1.4‐2.0){in S.Asians}; (3)Less education: 5.0%(4.9‐5.1) vs 3.3%(2.9‐3.7){in Blacks}, and 3.2%(2.9‐3.6){in S.Asians}; (4)Physical inactivity: 2.6%(2.6‐2.7), vs 2.1%(1.8‐2.5){in Blacks}, and 2.2%(1.8‐2.5){in S.Asian; (5)Social isolation: 2.3%(2.2‐2.3) vs 1.9%(1.6‐2.1){in Blacks}, and 1.9%(1.6‐2.2){in S.Asians. The remaining risk factor PAFs did not differ between all ethnic groups.ConclusionIn this relatively wealthy, and healthy population, there remain ethnic disparities in the effect of modifiable risk factors on dementia. Interventions for midlife hypertension are a priority in South Asians and Blacks, particularly depression and alcohol consumption in South Asians.

Causal associations between modifiable risk factors and intervertebral disc degeneration

BackgroundIntervertebral disc degeneration (IVDD) is a common degenerative condition, which is thought to be a major cause of lower back pain (LBP). However, the etiology and pathophysiology of IVDD are not yet completely clear. PurposeTo examine potential causal effects of modifiable risk factors on IVDD. Study DesignBidirectional Mendelian randomization (MR) study. Patient SampleGenome-wide association studies (GWAS) with sample sizes between 54,358 and 766,345 participants. Outcome MeasuresOutcomes included (1) modifiable risk factors associated with IVDD use in the forward MR; and (2) modifiable risk factors that were determined to have a causal association with IVDD in the reverse MR, including smoking, alcohol intake, standing height, education level, household income, sleeplessness, hypertension, hip osteoarthritis, HDL, triglycerides, apolipoprotein A-I, type 2 diabetes, fasting glucose, HbA1c, BMI and obesity trait. MethodsWe obtained genetic variants associated with 33 exposure factors from genome-wide association studies. Summary statistics for IVDD were obtained from the FinnGen consortium. The risk factors of IVDD were analyzed by inverse variance weighting method, MR-Egger method, weighted median method, MR-PRESSO method and multivariate MR Method. Reverse Mendelian randomization analysis was performed on risk factors found to be caustically associated with IVDD in the forward Mendelian randomization analysis. The heterogeneity of instrumental variables was quantified using Cochran's Q statistic. ResultsGenetic predisposition to smoking (OR=1.221, 95% CI: 1.068–1.396), alcohol intake (OR=1.208, 95% CI: 1.056–1.328) and standing height (OR=1.149, 95% CI: 1.072–1.231) were associated with increased risk of IVDD. In addition, education level (OR=0.573, 95%CI: 0.502–0.654)and household income (OR=0.614, 95%CI: 0.445–0.847) had a protective effect on IVDD. Sleeplessness (OR=1.799, 95%CI: 1.162–2.783), hypertension (OR=2.113, 95%CI: 1.132–3.944) and type 2 diabetes (OR=1.069, 95%CI: 1.024–1.115) are three important risk factors causally associated with the IVDD. In addition, we demonstrated that increased levels of triglycerides (OR=1.080, 95%CI:1.013–1.151), fasting glucose (OR=1.189, 95%CI:1.007–1.405), and HbA1c (OR=1.308, 95%CI:1.017–1.683) could significantly increase the odds of IVDD. Hip osteoarthritis, HDL, apolipoprotein A-I, BMI and obesity trait factors showed bidirectional causal associations with IVDD, therefore we considered the causal associations between these risk factors and IVDD to be uncertain. ConclusionSThis MR study provides evidence of complex causal associations between modifiable risk factors and IVDD. It is noteworthy that metabolic disturbances appear to have a more significant effect on IVDD than biomechanical alterations, as individuals with type 2 diabetes, elevated triglycerides, fasting glucose, and elevated HbA1c are at higher risk for IVDD, and the causal association of obesity-related characteristics with IVDD incidence is unclear. These findings provide new insights into potential therapeutic and prevention strategies. Further research is needed to clarify the mechanisms of these risk factors on IVDD.

The associations and mediators between visual disabilities and anxiety disorders in middle-aged and older adults: A population-based study.

Visual disabilities significantly impact an individual's mental health. Little is known about the prospective relationship between visual disabilities and anxiety disorders and the underlying effects of modifiable risk factors. Our analysis was based on 117,252 participants from the U.K. Biobank, with baseline data collected between 2006 and 2010. Habitual visual acuity was measured by a standardized logarithmic chart, and ocular disorders reported using questionnaires were collected at baseline. Incident hospitalized anxiety recorded using longitudinal linkage with hospital inpatient data, lifetime anxiety disorder, and current anxiety symptoms assessed by a comprehensive online mental health questionnaire were identified over a 10-year follow-up. After adjustments for confounding factors, one-line worse visual acuity (0.1 logarithm of the minimum angle of resolution [logMAR]) was associated with an increased risk of incident hospitalized anxiety (HR = 1.05, 95% CI = 1.01-1.08), lifetime anxiety disorder (OR = 1.07, 95% CI [1.01-1.12]), and current anxiety scores (β = 0.028, 95% CI [0.002-0.054]). Besides poorer visual acuity, the longitudinal analysis also supported that each ocular disorder (including cataracts, glaucoma, macular degeneration, and diabetes-related eye disease) was significantly associated with at least two anxiety outcomes. Mediation analyses highlighted that subsequent onsets of eye diseases, especially cataracts, and lower socioeconomic status (SES) partly mediated the association between poorer visual acuity and anxiety disorders. This study demonstrates an overall association between visual disabilities and anxiety disorders in middle-aged and older adults. In particular, early interventions involving treatments for visual disabilities and effective psychological counseling services sensitive to socioeconomic status may help prevent anxiety in those living with poor vision. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Modifiable risk factors for multiple sclerosis have consistent directions of effect across diverse ethnic backgrounds: a nested case–control study in an English population-based cohort

BackgroundMultiple sclerosis is a leading cause of non-traumatic neurological disability among young adults worldwide. Prior studies have identified modifiable risk factors for multiple sclerosis in cohorts of White ethnicity, such as infectious mononucleosis, smoking, and obesity during adolescence/early adulthood. It is unknown whether modifiable exposures for multiple sclerosis have a consistent impact on risk across ethnic groups.AimTo determine whether modifiable risk factors for multiple sclerosis have similar effects across diverse ethnic backgrounds.MethodsWe conducted a nested case–control study using data from the UK Clinical Practice Research Datalink. Multiple sclerosis cases diagnosed from 2001 until 2022 were identified from electronic healthcare records and matched to unaffected controls based on year of birth. We used stratified logistic regression models and formal statistical interaction tests to determine whether the effect of modifiable risk factors for multiple sclerosis differed by ethnicity.ResultsWe included 9662 multiple sclerosis cases and 118,914 age-matched controls. The cohort was ethnically diverse (MS: 277 South Asian [2.9%], 251 Black [2.6%]; Controls: 5043 South Asian [5.7%], 4019 Black [4.5%]). The age at MS diagnosis was earlier in the Black (40.5 [SD 10.9]) and Asian (37.2 [SD 10.0]) groups compared with White cohort (46.1 [SD 12.2]). There was a female predominance in all ethnic groups; however, the relative proportion of males was higher in the South Asian population (proportion of women 60.3% vs 71% [White] and 75.7% [Black]). Established modifiable risk factors for multiple sclerosis—smoking, obesity, infectious mononucleosis, low vitamin D, and head injury—were consistently associated with multiple sclerosis in the Black and South Asian cohorts. The magnitude and direction of these effects were broadly similar across all ethnic groups examined. There was no evidence of statistical interaction between ethnicity and any tested exposure, and no evidence to suggest that differences in area-level deprivation modifies these risk factor-disease associations. These findings were robust to a range of sensitivity analyses.Conclusions and relevanceEstablished modifiable risk factors for multiple sclerosis are applicable across diverse ethnic backgrounds. Efforts to reduce the population incidence of multiple sclerosis by tackling these risk factors need to be inclusive of people from diverse ethnicities.

Effects of Allergen Exposure and Environmental Risk Factors in Schools on Childhood Asthma.

This review aims to assess the prevalence of common allergen exposures and environmental risk factors for asthma in schools, examine the underlying mechanisms of these environmental risk factors, and explore possible prevention strategies. Cockroach, mouse, dust mites, fungi, viral infections, ozone pollution, and cleaning products are common allergen exposures and environmental risk factors in schools which may affect asthma morbidity. Novel modifiable environmental risk factors in schools are also being investigated to identify potential associations with increased asthma morbidity. While several studies have investigated the benefit of environmental remediation strategies in schools and their impact on asthma morbidity, future studies are warranted to further define the effects of modifiable risk factors in schools and determine whether school mitigation strategies may help improve asthma symptoms in students with asthma.

Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality

BackgroundFive modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking.MethodsWe pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non–high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality.ResultsAmong 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6).ConclusionsHarmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.)

Association Between Educational Attainment and Thyroid Function: Results From Mendelian Randomization and the NHANES Study.

Many observational studies have reported on the association between educational attainment (EA) and thyroid function, but the causal relationship remains unclear. We aimed to obtain causal effects of EA on thyroid function and to quantify the mediating effects of modifiable risk factors. Two-sample mendelian randomization (MR) was performed by using summary statistics from large genome-wide association studies (GWAS) to assess the effect of EA on thyroid function, including hypothyroidism, hyperthyroidism, thyrotropin (TSH), and free thyroxine (FT4). A multivariable analysis was conducted to assess the mediating role of smoking and help to explain the association between EA and thyroid function. Similar analysis was further performed using data from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2002. In MR analysis, EA was causally associated with TSH (β = .046; 95% CI, 0.015-0.077; P = 4.00 × 10-3), rather than hypothyroidism, hyperthyroidism, and FT4. Importantly, smoking could serve as a mediator in the association between EA and TSH, in which the mediating proportion was estimated to be 10.38%. After adjusting for smoking in the multivariable MR analysis, the β value of EA on TSH was attenuated to 0.030 (95% CI, 0.016-0.045; P = 9.32 × 10-3). Multivariable logistic regression model in NHANES suggested a dose-response relationship between TSH (quartile [Q]4 vs Q1: odds ratio = 1.33; 95% CI, 1.05-1.68; P for trend = .023) and EA. Smoking, systolic blood pressure, and body mass index partially mediated the association between EA and TSH, with the proportion of the mediation effects being 43.82%, 12.28%, and 6.81%, respectively. There is a potentially causal association between EA and TSH, which could be mediated by several risk factors, such as smoking.

PO-02-219 MODIFIABLE RISK FACTORS PREDICT THE RECURRENCE OF ARRHYTHMIA AFTER PERSISTENT AF ABLATION: ANALYSIS OF THE DECAAF II STUDY

The role of risk factors in the development and maintenance of AF is recognized. Isolated risk factors have been implicated in AF recurrence after ablation. However, these have been largely from observational cohorts and in predominantly paroxysmal AF populations. To evaluate the effect of modifiable risk factors on outcomes of catheter ablation in patients with persistent AF. The DECAAF II study randomized 831 patients with persistent AF from 44 centres to pulmonary vein isolation with or without atrial fibrosis ablation. AF recurrence was determined by daily smart phone ECGs, clinical ECGs and ambulatory monitoring. The presence of modifiable risk factors was ascertained at baseline. For this analysis, the population was dichotomized as: Group 1, none or 1 modifiable risk factor; and Group 2, 2 or more modifiable risk factors. Complete risk factor data was available on 823 patients. Compared to Group 1, Group 2 had more modifiable risk factors: greater BMI (P<0.0001); hypertension (P<0.0001); diabetes mellitus (P<0.001); hyperlipidemia (P<0.0001); sleep apnea (P<0.0001); and smoking history (P<0.0001). Additionally, Group 2 were older (P=0.01) and had more vascular disease (P=0.005), coronary artery disease (P<0.0001) and larger left arial volumes (P<0.0001); however, there was no between group difference in atrial fibrosis (P=0.9). Group 2 had greater arrhythmia recurrence (47.8% vs. 37.7%; P=0.005), greater post ablation burden of AF (P=0.006) and shorter time to recurrence (271±195 vs. 310±188 days; P=0.007; Figure). This large multicentre prospective study in patients with persistent AF undergoing catheter ablation demonstrates the effect of modifiable risk factors in determining ablation outcomes. This study highlights the need for risk factor management to improve ablation outcomes in persistent AF.

Causal effects of modifiable risk factors on kidney stones: a bidirectional mendelian randomization study

BackgroundIncreasing epidemiological studies demonstrated that modifiable risk factors affected the risk of kidney stones. We aimed to systemically assess these causal associations using a bidirectional Mendelian randomization study.MethodsWe obtained instrumental variables related to each exposure at the genome-wide significant threshold (P < 5 × 10–8). Summary level data for outcomes from the FinnGen consortium and UK Biobank were utilized in the discovery and replication stage. The Inverse-variance weighted (IVW) method was used as the primary analysis, with additional sensitivity analyses and fix-effect meta-analysis to verify the robustness of IVW results.ResultsAmong 46 risk factors, five were significantly associated with nephrolithiasis risk in the FinnGen consortium, UK Biobank, and meta-analyses collectively. The odds ratios (ORs) (95% confidence intervals [95%CIs]) of kidney stones were 1.21 (1.13, 1.29) per standard deviation (SD) increase in serum calcium, 1.55 (1.01, 2.36) per SD increase in serum 25(OH)D, 1.14 (1.00, 1.29) per SD increase in total triglycerides, 2.38 (1.34, 4.22) per SD increase in fasting insulin, and 0.28 (0.23, 0.35) per unit increase in log OR of urine pH. In addition, genetically predicted serum phosphorus, urinary sodium, tea consumption, and income affected the risk of kidney stones (false discovery rate [FDR] P < 0.05) based on the outcome data from the FinnGen consortium, and the significant associations of education and waist-to-hip ratio with nephrolithiasis risks were found after FDR correction (FDR P < 0.05) based on the outcome data from UK Biobank.ConclusionsOur findings comprehensively provide modifiable risk factors for the prevention of nephrolithiasis. Genome-wide association studies with larger sample sizes are needed to verify these causal associations in the future further.

The contribution of modifiable risk factors to socioeconomic inequities in cardiovascular disease morbidity and mortality: A nationally representative population-based cohort study

This study examined the individual and joint effects of modifiable risk factors mediating the associations between socioeconomic position (SEP) and morbidity and mortality from cardiovascular diseases (CVD) in a nationally representative sample of adults in Canada.Participants in the Canadian Community Health Survey (n = 289,800) were followed longitudinally for CVD morbidity and mortality using administrative health and mortality data. SEP was measured as a latent variable consisting of household income and individual educational attainment. Mediators included smoking, physical inactivity, obesity, diabetes and hypertension. The primary outcome was CVD morbidity and mortality, defined as the first fatal/nonfatal CVD event during follow-up (median 6.2 years). Generalized structural equation modeling tested the mediating effects of modifiable risk factors in associations between SEP and CVD in the total population and stratified by sex.Lower SEP was associated with 2.5 times increased odds of CVD morbidity and mortality (OR: 2.52, 95% CI: 2.28, 2.76). Modifiable risk factors mediated 74% of associations between SEP and CVD morbidity and mortality in the total population and were more important mediators of associations in females (83%) than males (62%). Smoking mediated these associations independently and jointly with other mediators. The mediating effects of physical inactivity were through joint mediating effects with obesity, diabetes or hypertension. There were additional joint mediating effects of obesity through diabetes or hypertension in females.Findings point to modifiable risk factors as important targets for interventions along with interventions that target structural determinants of health to reduce socioeconomic inequities in CVD.

Antiphospholipid Syndrome and Pregnancy

Antiphospholipid syndrome is an autoimmune disease with a wide spectrum of manifestations from different organs, therefore it is challenging to diagnose. The disease presents antiphospholipid antibodies such as anticardiolipin antibodies (aCL), lupus anticoagulant (LA) and antiβ2-glycoprotein 1 antibodies (β2GPI). The most common symptoms include thrombosis in veins and arteries and obstretical complications such as early miscarriage, intrauterine fetal death, intrauterine growth restriction (IUGR), placental insufficiency, premature labor and eclampsia. To diagnose a patient with APS certain criteria have been chosen, where at least one clinical and one laboratory criterion must be present. In many cases it takes a lot of time before a proper diagnosis has been made, when a female patient presents obstretical complications. Adequate pharmacological treatment increases the odds of live birth rate from 20-30% to 70-80%. Scientific research shows correlation between antiphospholipid syndrome, infertility and premature ovarian insufficiency. Treatment mostly consists of heparin and low-dose aspirin, in certain cases hydrochloroquine is prescribed. Aside from pharamcological therapy, it is very important to minimize the effects of modifiable risk factors. The following article focuses on complications, diagnosing and therapy in pregnant women suffering from Antiphospholipid syndrome. All sources can be found in Pubmed’s website database.

Incidence of Parkinson's disease and modifiable risk factors in Korean population: A longitudinal follow-up study of a nationwide cohort.

We aimed to investigate the incidence of Parkinson's disease (PD) by age and year for each sex as well as the modifiable risk factors for PD. Using data from the Korean National Health Insurance Service, 938,635 PD and dementia-free participants aged ≥40 years who underwent general health examinations were followed to December 2019. We analyzed the PD incidence rates according to age, year and sex. To investigate the modifiable risk factors for PD, we used the Cox regression model. Additionally, we calculated the population-attributable fraction to measure the impact of the risk factors on PD. During follow-up, 9,924 of the 938,635 (1.1%) participants developed PD. The incidence of PD increased continuously from 2007 to 2018, reaching 1.34 per 1,000 person-years in 2018. The incidence of PD also increases with age, up to 80 y. Presence of hypertension (SHR = 1.09, 95% CI 1.05 to 1.14), diabetes (SHR = 1.24, 95% CI 1.17 to 1.31), dyslipidemia (SHR = 1.12, 95% CI 1.07 to 1.18), ischemic stroke (SHR = 1.26, 95% CI 1.17 to 1.36), hemorrhagic stroke (SHR = 1.26, 95% CI 1.08 to 1.47), ischemic heart disease (SHR = 1.09, 95% CI 1.02 to 1.17), depression (SHR = 1.61, 95% CI 1.53 to 1.69), osteoporosis (SHR = 1.24, 95% CI 1.18 to 1.30), and obesity (SHR = 1.06, 95% CI 1.01 to 1.10) were independently associated with a higher risk for PD. Our results highlight the effect of modifiable risk factors for PD in the Korean population, which will help establish health care policies to prevent the development of PD.

Arrhythmia and other modifiable risk factors in incident dementia and MCI among elderly individuals with low educational levels in Taiwan.

There is increasing evidence that arrhythmia is a risk factor for dementia; however, it appears that arrhythmia affects the cognitive function of individuals differentially across age groups, races, and educational levels. Demographic differences including educational level have also been found to moderate the effects of modifiable risk factors for cognitive decline. This study recruited 1,361 individuals including a group of cognitively unimpaired (CU) individuals, a group of patients with mild cognitive impairment (MCI), and a group of patients with dementia with low education levels. The participants were evaluated in terms of modifiable risk factors for dementia, including arrhythmia and neuropsychiatric symptoms. Cox proportional hazard regression models revealed that among older MCI patients (>75 years), those with arrhythmia faced an elevated risk of dementia. Among younger MCI patients, those taking anti-hypertensive drugs faced a relatively low risk of dementia. Among younger MCI patients, male sex and higher educational level were associated with an elevated risk of dementia. Among CU individuals, those with coronary heart disease and taking anti-lipid compounds faced an elevated risk of MCI and those with symptoms of depression faced an elevated risk of dementia. The risk and protective factors mentioned above could potentially be used as markers in predicting the onset of dementia in clinical settings, especially for individuals with low educational levels.