Exposome-wide ranking of modifiable risk factors for cardiometabolic disease traits.
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ABSTRACT:
SUBMITTER: Poveda A
PROVIDER: S-EPMC8904494 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
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Exposome-wide ranking of modifiable risk factors for cardiometabolic disease traits.
Poveda Alaitz A Pomares-Millan Hugo H Chen Yan Y Kurbasic Azra A Patel Chirag J CJ Renström Frida F Hallmans Göran G Johansson Ingegerd I Franks Paul W PW
Scientific reports 20220308 1
The present study assessed the temporal associations of ~ 300 lifestyle exposures with nine cardiometabolic traits to identify exposures/exposure groups that might inform lifestyle interventions for the reduction of cardiometabolic disease risk. The analyses were undertaken in a longitudinal sample comprising > 31,000 adults living in northern Sweden. Linear mixed models were used to assess the average associations of lifestyle exposures and linear regression models were used to test associatio ...[more]
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Project description:BackgroundSensitive general cardiometabolic risk assessment tools of modifiable risk factors would be helpful and practical in a range of primary prevention interventions or for preventive health maintenance.PurposeTo develop and validate a cumulative general cardiometabolic risk score that focuses on non-self-reported modifiable risk factors such as glycosylated hemoglobin (HbA1c) and BMI so as to be sensitive to small changes across a span of major modifiable risk factors, which may not individually cross clinical cut-off points for risk categories.MethodsWe prospectively followed 2,359 cardiovascular disease (CVD)-free subjects from the Framingham offspring cohort over a 14-year follow-up. Baseline (fifth offspring examination cycle) included HbA1c and cholesterol measurements. Gender-specific Cox proportional hazards models were considered to evaluate the effects of non-self-reported modifiable risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, BMI, and HbA1c) on general CVD risk. We constructed 10-year general cardiometabolic risk score functions and evaluated its predictive performance in 2012-2013.ResultsHbA1c was significantly related to general CVD risk. The proposed cardiometabolic general CVD risk model showed good predictive performance as determined by cross-validated discrimination (male C-index=0.703, 95% CI=0.668, 0.734; female C-index=0.762, 95% CI=0.726, 0.801) and calibration (lack-of-fit chi-square=9.05 [p=0.338] and 12.54 [p=0.128] for men and women, respectively).ConclusionsThis study presents a risk factor algorithm that provides a convenient and informative way to quantify cardiometabolic risk on the basis of modifiable risk factors that can motivate an individual's commitment to prevention and intervention.
| S-EPMC4107093 | biostudies-literature
Project description:Considerable uncertainty remains regarding the associations of multiple factors with brain health. We aimed to conduct an exposome-wide association study on neurodegenerative disease and neuropsychiatry disorders using data of participants from the UK Biobank. Multivariable Cox regression models with the least absolute shrinkage and selection operator technique as well as principal component analyses were used to evaluate the exposures in relation to common disorders of central nervous system (CNS). Restricted cubic splines were conducted to explore potential nonlinear correlations. Then, weighted standardized scores were generated based on the coefficients to calculate the joint effects of risk factors. We also estimated the potential impact of eliminating the unfavorable profiles of risk domains on CNS disorders using population attributable fraction (PAF). Finally, sensitivity analyses were performed to reduce the risk of reverse causality. The current study discovered the significantly associated exposures fell into six primary exposome categories. The joint effects of identified risk factors demonstrated higher risks for common disorders of CNS (HR = 1.278 ~ 3.743, p < 2e-16). The PAF varied by exposome categories, with lifestyle and medical history contributing to majority of disease cases. In total, we estimated that up to 3.7 ~ 64.1% of disease cases could be prevented.This study yielded modifiable variables of different categories and assessed their joint effects on common disorders of CNS. Targeting the identified exposures might help formulate effective strategies for maintaining brain health.
| S-EPMC11493923 | biostudies-literature
Project description:BackgroundCardiovascular disease (CVD) remains a paramount contemporary health challenge. This study examined age-specific effects of 14 risk factors on CVD and mortality in different age groups.MethodsWe analyzed data from 226,759 CVD-free participants aged 40 years and older in the UK Biobank during the period from baseline time (2006-2010) to September 30, 2021. The primary CVD outcome was a composite of incident coronary artery disease, heart failure, and stroke. We calculated age-specific hazard ratios (HRs) and population-attributable fractions (PAF) for CVD and mortality associated with 14 potentially modifiable risk factors.FindingsDuring 12.17-year follow-up, 23,838 incident CVD cases and 11,949 deaths occurred. Age-specific disparities were observed in the risk factors contributing to CVD, and the overall PAF declined with age (PAF of 56.53% in middle-age; 49.78% in quinquagenarian; 42.45% in the elderly). Metabolic factors had the highest PAF in each age group, with hypertension (14.04% of the PAF) and abdominal obesity (9.58% of the PAF) being prominent. Behavioral factors had the highest PAF in the middle-aged group (10.68% of the PAF), and smoking was the leading behavioral factor in all age groups. In socioeconomic and psychosocial risk clusters, low income contributed most among middle-aged (3.74% of the PAF) and elderly groups (3.66% of the PAF), while less education accounted more PAF for quinquagenarian group (4.46% of the PAF). Similar age-specific patterns were observed for cardiovascular subtypes and mortality.InterpretationA large fraction of CVD cases and deaths were associated with modifiable risk factors in all age groups. Targeted efforts should focus on the most impactful risk factors, as well as age-specific modifiable risk factors. These findings may inform the development of more precise medical strategies to prevent and manage CVD and related mortality.FundingThe work was supported by the Bill & Melinda Gates Foundation (grant number: INV-016826 to Hualiang Lin) and the National Natural Science Foundation of China (grant number: 82373534 to Hualiang Lin).
| S-EPMC10626167 | biostudies-literature
Project description:BackgroundDue to the ubiquitous use of chemicals in modern society, humans are increasingly exposed to thousands of chemicals that contribute to a major portion of the human exposome. Should a comprehensive and risk-based human exposome database be created, it would be conducive to the rapid progress of human exposomics research. In addition, once a xenobiotic is biotransformed with distinct half-lives upon exposure, monitoring the parent compounds alone may not reflect the actual human exposure. To address these questions, a comprehensive and risk-prioritized human exposome database is needed.ObjectivesOur objective was to set up a comprehensive risk-prioritized human exposome database including physicochemical properties as well as risk prediction and develop a graphical user interface (GUI) that has the ability to conduct searches for content associated with chemicals in our database.MethodsWe built a comprehensive risk-prioritized human exposome database by text mining and database fusion. Subsequently, chemicals were prioritized by integrating exposure level obtained from the Systematic Empirical Evaluation of Models with toxicity data predicted by the Toxicity Estimation Software Tool and the Toxicological Priority Index calculated from the ToxCast database. The biotransformation half-lives (HLBs) of all the chemicals were assessed using the Iterative Fragment Selection approach and biotransformation products were predicted using the previously developed BioTransformer machine-learning method.ResultsWe compiled a human exposome database of >20,000 chemicals, prioritized 13,441 chemicals based on probabilistic hazard quotient and 7,770 chemicals based on risk index, and provided a predicted biotransformation metabolite database of >95,000 metabolites. In addition, a user-interactive Java software (Oracle)-based search GUI was generated to enable open access to this new resource.DiscussionOur database can be used to guide chemical management and enhance scientific understanding to rapidly and effectively prioritize chemicals for comprehensive biomonitoring in epidemiological investigations. https://doi.org/10.1289/EHP7722.
| S-EPMC8086799 | biostudies-literature
Project description:Previous studies have shown certain exposure factors (such as lifestyle and metabolism) are associated with colorectal cancer (CRC) events. However, the application of the exposome theoretical frame and the extent to which the exposome domain can modulate the risk of CRC remain unknown. Our study aimed to construct valid exposome measurements and examine the relationship between exposome counts and the risk of CRC. This study included 335,370 individuals in the UK Biobank. We used exploratory factor analysis to identify a valid construct of exposome factors. We then summed the exposome counts within each domain. Cox proportional hazard models were used to estimate the hazard ratios and 95% confidence intervals of CRC risk related to the exposome factors and counts. During an 8.69 year median follow-up, 10,702 CRC cases were identified. Five domains were extracted from 12 variables, including ecosystem, lifestyle, tobacco and alcohol use, social economics, and social support. The Cox model results showed that the ecosystem was positively related to the reduced CRC risk (HR = 0.970; 95% CI 0.952-0.989). Similar results were also found among the domains of healthy lifestyles (HR = 0. 889; 95% CI 0.871-0.907), and no tobacco and alcohol use (HR = 0.892; 95% CI 0.876-0.909). The disadvantageous social economic (HR = 1.081; 95% CI 1.058-1.105) and insufficient social support domains (HR = 1.036; 95% CI 1.017-1.056) were associated with an increased risk of CRC. Similar risk trends were also observed across the exposome count groups with CRC incidence. Our findings suggest that certain exposure domains are related to the incidence of CRC. Ecosystem, lifestyle, and social factors can be incorporated into prediction models to identify individuals at high risk of CRC.
| S-EPMC9750985 | biostudies-literature
Project description:ImportanceAn estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.ObjectiveTo comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.Design, setting, and participantsThis genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022.ExposuresGenetically determined modifiable risk factors.Main outcomes and measuresOdds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors.ResultsThe EADB-diagnosed cohort included 39 106 participants with clinically diagnosed AD and 401 577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]).Conclusions and relevanceThis genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.
| S-EPMC10193187 | biostudies-literature
Project description:To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single-study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 incident BCL cases were diagnosed from 475 426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component analysis (PCA) were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, diet and BCL and/or the subtypes. PCAs confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL) and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL.
| S-EPMC8048490 | biostudies-literature
Project description:Background There have been limited data examining the age-dependent relationship of wide-range risk factors with the incidence of each subtype of cardiovascular disease (CVD) event. We assessed age-related associations between modifiable risk factors and the incidence of CVD. Methods and Results We analyzed 3 027 839 participants without a CVD history enrolled in the JMDC Claims Database (mean age, 44.8±11.0 years; 57.6% men). Each participant was categorized as aged 20 to 49 years (n=2 008 559), 50 to 59 years (n=712 273), and 60 to 75 years (n=307 007). Using Cox proportional hazards models and the relative risk reduction, we identified associations between risk factors and incident CVD, consisting of myocardial infarction, angina pectoris, stroke, and heart failure (HF). We assessed whether the association of risk factors for developing CVD would be modified by age category. Over a mean follow-up of 1133 days, 6315 myocardial infarction, 56 447 angina pectoris, 28 079 stroke, and 56 369 HF events were recorded. The incidence of myocardial infarction, angina pectoris, stroke, and HF increased with age category. Hazard ratios of obesity, hypertension, and diabetes in the multivariable Cox regression analyses for myocardial infarction, angina pectoris, stroke, and HF decreased with age category. The relative risk reduction of obesity, hypertension, and diabetes for CVD events decreased with age category. For example, the relative risk reduction of hypertension for HF decreased from 59.2% in participants aged 20 to 49 years to 38.1% in those aged 60 to 75 years. Conclusions The contribution of modifiable risk factor to the development of CVD is greater in younger compared with older individuals. Preventive efforts for risk factor modification may be more effective in younger people.
| S-EPMC9939069 | biostudies-literature
Project description: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.).
| S-EPMC10589462 | biostudies-literature
Project description:ObjectiveCardiovascular comorbidities associate with neurodegeneration in the elderly and may contribute to extranigral pathologies and medically refractory axial motor features in Parkinson disease (PD).MethodsWe explored differences in the estimated rate of axial motor feature accrual between patients with PD with and without elevated cardiovascular risk factors as estimated by the Framingham General Cardiovascular Disease risk-scoring algorithm in a cross-sectional cohort study. All participants underwent motor evaluations with the Movement Disorders Society revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS), [(11)C]dihydrotetrabenazine (DTBZ) monoaminergic brain PET imaging, and MRI.ResultsParticipants with PD with elevated Framingham risk (FR) scores (n = 63, 74.1%) showed higher unadjusted rates of total MDS-UPDRS (t = 3.60, p = 0.0006) and axial motor scores (t = 3.98, p = 0.0001) per estimated year of motor symptoms compared to participants with normal-range risk scores (n = 22, 25.9%). After controlling for sex, Montreal Cognitive Assessment score, frontal leukoaraiosis severity, and striatal DTBZ activity, elevated risk factor status was associated with the rate of accrual of axial motor impairments (R(2) = 0.206; t = 2.62, p = 0.011) but not with total MDS-UPDRS motor score (R(2) = 0.198; t = 1.51, p = 0.135). Frontal leukoaraiosis was associated with the rate of axial and total MDS-UPDRS scores per year of symptoms and also with elevated systolic blood pressure (R(2) = 0.291; t = 2.30, p = 0.024) in a separate risk-factor model.ConclusionCardiovascular risk factors may contribute to axial motor features in PD. Early modification of cardiovascular risk factors, including hypertension, deserves further study as a novel disease-modifying strategy in PD.
| S-EPMC4011463 | biostudies-literature