Identification of gene networks jointly associated with depressive symptoms and cardiovascular health metrics using whole blood transcriptome in the Young Finns Study.

Background: Studies have shown that cardiovascular health (CVH) is related to depression. We aimed to identify gene networks jointly associated with depressive symptoms and cardiovascular health metrics using the whole blood transcriptome. Materials and methods: We analyzed human blood transcriptomic data to identify gene co-expression networks, termed gene modules, shared by Beck's depression inventory (BDI-II) scores and cardiovascular health (CVH) metrics as markers of depression and cardiovascular health, respectively. The BDI-II scores were derived from Beck's Depression Inventory, a 21-item self-report inventory that measures the characteristics and symptoms of depression. CVH metrics were defined according to the American Heart Association criteria using seven indices: smoking, diet, physical activity, body mass index (BMI), blood pressure, total cholesterol, and fasting glucose. Joint association of the modules, identified with weighted co-expression analysis, as well as the member genes of the modules with the markers of depression and CVH were tested with multivariate analysis of variance (MANOVA). Results: We identified a gene module with 256 genes that were significantly correlated with both the BDI-II score and CVH metrics. Based on the MANOVA test results adjusted for age and sex, the module was associated with both depression and CVH markers. The three most significant member genes in the module were YOD1, RBX1, and LEPR. Genes in the module were enriched with biological pathways involved in brain diseases such as Alzheimer's, Parkinson's, and Huntington's. Conclusions: The identified gene module and its members can provide new joint biomarkers for depression and CVH.

Association of Ideal Cardiovascular Health in Youth with Cancer Risk in Adulthood: Cardiovascular Risk in Young Finns Study.

BACKGROUND: Lifestyle factors may affect cancer risk. This study aimed to identify whether American Heart Association (AHA) Ideal Cardiovascular Health (ICH) score and its individual variables in youth associate with subsequent cancer incidence. METHODS: Study comprised of participants of the Cardiovascular Risk in Young Finns Study free of cancer at analysis baseline in 1986 (n=1873). Baseline age was 12-24 years and the follow-up occurred between 1986-2018. RESULTS: Among 1873 participants (mean age 17.3±4.1 years; 53.4% females at baseline), 72 incident cancer cases occurred during the follow-up (mean follow-up time 31.4±3.4 years). Baseline ICH score was not associated with future cancer risk (HR 0.96, 95% CI 0.78-1.12 per 1-point increment). Of individual ICH score variables, ideal physical activity (PA) was inversely associated with cancer incidence (age- and sex-adjusted HR 0.45 (0.23-0.88) per 1-category change [nonideal/ideal]), and remained significant in multivariable-adjusted model including also BMI, smoking, diet and socioeconomic status. A continuous physical activity index at ages 9-24 years and moderate to vigorous physical activity in youth were also related to decreased cancer incidence (p<0.05). BMI, smoking, diet, total cholesterol, glucose and blood pressure were not related to cancer risk. Of the dietary components, meat consumption was associated with cancer incidence (p=0.023). CONCLUSIONS: These findings indicate that higher PA levels in youth associate with a reduced subsequent cancer incidence whereas AHA´s ICH score in youth does not. IMPACT: This finding supports the efforts in promoting healthy lifestyle and encourages in physical activity during childhood yielding in subsequent healthier life.

Tracking of serum lipid levels from childhood to adulthood: Systematic review and meta-analysis.

BACKGROUND AND AIMS: The utility of lipid screening in pediatric settings for preventing adult atherosclerotic cardiovascular diseases partly depends on the lifelong tracking of lipid levels. This systematic review aimed to quantify the tracking of lipid levels from childhood and adolescence to adulthood. METHODS: We systematically searched MEDLINE, Embase, Web of Science, and Google Scholar in March 2022. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO; ID: CRD42020208859). We included cohort studies that measured tracking of lipids from childhood or adolescence (<18 years) to adulthood (≥18) with correlation or tracking coefficients. We estimated pooled correlation and tracking coefficients using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool. RESULTS: Thirty-three studies of 19 cohorts (11,020 participants) were included. The degree of tracking from childhood and adolescence to adulthood differed among lipids. Tracking was observed for low-density lipoprotein cholesterol (pooled r = 0.55-0.65), total cholesterol (pooled r = 0.51-0.65), high-density lipoprotein cholesterol (pooled r = 0.46-0.57), and triglycerides (pooled r = 0.32-0.40). Only one study included tracking of non-high-density lipoprotein cholesterol (r = 0.42-0.59). Substantial heterogeneity was observed. Study risk of bias was moderate, mostly due to insufficient reporting and singular measurements at baseline and follow-up. CONCLUSIONS: Early-life lipid measurements are important for predicting adult levels. However, further research is needed to understand the tracking of non-high-density lipoprotein cholesterol and the stability of risk classification over time, which may further inform pediatric lipid screening and assessment strategies.

Non-High-Density Lipoprotein Cholesterol Levels From Childhood to Adulthood and Cardiovascular Disease Events.

Importance: Elevated non-high-density lipoprotein cholesterol (non-HDL-C; a recommended measure of lipid-related cardiovascular risk) is common in children and increases risk of adult cardiovascular disease (CVD). Whether resolution of elevated childhood non-HDL-C levels by adulthood is associated with reduced risk of clinical CVD events is unknown. Objective: To examine the associations of non-HDL-C status between childhood and adulthood with incident CVD events. Design, Setting, and Participants: Individual participant data from 6 prospective cohorts of children (mean age at baseline, 10.7 years) in the US and Finland. Recruitment took place between 1970 and 1996, with a final follow-up in 2019. Exposures: Child (age 3-19 years) and adult (age 20-40 years) non-HDL-C age- and sex-specific z scores and categories according to clinical guideline-recommended cutoffs for dyslipidemia. Main Outcomes and Measures: Incident fatal and nonfatal CVD events adjudicated by medical records. Results: Over a mean length of follow-up of 8.9 years after age 40 years, 147 CVD events occurred among 5121 participants (60% women; 15% Black). Both childhood and adult non-HDL-C levels were associated with increased risk of CVD events (hazard ratio [HR], 1.42 [95% CI, 1.18-1.70] and HR, 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively), but the association for childhood non-HDL-C was reduced when adjusted for adult levels (HR, 1.12 [95% CI, 0.89-1.41]). A complementary analysis showed that both childhood non-HDL-C levels and the change between childhood and adulthood were independently associated with the outcome, suggesting that from a preventive perspective, both childhood non-HDL-C levels and the change into adulthood are informative. Compared with those whose non-HDL-C levels remained within the guideline-recommended range in childhood and adulthood, participants who had incident non-HDL-C dyslipidemia from childhood to adulthood and those with persistent dyslipidemia had increased risks of CVD events (HR, 2.17 [95% CI, 1.00-4.69] and HR, 5.17 [95% CI, 2.80-9.56], respectively). Individuals who had dyslipidemic non-HDL-C in childhood but whose non-HDL-C levels were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR, 1.13 [95% CI, 0.50-2.56]). Conclusions and Relevance: Individuals with persistent non-HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events, but those in whom dyslipidemic non-HDL-C levels resolve by adulthood have similar risk to individuals who were never dyslipidemic. These findings suggest that interventions to prevent and reduce elevated childhood non-HDL-C levels may help prevent premature CVD.

Subclinical atherosclerosis in young adults predicting cardiovascular disease: The Cardiovascular Risk in Young Finns Study.

BACKGROUND AND AIMS: Atherosclerosis is accompanied by pre-clinical vascular changes that can be detected using ultrasound imaging. We examined the value of such pre-clinical features in identifying young adults who are at risk of developing atherosclerotic cardiovascular disease (ASCVD). METHODS: A total of 2641 individuals free of ASCVD were examined at the mean age of 32 years (range 24-45 years) for carotid artery intima-media thickness (IMT) and carotid plaques, carotid artery elasticity, and brachial artery flow-mediated endothelium-dependent vasodilation (FMD). The average follow-up time to event/censoring was 16 years (range 1-17 years). RESULTS: Sixty-seven individuals developed ASCVD (incidence 2.5%). The lowest incidence (1.1%) was observed among those who were estimated of having low risk according to the SCORE2 risk algorithm (<2.5% 10-year risk) and who did not have plaque or high IMT (upper decile). The highest incidence (11.0%) was among those who were estimated of having a high risk (≥2.5% 10-year risk) and had positive ultrasound scan for carotid plaque and/or high IMT (upper decile). Carotid plaque and high IMT remained independently associated with higher risk in multivariate models. The distributions of carotid elasticity indices and brachial FMD did not differ between cases and non-cases. CONCLUSIONS: Screening for carotid plaque and high IMT in young adults may help identify individuals at high risk for future ASCVD.

Association of Long-Term Habitual Dietary Fiber Intake since Infancy with Gut Microbiota Composition in Young Adulthood.

BACKGROUND: Dietary fiber is an important health-promoting component of the diet, which is fermented by the gut microbes that produce metabolites beneficial for the host's health. OBJECTIVES: We studied the associations of habitual long-term fiber intake from infancy with gut microbiota composition in young adulthood by leveraging data from the Special Turku Coronary Risk Factor Intervention Project, an infancy-onset 20-y dietary counseling study. METHODS: Fiber intake was assessed annually using food diaries from infancy ≤ age 20 y. At age 26 y, the first postintervention follow-up study was conducted including food diaries and fecal sample collection (N = 357). Cumulative dietary fiber intake was assessed as the area under the curve for energy-adjusted fiber intake throughout the study (age 0-26 y). Gut microbiota was profiled using 16S ribosomal ribonucleic acid amplicon sequencing. The primary outcomes were 1) α diversity expressed as the observed richness and Shannon index, 2) ß diversity using Bray-Curtis dissimilarity scores, and 3) differential abundance of each microbial taxa with respect to the cumulative energy-adjusted dietary fiber intake. RESULTS: Higher cumulative dietary fiber intake was associated with decreased Shannon index (ß = -0.019 per unit change in cumulative fiber intake, P = 0.008). Overall microbial community composition was related to the amount of fiber consumed (permutational analysis of variation R2 = 0.005, P = 0.024). The only genus that was increased with higher cumulative fiber intake was butyrate-producing Butyrivibrio (log2 fold-change per unit change in cumulative fiber intake 0.40, adjusted P = 0.023), whereas some other known butyrate producers such as Faecalibacterium and Subdoligranulum were decreased with higher cumulative fiber intake. CONCLUSIONS: As early-life nutritional exposures may affect the lifetime microbiota composition and disease risk, this study adds novel information on the associations of long-term dietary fiber intake with the gut microbiota. This trial was registered at clinicaltrials.gov as NCT00223600.

Association of tobacco smoke exposure with metabolic profile from childhood to early adulthood: the Special Turku Coronary Risk Factor Intervention Project.

AIMS: To investigate the associations between passive tobacco smoke exposure and daily smoking with a comprehensive metabolic profile, measured repeatedly from childhood to adulthood. METHODS AND RESULTS: Study cohort was derived from the Special Turku Coronary Risk Factor Intervention Project (STRIP). Smoking status was obtained by questionnaire, while serum cotinine concentrations were measured using gas chromatography. Metabolic measures were quantified by nuclear magnetic resonance metabolomics at 9 (n = 539), 11 (n = 536), 13 (n = 525), 15 (n = 488), 17 (n = 455), and 19 (n = 409) years. Association of passive tobacco smoke exposure with metabolic profile compared participants who reported less-than-weekly smoking and had serum cotinine concentration <1 ng/mL (no exposure) with those whose cotinine concentration was ≥10 ng/mL (passive tobacco smoke exposure). Associations of daily smoking with metabolic profile in adolescence were analysed by comparing participants reporting daily smoking with those reporting no tobacco use and having serum cotinine concentrations <1 ng/mL. Passive tobacco smoke exposure was directly associated with the serum ratio of monounsaturated fatty acids to total fatty acids [ß = 0.34 standard deviation (SD), (0.17-0.51), P < 0.0001] and inversely associated with the serum ratios of polyunsaturated fatty acids. Exposure to passive tobacco smoke was directly associated with very-low-density lipoprotein particle size [ß = 0.28 SD, (0.12-0.45), P = 0.001] and inversely associated with HDL particle size {ß = -0.21 SD, [-0.34 to -0.07], P = 0.003}. Daily smokers exhibited a similar metabolic profile to those exposed to passive tobacco smoke. These results persisted after adjusting for body mass index, STRIP study group allocation, dietary target score, pubertal status, and parental socio-economic status. CONCLUSION: Both passive and active tobacco smoke exposures during childhood and adolescence are detrimentally associated with circulating metabolic measures indicative of increased cardio-metabolic risk.

A substantial proportion of children are affected by tobacco smoke exposure worldwide, and early life exposure to passive tobacco smoke may be even more harmful than active smoking in terms of cardiovascular disease risk. Our study suggests the following: Passive tobacco smoke exposure during childhood is associated with metabolic measures indicative of increased cardio-metabolic risk and that the association profile is similar with active daily smoking during adolescence.Reducing both active and passive tobacco smoke exposures during childhood and adolescence could reduce the risk of future cardio-metabolic disease.

Blood Pressure at Different Life Stages Over the Early Life Course and Intima-Media Thickness.

Importance: Although cardiovascular disease (CVD) begins in early life, the extent to which blood pressure (BP) at different life stages contributes to CVD is unclear. Objective: To determine the relative contribution of BP at different life stages across the early-life course from infancy to young adulthood with carotid intima-media thickness (IMT). Design, setting, and participants: The analyses were performed in 2022 using data gathered from July 1989 through January 2018 within the Special Turku Coronary Risk Factor Intervention Project, a randomized, infancy-onset cohort of 534 participants coupled with annual BP (from age 7 months to 20 years), biennial IMT measurements (from ages 13 to 19 years), who were followed up with again at age 26 years. Exposures: BP measured from infancy (aged 7 to 13 months), preschool (2 to 5 years), childhood (6 to 12 years), adolescence (13 to 17 years), and young adulthood (18 to 26 years). Main outcomes and measures: Primary outcomes were carotid IMT measured in young adulthood at age 26 years. Bayesian relevant life-course exposure models assessed the relative contribution of BP at each life stage. Results: Systolic BP at each life stage contributed to the association with young adulthood carotid IMT (infancy: relative weight, 25.3%; 95% credible interval [CrI], 3.6-45.8; preschool childhood: relative weight, 27.0%; 95% CrI, 3.3-57.1; childhood: relative weight, 18.0%; 95% CrI, 0.5-40.0; adolescence: relative weight, 13.5%; 95% CrI, 0.4-37.1; and young adulthood: relative weight, 16.2%; 95% CrI, 1.6-46.1). A 1-SD (at single life-stage) higher systolic BP accumulated across the life course was associated with a higher carotid IMT (0.02 mm; 95% CrI, 0.01-0.03). The findings for carotid IMT were replicated in the Cardiovascular Risk in Young Finns Study that assessed systolic BP from childhood and carotid IMT in adulthood (33 to 45 years). Conclusion and relevance: In this cohort study, a life-course approach indicated that accumulation of risk exposure to BP levels at all life stages contributed to adulthood carotid IMT. Of those, the contribution attributed to each observed life stage was approximately equal. These results support prevention efforts that achieve and maintain normal BP levels across the life course, starting in infancy.

Tracking of apolipoprotein B levels measured in childhood and adolescence: systematic review and meta-analysis.

To quantify the tracking of apolipoprotein B (apoB) levels from childhood and adolescence and compare the tracking of apoB with low-density lipoprotein (LDL) cholesterol, a systematic search of MEDLINE, Embase, Web of Science, and Google Scholar was performed in October 2023 (PROSPERO protocol: CRD42022298663). Cohort studies that measured tracking of apoB from childhood/adolescence (< 19 years) with a minimum follow-up of 1 year, using tracking estimates such as correlation coefficients or tracking coefficients, were eligible. Pooled correlations were estimated using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool. Ten studies of eight unique cohorts involving 4677 participants met the inclusion criteria. Tracking of apoB was observed (pooled r = 0.63; 95% confidence interval [CI] = 0.53-0.71; I2 = 96%) with no significant sources of heterogeneity identified. Data from five cohorts with tracking data for both lipids showed the degree of tracking was similar for apoB (pooled r = 0.59; 95% CI = 0.55-0.63) and LDL cholesterol (pooled r = 0.58; 95% CI = 0.47-0.68). Study risk of bias was moderate, mostly due to attrition and insufficient reporting. CONCLUSION: ApoB levels track strongly from childhood, but do not surpass LDL cholesterol in this regard. While there is strong evidence that apoB is more effective at predicting ASCVD risk than LDL cholesterol in adults, there is currently insufficient evidence to support its increased utility in pediatric settings. This also applies to tracking data, where more comprehensive data are required. WHAT IS KNOWN: • Apolipoprotein B is a known cause of atherosclerotic cardiovascular disease. • Apolipoprotein B levels are not typically measured in pediatric settings, where low-density lipoprotein cholesterol remains the primary lipid screening measure. WHAT IS NEW: • This meta-analysis of 10 studies showed apolipoprotein B levels tracked strongly from childhood but did not exceed low-density lipoprotein cholesterol in this regard. • More comprehensive tracking data are needed to provide sufficient evidence for increased utility of apolipoprotein B in pediatric settings.

Childhood Non-HDL Cholesterol and LDL Cholesterol and Adult Atherosclerotic Cardiovascular Events.

BACKGROUND: Although low-density lipoprotein cholesterol (LDL-C) remains the primary cholesterol target in clinical practice in children and adults, non-high-density lipoprotein cholesterol (non-HDL-C) has been suggested as a more accurate measure of atherosclerotic cardiovascular disease (ASCVD) risk. We examined the associations of childhood non-HDL-C and LDL-C levels with adult ASCVD events and determined whether non-HDL-C has better utility than LDL-C in predicting adult ASCVD events. METHODS: This prospective cohort study included 21 126 participants from the i3C Consortium (International Childhood Cardiovascular Cohorts). Proportional hazards regressions were used to estimate the risk for incident fatal and fatal/nonfatal ASCVD events associated with childhood non-HDL-C and LDL-C levels (age- and sex-specific z scores; concordant/discordant categories defined by guideline-recommended cutoffs), adjusted for sex, Black race, cohort, age at and calendar year of child measurement, body mass index, and systolic blood pressure. Predictive utility was determined by the C index. RESULTS: After an average follow-up of 35 years, 153 fatal ASCVD events occurred in 21 126 participants (mean age at childhood visits, 11.9 years), and 352 fatal/nonfatal ASCVD events occurred in a subset of 11 296 participants who could be evaluated for this outcome. Childhood non-HDL-C and LDL-C levels were each associated with higher risk of fatal and fatal/nonfatal ASCVD events (hazard ratio ranged from 1.27 [95% CI, 1.14-1.41] to 1.35 [95% CI, 1.13-1.60] per unit increase in the risk factor z score). Non-HDL-C had better discriminative utility than LDL-C (difference in C index, 0.0054 [95% CI, 0.0006-0.0102] and 0.0038 [95% CI, 0.0008-0.0068] for fatal and fatal/nonfatal events, respectively). The discordant group with elevated non-HDL-C and normal LDL-C had a higher risk of ASCVD events compared with the concordant group with normal non-HDL-C and LDL-C (fatal events: hazard ratio, 1.90 [95% CI, 0.98-3.70]; fatal/nonfatal events: hazard ratio, 1.94 [95% CI, 1.23-3.06]). CONCLUSIONS: Childhood non-HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non-HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non-HDL-C. These findings suggest that both non-HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non-HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical advantage of being determined without a fasting sample.

Association of number of siblings with preclinical markers of cardiovascular disease. The cardiovascular risk in Young Finns study.

To investigate the association of number of siblings with preclinical cardiovascular disease (CVD) markers in adulthood. The sample comprised 2776 participants (54 % female) from the Cardiovascular Risk in Young Finns Study who had CVD risk factor data measured in childhood in 1980 (aged 3-18 years) and markers of preclinical CVD measured in adulthood. Echocardiography was performed in 2011, and carotid intima-media thickness, carotid distensibility, brachial flow-mediated dilatation, and arterial pulse wave velocity were measured in 2001 or 2007. The association between the number of siblings and preclinical CVD was assessed using generalized linear and logistic regression models. Analyses were stratified by sex as associations differed between sexes. Women with 1 sibling had lower E/e'-ratio (4.9, [95%CI 4.8-5.0]) in echocardiography compared with those without siblings (5.1[4.9-5.2]) and those with ≥2 more siblings (5.1[5.0-5.2]) (P for trend 0.01). Men without siblings had the lowest E/A-ratio (1.4[1.3-1.5]) compared with those with 1 sibling (1.5[1.5-1.5]), or ≥2 siblings (1.5[1.5-1.5]) (P for trend 0.01). Women without siblings had highest left ventricular ejection fraction (59.2 %[58.6-59.7 %]) compared with those with 1 sibling (59.1 %[58.8-59.4 %]), or ≥2 siblings (58.4 %[58.1-58.8 %])(P for trend 0.01). In women, brachial flow-mediated dilatation, a measure of endothelial function, was the lowest among participants with ≥2 siblings (9.4 %[9.0-9.8 %]) compared with those with 1 sibling (10.0 %[9.6-10.3 %]) and those without siblings (10.4 %[9.7-11.0 %])(P for trend 0.03). We observed that number of siblings may be associated with increased risk of heart failure in women. As the associations were somewhat inconsistent in males and females, further research is warranted.

The Influence of Dietary Counseling Over 20 Years on Tracking of Non-High-Density Lipoprotein Cholesterol from Infancy to Young Adulthood.

This 26-year study found that non-high-density lipoprotein cholesterol (non-HDL-C) levels tracked from infancy to young adulthood suggesting early-life non-HDL-C could predict future levels. However, infancy-onset dietary counseling reduced the odds of maintaining at-risk non-HDL-C, highlighting the potential importance of early interventions in preventing cardiovascular risk associated with high pediatric non-HDL-C.

Weekday and weekend physical activity patterns and their correlates among young adults.

BACKGROUND: Accelerometers enable assessment of within and between day variation in physical activity. The main aim was to examine weekday and weekend physical activity patterns among young adults. Additionally, correlates of the physical activity patterns were examined. METHODS: Overall 325 adults (mean age 26.0 years, standard deviation 0.03) from the Special Turku Coronary Risk Factor Intervention Project used a wrist-worn ActiGraph accelerometer continuously for 1 week. Physical activity patterns over weekdays and weekends were identified by using the group-based trajectory modeling. Adolescent leisure time physical activity (LTPA) and sociodemographic characteristics (sex, marital and family status, education, work status, occupation, and health consciousness) were examined as possible correlates of physical activity patterns using multinomial regression analysis. RESULTS: Five patterns were identified: consistently low activity (45%), active on weekday evenings and weekends (32%), consistently moderate activity (11%), active on weekdays (7%), and consistently high activity (5%). Low adolescent LTPA was associated with consistently low activity pattern in young adulthood. Women were more likely than men to belong in the more physically active groups (all other groups except active on weekdays, odds ratios between 2.26 and 6.17). Those in the active on weekdays group had lower education, were more often in the working life and in manual occupations than those in the consistently low activity group. CONCLUSIONS: Marked heterogeneity in physical activity patterns across the week was observed among young adults. Especially history of physical activity, sex, education, work status, and occupation were associated with different physical activity patterns.

Polygenic liabilities underlying job stress and exhaustion over a 10-year follow-up: A general population study.

We investigated whether individuals, who have a high polygenic loading for schizophrenia and major depression (PGL) but have not developed the respective disorders, are still susceptible to experience milder forms of ill-being in terms of job strain or exhaustion. We used the population-based Young Finns Study data (n = 928). PGL was assessed with a cumulative score of the polygenic risk scores for schizophrenia and depression. Participants (24-49-year-olds) evaluated their exhaustion levels and perceived job characteristics over a 10-year follow-up (2001, 2007, 2011). Participants with diagnosed psychotic or affective disorders were excluded. We found that high PGL did not predict less favorable perceptions of job environment (job strain, demands, control, satisfaction, social support at work) but high PGL predicted a higher trajectory of exhaustion in early adulthood and middle age. Additionally, high (vs. low) PGL predicted a stronger increase in exhaustion at increased levels of job strain. These findings remained after controlling for sex, socioeconomic factors, health behaviors, and cognitive performance. In conclusion, individuals with high PGL may have an elevated liability to experience exhaustion especially in early adulthood and middle age (despite they perceive their job environment similarly than others), and especially and at high levels of job strain.

Nonalcoholic Fatty Liver Disease Incidence and Remission and Their Predictors During 7 Years of Follow-up Among Finns.

CONTEXT: The incidence and remission of nonalcoholic fatty liver disease (NAFLD) are sparsely studied outside Asia. OBJECTIVE: This prospective study aimed to investigate NAFLD incidence and remission, and their predictors among a general Finnish population. METHODS: The applied cohort included 1260 repeatedly studied middle-aged participants with data on liver ultrasound and no excessive alcohol intake. Hepatic steatosis was assessed by liver ultrasound with a 7.2-year study interval. Comprehensive data on health parameters and lifestyle factors were available. RESULTS: At baseline, 1079 participants did not have NAFLD, and during the study period 198 of them developed NAFLD. Of the 181 participants with NAFLD at baseline, 40 achieved NAFLD remission. Taking multicollinearity into account, key predictors for incident NAFLD were baseline age (odds ratio 1.07; 95% CI, 1.02-1.13; P = .009), waist circumference (WC) (2.77, 1.91-4.01 per 1 SD; P < .001), and triglycerides (2.31, 1.53-3.51 per 1 SD; P < .001) and alanine aminotransferase (ALAT) (1.90, 1.20-3.00 per 1 SD; P = .006) concentrations as well as body mass index (BMI) change (4.12, 3.02-5.63 per 1 SD; P < .001). Predictors of NAFLD remission were baseline aspartate aminotransferase (ASAT) concentration (0.23, 0.08-0.67 per 1 SD; P = .007) and WC change (0.38, 0.25-0.59 per 1 SD; P < .001). CONCLUSION: During follow-up, NAFLD developed for every fifth participant without NAFLD at baseline, and one-fifth of those with NAFLD at baseline had achieved NAFLD remission. NAFLD became more prevalent during the follow-up period. From a clinical perspective, key factors predicting NAFLD incidence and remission were BMI and WC change independent of their baseline level.

Tracking of Cardiorespiratory Fitness and Physical Activity from Youth to Young Adulthood: Findings from the Prospective Special Turku Coronary Risk Factor Intervention Project (STRIP).

Using data from the Special Turku Coronary Risk Factor Intervention Project, cardiorespiratory fitness (rank-order correlation coefficient = 0.60-0.62) tracked stronger than physical activity (rank-order correlation coefficient = 0.27-0.38) between youth (age = 17 years) and young adulthood (age = 26 years). Cardiorespiratory fitness could help identify individuals at risk of maintaining poor fitness levels or developing adverse health in adulthood.

Dietary patterns from youth to adulthood and cognitive function in midlife: The cardiovascular risk in Young Finns Study.

OBJECTIVES: Diet plays an important role in cognitive health, but the long-term association of diet early in life with cognitive function in adulthood has not, to our knowledge, been rigorously studied. The aim of this study was to examine the association of youth, adulthood, and long-term dietary patterns from youth to adulthood with cognitive function in midlife. METHODS: This was a population-based cohort study that assessed dietary intake in 1980 (baseline, participants 3-18 y of age), 1986, 2001, 2007, and 2011 and cognitive function in 2011. Six dietary patterns were derived from 48-h food recall or food frequency questionnaires using factor analysis. The dietary patterns were traditional Finnish, high-carbohydrate, vegetables and dairy products, traditional Finnish and high-carbohydrate, red meat, and healthy. Scores of long-term dietary patterns were calculated as the average between youth and adulthood. Cognitive function outcomes assessed included episodic memory and associative learning, short-term working memory and problem solving, reaction and movement time, and visual processing and sustained attention. Standardized z-scores of exposures and outcomes were used for analyses. RESULTS: Participants (n = 790, mean age 11.2 y) were followed up for 31 y. Multivariable models showed that both youth and long-term vegetable and dairy products and healthy patterns were positively associated with episodic memory and associative learning scores (ß = 0.080-0.111, P < 0.05 for all). Both youth and long-term traditional Finnish patterns were negatively associated with spatial working memory and problem solving (ß = -0.085 and -0.097, respectively; P < 0.05 for both). Long-term high-carbohydrate and traditional Finnish and high-carbohydrate patterns were inversely associated with visual processing and sustained attention, whereas the vegetable and dairy products pattern was positively associated with this cognitive domain (ß = -0.117 to 0.073, P < 0.05 for all). Adulthood high-carbohydrate and traditional Finnish and high-carbohydrate patterns were inversely associated with all cognitive domains except for reaction and movement time (ß = -0.072 to -0.161, P < 0.05 for all). Both long-term and adulthood red meat pattern were positively associated with visual processing and sustained attention (ß = 0.079 and 0.104, respectively; P < 0.05 for both). These effect sizes correspond to approximately 1.6 to 16.1 y of cognitive aging on these cognitive domains. CONCLUSIONS: Higher adherence to traditional Finnish, high-carbohydrate, and traditional Finnish and high-carbohydrate patterns across the early life course was associated with poorer cognitive function in midlife, whereas higher adherence to healthy and vegetable and dairy product patterns was associated with better cognitive function. The findings, if causative, highlight the importance of maintaining a healthy dietary pattern from early life to adulthood in an attempt to promote cognitive health.

Associations of breastfeeding duration with serum lipid values from infancy until age 20 years - the STRIP study.

BACKGROUND AND AIMS: The effect of breastfeeding duration on childhood lipid levels has remained controversial. In this study, we aimed to establish the long-term associations of breastfeeding duration with future levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol and low-density lipoprotein cholesterol. In addition, we report lipid levels at the age of seven months depending on the child receiving any breastmilk. METHODS: The sample comprised 999 children participating in the prospective Special Turku Coronary Risk Factor Intervention Project (STRIP). Serum lipid profile was studied at the ages of seven months and 13 months, and annually thereafter until the age of 20 years. Duration of breastfeeding was inquired, and infants were divided into those who received or did not receive any breast milk at the age of seven months (n=533 and n=466, respectively). In addition, breastfeeding duration groups (any breastfeeding for 0-4 months, 4-6 months, 6-9 months, and >9 months) were formed. RESULTS: At the age of seven months infants who at that time received breast milk had higher serum HDL cholesterol (0.95±0.21mmol/l vs. 0.90±0.19 mmol/l; p=0.0018), non-HDL cholesterol (3.38±0.78 mmol/l vs. 3.01±0.67 mmol/l; p<0.001) and total cholesterol levels (4.33±0.80 mmol/l vs. 3.91±0.69 mmol/l; p<0.001) than their peers who did not receive breast milk. From two to 20 years of age serum lipid levels showed no consistent differences between the breastfeeding duration groups. CONCLUSIONS: Our long-term data showed that duration of breastfeeding has no consistent associations with serum lipid concentrations in healthy individuals aged two to 20 years. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov, unique identifier NCT00223600.

Gene Set Based Integrated Methylome and Transcriptome Analysis Reveals Potential Molecular Mechanisms Linking Cigarette Smoking and Related Diseases.

Advanced integrative analysis of DNA methylation and transcriptomics data may provide deeper insights into smoke-induced epigenetic alterations, their effects on gene expression and related biological processes, linking cigarette smoking and related diseases. We hypothesize that accumulation of DNA methylation changes in CpG sites across genomic locations of different genes might have biological significance. We tested the hypothesis by performing gene set based integrative analysis of blood DNA methylation and transcriptomics data to identify potential transcriptomic consequences of smoking via changes in DNA methylation in the Young Finns Study (YFS) participants (n = 1114, aged 34-49 years, women: 54%, men: 46%). First, we performed epigenome-wide association study (EWAS) of smoking. We then defined sets of genes based on DNA methylation status within their genomic regions, for example, sets of genes containing hyper- or hypomethylated CpG sites in their body or promoter regions. Gene set analysis was performed using transcriptomics data from the same participants. Two sets of genes, one containing 49 genes with hypomethylated CpG sites in their body region and the other containing 33 genes with hypomethylated CpG sites in their promoter region, were differentially expressed among the smokers. Genes in the two gene sets are involved in bone formation, metal ion transport, cell death, peptidyl-serine phosphorylation, and cerebral cortex development process, revealing epigenetic-transcriptomic pathways to smoking-related diseases such as osteoporosis, atherosclerosis, and cognitive impairment. These findings contribute to a deeper understanding of the pathophysiology of smoking-related diseases and may provide potential therapeutic targets.