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.

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.

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.

Intergenerational continuity of loneliness and potential mechanisms: Young Finns Multigenerational Study.

Evidence on the intergenerational continuity of loneliness and on potential mechanisms that connect loneliness across successive generations is limited. We examined the association between loneliness of (G0) parents (859 mothers and 570 fathers, mean age 74 years) and their children (G1) (433 sons and 558 daughters, mean age 47 years) producing 991 parent-offspring pairs and tested whether these associations were mediated through subjective socioeconomic position, temperament characteristics, cognitive performance, and depressive symptoms. Mean loneliness across parents had an independent effect on their adult children's experienced loneliness (OR = 1.72, 95% CI 1.23-2.42). We also found a robust effect of mothers' (OR = 1.64, 95% CI 1.17-2.29), but not of fathers' loneliness (OR = 1.47, 95% CI 0.96-2.25) on offspring's experienced loneliness in adulthood. The associations were partly mediated by offspring depressive (41-54%) and anxiety (29-31%) symptoms. The current findings emphasize the high interdependence of loneliness within families mediated partly by offspring's mental health problems.

Association of childhood socioeconomic status with adulthood maximal exercise blood pressure: the Cardiovascular Risk in Young Finns Study.

PURPOSE: Socioeconomic status has been related to resting blood pressure (BP) levels at different stages of life. However, the association of childhood socioeconomic status (SES) and adulthood exercise BP is largely unknown. Therefore, we studied the association of childhood SES with adulthood maximal exercise BP. MATERIALS AND METHODS: This investigation consisted of 373 individuals (53% women) participating in the Cardiovascular Risk in Young Finns Study who had data concerning family SES in childhood (baseline in 1980, at age of 6-18 years) and exercise BP response data in adulthood (follow-up in adulthood in 27-29 years since baseline). A maximal cardiopulmonary exercise test with BP measurements was performed by participants, and peak exercise BP was measured. RESULTS: In stepwise multivariable analysis including childhood risk factors and lifestyle factors (body mass index, systolic BP, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, insulin, fruit consumption, vegetable consumption, and physical activity), lower family SES in childhood was associated with higher maximal exercise BP in adulthood (ß value ± SE, 1.63 ± 0.77, p = 0.035). The association remained significant after further adjustment with participants SES in adulthood (ß value ± SE, 1.68 ± 0.65, p = 0.011) and after further adjustment with adulthood body-mass index, systolic BP, maximal exercise capacity, and peak heart rate in exercise (ß value ± SE, 1.25 ± 0.56, p = 0.027). CONCLUSIONS: These findings suggest that lower childhood family SES is associated with higher maximal exercise BP in adulthood.

Limited data are available about the association of childhood socioeconomic status and adulthood exercise blood pressure.We prospectively examined whether childhood socioeconomic status is associated with adulthood exercise blood pressure in 373 participants aged 6­18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns cohort study.In multivariable analysis, including childhood cardiovascular risk factors and lifestyle factors, lower family socioeconomic status in childhood was associated with higher maximal exercise blood pressure in adulthood.The association remained significant after further adjustment with participants socioeconomic status in adulthood and also after further adjustment with adulthood body mass index, systolic blood pressure, maximal exercise capacity and peak heart rate in exercise.Low childhood socioeconomic status predicted also higher risk of exaggerated exercise blood pressure response in adulthood, although this finding was diluted to non-significant after adjustment with adulthood body mass index and systolic blood pressure.These findings suggest that lower childhood family socioeconomic status is associated with higher maximal exercise blood pressure in adulthood.

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.

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.

Clinical and biochemical associations of urinary metabolites: quantitative epidemiological approach on renal-cardiometabolic biomarkers.

BACKGROUND: Urinary metabolomics has demonstrated considerable potential to assess kidney function and its metabolic corollaries in health and disease. However, applications in epidemiology remain sparse due to technical challenges. METHODS: We added 17 metabolites to an open-access urinary nuclear magnetic resonance metabolomics platform, extending the panel to 61 metabolites (n = 994). We also introduced automated quantification for 11 metabolites, extending the panel to 12 metabolites (+creatinine). Epidemiological associations between these 12 metabolites and 49 clinical measures were studied in three independent cohorts (up to 5989 participants). Detailed regression analyses with various confounding factors are presented for body mass index (BMI) and smoking. RESULTS: Sex-specific population reference concentrations and distributions are provided for 61 urinary metabolites (419 men and 575 women), together with methodological intra-assay metabolite variations as well as the biological intra-individual and epidemiological population variations. For the 12 metabolites, 362 associations were found. These are mostly novel and reflect potential molecular proxies to estimate kidney function, as the associations cannot be simply explained by estimated glomerular filtration rate. Unspecific renal excretion results in leakage of amino acids (and glucose) to urine in all individuals. Seven urinary metabolites associated with smoking, providing questionnaire-independent proxy measures of smoking status in epidemiological studies. Common confounders did not affect metabolite associations with smoking, but insulin had a clear effect on most associations with BMI, including strong effects on 2-hydroxyisobutyrate, valine, alanine, trigonelline and hippurate. CONCLUSIONS: Urinary metabolomics provides new insight on kidney function and related biomarkers on the renal-cardiometabolic system, supporting large-scale applications in epidemiology.

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.

A Proposed Pediatric Clinical Cardiovascular Health Reference Standard.

INTRODUCTION: Clinical cardiovascular health is a construct that includes 4 health factors-systolic and diastolic blood pressure, fasting glucose, total cholesterol, and body mass index-which together provide an evidence-based, more holistic view of cardiovascular health risk in adults than each component separately. Currently, no pediatric version of this construct exists. This study sought to develop sex-specific charts of clinical cardiovascular health for age to describe current patterns of clinical cardiovascular health throughout childhood. METHODS: Data were used from children and adolescents aged 8-19 years in six pooled childhood cohorts (19,261 participants, collected between 1972 and 2010) to create reference standards for fasting glucose and total cholesterol. Using the models for glucose and cholesterol as well as previously published reference standards for body mass index and blood pressure, clinical cardiovascular health charts were developed. All models were estimated using sex-specific random-effects linear regression, and modeling was performed during 2020-2022. RESULTS: Models were created to generate charts with smoothed means, percentiles, and standard deviations of clinical cardiovascular health for each year of childhood. For example, a 10-year-old girl with a body mass index of 16 kg/m2 (30th percentile), blood pressure of 100/60 mm Hg (46th/50th), glucose of 80 mg/dL (31st), and total cholesterol of 160 mg/dL (46th) (lower implies better) would have a clinical cardiovascular health percentile of 62 (higher implies better). CONCLUSIONS: Clinical cardiovascular health charts based on pediatric data offer a standardized approach to express clinical cardiovascular health as an age- and sex-standardized percentile for clinicians to assess cardiovascular health in childhood to consider preventive approaches at early ages and proactively optimize lifetime trajectories of cardiovascular health.

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.

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.

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.

Neighbourhood deprivation in childhood and adulthood and risk of arterial stiffness: the Cardiovascular Risk in Young Finns study.

Purpose: Individual socioeconomic status is associated with increased arterial stiffness, but limited data are available on the relations of neighbourhood deprivation with this vascular measure. We prospectively examined whether neighbourhood deprivation in childhood and adulthood predicts arterial stiffness indicated by pulse wave velocity (PWV).Materials and methods: The study population comprised 1,761 participants aged 3-18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns cohort study. PWV was measured in 2007 by whole-body impedance cardiography at ages 30-45 years. Cumulative lifetime neighbourhood deprivation was assessed using data from socioeconomic circumstances in participants' lifetime residential neighbourhoods, categorised as low versus high deprivation.Results: High deprivation in childhood and adulthood was associated with higher PWV in adulthood after adjustment for age, sex, and place of birth (mean difference = 0.57 m/s, 95%CI = 0.26-0.88, P for trend = 0.0004). This association was attenuated but remained statistically significant after further adjustment for childhood parental socioeconomic status and adulthood individual socioeconomic status (mean difference = 0.37 m/s, 95%CI = 0.05-0.70, P for trend 0.048). Also, low individual socioeconomic status in adulthood was associated with higher PWV when adjusted for age, sex, place of birth, parental socioeconomic status in childhood, and lifetime neighbourhood deprivation (mean difference = 0.54 m/s, 95%CI = 0.23-0.84, P for trend 0.0001).Conclusion: These findings suggest that lifetime neighbourhood deprivation and low adulthood socioeconomic status are independent risk factors for increased arterial stiffness in adulthood.

Limited data is available about the association between neighbourhood deprivation and arterial stiffening.We prospectively examined whether neighbourhood deprivation in childhood and adulthood predicts arterial stiffness indicated by pulse wave velocity (PWV) in 1,761 participants aged 3-18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns cohort study.PWV was measured by whole-body impedance cardiography at ages 30-45 years. Cumulative lifetime neighbourhood deprivation was assessed using data from socioeconomic circumstances in participants' lifetime residential neighbourhoods, categorised as low versus high deprivation.high lifetime neighbourhood deprivation was associated with high PWV in adulthood independently of childhood parental SES and adulthood individual SES.Low individual SES in adulthood was also associated with higher PWV in adulthood and this association was robust to adjustment for parental SES in childhood and lifetime neighbourhood deprivation.These findings suggest that neighbourhood deprivation and low adulthood socioeconomic status are independent risk factors for increased arterial stiffness in adulthood.

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.

Childhood Dyslipidemia and Carotid Atherosclerotic Plaque in Adulthood: The Cardiovascular Risk in Young Finns Study.

Background Childhood exposure to dyslipidemia is associated with adult atherosclerosis, but it is unclear whether the long-term risk associated with dyslipidemia is attenuated on its resolution by adulthood. We aimed to address this question by examining the links between childhood and adult dyslipidemia on carotid atherosclerotic plaques in adulthood. Methods and Results The Cardiovascular Risk in Young Finns Study is a prospective follow-up of children that began in 1980. Since then, follow-up studies have been conducted regularly. In 2001 and 2007, carotid ultrasounds were performed on 2643 participants at the mean age of 36 years to identify carotid plaques and plaque areas. For childhood lipids, we exploited several risk factor measurements to determine the individual cumulative burden for each lipid during childhood. Participants were categorized into the following 4 groups based on their childhood and adult dyslipidemia status: no dyslipidemia (reference), incident, resolved, and persistent. Among individuals with carotid plaque, linear regression models were used to study the association of serum lipids with plaque area. The prevalence of plaque was 3.3% (N=88). In models adjusted for age, sex, and nonlipid cardiovascular risk factors, the relative risk for carotid plaque was 2.34 (95% CI, 0.91-6.00) for incident adult dyslipidemia, 3.00 (95% CI, 1.42-6.34) for dyslipidemia resolved by adulthood, and 5.23 (95% CI, 2.57-10.66) for persistent dyslipidemia. Carotid plaque area correlated with childhood total, low-density lipoprotein, and non-high-density lipoprotein cholesterol levels. Conclusions Childhood dyslipidemia, even if resolved by adulthood, is a risk factor for adult carotid plaque. Furthermore, among individuals with carotid plaque, childhood lipids associate with plaque size. These findings highlight the importance of primordial prevention of dyslipidemia in childhood to reduce atherosclerosis development.

OTTERS: a powerful TWAS framework leveraging summary-level reference data.

Most existing TWAS tools require individual-level eQTL reference data and thus are not applicable to summary-level reference eQTL datasets. The development of TWAS methods that can harness summary-level reference data is valuable to enable TWAS in broader settings and enhance power due to increased reference sample size. Thus, we develop a TWAS framework called OTTERS (Omnibus Transcriptome Test using Expression Reference Summary data) that adapts multiple polygenic risk score (PRS) methods to estimate eQTL weights from summary-level eQTL reference data and conducts an omnibus TWAS. We show that OTTERS is a practical and powerful TWAS tool by both simulations and application studies.