Early intermittent hyperlipidaemia alters tissue macrophages to fuel atherosclerosis.

Hyperlipidaemia is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Risk of cardiovascular events depends on cumulative lifetime exposure to low-density lipoprotein cholesterol (LDL-C) and, independently, on the time course of exposure to LDL-C, with early exposure being associated with a higher risk1. Furthermore, LDL-C fluctuations are associated with ASCVD outcomes2-4. However, the precise mechanisms behind this increased ASCVD risk are not understood. Here we find that early intermittent feeding of mice on a high-cholesterol Western-type diet (WD) accelerates atherosclerosis compared with late continuous exposure to the WD, despite similar cumulative circulating LDL-C levels. We find that early intermittent hyperlipidaemia alters the number and homeostatic phenotype of resident-like arterial macrophages. Macrophage genes with altered expression are enriched for genes linked to human ASCVD in genome-wide association studies. We show that LYVE1+ resident macrophages are atheroprotective, and identify biological pathways related to actin filament organization, of which alteration accelerates atherosclerosis. Using the Young Finns Study, we show that exposure to cholesterol early in life is significantly associated with the incidence and size of carotid atherosclerotic plaques in mid-adulthood. In summary, our results identify early intermittent exposure to cholesterol as a strong determinant of accelerated atherosclerosis, highlighting the importance of optimal control of hyperlipidaemia early in life, and providing insights into the underlying biological mechanisms. This knowledge will be essential to designing effective therapeutic strategies to combat ASCVD.

Randomized 20-year infancy-onset dietary intervention, life-long cardiovascular risk factors and retinal microvasculature.

BACKGROUND AND AIMS: Retinal microvasculature characteristics predict cardiovascular morbidity and mortality. This study investigated associations of lifelong cardiovascular risk factors and effects of dietary intervention on retinal microvasculature in young adulthood. METHODS: The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project study. The Special Turku Coronary Risk Factor Intervention Project is a 20-year infancy-onset randomized controlled dietary intervention study with frequent study visits and follow-up extending to age 26 years. The dietary intervention aimed at a heart-healthy diet. Fundus photographs were taken at the 26-year follow-up, and microvascular measures [arteriolar and venular diameters, tortuosity (simple and curvature) and fractal dimensions] were derived (n = 486). Cumulative exposure as the area under the curve for cardiovascular risk factors and dietary components was determined for the longest available time period (e.g. from age 7 months to 26 years). RESULTS: The dietary intervention had a favourable effect on retinal microvasculature resulting in less tortuous arterioles and venules and increased arteriolar fractal dimension in the intervention group when compared with the control group. The intervention effects were found even when controlled for the cumulative cardiovascular risk factors. Reduced lifelong cumulative intake of saturated fats, main target of the intervention, was also associated with less tortuous venules. Several lifelong cumulative risk factors were independently associated with the retinal microvascular measures, e.g. cumulative systolic blood pressure with narrower arterioles. CONCLUSIONS: Infancy-onset 20-year dietary intervention had favourable effects on the retinal microvasculature in young adulthood. Several lifelong cumulative cardiovascular risk factors were independently associated with retinal microvascular structure.

Lipoprotein(a) in Youth and Prediction of Major Cardiovascular Outcomes in Adulthood.

BACKGROUND: Elevated lipoprotein(a) [Lp(a)] is a common risk factor for cardiovascular disease outcomes with unknown mechanisms. We examined its potential role in identifying youths who are at increased risk of developing adult atherosclerotic cardiovascular disease (ASCVD). METHODS: Lp(a) levels measured in youth 9 to 24 years of age were linked to adult ASCVD and carotid intima-media thickness in the YFS (Cardiovascular Risk in Young Finns Study), in which 95 of the original 3596 participants (2.7%) recruited as children have been diagnosed with ASCVD at a median of 47 years of age. Results observed in YFS were replicated with the use of data for White participants from the BHS (Bogalusa Heart Study). In BHS, 587 White individuals had data on youth Lp(a) (measured at 8-17 years of age) and information on adult events, including 15 cases and 572 noncases. Analyses were performed with the use of Cox proportional hazard regression. RESULTS: In YFS, those who had been exposed to high Lp(a) level in youth [defined as Lp(a) ≥30 mg/dL] had ≈2 times greater risk of developing adult ASCVD compared with nonexposed individuals (hazard ratio, 2.0 [95% CI, 1.4-2.6]). Youth risk factors, including Lp(a), low-density lipoprotein cholesterol, body mass index, and smoking, were all independently associated with higher risk. In BHS, in an age- and sex-adjusted model, White individuals who had been exposed to high Lp(a) had 2.5 times greater risk (95% CI, 0.9-6.8) of developing adult ASCVD compared with nonexposed individuals. When also adjusted for low-density lipoprotein cholesterol and body mass index, the risk associated with high Lp(a) remained unchanged (hazard ratio, 2.4 [95% CI, 0.8-7.3]). In a multivariable model for pooled data, individuals exposed to high Lp(a) had 2.0 times greater risk (95% CI, 1.0-3.7) of developing adult ASCVD compared with nonexposed individuals. No association was detected between youth Lp(a) and adult carotid artery thickness in either cohort or pooled data. CONCLUSIONS: Elevated Lp(a) level identified in youth is a risk factor for adult atherosclerotic cardiovascular outcomes but not for increased carotid intima-media thickness.

Association of Serum Trimethylamine-N-Oxide Concentration from Childhood to Early Adulthood with Age and Sex.

BACKGROUND: Primary prevention is the cornerstone of cardiometabolic health. In the randomized, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP), dietary counseling intervention was given to children from infancy to 20 years of age and a follow-up was completed at age 26 years. We investigated the associations of age, sex, gut microbiome, and dietary intervention with the gut metabolite and the cardiac biomarker trimethylamine-N-oxide (TMAO). METHODS: Overall, 592 healthy participants (females 46%) from STRIP were investigated. Compared to the control group, the intervention group had received dietary counseling between ages 7 months and 20 years focused on low intakes of saturated fat and cholesterol and the promotion of fruit, vegetable, and whole-grain consumption. TMAO serum concentrations were measured by a liquid chromatography-tandem mass spectrometry method at ages 11, 13, 15, 17, 19, and 26 years. Microbiome composition was assessed using 16S rRNA gene sequencing at 26 years of age. RESULTS: TMAO concentrations increased from age 11 to 26 years in both sexes. At all measurement time points, males showed significantly higher serum TMAO concentrations compared to females, but concentrations were similar between the intervention and control groups. A direct association between TMAO concentrations and reported fiber intake was found in females. Gut microbiome analysis did not reveal associations with TMAO. CONCLUSIONS: TMAO concentration increased from childhood to early adulthood but was not affected by the given dietary intervention. In females, TMAO concentrations could be directly associated with higher fiber intake suggesting sex-specific differences in TMAO metabolism.

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.

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.

Trajectories of cardiovascular risk predict pregnancy outcomes: The Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study.

BACKGROUND: Life course patterns of change in risk-trajectories-affect health. OBJECTIVES: To examine how trajectories of cardiovascular risk factors are associated with pregnancy and birth outcomes. METHODS: Data from two cohort studies participating in the International Childhood Cardiovascular Consortium-The Bogalusa Heart Study (BHS; started in 1973, N = 903 for this analysis) and the Cardiovascular Risk in Young Finns Study (YFS; started in 1980, N = 499) were used. Both followed children into adulthood and measured cardiovascular risk factors, including body mass index (BMI), systolic and diastolic blood pressure (SBP/DBP), total, lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol and serum triglycerides. Discrete mixture modelling was used to divide each cohort into distinct trajectories according to these risk factors from childhood to early adulthood, and these groups were then used to predict pregnancy outcomes including small for gestational age (SGA; <10th study-specific percentile of gestational age by sex), preterm birth (PTB; <37 weeks' gestation), hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM), with control for age at baseline and at first birth, parity, socioeconomic status, BMI and smoking. RESULTS: The models created more trajectories for BMI, SBP and HDL-cholesterol in the YFS than in BHS, for which three classes generally seemed to be sufficient to represent the groups in the population across risk factors. In BHS, the association between the higher and flatter DBP trajectory and PTB was aRR 1.77, 95% confidence interval [CI] 1.06, 2.96. In BHS the association between consistent total cholesterol and PTB was aRR 2.16, 95% CI 1.22, 3.85 and in YFS the association between elevated high trajectory and PTB was aRR 3.35, 95% CI 1.28, 8.79. Elevated-increasing SBP was associated with a higher risk of GH in BHS and increasing or persistent-obese BMI trajectories were associated with GDM in both cohorts (BHS: aRR 3.51, 95% CI 1.95, 6.30; YFS: aRR 2.61, 95% CI 0.96, 7.08). CONCLUSIONS: Trajectories of cardiovascular risk, particularly those that represent a consistent or more rapid worsening of cardiovascular health, are associated with a higher risk of pregnancy complications.

Exploring machine learning strategies for predicting cardiovascular disease risk factors from multi-omic data.

BACKGROUND: Machine learning (ML) classifiers are increasingly used for predicting cardiovascular disease (CVD) and related risk factors using omics data, although these outcomes often exhibit categorical nature and class imbalances. However, little is known about which ML classifier, omics data, or upstream dimension reduction strategy has the strongest influence on prediction quality in such settings. Our study aimed to illustrate and compare different machine learning strategies to predict CVD risk factors under different scenarios. METHODS: We compared the use of six ML classifiers in predicting CVD risk factors using blood-derived metabolomics, epigenetics and transcriptomics data. Upstream omic dimension reduction was performed using either unsupervised or semi-supervised autoencoders, whose downstream ML classifier performance we compared. CVD risk factors included systolic and diastolic blood pressure measurements and ultrasound-based biomarkers of left ventricular diastolic dysfunction (LVDD; E/e' ratio, E/A ratio, LAVI) collected from 1,249 Finnish participants, of which 80% were used for model fitting. We predicted individuals with low, high or average levels of CVD risk factors, the latter class being the most common. We constructed multi-omic predictions using a meta-learner that weighted single-omic predictions. Model performance comparisons were based on the F1 score. Finally, we investigated whether learned omic representations from pre-trained semi-supervised autoencoders could improve outcome prediction in an external cohort using transfer learning. RESULTS: Depending on the ML classifier or omic used, the quality of single-omic predictions varied. Multi-omics predictions outperformed single-omics predictions in most cases, particularly in the prediction of individuals with high or low CVD risk factor levels. Semi-supervised autoencoders improved downstream predictions compared to the use of unsupervised autoencoders. In addition, median gains in Area Under the Curve by transfer learning compared to modelling from scratch ranged from 0.09 to 0.14 and 0.07 to 0.11 units for transcriptomic and metabolomic data, respectively. CONCLUSIONS: By illustrating the use of different machine learning strategies in different scenarios, our study provides a platform for researchers to evaluate how the choice of omics, ML classifiers, and dimension reduction can influence the quality of CVD risk factor predictions.

Longitudinal associations of participation in organized and unorganized sports in youth with physical activity in mid-adulthood: The Young Finns Study.

We investigated the longitudinal associations between sports participation patterns in youth and physical activity (PA) in adulthood. PA was self-reported triannually between ages 9-18 (n = 2550, 52% females) and measured by accelerometers in mid-adulthood (n = 1002, 61% females, aged 48 ± 4 years). Three latent classes of youth sports participation emerged for both genders: 1) "organized sports" (persistent high PA with regular sports club activities), 2) "unorganized sports" (persistent high PA without sports club activities and 3) "low activity" (low PA with decreasing sports involvement). These groups comprised 29%, 34% and 37% of males, and 23%, 27% and 50% of females, respectively. Youth "organized sports" was associated with higher adult PA in both males (+1166 steps/day, p = 0.012) and females (+15 min/day moderate-to-vigorous PA [MVPA], +1064 steps/day, +1066 leisure-time steps/day; p ≤ 0.005) compared to "low activity". In males, youth "organized sports" was associated with higher adult PA (+1103 steps/day, -26 min/day sedentary time and +133 counts/minute higher total PA, p ≤ 0.039) compared to "unorganized sports". In females, "unorganized sports" in youth was related to higher adult PA (+10 min/day MVPA, p = 0.034) when compared to "low activity". Sustained participation in youth organized sports, and for females, also in unorganized sports, is positively linked with adult PA.

Parenthood and changes in physical activity from early adulthood to mid-life among Finnish adults.

This study examined longitudinal associations between parenthood-related factors and physical activity from young adulthood to midlife over a 19-year follow-up period. Participants (n = 761) at the ongoing Cardiovascular Risk in Young Finns Study responded to a self-report questionnaire in their adulthood (in 1992, 2001, 2007, and 2011). Participants were classified as meeting or not meeting an aerobic physical activity recommendation. Parenthood-related factors included the age of having their first child and the number and age of the children. Analyses of generalized estimation equations were performed and adjusted for several demographic and health-related covariates. Both mothers and fathers with children under 6 years were less likely to be involved in physical activity than participants without children. However, meeting the aerobic physical activity recommendations did not differ between parents with a youngest child who was 6 years old or older as compared to the childless participants. The older the youngest child was, the more likely the parents were to be physically active. Participants who became a parent relatively late, at the age of 30 or older, seemed less likely to meet the aerobic physical activity recommendation during follow-up than those who had their first child at the age of 26-29. The results indicate that parenthood does not seem to have a long-lasting negative impact on adults' physical activity, and the individuals reached a similar level of physical activity in midlife than they had before parenthood.

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.

Association of physical activity with metabolic profile from adolescence to adulthood.

OBJECTIVE: Physical activity benefits cardiometabolic health, but little is known about its detailed links with serum lipoproteins, amino acids, and glucose metabolism at young age. We therefore studied the association of physical activity with a comprehensive metabolic profile measured repeatedly in adolescence. METHODS: The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project. At ages 13, 15, 17, and 19 years, data on physical activity were collected by a questionnaire, and circulating metabolic measures were quantified by nuclear magnetic resonance metabolomics from repeatedly assessed serum samples (age 13: n = 503, 15: n = 472, 17: n = 466, and 19: n = 361). RESULTS: Leisure-time physical activity (LTPA;MET h/wk) was directly associated with concentrations of polyunsaturated fatty acids, and inversely with the ratio of monounsaturated fatty acids to total fatty acids (-0.006SD; [-0.008, -0.003]; p < 0.0001). LTPA was inversely associated with very-low-density lipoprotein (VLDL) particle concentration (-0.003SD; [-0.005, -0.001]; p = 0.002) and VLDL particle size (-0.005SD; [-0.007, -0.003]; p < 0.0001). LTPA showed direct association with the particle concentration and size of high-density lipoprotein (HDL), and HDL cholesterol concentration (0.004SD; [0.002, 0.006]; p < 0.0001). Inverse associations of LTPA with triglyceride and total lipid concentrations in large to small sized VLDL subclasses were found. Weaker associations were seen for other metabolic measures including inverse associations with concentrations of lactate, isoleucine, glycoprotein acetylation, and a direct association with creatinine concentration. The results remained after adjusting for body mass index and proportions of energy intakes from macronutrients. CONCLUSIONS: Physical activity during adolescence is beneficially associated with the metabolic profile including novel markers. The results support recommendations on physical activity during adolescence to promote health and possibly reduce future disease risks.

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.

Cardiovascular Risk Factor Trajectories Since Childhood and Cognitive Performance in Midlife: The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Cardiovascular risk factors, such as high blood pressure, adverse serum lipids, and elevated body mass index in midlife, may harm cognitive performance. It is important to note that longitudinal accumulation of cardiovascular risk factors since childhood may be associated with cognitive performance already since childhood, but the previous evidence is scarce. We studied the associations of cardiovascular risk factors from childhood to midlife, their accumulation, and midlife cognitive performance. METHODS: From 1980, a population-based cohort of 3596 children (3-18 years of age) have been repeatedly followed up for 31 years. Blood pressure, serum lipids, and body mass index were assessed in all follow-ups. Cardiovascular risk factor trajectories from childhood to midlife were identified using latent class growth mixture modeling. Cognitive testing was performed in 2026 participants 34 to 49 years of age using a computerized test. The associations of the cardiovascular risk factor trajectories and cognitive performance were studied for individual cardiovascular risk factors and cardiovascular risk factor accumulation. RESULTS: Consistently high systolic blood pressure (ß=-0.262 SD [95% CI, -0.520 to -0.005]) and serum total cholesterol (ß=-0.214 SD [95% CI, -0.365 to -0.064]) were associated with worse midlife episodic memory and associative learning compared with consistently low values. Obesity since childhood was associated with worse visual processing and sustained attention (ß=-0.407 SD [95% CI, -0.708 to -0.105]) compared with normal weight. An inverse association was observed for the cardiovascular risk factor accumulation with episodic memory and associative learning (P for trend=0.008; 3 cardiovascular risk factors: ß=-0.390 SD [95% CI, -0.691 to -0.088]), with visual processing and sustained attention (P for trend<0.0001; 3 cardiovascular risk factors: ß=-0.443 SD [95% CI, -0.730 to -0.157]), and with reaction and movement time (P for trend=0.048; 2 cardiovascular risk factors: ß=-0.164 SD [95% CI, -0.318 to -0.010]). CONCLUSIONS: Longitudinal elevated systolic blood pressure, high serum total cholesterol, and obesity from childhood to midlife were inversely associated with midlife cognitive performance. It is important to note that the higher the number of cardiovascular risk factors, the worse was the observed cognitive performance. Therefore, launching preventive strategies against cardiovascular risk factors beginning from childhood might benefit primordial promotion of cognitive health in adulthood.

Dietary Intervention in Infancy and Cognitive Function in Young Adulthood: The Special Turku Coronary Risk Factor Intervention Project.

OBJECTIVE: Consumption of saturated fatty acids (SAFAs), polyunsaturated fatty acids (PUFAs), cholesterol, and fiber have been linked with cognitive function in adults. We evaluated these associations from childhood by leveraging data from the Special Turku Coronary Risk Factor Intervention Project (STRIP). STUDY DESIGN: STRIP recruited children aged 5 months and randomly assigned them into intervention/control groups. The intervention introduced a heart-healthy diet, characterized mainly by low consumption of SAFAs and cholesterol, through counseling at least biannually between age 7 months and 20 years. Diet was assessed repeatedly using food diaries. Six years after the end of the intervention phase, at age 26 years, the participants were invited to the first postintervention follow-up, which included cognitive testing that covered learning and memory, verbal memory, short-term working memory, reaction time, information processing, and cognitive flexibility and inhibitory control. We studied the associations of the STRIP intervention and the consumptions of SAFAs, PUFAs, cholesterol, and fiber within these cognitive domains. RESULTS: Participants in the STRIP intervention group had better cognitive flexibility and inhibitory control and were better able to manage conflicting information and ignore task-irrelevant information (0.18 SD higher in the intervention group, adjusted for sex and socioeconomic status). No associations were observed with the dietary components studied. CONCLUSIONS: The infancy-onset STRIP intervention, which promoted a heart-healthy diet, was favorably associated with cognitive flexibility and inhibitory control at age 26 years. No associations were found for the intervention targets studied, indicating that these specific dietary components did not underlie the observed effect of the intervention.

Risk Factor Profile in Youth, Genetic Risk, and Adulthood Cognitive Function: The Cardiovascular Risk in Young Finns Study.

INTRODUCTION: The role of risk factor profile in childhood and adolescence on adulthood cognitive function and whether it differs by genetic risk is still obscure. To bring this evidence, we determined cognitive domain-specific youth risk factor profiles leveraging the childhood/adolescence data from the Cardiovascular Risk in Young Finns Study and examined whether genetic propensity for poor cognitive function modifies the association between the risk profiles and adulthood cognitive function. METHODS: From 1980, a population-based cohort of 3,596 children (age 3-18 years) has been repeatedly followed up for 31 years. Computerized cognitive test measuring (1) memory and learning, (2) short-term working memory, (3) reaction time, and (4) information processing was performed for 2,026 participants (age 34-49 years). Cognitive domain-specific youth risk profile scores, including physical and environmental factors, were assessed from the data collected at baseline and categorized into favourable, intermediate, and unfavourable. A polygenic risk score for a poor cognitive function was categorized into low, intermediate, and high risk. RESULTS: At all genetic risk levels, a favourable youth risk factor profile is associated with better learning and memory, short-term working memory, and information processing compared to unfavourable risk profile (e.g., ß = 0.501 SD, 95% CI: 0.043-0.959 for memory and learning among participants with high genetic risk). However, no significant interactions were observed between the youth risk factor profile score and genetic propensity for any cognitive domain (p > 0.299 for all). CONCLUSION: A favourable youth risk factor profile may be beneficial for cognitive function in adulthood, irrespective of genetic propensity for poor cognitive function.

Associations of parental physical activity trajectories with offspring's physical activity patterns from childhood to middle adulthood: The Young Finns Study.

We investigated the association of parental physical activity (PA) trajectories with offspring's youth and adult PA. Self-reported PA data were extracted from the Young Finns Study with three follow-ups for parents between 1980 and 1986 and nine follow-ups for their offspring in youth between 1980 and 2011 (aged 9-39 years, n = 2402) and in adulthood in 2018. Accelerometer-derived PA was quantified in 2018-2020 (aged 43-58 years, n = 1134). Data were analyzed using mixture models and conducted in 2022. We identified three trajectories for fathers and mothers (high-stable activity, 20.2%/16.6%; moderate-stable activity, 50.5%/49.6%; and low-stable activity, 29.4%/33.7%) and four for youth male and female offspring (persistently active, 13.4%/5.1%; increasingly active, 32.1%/43.1%; decreasingly active, 14.4%/12.6%; and persistently low-active, 40.1%/39.1%). Compared to low-stable active parents, high-stable active fathers had a higher probability of having their sons and daughters classified as persistently active, increasingly active, and decreasingly active in youth (Brange = 0.50-1.79, all p < 0.008), while high- and moderate-stable active mothers had significantly increased likelihood of having their daughters classified as persistently active and decreasingly active in youth (Brange = 0.63-1.16, all p < 0.009). Fathers' and mothers' high-stable activity was associated with higher self-reported PA of adult offspring than parental low-stable activity. Persistently active and increasingly active offspring in youth accumulated more adult total PA, moderate-to-vigorous PA, step counts, and self-reported PA than persistently low-active ones (all p < 0.036). Parental persistent PA, particularly paternal persistent PA, predicts offspring's PA concurrently and prospectively. Increasing and maintaining PA in youth predicts higher PA levels in midlife.

Validity of fatty liver disease indices in the presence of alcohol consumption.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) and alcohol-related liver disease frequently coexist. While several blood-based indices exist for the detection of NAFLD, few studies have examined how alcohol use possibly impacts their diagnostic performance. We analysed the effects of alcohol use on the performance of indices for detecting fatty liver disease (FLD). METHODS: We included participants from the Cardiovascular Risk in Young Finns Study (Finnish sample) and KORA study (German sample) who underwent abdominal ultrasound or magnetic resonance imaging, respectively, for detection of FLD and had serum analyses available for calculation of Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI), Lipid Accumulation Product (LAP), and Dallas Steatosis Index (DSI). Alcohol use was estimated by questionnaires as mean daily consumption and binge drinking (Finnish sample only). Predictive performance for FLD was assessed according to alcohol consumption. RESULTS: The study included 1426 (Finnish sample) and 385 (German sample) individuals, of which 234 (16%) and 168 (44%) had FLD by imaging. When alcohol consumption was <50 g/day, all indices discriminated FLD with area under the receiver operating characteristics (AUROC) of 0.82-0.88. AUROCs were 0.61-0.66 among heavy drinkers (>50 g/day). AUROCs decreased to 0.74-0.80 in the highest binge-drinking category (>2 times/week). Alcohol use correlated with FLI and LAP (r-range 0.09-0.16, p-range <.001-.02) in both samples and with DSI (r = 0.13, p < .001) in the Finnish sample. CONCLUSIONS: Indices perform well and comparably for detection of FLD with alcohol consumption <50 g/day and with different binge-drinking behaviour.

Longitudinal associations between parental and offspring's leisure-time physical activity: The Young Finns Study.

PURPOSE: The longitudinal influence of parental leisure-time physical activity (LTPA) on their offspring's LTPA is poorly understood. This study examined the longitudinal associations between parental LTPA and offspring's LTPA at two-time intervals. METHOD: Child (offspring) participants (N = 3596) were enrolled from the Cardiovascular Risk in Young Finns Study in 1980. Their LTPA was self-rated through nine phases from baseline to 2018 and categorized by year into youth (1980-1986) and adult (1992-2018) LTPA. Parental LTPA was assessed with a single self-reported question at three phases from 1980 to 1986. Latent growth curve modeling stratified by gender was fitted to estimate the potential pathways between parental LTPA and offspring's youth and adult LTPA. RESULTS: Higher initial levels of paternal and maternal LTPA were independently associated with greater initial levels of youth and adult LTPA of offspring in both genders, respectively, except maternal LTPA, which did not associate with male offspring's adult LTPA. The initial levels of paternal LTPA were directly related to changes in male offspring's youth LTPA after adjusting for age, residential place, paternal education and occupation, having siblings, and offspring's body mass index. CONCLUSION: Our study demonstrates that the initial levels of parental LTPA are directly linked to the initial levels of offspring's LTPA during youth and adulthood, while changes in parental LTPA are unrelated to changes in offspring's youth and adult LTPA for either gender over time. These results imply that higher initial levels of LTPA in parents may serve as a predictor of offspring's LTPA across life stages.

Exposure to parental smoking and cardiac structure and function in adulthood: the Cardiovascular Risk in Young Finns Study.

BACKGROUND AND AIMS: The relationship between childhood tobacco smoke exposure and cardiac structure and function in midlife is unclear. We investigated the association between parental smoking with cardiac structure and function in adulthood. METHODS: 1250 participants (56.5% female) from the Cardiovascular Risk in Young Finns Study who had data on parental smoking and/or serum cotinine, a biomarker of exposure to tobacco smoke, at baseline 1980 (age 3-18 years) and echocardiography performed in 2011. Parental smoking hygiene (i.e., smoking in the vicinity of children) was categorized by parental smoking and serum cotinine levels in offspring. Dimensions of the left ventricle, diastolic and systolic function, and cardiac remodeling were used as outcomes. Analyses were adjusted for sex, age, and covariates (blood pressure (BP), serum lipids, body mass index, socioeconomic status, smoking (only in adulthood)) in childhood and adulthood. RESULTS: Parental smoking was not associated with systolic or diastolic function in adulthood. Participants exposed to parental smoking (odds ratio (OR) 1.90, 95%CI 1.23-2.92), hygienic parental smoking (OR 1.74, 95%CI 1.12-2.71), and non-hygienic parental smoking (OR 1.88, 95%CI 1.02-3.45) had higher odds of concentric remodeling (relative wall thickness >85th sex-specific percentile without left ventricular hypertrophy). These associations were attenuated after adjustment for child and adult covariates in the non-hygienic parental smoking group. CONCLUSIONS: Exposure to parental smoking in childhood was associated with a higher likelihood of concentric remodeling and thicker left ventricular and interventricular septal walls in midlife, which was not improved by parents who smoked hygienically. Parental smoking was not related to systolic or diastolic function in this relatively young population.