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ObjectiveAortic sinus dilatation can lead to aortic valve regurgitation or even aortic dissection. Our objective was to examine the association between body surface area (BSA) measures from childhood to middle age and aortic sinus diameter in middle age. Understanding the relation of these two clarifies how aortic size is normally determined.MethodsCardiovascular Risk in Young Finns Study is a longitudinal study with follow-up of over 31 years (1980–2011). The study comprises information of body composition from multiple time points of 1950 subjects with cardiac ultrasound measurements made in 2011. The association between BSA in different ages and aortic sinus diameter in middle age was analysed by linear regression modelling adjusted with age, sex and diastolic blood pressure. Missing BSA values were derived for each life year (ages 3–33 years) from subject-specific curves for body weight and height estimated from longitudinal measurements using mixed model regression splines.ResultsBSA estimates in early 20s are most strongly associated with aortic sinus diameter in middle age. Top association was observed at age 23 years with one SD increase in estimated BSA corresponding to 1.04 mm (0.87–1.21 mm) increase in aortic diameter. Increase in body weight beyond early 20s does not associate with aortic sinus diameter, and the association between middle age BSA and aortic size is substantially weaker (0.74 mm increase (0.58–0.89 mm)). These results were confirmed in a subpopulation using only measured data.ConclusionThe association between aortic sinus diameter and BSA is stronger when considering BSA in young adulthood compared with BSA in middle age.

Increasing evidence supports the importance of socioeconomic factors in the development of atherosclerotic cardiovascular disease. However, the association of childhood socioeconomic status (SES) with arterial stiffness in adulthood has not been reported. Our aim was to determine whether higher childhood family-level SES is associated with lower arterial stiffness in adulthood. The analyses were performed using data gathered within the longitudinal Young Finns Study. The sample comprised 2566 participants who had data concerning family SES at ages 3 to 18 years in 1980 and arterial pulse wave velocity and carotid artery distensibility measured 21 or 27 years later in adulthood. Higher family SES in childhood was associated with lower arterial stiffness in adulthood; carotid artery distensibility being higher ( β value±SE, 0.029±0.0089%/10 mm Hg; P =0.001) and pulse wave velocity lower ( β value±SE, −0.062±0.022 m/s; P =0.006) among those with higher family SES in a multivariable analysis adjusted with age, sex, and conventional childhood cardiometabolic risk factors. The association remained significant after further adjustment for participant’s SES in adulthood ( β value±SE, 0.026±0.010%/10 mm Hg; P =0.01 for carotid artery distensibility and β value±SE, −0.048±0.023 m/s; P =0.04 for pulse wave velocity) but attenuated after adjustment for adulthood cardiometabolic risk factors ( β value±SE, 0.015±0.008%/10 mm Hg; P =0.08 for carotid artery distensibility and β value±SE, −0.019±0.02 m/s; P =0.38 for pulse wave velocity). In conclusion, we observed an association between higher family SES in childhood and lower arterial stiffness in adulthood. Our findings suggest that special attention could be paid to children from low SES families to prevent cardiometabolic diseases primordially.

Fatty liver is an expanding health concern associated with metabolic disturbances and increased risk of cardiovascular disease. Experimental studies in animals have shown associations between fatty liver and cardiorespiratory fitness but limited data exist in humans. The aim of this study was to analyze the links between cardiorespiratory fitness and fatty liver in a population-based sample of adults.Participants were 463 adults (48% men) from the Cardiovascular Risk in Young Finns Study. Cardiorespiratory fitness was measured with a cycle ergometer exercise test as peak oxygen uptake (V˙O2peak [mL·kg·min]) in 2008 to 2009. Hepatic ultrasonographic imaging was performed in 2011 to determine fatty liver.Cardiorespiratory fitness was associated with lower risk of fatty liver (1 mL·kg·min increase in V˙O2peak: risk ratio, 0.90; 95% confidence interval, 0.88-0.93, P0.0001; adjusted for age and sex). This association remained significant after further adjustments with physical activity, adiposity, smoking, alcohol consumption, serum lipids, insulin, glucose, and C-reactive protein. Participants who were obese (waist circumference,80 cm in women and94 cm in men) but fit (V˙O2peak in the upper age- and sex-specific median) had lower prevalence of fatty liver than participants who were obese and unfit (below median), (11.7% vs 34.8%, P = 0.0003).In a population-based sample of adults, cardiorespiratory fitness is strongly, inversely and independently related with the risk of fatty liver. Importantly, the association is evident also among obese.

Background The child-oriented dietary intervention given in the prospective Special Turku Coronary Risk Factor Intervention Project (STRIP) has decreased the intake of saturated fat and lowered serum cholesterol concentration in children from infancy until early adulthood. In this study, we investigated whether the uniquely long-term child-oriented intervention has affected also secondarily parental diet and cardio-metabolic risk factors. Methods The STRIP study is a longitudinal, randomized infancy-onset atherosclerosis prevention trial continued from the child's age of 8 months to 20 years. The main aim was to modify the child's diet towards reduced intake of saturated fat. Parental dietary intake assessed by a one-day food record and cardio-metabolic risk factors were analysed between the child's ages of 9-19 years. Results Saturated fat intake of parents in the intervention group was lower [mothers: 12.0 versus 13.9 daily energy (E%), p 0.0001; fathers: 12.5 versus 13.9 E%, p 0.0001] and polyunsaturated fat intake was higher (mothers: 6.1 versus 5.4 E%, p 0.0001; fathers: 6.3 versus 5.9 E%, p = 0.0003) compared with the control parents. Maternal total and low-density lipoprotein cholesterol concentrations were lower in the intervention compared with the control group (mean ± SE 5.02 ± 0.04 versus 5.14 ± 0.04 mmol/l, p = 0.04 and 3.19 ± 0.04 versus 3.30 ± 0.03 mmol/l, p = 0.03, respectively). Paternal cholesterol values did not differ between the intervention and control groups. Other cardio-metabolic risk factors were similar in the study groups. Conclusions Child-oriented dietary intervention shifted the dietary fat intakes of parents closer to the recommendations and tended to decrease total and low-density lipoprotein cholesterol in the intervention mothers. Dietary intervention directed to children benefits also parents.

Introduction: Type 2 diabetes is a public health concern, but psychosocial factors that may protect against the disease are unknown. This study examines whether a positive psychosocial environment in childhood is associated with lower risk for Type 2 diabetes in adulthood or healthier glucose trajectories over the life course, and whether BMI mediates the associations. Methods: A cohort of 3,596 Finnish children was followed into adulthood over 32 years. An overall positive psychosocial score, consisting of six subdomains, was measured at study baseline (1980). Relative risk ratios and multilevel growth curve modeling were used to examine associations of the psychosocial score with Type 2 diabetes (2012) and glucose trajectories (1986-2012). The mediating effect by BMI was examined using mediation analysis. The analyses were conducted between June 2015 and January 2016. Results: There was a 21% decrease in the rate of Type 2 diabetes (relative risk ratio, 0.79; 95% CI = 0.66, 0.94) for each 1-SD increase in the positive psychosocial score after adjustment for childhood cardiovascular risk factors and dietary behaviors. Adult BMI mediated 52% and weight gain mediated 25% of the association. The growth curve model showed healthier glucose trajectories (age X psychosocial score interaction, b = -0.01; p = 0.010) for participants with higher versus lower positive psychosocial score in childhood. Conclusions: Positive psychosocial environment in childhood seems to have beneficial influences on the risk for Type 2 diabetes over the life span. RCTs will be required to see if interventions directed at early-life circumstances are warranted. (C) 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Background In adults, high blood pressure (BP), adverse serum lipids, and smoking associate with cognitive deficits. The effects of these risk factors from childhood on midlife cognitive performance are unknown. Objectives This study sought to investigate the associations between childhood/adolescence cardiovascular risk factors and midlife cognitive performance. Methods From 1980, a population-based cohort of 3,596 children (baseline age: 3 to 18 years) have been followed for 31 years in 3- to 9-year intervals. BP, serum lipids, body mass index, and smoking were assessed in all follow-ups. Cumulative exposure as the area under the curve for each risk factor was determined in childhood (6 to 12 years), adolescence (12 to 18 years), and young adulthood (18 to 24 years). In 2011, cognitive testing was performed in 2,026 participants aged 34 to 49 years. Results High systolic BP, elevated serum total-cholesterol, and smoking from childhood were independently associated with worse midlife cognitive performance, especially memory and learning. The number of early life risk factors, including high levels (extreme 75th percentile for cumulative risk exposure between ages 6 and 24 years) of systolic BP, total-cholesterol, and smoking associated inversely with midlife visual and episodic memory and visuospatial associative learning (–0.140 standard deviations per risk factor, p Conclusions Cumulative burden of cardiovascular risk factors from childhood/adolescence associate with worse midlife cognitive performance independent of adulthood exposure.

Pregnancy complications predict or even predispose to later cardiovascular disease in the mother. We examined whether pregnancy complications are associated with post-pregnancy measures of endothelial dysfunction and arterial stiffness.Prospective cohort; Data for 847 women female participants in the Cardiovascular Risk in Young Finns study were linked with the national birth registry. Preterm birth (37weeks), low birthweight (2500g), small-for-gestational-age (weight10th percentile for gestational age), and hypertensive disorders of pregnancy were examined as predictors of later vascular measures.Flow-mediated dilatation (FMD), carotid intima-media thickness (IMT), Young's elastic modulus (YEM), and carotid artery distensibility.In some analyses, gestational hypertension and pre-eclampsia were associated with increased YEM. Low birthweight was also associated with an increase in IMT, and this increased risk was present prior to the pregnancy.The increased cardiovascular risk in the mother observed after low birthweight and hypertensive disorders may be due to vascular changes, and some of this increased risk may be present before pregnancy.

Low adiponectin levels may predict the development of atherosclerosis. We examined the association of childhood adiponectin with preclinical carotid atherosclerosis that is defined as plaque and/or high (≥95th percentile) intima-media thickness (IMT) at the carotid bifurcation in adulthood.The Cardiovascular Risk in Young Finns Study is a cohort study on cardiovascular risk factors. We used risk factor data from the baseline study (1980) and ultrasound findings from the follow-ups (2001 and 2007). The study population included 1708 participants, aged 3-18 years at baseline.In multivariate analysis, childhood adiponectin was inversely associated with preclinical carotid atherosclerosis: odds ratio 0.68, 95% confidence interval (CI) 0.53-0.86, p = .001, for 1-SD increase in childhood adiponectin after adjusting for childhood non-high-density lipoprotein cholesterol, body mass index, and blood pressure. When examining the incremental predictive ability, we observed that compared to an approach utilizing only conventional risk factors, the model additionally including adiponectin levels improved c-statistics area under curve from 0.733 (95% Cl 0.694-0.771) to 0.748 (95% Cl 0.710-0.786), p = .02.Childhood adiponectin levels improve the prediction of carotid atherosclerosis in adulthood over conventional risk factors. This supports the idea that low adiponectin levels may have a role in the development of preclinical atherosclerosis. Key messages Childhood adiponectin levels improve the prediction of increased carotid intima-media thickness in adulthood over conventional cardiovascular risk factors. These results suggest that adiponectin levels measured in childhood may have a role in the atherosclerotic process.

Background: Traditionally, a self-reported questionnaire has been a cost-effective method of gathering information about physical activity (PA). An objective measurement, such as the use of a pedometer, can be used to validate the findings of a PA questionnaire in a large population. Objective: The study objective was to determine the convergent validity of a PA questionnaire against objectively measured PA in adults obtained with the use of a pedometer. Methods: Data from the Cardiovascular Risk in Young Finns Study (YFS) were collected from 1853 participants aged 30 - 45 years. The participants completed a self-reported questionnaire that included items on leisure time, commuting and habitual PA. PA was expressed as leisure-time physical activity index (PAI) and metabolic equivalent hours/week (METh/wk). The participants wore a pedometer for seven consecutive days and used it to record their total daily and aerobic steps. Results: There was a low to moderate association between the self-reported questionnaire and pedometer measurements regarding both total steps and aerobic steps taken during leisure time and commuting PA. An association was not observed between pedometer data and habitual PA. Of the individual items in the questionnaire, questions that described the frequency of PA and the duration of vigorous PA correlated the most strongly with the pedometer values obtained for total and aerobic steps (r = 0.28 - 0.44, p ≤ 0.010). Conclusions: These findings suggest that the YFS PA questionnaire showed acceptable convergent validity in assessing, in particular, exercise-type PA in an adult population. peerReviewed

Nonalcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34-49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P < 0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48-6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51-3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30-0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32-0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P < 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. Conclusion: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491-500).

Background: Data are limited regarding the association of cumulative burden and trajectory of body mass index (BMI) from early life with adult lipid disorders. Methods: The study cohort consisted of 5195 adults who had BMI repeatedly measured 4 to 21 times from childhood and had blood lipid measurements of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and information on lipid-lowering medications in the last adult survey. The area under the curve (AUC) was calculated as a measure of long-term burden (total AUC) and trends (incremental AUC) of BMI. Results: Participants with dyslipidemia, high LDL-C, low HDL-C and high TG had consistently and significantly higher BMI levels from childhood to adulthood compared to those with normal lipid levels. After adjusting for age, race, sex, and cohort, increased risk of adult dyslipidemia was significantly associated with higher values of childhood BMI, adulthood BMI, total AUC and incremental AUC, with odds ratio (95% confidence interval) = 1.22 (1.15&ndash, 1.29), 1.85 (1.74&ndash, 1.97), 1.61 (1.52&ndash, 1.71), and 1.59 (1.50&ndash, 1.69), respectively, and p &lt, 0.001 for all. The association patterns were similar in most race&ndash, sex subgroups. Conclusions: Adults with dyslipidemia versus normal lipid levels have consistently higher levels and distinct life-course trajectories of BMI, suggesting that the impact of excessive body weight on dyslipidemia originates in early life.

Background Indoleamine 2,3-dioxygenase (IDO) is an intracellular enzyme that has an important immunomodulator function. Human inflammatory response promotes upregulation of IDO level in blood. This may lead to suppression of inflammation in atherosclerotic vessel wall and consequently may slow the progression of the disease. Previous studies have shown that IDO activity correlates with early signs of atherosclerosis especially in females but is not an atherosclerosis-specific marker. Materials and methods IDO levels were measured from females (n=544; age 24–39; weight 40.5–134.4 kg) in 2001 along with several risk factors for atherosclerosis. Follow-up risk factor measurements were performed in 2007 and 2011. Here we aimed to elucidate the relationship between IDO measurements from 2001 and several atherosclerotic risk factors from 2007 and 2011 by analyzing correlations and risk ratios from the Cardiovascular Risk in Young Finns Study patient cohort. Results After age standardization, IDO correlated significantly with BMI (p=0.0008), waist (p=0.0009) and logarithmically modified triglycerides (p=0.0488) and CRP (p=0.0014) in female samples (n=434) from 2007. When female samples (n=384) from 2011 were examined, statistically significant correlations were discovered in BMI and Waist in both unadjusted (p Conclusions It is concluded that IDO activity forecasts obesity – a well-characterized risk factor for diabetes and atherosclerosis – in premenopausal females.

Key Points Question Is birth weight associated with type 2 diabetes and glycemic traits? Findings This mendelian randomization study found that a 1-SD decrease in birth weight due to the genetic risk score was associated with a higher risk of type 2 diabetes among European and East Asian populations. In addition, a 1-SD decrease in birth weight was associated with a 0.189-SD increase in fasting glucose concentration, but not with fasting insulin, 2-hour glucose, or hemoglobin A1c level. Meaning A genetic predisposition to lower birth weight was associated with an increased risk of type 2 diabetes and increased fasting glucose, suggesting potential mechanisms through which perturbation of the antenatal and early-life environment affect predisposition to diabetes in later life., This mendelian randomization study examines the association of birth weight with type 2 diabetes and glycemic traits., Importance Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. Objective To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. Design, Setting, and Participants This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Main Outcomes and Measures Type 2 diabetes and glycemic traits. Results This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10−5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (β = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. Conclusions and Relevance In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.

Aims: Disparity in cardiovascular disease (CVD) mortality and risk factor levels between urban and rural regions has been confirmed worldwide. The aim of this study was to examine how living in different community types (urban–rural) in childhood and adulthood are related to cardiovascular risk factors and surrogate markers of CVD such as carotid intima-media thickness (IMT) and left ventricular mass (LVM). Methods: The study population comprised 2903 participants (54.1% female, mean age 10.5 years in 1980) of the Cardiovascular Risk in Young Finns Study who had been clinically examined in 1980 (age 3–18 years) and had participated in at least one adult follow-up (2001–2011). Results: In adulthood, urban residents had lower systolic blood pressure (–1 mmHg), LDL-cholesterol (–0.05 mmol/l), lower body mass index (–1.0 kg/m2) and glycosylated haemoglobin levels (–0.05 mmol/mol), and lower prevalence of metabolic syndrome (19.9 v. 23.7%) than their rural counterparts. In addition, participants continuously living in urban areas had significantly lower IMT (–0.01 mm), LVM (1.59 g/m2.7) and pulse wave velocity (–0.22 m/s) and higher carotid artery compliance (0.07%/10 mmHg) compared to persistently rural residents. The differences in surrogate markers of CVD were only partially attenuated when adjusted for cardiovascular risk factors. Conclusions: Participants living in urban communities had a more favourable cardiovascular risk factor profile than rural residents. Furthermore, participants continuously living in urban areas had less subclinical markers related to CVD compared with participants living in rural areas. Urban–rural differences in cardiovascular health might provide important opportunities for optimizing prevention by targeting areas of highest need.

Background and objectives: Temperament may be associated with eating behaviors over the lifespan. This study examined the association of toddlerhood temperament with dietary behavior and dietary intervention outcomes across 18 years. Methods: The study comprised 660 children (52% boys) from The Special Turku Intervention Project (STRIP), which is a longitudinal randomized controlled trial from the age of 7 months until the age of 20 years (1990-2010). Temperament was assessed using Carey temperament scales when the participants were 2 years of age. Latent profile analysis yielded three temperament groups, which were called negative/low regulation (19% of the children), neutral/average regulation (52%) and positive/high regulation (28%). Dietary behavior was examined from 2 to 20 years of age using food records, which were converted into a diet score (mean= 15.7, SD 4.6). Mixed random-intercept growth curve analysis was the main analytic method. Results: Dietary behavior showed a significant quadratic U-shaped curve over time (B for quadratic association = 0.39, P

BACKGROUND: Adiposity in childhood and adolescence (youth) has been shown to associate with adult metabolic health. What is not known, is whether youth body mass index (BMI) associates with metabolically healthy obesity (MHO) in adulthood, and if so, the age when the BMI to MHO association emerges. This study aimed to determine if BMI trajectories from youth to adulthood differed between adults with MHO and metabolically unhealthy obesity (MUHO). METHODS: The Cardiovascular Risk in Young Finns Study had measured weight and height up to eight times in individuals from youth (3-18 years in 1980) to adulthood (24-49 years). Adult MHO was defined as BMI ≥ 30 kg m-2, normal fasting glucose (

CONTEXT Passive smoke exposure has been linked to the risk of osteoporosis in adults. OBJECTIVE We examined the independent effects of childhood passive smoke exposure on adult bone health. DESIGN/SETTING Longitudinal, the Cardiovascular Risk in Young Finns Study. PARTICIPANTS The study cohort included 1422 individuals followed for 28 years since baseline in 1980 (age 3 to 18 years). Exposure to passive smoking was determined in childhood. In adulthood, peripheral bone traits were assessed with peripheral quantitative CT (pQCT) at the tibia and radius, and calcaneal mineral density was estimated with quantitative ultrasound. Fracture data were gathered by questionnaires. RESULTS Parental smoking in childhood was associated with lower pQCT-derived bone sum index in adulthood (β± SE, -0.064 ± 0.023 per smoking parent; P = 0.004) in multivariate models adjusted for age, sex, active smoking, body mass index, serum 25-OH vitamin D concentration, physical activity, and parental socioeconomic position. Similarly, parental smoking was associated with lower heel ultrasound estimated bone mineral density in adulthood (β± SE, -0.097 ± 0.041 per smoking parent; P = 0.02). Parental smoking was also associated with the incidence of low-energy fractures (OR, 1.28; 95% CI, 1.01 to 1.62). Individuals with elevated cotinine levels (3 to 20 ng/mL) in childhood had lower bone sum index with pQCT (β± SE, -0.206 ± 0.057; P = 0.0003). Children whose parents smoked and had high cotinine levels (3 to 20 ng/mL) had significantly lower pQCT-derived bone sum index compared with those with smoking parents but had low cotinine levels (

Decreased left ventricular (LV) diastolic function is associated with increased all-cause mortality and risk for a heart failure. The determinants of LV diastolic function have been mainly studied in elderly populations; however, the origin of LV heart failure may relate to the lifestyle factors acquired during the life course. Therefore, we examined biochemical, physiological, and lifestyle determinants of LV diastolic function in 34-49-year-old participants of the Cardiovascular Risk in Young Finns Study (Young Finns Study). In 2011, clinical examination and echocardiography were performed for 1928 participants (880 men and 1048 women; aged 34-49 years). LV diastolic function was primarily defined using E/e-ratio (population mean 4.8, range 2.1-9.0). In a multivariate model, systolic blood pressure (P

Birth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individual’s own genotype on BW and subsequent disease risk from indirect effects of their mother’s correlated genotype, mediated by the intrauterine environment. Here, we describe expanded genome-wide association analyses of own BW (n=321,223) and offspring BW (n=230,069 mothers), which identified 278 independent association signals influencing BW (214 novel). We used structural equation modelling to decompose the contributions of direct fetal and indirect maternal genetic influences on BW, implicating fetal- and maternal-specific mechanisms. We used Mendelian randomization to explore the causal relationships between factors influencing BW through fetal or maternal routes, for example, glycemic traits and blood pressure. Direct fetal genotype effects dominate the shared genetic contribution to the association between lower BW and higher type 2 diabetes risk, whereas the relationship between lower BW and higher later blood pressure (BP) is driven by a combination of indirect maternal and direct fetal genetic effects: indirect effects of maternal BP-raising genotypes act to reduce offspring BW, but only direct fetal genotype effects (once inherited) increase the offspring’s later BP. Instrumental variable analysis using maternal BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring BP. In successfully separating fetal from maternal genetic effects, this work represents an important advance in genetic studies of perinatal outcomes, and shows that the association between lower BW and higher adult BP is attributable to genetic effects, and not to intrauterine programming.

RationaleApolipoprotein A-I (apoA-I) infusions represent a potential novel therapeutic approach for the prevention of coronary artery disease (CAD) with phase III cardiovascular outcome trials currently underway. Although circulating apoA-I levels inversely associate with risk of CAD, the evidence base of this representing a causal relationship is lacking.ObjectiveTo assess the causal role of apoA-I in CAD using human genetics.Methods and ResultsWe identified a variant (rs12225230) in APOA1 locus that associated with circulating apoA-I concentrations at GWAS significance (P−8) in 20,370 Finnish participants and meta-analyzed our data with a previous genome-wide association study of apoA-I. We obtained genetic estimates of CAD from UK Biobank and CARDIoGRAMplusC4D (totaling 122,733 CAD cases) and conducted a two-sample Mendelian randomization analysis. We compared our genetic findings to observational associations of apoA-I with risk of CAD in 918 incident CAD cases among 11,535 individuals from population-based prospective cohorts. We also summarized the available evidence from randomized controlled trials (RCTs) of apoA-I infusion therapies reporting CAD events. ApoA-I was associated with a lower risk of CAD in observational analyses (HR 0.81; 95%CI: 0.75, 0.88; per 1-SD higher apoA-I), with the association showing a dose-response relationship. Rs12225230 associated with apoA-I concentrations (per-C allele beta 0.076 SD; SE: 0.013; P=1.5×10−9) but not with potential confounders. In Mendelian randomization analyses, apoA-I was not related to risk of CAD (OR 1.13; 95%CI: 0.98, 1.30 per 1-SD higher apoA-I), which was different to the observational association (P-hetConclusionsGenetic evidence fails to support a cardioprotective role for apoA-I. This casts doubt on the likely benefit of apoA-I infusion therapy in the ongoing phase III cardiovascular outcome trial.

Background: Atherosclerosis develops silently for decades before clinical cardiovascular disease (cCVD) occurs. Longitudinally, childhood risk factors predict adult pre-clinical atherosclerosis (carotid artery plaques, coronary artery calcification). There is currently no evidence directly linking childhood risk factors to cCVD. Methods: Using data from the i3C Consortium, consisting of five cohorts from the United States, one from Australia and one from Finland, we linked youth risk factors to adult cCVD. cCVD events were ascertained by re-contacting the participants in the US and Australia, then obtaining and medically adjudicating hospital records; and using the Finnish national health registry. Of 16,964 of these adult participants (mean age 49 years, range 24-67 years) who had been examined during ages 3-19 years, 201 people with any cCVD event (coronary artery, cerebrovascular, and peripheral artery disease, 70%, 25%, and 5% of events, respectively) have so far been ascertained. Analysis of deaths is in process. The associations between each youth risk variable and adult cCVD were examined in Cox proportional hazard models. Each model was additionally adjusted for childhood age, age at followup, sex and cohort/race. Continuous youth variables were z-scored for each participant’s last repeated measure during childhood. Results: Youth body mass index (BMI), serum total cholesterol (TC) and triglycerides, and systolic blood pressure were (all P Conclusion: These international data find that exposure to CVD risk factors in youth predicts adult cCVD with implications for primordial CVD prevention.

Background: New pediatric hypertension (HTN) definitions were recently introduced in a clinical practice guideline (CPG). We evaluated the impact of the CPG (compared to the previous guideline, the “Fourth Report”) on the prevalence of pediatric HTN and associations with HTN in adulthood. Methods: Data from the International Childhood Cardiovascular Cohort (i3C), a consortium comprising seven large, long-standing study cohorts from the United States, Finland, and Australia, were used. The mean of 2-6 BP measurements using an auscultatory technique were obtained. BP was categorized as normal, elevated, and hypertensive (stage 1 and 2) using the Fourth Report and CPG. For those with multiple BP assessments within an age category, a random assessment was selected for analysis. Childhood participants were contacted in adulthood and data on self-reported HTN was recorded. Results: There were 34,014 youth (mean age 10.4 ± 3.1 years, 49.4% male) with 92,751 BP assessments available for analysis. Use of the CPG increased hypertension prevalence from 7.6% to 13.5% (stage 1) and 1.3% to 2.5% (stage 2, p Conclusion: The CPG resulted in a significantly increased prevalence of HTN in children and adolescents due to significant re-classification to higher BP categories. While the observed increases were not consistent across age groups, the results suggest increased sensitivity regarding the development of HTN in adulthood.

Background: Smoking is known to cause clinical cardiovascular disease. We report the natural history of smoking from childhood until average age 47 years in the large cohort followed in the International Childhood Cardiovascular Cohort (i3C) Consortium, which consists of seven long-standing cohorts in the US, Finland and Australia. Methods: Data on childhood smoking status were obtained from questionnaires answered during age 6-19 during the 1980s. Childhood smoking status was categorized as never smoker, tried smoking only a few times, tried more extensively (including quitters), and regular smoker. The i3C participants had follow-up visits until 2015-18 (Finland 2010-12), when they reported whether they were smokers during their 20s and/or 40s. Results: Of the 9977 participants, prevalence of regular smoking decreased from 35.5% in their 20s, to 20.5% in their 40s; cessation was unrelated to childhood smoking status. As shown in the Figure, among 1816 participants queried at age 18/19, prevalence of regular smoking in their 20s was 4.1% (36/886) in those who never smoked even during adolescence, 12% (22/183) in those who tried only a few times, 21.5% (40/186) in those who tried more extensively, and 76.5% (429/561) in those who were regular smokers during childhood. The pattern was similar among 860 whose last childhood smoking status was queried at age 16/17 (some probably experimented more during the remainder of childhood), but smoking in their 20s was more common for all smoking experimentation groups than in 18/19 year olds. Conclusions: These long-term follow-up data suggest that prevalence of adult smoking was significantly related to level of smoking experimentation during adolescence. However, cessation during adulthood does not depend on childhood smoking status. Policy change (such as taxes and restrictions on smoking indoors) has proven to be one of the most powerful tobacco control tools. These data support an emerging new policy strategy, namely raising the legal cigarette purchase age to 21 years

Background: To examine if major life changes over a 4-year period among 34- to 49-year-old adults (mean = 41.8, SD = 5.0) were associated with a change in physical activity in men (37.7%) and women (62.3%). Methods: Daily steps and aerobic steps (steps that lasted for at least 10 min without interruption at a pace of >60 steps/min) were collected from 1051 participants in 2007 and 2011. Changes in marital status, work status, and residence and the birth of a child were determined from both time points. A latent change score model was used to examine mean changes in daily total steps, aerobic steps, and nonaerobic steps (total steps minus aerobic steps). Results: Women who had a first child in the 4-year period had a decrease in their nonaerobic steps (P = .001). Men who divorced in the 4-year period had a decrease in their nonaerobic steps (P = .020), whereas women who recoupled decreased their total steps (P = .030). Conclusions: Counseling for parents having a first child on how to increase physical activity in their everyday life could potentially have an influence on an individual’s physical activity.

Objective: Secretory phospholipase A2 (sPLA2) enzyme activity is a potential inflammatory biomarker for cardiovascular disease. We examined the tracking, or persistence, of sPLA2 enzyme activity levels from childhood to adulthood, and identify potentially modifiable factors affecting tracking. Method: Prospective cohort of 1735 children (45% females) who had serum sPLA2 enzyme activity levels and other cardiovascular disease risk factors measured in 1980 that were followed-up in 2001. Results: sPLA2 activity tracked from childhood to adulthood for males (r = 0.39) and females (r = 0.45). Those who decreased body mass index relative to their peers were more likely to resolve elevated childhood sPLA2 levels than have persistent elevated sPLA2 levels in childhood and adulthood. Those who consumed less fruit, and gained more body mass index relative to their peers, began smoking or were a persistent smoker between childhood and adulthood were more likely to develop incident elevated sPLA2 levels than those with persistent not elevated sPLA2 levels. Conclusions: Childhood sPLA2 enzyme activity levels associate with adult sPLA2 levels 21 years later. Healthful changes in modifiable risk factors that occur between childhood and adulthood might prevent children from developing elevated sPLA2 levels in adulthood. Resumo: Objetivo: A atividade da enzima fosfolipase A2 secretória (sPLA2) é um possível biomarcador inflamatório de doença cardiovascular. Examinamos o monitoramento, ou a persistência, dos níveis de atividade da enzima sPLA2 da infância à vida adulta e identificamos fatores possivelmente modificáveis que afetam o monitoramento. Método: Coorte prospectiva de 1.735 crianças (45% do sexo feminino) cujos níveis de atividade da enzima sPLA2 no soro e outros fatores de risco para doença cardiovascular foram medidos em 1980 e acompanhados até 2011. Resultados: Atividade da enzima sPLA2 monitorada da infância à vida adulta para indivíduos do sexo masculino (r = 0,39) e sexo feminino (r = 0,45). Aqueles que diminuíram seus índices de massa corporal com relação a seus pares foram mais propensos à redução dos níveis elevados de sPLA2 na infância do que a manter níveis persistentemente elevados de sPLA2 na infância e vida adulta. Aqueles que consumiram menos frutas e ganharam mais índice de massa corporal com relação a seus pares, que começaram a fumar ou foram fumantes persistentes entre a infância e vida adulta foram mais propensos a desenvolver níveis de sPLA2 elevados do que aqueles com níveis de sPLA2 não elevados persistentes. Conclusões: Os níveis de atividade da enzima sPLA2 na infância estão associados aos níveis de sPLA2 na vida adulta, 21 anos mais tarde. As mudanças saudáveis nos fatores de risco modificáveis que ocorrem entre a infância e a vida adulta podem evitar que as crianças desenvolvam níveis elevados de sPLA2 na vida adulta. Keywords: Atherosclerosis, Cohort study, Inflammation, Prevention, Palavras-chave: Aterosclerose, Estudo de coorte, Inflamação, Prevenção

Introduction: Physical activity (PA) has been suggested to protect against old-age cognitive deficits. However, the independent role of childhood/youth PA for adulthood cognitive performance is unknown. This study investigated the association between PA from childhood to adulthood and midlife cognitive performance. Methods: This study is a part of the Cardiovascular Risk in Young Finns Study. Since 1980, a population-based cohort of 3596 children (age, 3–18 yr) have been followed up in 3- to 9-yr intervals. PA has been queried in all study phases. Cumulative PA was determined in childhood (age, 6–12 yr), adolescence (age, 12–18 yr), young adulthood (age, 18–24 yr), and adulthood (age, 24–37 yr). Cognitive performance was assessed using computerized neuropsychological test, CANTAB (N = 2026; age, 34–49 yr) in 2011. Results: High PA in childhood (A = 0.119; 95% confidence interval [CI], 0.055–0.182) and adolescence (A = 0.125; 95% CI, 0.063–0.188) were associated with better reaction time in midlife independent of PA in other age frames. Additionally, an independent association of high PA in young adulthood with better visual processing and sustained attention in midlife was observed among men (A = 0.101; 95% CI, 0.001–0.200). There were no associations for other cognitive domains. Conclusions: Cumulative exposure to PA from childhood to adulthood was found to be associated with better midlife reaction time. Furthermore, cumulative PA exposure in young adulthood and adulthood was associated with better visual processing and sustained attention in men. All associations were independent of participants PA level in other measured age frames. Therefore, a physically active lifestyle should be adopted already in childhood, adolescence, and young adulthood and continued into midlife to ensure the plausible benefits of PA on midlife cognitive performance. peerReviewed

Background Recent studies have revealed sexually dimorphic associations between the carbamoyl‐phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease ( CAD ) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl‐phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels. Methods and Results We sought to identify additional genetic determinants of circulating glycine levels by carrying out a meta‐analysis of genome‐wide association study data in up to 30 118 subjects of European ancestry. Mendelian randomization and other analytical approaches were used to determine whether glycine‐associated variants were associated with CAD and traditional risk factors. Twelve loci were significantly associated with circulating glycine levels, 7 of which were not previously known to be involved in glycine metabolism ( ACADM , PHGDH , COX 18‐ ADAMTS 3 , PSPH , TRIB 1 , PTPRD , and ABO ). Glycine‐raising alleles at several loci individually exhibited directionally consistent associations with decreased risk of CAD . However, these effects could not be attributed directly to glycine because of associations with other CAD ‐related traits. By comparison, genetic models that only included the 2 variants directly involved in glycine degradation and for which there were no other pleiotropic associations were not associated with risk of CAD or blood pressure, lipid levels, and obesity‐related traits. Conclusions These results provide additional insight into the genetic architecture of glycine metabolism, but do not yield conclusive evidence for a causal relationship between circulating levels of this amino acid and risk of CAD in humans.

To examine the relationship between pre-pregnancy indicators of cardiovascular risk and pregnancy complications and outcomes.Data from 359 female participants in the Cardiovascular Risk in Young Finns Study were linked with the national birth registry. Flow-mediated dilatation (FMD; maximum change in the left brachial artery diameter after rest and hyperemia); carotid intima-media thickness (IMT); Young's elastic modulus (YEM); and carotid artery distensibility (Cdist) at the visit prior to the pregnancy were examined as predictors of hypertensive disorders, birthweight, and gestational age using multivariable linear regression with adjustment for confounders (age, BMI, smoking, and socioeconomic status).No relations were seen between FMD, IMT, or the stiffness indices, and hypertensive disorders. Higher pre-pregnancy FMD was associated with lower gestational age, while increased Cdist was associated with reduced birthweight-for-gestational-age.Some cardiovascular ultrasound measures of pre-pregnancy may predict pregnancy complications, but the association is likely to be small.

Objective Age, education, and sex associate with cognitive performance. We investigated associations between age, sex, education, and cognitive performance in young or middle-aged adults and evaluated data reduction methods to optimally capture cognitive performance in our population-based data. Method This study is part of the Cardiovascular Risk in Young Finns Study. The 3,596 randomly selected subjects (aged 3-18 years in 1980) have been followed up for 30 years. In 2011, a computer-based cognitive testing battery (the Cambridge Neuropsychological Test Automated Battery [CANTAB]) was used to assess several cognitive domains. Principal component analysis, categorical and standardized classifications were applied to the cognitive data. Results Among 34- to 49-year-old participants, cognitive performance declined with age, while education associated with better cognitive functions in several cognitive domains. Men had higher performance on all cognitive domains except visual or episodic memory, in which women outperformed men. The results were similar regardless of the data reduction method used. Conclusions The associations between sex, age, education, and cognitive performance are already apparent in young adulthood or middle age. Principal component analyses, categorical and standardized classifications are useful tools to analyze CANTAB cognitive data. (PsycINFO Database Record

OBJECTIVE We examined whether the addition of novel genetic risk variant data to conventional childhood risk factors improves risk assessment of impaired fasting glucose (IFG) and type 2 diabetes in adulthood. RESEARCH DESIGN AND METHODS An association of a weighted genetic risk score (wGRS) based on 73 risk variants with IFG and type 2 diabetes was analyzed in 2,298 participants of the Cardiovascular Risk in Young Finns Study who were followed for 24–31 years from childhood to adulthood. In addition, the value of the wGRS in pediatric prediction of type 2 diabetes was examined. RESULTS Of the 2,298 participants, 484 (21.8%) and 79 (3.4%) had IFG or type 2 diabetes in adulthood, respectively. Adjusting for age, sex, baseline BMI, parental diabetes, mother’s BMI, fasting insulin concentration, systolic blood pressure, and smoking status, wGRS was associated with an increased risk of IFG (odds ratio 1.64 [95% CI 1.33–2.01] per unit increase in the wGRS) and type 2 diabetes (2.22 [1.43–3.44]). Incorporating wGRS into pediatric risk models improved model discrimination and reclassification properties. Area under the receiver operating curve improved for IFG (from 0.678 to 0.691, P = 0.015), combined IFG and type 2 diabetes outcome (from 0.678 to 0.692, P = 0.007), and type 2 diabetes (from 0.728 to 0.749, P = 0.158). The net reclassification improvement and integrated discrimination improvement were significant for all outcomes. CONCLUSIONS A multifactorial approach combining genetic and clinical risk factors may be useful in identifying children at high risk for adult IFG and type 2 diabetes.

BACKGROUND Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.OBJECTIVES This meta-analysis sought to gain insights into the genetic determinants of myocardial mass.METHODS We carried out a genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry, followed by extensive biological and functional assessment.RESULTS We identified 52 genomic loci, of which 32 are novel, that are reliably associated with 1 or more QRS phenotypes at p CONCLUSIONS Taken together, our findings provide new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets. (C) 2016 by the American College of Cardiology Foundation.

Oxidative reactions are thought to play a role in the inflammatory condition called fatty liver. It is unclear whether oxidized lipoprotein lipids or proteins are associated with future fatty liver. In the Cardiovascular Risk in Young Finns Study, we determined the circulating levels of LDL and HDL oxidized lipids and studied their associations with fatty liver assessed by ultrasonography. There were 1286 middle-aged subjects with normal liver and 288 subjects with fatty liver. Analysis of oxidized lipids consisted of conjugated dienes in isolated HDL (oxHDLlipids) and LDL (oxLDLlipids). Oxidized LDL was also measured with a method based on antibodies against oxidized apolipoprotein B (oxLDLprot). After adjustment for age, sex, leisure-time physical activity, body mass index, alcohol intake, smoking, serum LDL and HDL cholesterol as well as particle concentrations, participants with elevated oxLDLlipids (odds ratio for 1-SD change in oxLDLlipids = 1.27, p =0.011) had an increased risk for fatty liver. Similarly, a high oxidation score (oxLDLlipids + oxLDLprot) was directly associated with fatty liver (odds ratio=1.34, p = 0.012). The strongest direct association was seen with a high oxLDLlipids/oxHDLlipids ratio (odds ratio=1.49, p = 0.001). These data suggest that oxidized lipoprotein lipids are linked with the risk of fatty liver in middle-aged adults.

Background: Coronary heart disease mortality has been internationally high in eastern Finland. The excessive mortality risk in Eastern compared with western Finns is explained by differences in cardiometabolic risk profile. Current risk profile differences and association with migration have not been reported. We examined the association of place of residence (east–west) and specifically migration with cardiometabolic risk markers and carotid intima–media thickness (IMT). Methods: The study population included 2204 participants with data available from childhood/youth in 1980 and follow-up examination in 2007. Results: Participants residing in eastern Finland in adulthood had 0.022±0.004mm higher IMT than Western participants. Those who migrated east-to-west had lower IMT than those staying in the east (0.027±0.006mm, p2 vs. 26.2±4.5kg/m2, p=0.01), waist circumference (85.7±12.8cm vs. 88.6±12.8cm, p=0.001), prevalence of metabolic syndrome (13% vs. 21%, p=0.01), and higher socioeconomic status (16.6±3.3 vs. 15.0±3.3 school years, p

We evaluated the association of cardiovascular health in adolescence and young adulthood with alexithymia 25 years later. The study sample (n = 1122) participated in evaluations conducted in 1986 (baseline) and in 2011−2012 (T2). Baseline health factors and behaviors were assessed utilizing seven ideal cardiovascular health metrics (ICH index) including blood pressure, cholesterol and glucose levels, smoking, physical activity, body-mass-index, and diet. The stability of the ICH index was evaluated with corresponding assessments in 2007 (T1). At T2, alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20). The main analyses were conducted using ANCOVA and adjusted for depression, age, and present social and lifestyle factors. TAS-20 subscales, Difficulty Identifying Feelings (DIF), Difficulty Describing Feelings (DDF), and Externally Oriented Thinking, were analyzed separately. The ICH index was significantly associated with the TAS-20 total score, as well as both with DIF and DDF. A less ideal cardiovascular health was associated with higher alexithymia scores. However, regarding the separate factors, only the association between non-ideal dietary habits and DIF was significant in the multivariate analyses. The baseline ICH index score was stable from baseline to T1. We conclude that non-ideal cardiovascular lifestyle habits in adolescence and young adulthood are significantly associated with later alexithymia.

Objectives To estimate and compare tri-ponderal mass index (TMI) and body mass index (BMI) at each age from childhood to young adulthood in the prediction of adulthood obesity-related outcomes. Study design Participants of this observational study (n = 432) were from a 20-year infancy-onset randomized atherosclerosis prevention trial. BMI and TMI were calculated using weight and height measured annually from participants between ages 2 and 20 years. Outcomes were aortic intima-media thickness (at the age of 15, 17, or 19 years), impaired fasting glucose and elevated insulin levels, homeostasis model assessment of insulin resistance index, serum lipids, and hypertension at the age of 20 years. Poisson regressions, Pearson correlation, logistic regression, and area under the curve (AUC) were used to estimate and/or compare associations and predictive utilities between BMI and TMI with all outcomes. Results The associations and predictive utilities of BMI and TMI with all outcomes were stronger at older ages. BMI had significantly stronger correlations than TMI with insulin (at age 16 years), systolic blood pressure (age 5-20 years), and triglycerides (age 18 years). BMI had significantly greater predictive utilities than TMI for insulin resistance (at age 14-16 years; difference in AUC = 0.018-0.024), elevated insulin levels (age 14-16 years; difference in AUC = 0.018 and 0.025), and hypertension (age 16 to 20 years; difference in AUC = 0.017-0.022) but they were similar for other outcomes. Conclusions TMI is not superior to BMI at any ages from childhood to young adulthood in the prediction of obesity-related outcomes in young adulthood.

Background Studies have shown that osteoporosis and atherosclerosis are comorbid conditions sharing common risk factors and pathophysiological mechanisms. Understanding these is crucial in order to develop shared methods for risk stratification, prevention, diagnosis and treatment. The aim of this study was to apply a system-level bioinformatics approach to lipidome-wide data in order to pinpoint the lipidomic architecture jointly associated with surrogate markers of these complex comorbid diseases. Subjects and methods The study was based on the Cardiovascular Risk in Young Finns Study cohort from the 2007 follow-up (n = 1494, aged 30–45 years, women: 57%). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyse the serum lipidome, involving 437 molecular lipid species. The subclinical osteoporotic markers included indices of bone mineral density and content, measured using peripheral quantitative computer tomography from the distal and shaft sites of both the tibia and the radius. The subclinical atherosclerotic markers included carotid and bulbus intima media thickness measured with high-resolution ultrasound. Weighted co-expression network analysis was performed to identify networks of densely interconnected lipid species (i.e. lipid modules) associated with subclinical markers of both osteoporosis and atherosclerosis. The levels of lipid species (lipid profiles) of each of the lipid modules were summarized by the first principal component termed as module eigenlipid. Then, Pearson's correlation (r) was calculated between the module eigenlipids and the markers. Lipid modules that were significantly and jointly correlated with subclinical markers of both osteoporosis and atherosclerosis were considered to be related to the comorbidities. The hypothesis that the eigenlipids and profiles of the constituent lipid species in the modules have joint effects on the markers was tested with multivariate analysis of variance (MANOVA). Results Among twelve studied molecular lipid modules, we identified one module with 105 lipid species significantly and jointly associated with both subclinical markers of both osteoporosis (r = 0.24, p-value = 2 × 10−20) and atherosclerosis (r = 0.16, p-value = 2 × 10−10). The majority of the lipid species in this module belonged to the glycerolipid (n = 60), glycerophospholipid (n = 13) and sphingolipid (n = 29) classes. The module was also enriched with ceramides (n = 20), confirming their significance in cardiovascular outcomes and suggesting their joint role in the comorbidities. The top three of the 37 statistically significant (adjusted p-value Conclusion This study identified a novel lipid module associated with both surrogate markers of both subclinical osteoporosis and subclinical atherosclerosis. Alterations in the metabolism of the identified lipid module and, more specifically, the TAG related molecular lipids within the module may provide potential new biomarkers for testing the comorbidities, opening avenues for the emergence of dual-purpose prevention measures.

Aim: The aim of this prospective four-year follow-up study was to examine how socioeconomic status (SES) and change in marital status are associated with the change in pedometer-measured physical activity (PA) in adulthood among participants in the ‘Cardiovascular Risk in Young Finns Study’. Methods: Questionnaires were completed and pedometers worn at baseline in 2007 and again at follow-up in 2011 by 1051 Finnish adults (62.3% female, aged 30–45 years in 2007). A latent change score model was used to examine mean change in daily total steps, aerobic steps and non-aerobic steps during weekdays and weekend days between 2007 and 2011. Results: In women re-coupling or finding a new partner was associated with decrease in total steps ( p=0.010) and being single was associated with increase in non-aerobic steps ( p=0.047) during weekdays from 2007 to 2011 compared to women who were married. In men, divorcing was associated with decrease in non-aerobic steps ( p=0.049). Conclusions: In order to promote PA in the general population of adults, it is recommended to pay attention to people with lower SES and those who have had changes in their marital status. These factors could be taken into account when developing strategies to promote PA among the adult population.

Debate continues on the limitations of using body mass index (BMI) to assign youth overweight/obesity status. Calculated as weight in kilograms divided by height in meters squared, BMI might not be applicable in youth during periods of rapid growth. Although recent evidence has indicated that triponderal mass index (TMI, calculated as weight in kilograms divided by height in meters cubed) might have better accuracy in estimating youth body fat levels than BMI, its clinical importance in estimating adulthood outcomes has not been examined. Therefore, we assessed whether youth TMI and its combination with BMI or subscapular skin fold thickness (SST), compared with BMI alone, have better utility in estimating adult obesity-related outcomes.

BackgroundCETP inhibition reduces vascular event rates but confusion surrounds its low-density lipoprotein (LDL)-cholesterol effects. We sought to clarify associations of genetic inhibition of CETP on detailed lipoproteins.Methods and ResultsWe used variants associated withCETP(rs247617) andHMGCR(rs12916) expression in 62,400 Europeans with detailed lipoprotein profiling from nuclear magnetic resonance spectroscopy. Genetic associations were scaled to 10% lower risk of coronary heart disease (CHD). Associations of lipoprotein measures with risk of incident CHD in three population-based cohorts (770 cases) were examined.CETPandHMGCRhad near-identical associations with LDL-cholesterol concentration estimated by Friedewald-equation.HMGCRhad a relatively consistent effect on cholesterol concentrations across all apolipoprotein B-containing lipoproteins.CETPhad stronger effects on remnant and very-low-density lipoprotein cholesterol but no effect on cholesterol concentrations in LDL defined by particle size (diameter 18–26 nm) (-0.02SD 95%CI: -0.10, 0.05 forCETPversus -0.24SD, 95%CI -0.30, -0.18 forHMGCR).CETPhad profound effects on lipid compositions of lipoproteins, with strong reductions in the triglyceride content of all highdensity lipoprotein (HDL) particles. These alterations in triglyceride composition within HDL subclasses were observationally associated with risk of CHD, independently of total cholesterol and triglycerides (strongest HR per 1-SD higher triglyceride composition in very-large HDL 1.35; 95%CI: 1.18, 1.54).ConclusionCETP inhibition does not affect size-specific LDL cholesterol but may lower CHD risk by lowering cholesterol in other apolipoprotein-B containing lipoproteins and lowering triglyceride content of HDL particles. Conventional composite lipid assays may mask heterogeneous effects of lipid-altering therapies.

Aims: Eastern Finns have higher risk of coronary heart disease (CHD) and carotid intima-media thickness than western Finns although current differences in CHD risk factors are minimal. Left ventricular (LV) mass and diastolic function predict future cardiovascular events but their east–west differences are unknown. We examined the association of eastern/western baseline origin with LV mass and diastolic function. Methods : The study population included 2045 subjects of the Cardiovascular Risk in Young Finns Study with data from the baseline survey (1980) and the latest follow-up (2011) when echocardiography was performed at the age of 34–49 years. Results: Subjects with eastern baseline origin had in 2011 higher LV mass (139±1.0 vs. 135±1.0 g, p=0.006) and E/e′-ratio indicating weaker LV diastolic function (4.86±0.03 vs. 4.74±0.03, p=0.02) than western subjects. Results were independent of age, sex, area of examination and CHD risk factors such as blood pressure and BMI (LV mass indexed with height: p

Background & Aims: We aimed to determine how childhood body mass index and metabolic health, along with the change in body mass index between childhood and adulthood, determine the risk of adult non‐alcoholic fatty liver disease. Methods: Data from 2020 participants aged 3–18 years at baseline, followed up 31 years later, were examined to assess the utility of four childhood metabolic phenotypes (Metabolic Groups I: normal body mass index, no metabolic disturbances; II: normal body mass index, one or more metabolic disturbances; III: overweight/obese, no metabolic disturbances; IV: overweight/obese, one or more metabolic disturbances) and four life‐course adiposity phenotypes (Adiposity Group 1: normal child and adult body mass index; 2, high child, normal adult body mass index; 3, normal child body mass index, high adult body mass index; 4, high child and adult body mass index) in predicting adult non‐alcoholic fatty liver disease. Results: The risk for adult non‐alcoholic fatty liver disease was similar across all four groups after adjustment for age, sex, lifestyle factors and adult body mass index. Risk of adult non‐alcoholic fatty liver disease was not increased among individuals overweight/obese in childhood but non‐obese in adulthood. In contrast, overweight or obese adults, irrespective of their youth body mass index status, had ~eight‐fold to 10‐fold increased risk (P < 0.001). Conclusions: Childhood overweight/obesity, not metabolic health, is associated with increased risk for adult non‐alcoholic fatty liver disease. However, the increased risk associated with childhood overweight/obesity can be largely removed by obtaining a normal body mass index by adulthood.

Background Underweight in early adulthood increases risk for schizophrenia, but the effect of early childhood underweight on psychosis risk is not well known. Methods We studied whether underweight or overweight in childhood and adolescence increases risk for non-affective psychosis or other psychiatric disorders in a population-based cohort study ‘Cardiovascular Risk in Young Finns’. Body mass index (BMI) trajectories were recorded in the years 1980, 1983 and 1986 (in 3–18 years of age), before the first hospitalization due to a psychiatric disorder. BMI was categorized as underweight, normal weight or overweight, using the BMI classification for children and adolescents. We formed DSM-IV based diagnostic groups of non-affective psychosis (n = 69, including a schizophrenia subgroup, n = 41) and affective disorders (i.e. mood and anxiety disorders, n = 112) based on the Care Register for Health Care. Groups were compared with subjects with no psychiatric diagnoses (n = 3310). Sex, age, low birthweight and mother's mental disorders were included in the analyses. Results Underweight, but not overweight, independently predicted later development of non-affective psychosis. The risk of psychosis was over two-fold (relative risk (RR) [95% CI] 2.31 [1.2–4.4]) and of schizophrenia nearly 2.5-fold (RR 2.44 [1.03–5.8]) after underweight in childhood/adolescence. Underweight or overweight in childhood and adolescence was not associated with mood or anxiety disorders. Conclusions These results support the hypothesis of non-affective psychosis as a neurodevelopmental disorder with somatic manifestations throughout childhood and adolescence.

The life-course development of body mass index (BMI) may be driven by interactions between genes and obesity-inducing social environments. We examined whether lower parental or own education accentuates the genetic risk for higher BMI over the life course, and whether diet and physical activity account for the educational differences in genetic associations with BMI. The study comprised 2441 participants (1319 women, 3–18 years at baseline) from the prospective, population-based Cardiovascular Risk in Young Finns Study. BMI (kg/m2) trajectories were calculated from 18 to 49 years, using data from six time points spanning 31 years. A polygenic risk score for BMI was calculated as a weighted sum of risk alleles in 97 single-nucleotide polymorphisms. Education was assessed via self-reports, measured prospectively from participants in adulthood and from parents when participants were children. Diet and physical activity were self-reported in adulthood. Mean BMI increased from 22.6 to 26.6 kg/m2 during the follow-up. In growth curve analyses, the genetic risk score was associated with faster BMI increase over time (b=0.02, (95% CI, 0.01–0.02, P

Background Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. Objective To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. Design We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium Nutrition Working Group. Results from cohort-specific GWA analyses (additive model) for fish and EPA+DHA consumption were adjusted for age, sex, energy intake, and population stratification, and meta-analyzed separately using fixed-effect meta-analysis with inverse variance weights (METAL software). Additionally, heritability was estimated in 2 cohorts. Results Heritability estimates for fish and EPA+DHA consumption ranged from 0.13-0.24 and 0.12-0.22, respectively. A significant GWA for fish intake was observed for rs9502823 on chromosome 6: each copy of the minor allele (Freq(A) = 0.015) was associated with 0.029 servings/day (similar to 1 serving/month) lower fish consumption (P = 1.96x10(-8)). No significant association was observed for EPA+DHA, although rs7206790 in the obesity-associated FTO gene was among top hits (P = 8.18x10(-7)). Post-hoc calculations demonstrated 95% statistical power to detect a genetic variant associated with effect size of 0.05% for fish and 0.08% for EPA+DHA. Conclusions These novel findings suggest that non-genetic personal and environmental factors are principal determinants of the remarkable variation in fish consumption, representing modifiable targets for increasing intakes among all individuals. Genes underlying the signal at rs72838923 and mechanisms for the association warrant further investigation.

Both fetal growth restriction and prematurity have been associated with elevated blood pressure (BP). However, their combined effects on adult BP are unclear.Our analyses were based on 1756 participants in the population-based Cardiovascular Risk in Young Finns Study who had information on birth weight and gestational age, together with longitudinal data on cardiovascular risk markers from age 3-18 years in 1980 to age 34-49 years in 2011. Three groups were defined by birth data: those born at term (term); those born preterm (37 weeks) with an appropriate birth weight (-1 SD z score according to national sex and gestational week-stratified data) for gestational age (preterm appropriate birth weight for gestational age); and those born preterm with low birth weight (≤-1 SD z score) for gestational age [preterm small birth weight for gestational age (SGA)].There were no differences between the three groups in BP at baseline, but at the 31-year follow-up (mean age 41 years), mean SBP in the preterm SGA group was 7.2 mmHg (95% confidence interval = 2.3-12.1 mmHg, P = 0.004) higher than the preterm appropriate birth weight for gestational age group and 7.3 mmHg (95% confidence interval = 5.2-9.4 mmHg, P 0.0001) higher than the term group, adjusted for age and sex. In addition, preterm SGA individuals had a higher prevalence of adult hypertension compared with those born at term (36.9 vs. 25.4%; age, sex, and risk factors adjusted P = 0.006).These longitudinal data suggest that elevated BP levels associated with prematurity are more likely to be present in those with fetal growth restriction.

Aim This study examined whether there was an association between a repeated dietary and lifestyle intervention that began in infancy and participants' psychological wellbeing at the age of 20. Methods We examined the psychological wellbeing of 457 young adults participating in the Special Turku Coronary Risk Factor Intervention Project (STRIP), a randomised controlled trial conducted in Finland between 1989 and 2011. We assessed potential differences in psychological wellbeing between the intervention and control groups by examining participants' satisfaction with life, how they rated their health, their experiences of stress and the consequences of experiencing stress and symptoms of depression at the age of 20. We also assessed socio-economic status during childhood as a potential confounding factor. Results We found no association between the long-term dietary and lifestyle intervention and participants' psychological wellbeing in adulthood. Adjusting for sex and childhood socio-economic status did not affect the results and socio-economic status did not moderate the association between the intervention and psychological wellbeing. Conclusion Our findings showed no association between intensive dietary and lifestyle counselling that was initiated in infancy with psychological wellbeing in adulthood and the initiative did not appear to pose any psychological risks.

We studied prevalence of hypovitaminosis D, its determinants, and whether achievement of recommended dietary vitamin D intake (10 μg/d) is associated with absence of hypovitaminosis D in adults.The study is part of the Cardiovascular Risk in Young Finns Study. We collected serum samples of 25-hydroxyvitamin D as part of the 27-year follow-up (994 men and 1,210 women aged 30-45 years). Hypovitaminosis was defined as vitamin D concentration ≤ 50 nmol/L.Hypovitaminosis D was found in 38% of men and 34% of women. Dietary vitamin D intake (OR 0.90, 95% CI 0.86-0.93), use of vitamin-mineral supplements (0.66, 0.51-0.85), sunny holiday (0.55, 0.41-0.75), and oral contraceptive use in women (0.45, 0.27-0.75) were independently associated with reduced odds of hypovitaminosis. Increase in body mass index (1.06, 1.03-1.09), being a smoker (1.36, 0.97-1.92), investigation month (December versus other) (1.35, 1.12-1.61), and risk alleles in genotypes rs12785878 (1.31, 1.00-1.70) and rs2282679 (2.08, 1.66-2.60) increased odds of hypovitaminosis. Hypovitaminosis D was common also when recommended dietary intake was obtained (men 29%, women 24%).Several factors were associated with hypovitaminosis D. The condition was common even when recommended vitamin D intake was reported. The results support the importance of vitamin D fortification and nutrient supplement use.

The American Heart Association recently defined 7 ideal health behaviors and factors that can be used to monitor ideal cardiovascular health (ICH) over time. These relate to smoking, physical activity, diet, body mass index (BMI), blood pressure, blood glucose and total cholesterol. Associations between repeated measures of ICH across the life-course with outcomes of subclinical atherosclerosis in adult life have not been reported.The sample comprised 1465 children and young adults aged 12 to 24 years (mean age 17.5 years) from the Cardiovascular Risk in Young Finns Study cohort. Participants were followed-up for 21 years since baseline (1986) and had complete ICH data available at baseline and follow-up. Average lifetime ICH index was associated with reduced risk of coronary artery calcification (CAC) (P=0.0004), high-risk carotid intima-media thickness (IMT) (P=0.0005) and high-risk carotid distensibility (0.0001) in middle age. Participants with persistently low ICH status (lower than the median), as compared with persons with persistently high ICH status (higher than the median), had an increased risk of CAC (P=0.02), high-risk IMT (P=0.02), and high-risk distensibility (P0.0001). Participants who improved their ICH status from low to high did not have a different risk of CAC (P=0.90), high-risk IMT (P=0.25), or high-risk distensibility (P=0.80) than participants who always had high ICH status.The results show that ICH can be lost and regained, and importantly that regaining of ICH has a beneficial effect on cardiometabolic health. Health care providers should work to improve health behaviors especially in those who have lost ICH.