Geographic origin as a determinant of left ventricular mass and diastolic function - the Cardiovascular Risk in Young Finns Study.

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<0.0001; E/e'-ratio: p=0.01). LV end-diastolic volume was higher among subjects with eastern baseline origin (135±0.9 vs. 131±0.9 ml, p=0.0011) but left atrial end-systolic volume, also indicating LV diastolic function, was not different between eastern and western subjects (43.4±0.5 vs. 44.0±0.5 ml, p=0.45). Most of the subjects were well within the normal limits of these echocardiographic measurements. CONCLUSIONS: In our healthy middle-aged population, geographic origin in eastern Finland associated with higher LV mass compared to western Finland. Higher E/e'-ratio suggests that subjects with eastern baseline origin might have higher prevalence of diastolic dysfunction in the future than western subjects.

Longitudinal physical activity trajectories from childhood to adulthood and their determinants: The Young Finns Study.

Determining lifelong physical activity (PA) trajectories and their determinants is essential to promote a physically active lifestyle throughout the life-course. We aimed to identify PA trajectories from childhood to midlife and their determinants in a longitudinal population-based cohort. This study is a part of the Cardiovascular Risk in Young Finns Study. From 1980, a population-based cohort (N = 3596; 1764 boys/1832 girls, age 3-18 years) has been followed up for 31 years. PA indices were formed based on self-reported data (between age 9-49 years) on frequency, duration, and intensity of leisure (during childhood) or high-intensity (at later age) PA and on sports club participation/competitions. PA trajectories were analyzed using group-based trajectory modeling. Childhood (age 12 years), young adulthood (age 24 years), and early midlife (age 37 years) determinants were analyzed. Five PA trajectories were identified: persistently active (6.6%), decreasingly active (13.9%), increasingly active (13.5%), persistently low active (51.4%, reference group), persistently inactive (14.6%). In childhood, rural residential area (OR 0.45, 95% CI 0.21-0.96) and high academic performance (OR 2.18; 95% CI 1.58-3.00) associated with persistently active group. In early midlife, smoking (OR 1.66; 95% CI 1.07-2.58) associated with persistently inactive group, regular alcohol drinking (OR 2.91; 95% CI 1.12-7.55) with persistently active group and having children (OR 2.07; 95% CI 1.27-3.38) with decreasingly active group. High adulthood education associated with both decreasingly (OR 1.87; 95% CI 1.05-3.35) and increasingly (OR 2.09; 95% CI 1.19-3.68) active groups. We identified five PA trajectories from childhood into midlife. Most prominent determinants were academic achievement, education, having children and health habits (i.e. smoking/alcohol use).

Early work-related physical exposures and low back pain in midlife: the Cardiovascular Risk in Young Finns Study.

OBJECTIVE: To examine whether heavy physical workload in young adulthood increases the risk of local and radiating low back pain (LBP) in midlife. METHODS: Longitudinal nationally representative Young Finns Study data among women (n=414) and men (n=324), aged 18-24 years in 1986 (baseline), were used. Physical heaviness of work was reported at baseline and follow-up (2007), and local and radiating LBP at follow-up. Covariates were age, smoking and body mass index. Logistic regression was used to examine the associations between physical heaviness of work and LBP. Additionally, the mediating effect of back pain at baseline was examined (the Sobel test). RESULTS: After adjustment for the covariates, and as compared with sedentary/light physical workload, heavy physical workload was associated with radiating LBP among women (OR 4.09, 95% CI 1.62 to 10.31) and men (OR 2.01, 95% CI 1.06 to 3.82). Among men, early back pain mediated the association (p value from the Sobel test=0.006). Among women, early exposure to physically heavy work showed the most consistent associations, while early and late exposures were associated with radiating and local LBP among men. Persistently heavy physical work was associated with radiating LBP among women and men. CONCLUSIONS: Physically heavy work at a young age can have a long-lasting effect on the risk of LBP, radiating LBP in particular. These results highlight the need to consider early and persistent exposures to prevent the adverse consequences of physical workload for the low back.

The trajectory of the blood DNA methylome ageing rate is largely set before adulthood: evidence from two longitudinal studies.

The epigenetic clock, defined as the DNA methylome age (DNAmAge), is a candidate biomarker of ageing. In this study, we aimed to characterize the behaviour of this marker during the human lifespan in more detail using two follow-up cohorts (the Young Finns study, calendar age i.e. cAge range at baseline 15-24 years, 25-year-follow-up, N = 183; The Vitality 90+ study, cAge range at baseline 19-90 years, 4-year-follow-up, N = 48). We also aimed to assess the relationship between DNAmAge estimate and the blood cell distributions, as both of these measures are known to change as a function of age. The subjects' DNAmAges were determined using Horvath's calculator of epigenetic cAge. The estimate of the DNA methylome age acceleration (Δ-cAge-DNAmAge) demonstrated remarkable stability in both cohorts: the individual rank orders of the DNAmAges remained largely unchanged during the follow-ups. The blood cell distributions also demonstrated significant intra-individual correlation between the baseline and follow-up time points. Interestingly, the immunosenescence-associated features (CD8+CD28- and CD4+CD28- cell proportions and the CD4/CD8 cell ratio) were tightly associated with the estimate of the DNA methylome age. In summary, our data demonstrate that the general level of Δ-cAge-DNAmAge is fixed before adulthood and appears to be quite stationary thereafter, even in the oldest-old ages. Moreover, the blood DNAmAge estimate seems to be tightly associated with ageing-associated shifts in blood cell composition, especially with those that are the hallmarks of immunosenescence. Overall, these observations contribute to the understanding of the longitudinal aspects of the DNAmAge estimate.

Aging-associated DNA methylation changes in middle-aged individuals: the Young Finns study.

BACKGROUND: Chronological aging-associated changes in the human DNA methylome have been studied by multiple epigenome-wide association studies (EWASs). Certain CpG sites have been identified as aging-associated in multiple studies, and the majority of the sites identified in various studies show common features regarding location and direction of the methylation change. However, as a whole, the sets of aging-associated CpGs identified in different studies, even with similar tissues and age ranges, show only limited overlap. In this study, we further explore and characterize CpG sites that show close relationship between their DNA methylation level and chronological age during adulthood and which bear the relationship regardless of blood cell type heterogeneity. RESULTS: In this study, with a multivariable regression model adjusted for cell type heterogeneity, we identified 1202 aging-associated CpG sites (a-CpGs, FDR < 5%), in whole blood in a population with an especially narrow age range (40 - 49 years). Repeatedly reported a-CpGs located in genes ELOVL2, FHL2, PENK and KLF14 were also identified. Regions with aging-associated hypermethylation were enriched regarding several gene ontology (GO) terms (especially in the cluster of developmental processes), whereas hypomethylated sites showed no enrichment. The genes with higher numbers of a-CpG hits were more often hypermethylated with advancing age. The comparison analysis revealed that of the 1202 a-CpGs identified in the present study, 987 were identified as differentially methylated also between nonagenarians and young adults in a previous study (The Vitality 90+ study), and importantly, the directions of changes were identical in the previous and in the present study. CONCLUSIONS: Here we report that aging-associated DNA methylation features can be identified in a middle-aged population with an age range of only 9 years. A great majority of these sites have been previously reported as aging-associated in a population aged 19 to 90 years. Aging is associated with different types of changes in DNA methylation, clock-like as well as random. We speculate that the a-CpGs identified here in a population with a narrow age-range represent clock-like changes, as they showed concordant methylation behavior in population spanning whole adulthood as well.

Longitudinal investigation of adenovirus 36 seropositivity and human obesity: the Cardiovascular Risk in Young Finns Study.

BACKGROUND/OBJECTIVES: Adenovirus-36 (Adv-36) infection is associated with exaggerated adipogenesis in cell culture and the development of obesity in animal models and humans, but a causal relationship remains unproven. Our objective was to determine whether serological evidence of Adv-36 infection in childhood and/or adulthood is associated with adult obesity. SUBJECTS/METHODS: Paired plasma concentrations of Adv-36 antibodies were measured by a novel enzyme-linked immunosorbent assay in a subgroup (n=449) of the Cardiovascular Risk in Young Finns Study in childhood (mean age 11.9 years) and adulthood (mean age 41.3 years). The study group included (1) individuals who had maintained normal-weight status (2) those who became obese adults from a normal-weight status in childhood and (3) those that were overweight/obese as a child and obese as an adult. RESULTS: Mean (s.d.) time between baseline and follow-up was 29.4 (3.2) years (range 21-31 years). A total of 24.4% of individuals who were normal weight throughout life were seropositive for Adv-36 during child and/or adulthood as compared with 32.3% of those who became obese adults (P=0.11). Those who became obese in adulthood were more likely to be Adv-36 seropositive as adults compared with those who maintained normal weight (21.3% vs. 11.6%, P=0.02). This difference was mediated by a decline in Adv-36 seropositivity between child and adulthood in those maintaining normal weight. No differences were observed in body mass index across the life course, nor in waist circumference in adult life, between those who were Adv-36 seronegative or seropositive at any age. CONCLUSIONS: Individuals who gained weight across the life course were more likely to be Adv-36 seropositive in adult life than those who did not gain weight. However, analysis of change in weight status in relation to Adv-36 positivity did not support a causal role for Adv-36 in the development of obesity.

Adolescence physical activity is associated with higher tibial pQCT bone values in adulthood after 28-years of follow-up--the Cardiovascular Risk in Young Finns Study.

High peak bone mass and strong bone phenotype are known to be partly explained by physical activity during growth but there are few prospective studies on this topic. In this 28-year follow-up of Cardiovascular Risk in Young Finns Study cohort, we assessed whether habitual childhood and adolescence physical activity or inactivity at the age of 3-18 years were associated with adult phenotype of weight-bearing tibia and the risk of low-energy fractures. Baseline physical activity and data on clinical, nutritional and lifestyle factors were assessed separately for females and males aged 3-6-years (N=395-421) and 9-18-years (N=923-965). At the age of 31-46-years, the prevalence of low-energy fractures was assessed with a questionnaire and several tibial traits were measured with pQCT (bone mineral content (BMC; mg), total and cortical cross-sectional areas (mm(2)), trabecular (for the distal site only) and cortical (for the shaft only) bone densities (mg/cm(3)), stress-strain index (SSI; mm(3), for the shaft only), bone strength index (BSI; mg(2)/cm(4), for the distal site only) and the cortical strength index (CSI, for the shaft only)). For the statistical analysis, each bone trait was categorized as below the cohort median or the median and above and the adjusted odds ratios (OR) were determined. In females, frequent physical activity at the age of 9-18-years was associated with higher adulthood values of BSI, total and cortical areas, BMC, CSI and SSI at the tibia independently of many health and lifestyle factors (ORs 0.33-0.53, P≤0.05; P-values for trend 0.002-0.05). Cortical density at the tibial shaft showed the opposite trend (P-value for trend 0.03). Similarly in males, frequent physical activity was associated with higher values of adult total and cortical areas and CSI at the tibia (ORs 0.48-0.53, P≤0.05; P-values for trend 0.01-0.02). However, there was no evidence that childhood or adolescence physical activity was associated with lower risk of low energy fractures during the follow-up. In conclusion, frequent habitual physical activity in adolescence seems to confer benefits on tibial bone size and geometry in adulthood.

High serum n6 fatty acid proportion is associated with lowered LDL oxidation and inflammation: the Cardiovascular Risk in Young Finns Study.

The intake of polyunsaturated fatty acids (PUFAs) is generally linked with a reduced cardiovascular disease (CVD) risk, but an elevated n6PUFA intake, without simultaneous n3PUFA supply, may elevate the risk. PUFAs are suspected as being easily oxidized and have a potential role in lipoprotein oxidation and inflammation. Saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) are resistant to oxidation. However, in a Western diet, their most important source is red meat, a food stuff rich in heme iron which can catalyze oxidative reactions. Therefore, different serum fatty acid (FA) proportions (free + esterified) were correlated with the status of low-density lipoprotein (LDL) oxidation in vivo (conjugated dienes = oxLDLlipids and antibody-based oxidized proteins = oxLDLprot) and inflammation (serum CRP) in 2196 Finnish subjects (age: 24-39 years) using CVD risk factor-adjusted linear regression models. High n6PUFA, PUFA/SFA and n6/n3 ratios, and low SFA and MUFA were all associated with reduced levels of oxLDLlipids, oxLDLprot, and CRP. These findings at the population level suggest that PUFAs are negatively and SFAs and MUFAs positively related with LDL oxidation and inflammation; these conclusions are in line with previous observations linking PUFAs, particularly n6PUFAs, with lower CVD risk, and SFAs with increased risk.

Childhood and adult socio-economic position and social mobility as determinants of low back pain outcomes.

BACKGROUND: Low back pain (LBP) is a prevalent problem and tends to be socio-economically patterned. Relatively little is known about life-course socio-economic circumstances as determinants of different types of LBP. Our aim was to examine whether childhood and adult socio-economic position and social mobility are associated with radiating and non-specific LBP and sciatica. METHOD: Data were derived from the Young Finns Study (n = 2231). Childhood socio-economic position was based on parental education, occupational class and family income at baseline in 1980. Data on own education and LBP outcomes were collected at the end of follow-up in 2007. Social mobility was based on parental and own education. Covariates were composed of age, parental body mass index and smoking. RESULTS: Both childhood and own socio-economic position remained associated with radiating LBP and sciatica after adjustments. However, the associations varied by socio-economic indicator and gender. Stable lower socio-economic position and downward mobility were associated with radiating LBP. CONCLUSION: Childhood socio-economic circumstances affect the risk of radiating LBP and sciatica in adulthood. To prevent low back disorders, early socio-economic circumstances need to be considered alongside own socio-economic position.

Depressive symptoms are associated with lower bone mineral density in young adults with high job strain. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Job strain has been associated with depressive symptoms, and depression has been associated with low bone mineral density (BMD). PURPOSE: The associations between BMD and job strain have not been studied. We examined the relations between BMD, job strain, and depressive symptoms in a population-based group of young adults in Finland. METHOD: Ultrasonic measurement of BMD at the calcaneus was performed on 777 participants (men 45 %, aged 30-45) drawn from the Cardiovascular Risk in Young Finns Study. Job strain was assessed by self-administered questionnaires by the combination of job demands and job control. Depressive symptoms were assessed with a modified Beck Depression Inventory. The effects of job strain on BMD were studied with multivariable analyses with age, sex, BMI, vitamin D, and calcium intake, physical activity, cigarette smoking, alcohol use, and depressive symptoms as covariates. RESULTS: Depressive symptoms were independently associated with lower BMD T score in participants with high job strain (ß = -0.241, p = 0.02), but depressive symptoms were not significantly associated with BMD in the low (ß = -0.160, p = 0.26) and intermediate (ß = -0.042, p = 0.66) job strain categories. CONCLUSION: The results suggest that job strain modifies the association between depressive symptoms and BMD. Depressed individuals with high work-related stress might be in increased risk of lower bone mineral density.

Sedentary behaviours and obesity in adults: the Cardiovascular Risk in Young Finns Study.

OBJECTIVE: Sedentary behaviour may contribute to the development of obesity. We investigated the relations between different types of sedentary behaviour and adiposity markers in a well-characterised adult population after controlling for a wide range of potential confounders. DESIGN: Cross-sectional study. SETTING: The Cardiovascular Risk in Young Finns Multicenter Study. Participants Sedentary time (TV viewing, computer time, reading, music/radio listening and other relaxation) was assessed with a questionnaire for 1084 women and 909 men aged 30-45 years. Other study variables included occupational and leisure-time physical activity, sleep duration, socioeconomic status, smoking, alcohol consumption, energy intake, adherence to the recommended diet, multiple individual food items, age and genetic variants associated with body mass index (BMI). Primary outcome measures BMI in kg/m(2) and waist circumference (WC in cm). RESULTS: Of the different sedentary behaviour types, TV viewing was most consistently related to higher BMI and WC, both in men and women. One additional daily TV hour was associated with a 1.81±0.44 cm larger WC in women and 2 cm±0.44 cm in men (both p<0.0001). The association with TV was diluted, but remained highly significant after adjustments with all measured covariates, including several potentially obesogenic food items associated with TV viewing. The intakes of food items such as sausage, beer and soft drinks were directly associated with TV viewing, while the intakes of oat and barley, fish, and fruits and berries were associated indirectly. After these adjustments, non-TV sedentary behaviour remained associated with adiposity indices only in women. CONCLUSIONS: Out of the different types of sedentary behaviour, TV viewing was most consistently associated with adiposity markers in adults. Partial dilution of these associations after adjustments for covariates suggests that the obesogenic effects of TV viewing are partly mediated by other lifestyle factors.

Childhood family factors predict developmental trajectories of hostility and anger: a prospective study from childhood into middle adulthood.

BACKGROUND: Low socio-economic status (SES), and a conflictive, cold and unsupportive family environment in childhood have been associated with early adulthood hostility. However, it is unknown whether this association changes in magnitude with age from childhood to adulthood. We investigated whether childhood family factors (SES and parental child-rearing style) predicted differential development of offspring hostility and anger from early to middle adulthood. METHOD: Between 2041 and 2316 participants (age range 3-18 years at baseline) were selected from the longitudinal Young Finns study. The participants were followed for 27 years between 1980 and 2007. Childhood SES and parent's self-reported child-rearing style were measured twice: at baseline and 3 years after baseline. Hostility and anger were assessed with self-report questionnaires at 12, 17, 21 and 27 years after baseline. RESULTS: Low parental SES and hostile child-rearing style at baseline predicted higher mean levels of offspring anger and hostility. Low parental SES and one of the hostile child-rearing style components (strict disciplinary style) became more strongly associated with offspring hostility with age, suggesting an accumulating effect. CONCLUSIONS: Childhood family factors predict the development of hostility and anger over 27 years and some of these family factors have a long-term accumulating effect on the development of hostility.

Triglyceride-cholesterol imbalance across lipoprotein subclasses predicts diabetic kidney disease and mortality in type 1 diabetes: the FinnDiane Study.

BACKGROUND: Circulating cholesterol (C) and triglyceride (TG) levels are associated with vascular injury in type 1 diabetes (T1DM). Lipoproteins are responsible for transporting lipids, and alterations in their subclass distributions may partly explain the increased mortality in individuals with T1DM. DESIGN AND SUBJECTS: A cohort of 3544 individuals with T1DM was recruited by the nationwide multicentre FinnDiane Study Group. At baseline, six very low-density lipoprotein VLDL, one intermediate-density lipoprotein IDL, three low-density lipoprotein LDL and four higher high-density lipoprotein HDL subclasses were quantified by proton nuclear magnetic resonance spectroscopy. At follow-up, the baseline data were analysed for incident micro- or macroalbuminuria (117 cases in 5.3 years), progression from microalbuminuria (63 cases in 6.1 years), progression from macroalbuminuria (109 cases in 5.9 years) and mortality (385 deaths in 9.4 years). Univariate associations were tested by age-matched cases and controls and multivariate lipoprotein profiles were analysed using the self-organizing map (SOM). RESULTS: TG and C levels in large VLDL were associated with incident albuminuria, TG and C in medium VLDL were associated with progression from microalbuminuria, and TG and C in all VLDL subclasses were associated with mortality. Large HDL-C was inversely associated with mortality. Three extreme phenotypes emerged from SOM analysis: (i) low C (<3% mortality), (ii) low TG/C ratio (6% mortality), and (iii) high TG/C ratio (40% mortality) in all subclasses. CONCLUSIONS: TG-C imbalance is a general lipoprotein characteristic in individuals with T1DM and high vascular disease risk.

Body mass index and depressive symptoms: instrumental-variables regression with genetic risk score.

The causal role of obesity in the development of depression remains uncertain. We applied instrumental-variables regression (Mendelian randomization) to examine the association of adolescent and adult body mass index (BMI) with adult depressive symptoms. Participants were from the Young Finns prospective cohort study (n = 1731 persons, 2844 person-observations), with repeated measurements of BMI and depressive symptoms (modified Beck's Depression Inventory). Genetic risk score of 31 single nucleotide polymorphisms previously identified as robust genetic markers of body weight was used as a proxy for variation in BMI. In standard linear regression analysis, higher adult depressive symptoms were predicted by higher adolescent BMI (B = 0.33, CI = 0.06-0.60, P = 0.017) and adult BMI (B = 0.47, CI = 0.32-0.63, P < 0.001). These associations were replicated in instrumental-variables analysis with genetic risk score as instrument (B = 1.96, CI = 0.03-3.90, P = 0.047 for adolescent BMI; B = 1.08, CI = 0.11-2.04, P = 0.030 for adult BMI). The association for adolescent BMI was significantly stronger in the instrumented analysis compared to standard regression (P = 0.04). These findings provide additional evidence to support a causal role for high BMI in increasing symptoms of depression. However, the present analysis also demonstrates potential limitations of applying Mendelian randomization when using complex phenotypes.

Relation of high cytomegalovirus antibody titres to blood pressure and brachial artery flow-mediated dilation in young men: the Cardiovascular Risk in Young Finns Study.

Human cytomegalovirus (CMV) infection is associated with a higher risk of cardiovascular disease in immunocompromised organ transplant patients. It has been linked with the pathogenesis of elevated arterial blood pressure. However, controversy exists as to whether CMV infection is associated with endothelial function, and little is known about its role as a potential risk factor for early atherosclerosis development at a young age. We aimed to discover if CMV antibody titres are associated with early vascular changes (carotid intima-media thickness, carotid artery distensibility and brachial artery flow-mediated dilation), blood pressure elevation or other traditional cardiovascular risk factors. CMV antibody titres were measured in 1074 women and 857 men (aged 24-39 years) taking part in the Cardiovascular Risk in Young Finns study. CMV antibody titres were significantly higher in women compared to men. In men, high CMV antibody titres were associated directly with age (P < 0·001) and systolic (P = 0·053) and diastolic (P = 0·002) blood pressure elevation, and associated inversely with flow-mediated dilation (P = 0·014). In women, CMV antibody titres did not associate with any of the analysed parameters. In a multivariate regression model, which included traditional atherosclerotic risk factors, CMV antibody titres were independent determinants for systolic (P = 0·029) and diastolic (P = 0·004) blood pressure elevation and flow-mediated dilation (P = 0·014) in men. High CMV antibody titres are associated independently with blood pressure and brachial artery flow-mediated dilation in young men. This association supports the hypothesis that common CMV infection and/or an immune response to CMV may lead to impaired vascular function at a young age.

Overweight in childhood and bone density and size in adulthood.

UNLABELLED: We evaluated the adult bone structural traits in relation to childhood overweight in 832 men and women. Childhood overweight was associated with larger cross-sections at long bones in both sexes. Excess weight in childhood may also lead to higher trabecular density in females and somewhat lower cortical density in men. INTRODUCTION: Excess body weight in childhood may impose more loading on growing skeleton and thus lead to more robust structure in adulthood. METHODS: This prospective cohort study evaluated the adult bone structural traits in relation to childhood overweight in a subgroup of 456 women and 376 men from the population-based cohort of Cardiovascular Risks in Young Finns Study. Between-group differences were evaluated with analysis of covariance. RESULTS: According to established body mass index (BMI) criterion at the age of 12 years, 31 women and 34 men were classified overweight in childhood. At the mean age (SD) of 36.1 (2.7) years, total cross-sectional (ToA) and cortical area (CoA) at the distal and shaft sites and cortical (shaft CoD) and trabecular (distal TrD) bone density of the nonweight-bearing radius and weight-bearing tibia were evaluated with pQCT. Despite being taller in adolescence, the adult body height of overweight children was similar. In both sexes, childhood overweight was consistently associated with 5-10% larger ToA at all bone sites measured in adulthood. CoA did not show such a consistent pattern. Women, who were overweight in childhood, had ~5% denser TrD with no difference in CoD. In contrast, TrD in men who were overweight in childhood was not different but their CoD was ~1% lower. CONCLUSIONS: Childhood overweight was consistently associated with larger long bone cross-sections in both sexes. Excess weight in childhood may also lead to higher trabecular density in women and somewhat lower cortical density in men. Specific mechanisms underlying these associations are not known.

Selenium status and blood lipids: the cardiovascular risk in Young Finns study.

BACKGROUND: Concern has been recently raised about possible adverse cardio-metabolic effects of high selenium status, such as increased risks of diabetes and hyperlipidaemia. However, most of the evidence comes from selenium-replete populations such as that of the United States. OBJECTIVES: To examine cross-sectional and longitudinal associations of serum selenium with cardiovascular risk factors in Finland where selenium levels were amongst the lowest in the world until the early 1980s before the implementation of a nationwide selenium fertilization programme. METHODS: Serum selenium was measured in 1235 young Finns aged 3-18 years at baseline in 1980 (prefertilization) and in a subgroup (N = 262) at the 6-year follow-up (1986, postfertilization). During the 27-year follow-up, serum lipids, blood pressure, body mass index and smoking were assessed five times (1980, 1983, 1986, 2001 and 2007). RESULTS: Mean (±SD) serum selenium concentrations were 74.3 ± 14.0 ng mL(-1) in 1980 and 106.6 ± 12.5 ng mL(-1) in 1986 (average increase 32.3 ng mL(-1); 95% CI: 30.3 to 34.3, P < 0.0001). In univariate and multivariable cross-sectional models in 1980 and 1986, increased serum selenium levels were consistently associated with increased total, HDL and Low-density lipoprotein (LDL) cholesterol. However, the average longitudinal changes in lipids were -0.20 mmol L(-1) (95% CI: -0.30 to -0.10, P < 0.0001) for total cholesterol, 0.06 mmol L(-1) (95% CI: 0.03 to 0.10, P < 0.0001) for HDL cholesterol, and -0.23 mmol L(-1) (95% CI: -0.31 to -0.14, P < 0.0001) for LDL cholesterol. Selenium measured in 1986 was not associated with lipids assessed in 2001 and 2007. CONCLUSIONS: Cross-sectional findings from the Young Finns study corroborate positive associations of selenium status with serum lipids. However, longitudinal evidence does not support the causality of this link.

Hostility in adolescents and adults: a genome-wide association study of the Young Finns.

Hostility is a multidimensional personality trait with changing expression over the life course. We performed a genome-wide association study (GWAS) of the components of hostility in a population-based sample of Finnish men and women for whom a total of 2.5 million single-nucleotide polymorphisms (SNPs) were available through direct or in silico genotyping. Hostility dimensions (anger, cynicism and paranoia) were assessed at four time points over a 15-year interval (age range 15-30 years at phase 1 and 30-45 years at phase 4) in 982-1780 participants depending on the hostility measure. Few promising areas from chromosome 14 at 99 cM (top SNPs rs3783337, rs7158754, rs3783332, rs2181102, rs7159195, rs11160570, rs941898, P values <3.9 × 10(-8) with nearest gene Enah/Vasp-like (EVL)) were found suggestively to be related to paranoia and from chromosome 7 at 86 cM (top SNPs rs802047, rs802028, rs802030, rs802026, rs802036, rs802025, rs802024, rs802032, rs802049, rs802051, P values <6.9 × 10(-7) with nearest gene CROT (carnitine O-octanoyltransferase)) to cynicism, respectively. Some shared suggestive genetic influence for both paranoia and cynicism was also found from chromosome 17 at 2.8 cM (SNPs rs12936442, rs894664, rs6502671, rs7216028) and chromosome 22 at 43 cM (SNPs rs7510759, rs7510924, rs7290560), with nearest genes RAP1 GTPase activating protein 2 (RAP1GAP2) and KIAA1644, respectively. These suggestive associations did not replicate across all measurement times, which warrants further study on these SNPs in other populations.

Sustained involvement in youth sports activities predicts reduced chronic job strain in early midlife.

OBJECTIVE: We examined the long-term effects of youth leisure time physical activity (LTPA) and sports participation on the prevalence of chronic work stress in adulthood. METHODS: Participants (326 men and 338 women) aged 9 to 18 years were initially enrolled in 1980 and followed until 2007. Data were collected using questionnaires and bicycle ergometry in a subgroup. RESULTS: High youth LTPA and sports participation predicted lower chronic job strain in both sexes. The association was mediated by type A leadership. Participation and persistence in organized youth sports followed a similar pattern. In the subgroup, adult physical fitness only partly accounted for the association. CONCLUSIONS: Sustained involvement in youth physical activity and sport lasting at least 3 years is associated with reduced chronic job strain in adulthood. The association was partially explained by type A leadership and physical fitness.

The Leu7Pro polymorphism of the signal peptide of neuropeptide Y (NPY) gene is associated with increased levels of inflammatory markers preceding vascular complications in patients with type 2 diabetes.

AIMS/HYPOTHESIS: The Leucine7 to Proline7 (Leu7Pro) polymorphism of the signal peptide of neuropeptide Y (NPY) increases risk for vascular complications in diabetes. Diabetes is associated with low-grade inflammation, which has an important role in the development of atherosclerosis. Currently, we followed diabetes patients to investigate, if the Pro7 allele is associated with the inflammation related to atherosclerosis. METHODS: In the 5-year follow-up, the genotyped, pair-matched type 2 diabetes patients (12 with the Pro7 allele and 19 without) were investigated using non-invasive ultrasound based methods to measure the development of atherosclerosis (intima media thickness=IMT) and endothelium-dependent (FMD) and -independent nitrate-mediated (NMD) vasodilatation. The development of diabetic complications was followed annually, and the concentrations of inflammatory markers and NPY in plasma were determined. RESULTS: Patients with the Pro7 had increased U-albumin/creatinine (p=0.037), E-selectin (p=0.016), fasting insulin (p=0.011) and HOMA index (p=0.013) but decreased serum amyloid P concentrations (p=0.021). Furthermore, men with the Pro7 had increased CRP (p=0.010) and NPY (p=0.026) concentrations. IMT and FMD were similar in all patients, however, NMD decreased more during the follow-up in the patients with the Pro7 (p=0.002). NPY correlated positively with bIMT [r 0.04 (SE 0.02), p=0.007] and E-selectin negatively with FMD [r -0.05 (S.E 0.02), p=0.039]. CONCLUSIONS/INTERPRETATIONS: Diabetes patients with the Pro7 allele display increased levels of inflammatory molecules and NPY in blood, preceding vascular wall thickening and impaired endothelial dilatation, especially in male patients.