Association of dietary folate and vitamin B-12 intake with genome-wide DNA methylation in blood: a large-scale epigenome-wide association analysis in 5841 individuals.

BACKGROUND: Folate and vitamin B-12 are essential micronutrients involved in the donation of methyl groups in cellular metabolism. However, associations between intake of these nutrients and genome-wide DNA methylation levels have not been studied comprehensively in humans. OBJECTIVE: The aim of this study was to assess whether folate and/or vitamin B-12 intake are asssociated with genome-wide changes in DNA methylation in leukocytes. METHODS: A large-scale epigenome-wide association study of folate and vitamin B-12 intake was performed on DNA from 5841 participants from 10 cohorts using Illumina 450k arrays. Folate and vitamin B-12 intakes were calculated from food-frequency questionnaires (FFQs). Continuous and categorical (low compared with high intake) linear regression mixed models were applied per cohort, controlling for confounders. A meta-analysis was performed to identify significant differentially methylated positions (DMPs) and regions (DMRs), and a pathway analysis was performed on the DMR annotated genes. RESULTS: The categorical model resulted in 6 DMPs, which are all negatively associated with folate intake, annotated to FAM64A, WRAP73, FRMD8, CUX1, and LCN8 genes, which have a role in cellular processes including centrosome localization, cell proliferation, and tumorigenesis. Regional analysis showed 74 folate-associated DMRs, of which 73 were negatively associated with folate intake. The most significant folate-associated DMR was a 400-base pair (bp) spanning region annotated to the LGALS3BP gene. In the categorical model, vitamin B-12 intake was associated with 29 DMRs annotated to 48 genes, of which the most significant was a 1100-bp spanning region annotated to the calcium-binding tyrosine phosphorylation-regulated gene (CABYR). Vitamin B-12 intake was not associated with DMPs. CONCLUSIONS: We identified novel epigenetic loci that are associated with folate and vitamin B-12 intake. Interestingly, we found a negative association between folate and DNA methylation. Replication of these methylation loci is necessary in future studies.

Metabolic profiling of fatty liver in young and middle-aged adults: Cross-sectional and prospective analyses of the Young Finns Study.

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).

Childhood predictors of adult fatty liver. The Cardiovascular Risk in Young Finns Study.

BACKGROUND & AIMS: Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults. METHODS: Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3-18years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver. RESULTS: Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio=1.71, 95% confidence interval=1.07-2.72), variant in PNPLA3 (1.63, 1.29-2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08-2.30), BMI (1.30, 1.07-1.59 per standard deviation) and insulin (1.25, 1.05-1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p=0.002). CONCLUSIONS: Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes. LAY SUMMARY: The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3-18years) risk variables with fatty liver assessed in adulthood at the age of 34-49years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver.

Longitudinal study of circulating oxidized LDL and HDL and fatty liver: the Cardiovascular Risk in Young Finns Study.

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.

Television viewing and fatty liver in early midlife. The Cardiovascular Risk in Young Finns Study.

INTRODUCTION: Both sedentary behaviour and fatty liver are associated with increased risk of obesity and non-communicable diseases, but their relationship remains unknown. We investigated the relationship of television (TV) viewing time with serum gamma-glutamyltransferase (GGT) and Fatty Liver Index (FLI), and ultrasonographically assessed liver fat. METHODS: A total of 1,367 adults of the population-based Cardiovascular Risk in Young Finns study (748 women, 619 men, aged 34-49 years) had fasting serum GGT, triglycerides, weight, height, and waist circumference, and self-reported TV time data from 2001, 2007, and 2011. Changes in GGT and FLI, and liver ultrasound images in 2011 were studied in groups with constantly low (≤ 1 h/d), moderate (1-3 h/d), or high (≥ 3 h/d) daily TV time, and in groups with ≥ 1 hour increase/decrease in daily TV time between 2001 and 2011. RESULTS: Constantly high TV time was associated with higher GGT and FLI (P < 0.02 in both), and 2.3-fold (95% CI 1.2-4.5) increased risk of fatty liver regardless of age, sex, leisure-time and occupational physical activity, energy intake, diet composition, alcohol use, sleep duration, socioeconomic status, and smoking. Adjustment for BMI partly attenuated the associations. CONCLUSIONS: High TV viewing increases fatty liver risk. It may be one mechanism linking sedentary behaviour with increased cardiometabolic disease risks.

Is dispositional optimism or dispositional pessimism predictive of ideal cardiovascular health? The Young Finns Study.

OBJECTIVE: We examined the independent association between dispositional optimism compared to dispositional pessimism and ideal cardiovascular health (defined by the American Heart Association). DESIGN: A prospective design with a study sample of 1113 participants aged 24-39 years from the longitudinal Young Finns Study. MAIN OUTCOME MEASURES: Ideal cardiovascular health (comprised of seven ideal cardiovascular health metrics) was measured in 2001. The ideal cardiovascular health metrics were reassessed in 2007. RESULTS: Low pessimism rather than high optimism was a better predictor of ideal cardiovascular health in 2007. When examining the association between optimism and pessimism and the seven ideal cardiovascular health metrics in 2007 (BMI, diet, physical activity, smoking status, blood pressure, total cholesterol and plasma glucose), low pessimism predicted non-smoking status, ideal physical activity and eating a healthy diet, while high optimism was associated with eating a healthy diet. CONCLUSION: Our findings suggest that low pessimism rather than high optimism is associated with ideal cardiovascular health, especially with health behaviours such as not smoking, being physically active and eating a healthy diet. Socio-economic status was the potential mediating or confounding factor. Future studies should examine the differential meaning of the optimism/pessimism concepts to further clarify their relation to health outcomes.

Lifetime measures of ideal cardiovascular health and their association with subclinical atherosclerosis: The Cardiovascular Risk in Young Finns Study.

BACKGROUND: 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. METHODS AND RESULTS: 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 (P<0.0001). 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. CONCLUSIONS: 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.

Metabolite profiling and cardiovascular event risk: a prospective study of 3 population-based cohorts.

BACKGROUND: High-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established risk factors. METHODS AND RESULTS: We applied quantitative nuclear magnetic resonance metabolomics to identify the biomarkers for incident cardiovascular disease during long-term follow-up. Biomarker discovery was conducted in the National Finnish FINRISK study (n=7256; 800 events). Replication and incremental risk prediction was assessed in the Southall and Brent Revisited (SABRE) study (n=2622; 573 events) and British Women's Health and Heart Study (n=3563; 368 events). In targeted analyses of 68 lipids and metabolites, 33 measures were associated with incident cardiovascular events at P<0.0007 after adjusting for age, sex, blood pressure, smoking, diabetes mellitus, and medication. When further adjusting for routine lipids, 4 metabolites were associated with future cardiovascular events in meta-analyses: higher serum phenylalanine (hazard ratio per standard deviation, 1.18; 95% confidence interval, 1.12-1.24; P=4×10(-10)) and monounsaturated fatty acid levels (1.17; 1.11-1.24; P=1×10(-8)) were associated with increased cardiovascular risk, while higher omega-6 fatty acids (0.89; 0.84-0.94; P=6×10(-5)) and docosahexaenoic acid levels (0.90; 0.86-0.95; P=5×10(-5)) were associated with lower risk. A risk score incorporating these 4 biomarkers was derived in FINRISK. Risk prediction estimates were more accurate in the 2 validation cohorts (relative integrated discrimination improvement, 8.8% and 4.3%), albeit discrimination was not enhanced. Risk classification was particularly improved for persons in the 5% to 10% risk range (net reclassification, 27.1% and 15.5%). Biomarker associations were further corroborated with mass spectrometry in FINRISK (n=671) and the Framingham Offspring Study (n=2289). CONCLUSIONS: Metabolite profiling in large prospective cohorts identified phenylalanine, monounsaturated fatty acids, and polyunsaturated fatty acids as biomarkers for cardiovascular risk. This study substantiates the value of high-throughput metabolomics for biomarker discovery and improved risk assessment.

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

Prevalence and determinants of fatty liver in normal-weight and overweight young adults. The Cardiovascular Risk in Young Finns Study.

BACKGROUND AND AIMS: Fatty liver may have different determinants in normal-weight and in obese individuals. We measured factors associated with fatty liver in 863 normal-weight (BMI < 25) and 1135 overweight/obese (BMI ≥ 25) young and middle-aged adults (45% male, age 34-49 years) in the population-based Cardiovascular Risk in Young Finns Study. METHODS AND RESULTS: The prevalence of fatty liver detected with ultrasound was 29% in overweight/obese and 5% in normal-weight participants. In overweight/obese, the independent correlates were waist circumference (odds ratio for 1 standard deviation increase = 3.78), alanine transaminase (2.11), BMI (2.00), male sex (1.74), triglycerides (1.44), systolic blood pressure (1.31), fasting insulin (1.23), and physical activity (0.76). In normal weight, the independent correlates included alanine transaminase (3.05), smoking (2.56), systolic blood pressure (1.54), and alcohol intake (1.41). In normal-weight participants, the associations with fatty liver were stronger for alcohol intake and smoking, and weaker for triglycerides, than in overweight/obese participants (P for interaction < 0.05). CONCLUSION: Prevalence of fatty liver was 29% in overweight/obese and 5% in normal-weight adults. Differences in factors associated with fatty liver were seen between these two groups: alcohol intake and smoking were more strongly and triglycerides more weakly associated in normal-weight than in overweight/obese participants.

Childhood lifestyle and clinical determinants of adult ideal cardiovascular health: the Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Princeton Follow-Up Study.

BACKGROUND: The American Heart Association recently defined ideal cardiovascular health by simultaneous presence of seven health behaviors and factors. The concept is associated with cardiovascular disease incidence, and cardiovascular disease and all-cause mortality. To effectively promote ideal cardiovascular health already early in life, childhood factors predicting future ideal cardiovascular health should be investigated. Our aim was thus to comprehensively explore childhood determinants of adult ideal cardiovascular health in population based cohorts from three continents. METHODS: The sample comprised a total of 4409 participants aged 3-19 years at baseline from the Cardiovascular Risk in Young Finns Study (YFS; N = 1883) from Finland, Childhood Determinants of Adult Health Study (CDAH; N = 1803) from Australia and Princeton Follow-up Study (PFS; N = 723) from the United States. Participants were re-examined 19-31 years later when aged 30-48 years. RESULTS: In multivariable analyses, independent childhood predictors of adult ideal cardiovascular health were family socioeconomic status (P < 0.01; direct association) and BMI (P < 0.001; inverse association) in all cohorts. In addition, blood pressure (P = 0.007), LDL-cholesterol (P < 0.001) and parental smoking (P = 0.006) in the YFS, and own smoking (P = 0.001) in CDAH were inversely associated with future ideal cardiovascular health. CONCLUSIONS: Among several lifestyle and clinical indicators studied, higher family socioeconomic status and non-smoking (parental/own) in childhood independently predict ideal cardiovascular health in adulthood. As atherosclerotic cardiovascular diseases are rooted in childhood, our findings suggest that special attention could be paid to children who are from low socioeconomic status families, and who smoke or whose parents smoke, to prevent cardiovascular disease morbidity and mortality.

Sense of coherence, food selection and leisure time physical activity in type 1 diabetes.

BACKGROUND: Successful management of type 1 diabetes depends on the self-care practices. Sense of coherence has been associated with various measures of lifestyle choices. We aimed to study the associations between sense of coherence and self-care practices in patients with type 1 diabetes. We hypothesized that patients with weak sense of coherence have less prudent food choices and lower physical activity. METHODS: Cross-sectional data from 1104 patients (44% men, mean age 45±12 years) from the FinnDiane Study were available. Sense of coherence, dietary intake, and leisure time physical activity were evaluated using self-reported questionnaires. Diet score was calculated based on the degree to which food choices complied with dietary guidelines. Weekly metabolic equivalent hours were calculated by multiplying the activity duration by the activity- and intensity-specific metabolic equivalent. RESULTS: The sense of coherence score correlated positively both with the diet score and the weekly metabolic equivalent hours. Those in the lowest sense of coherence tertile had both the lowest diet scores and the lowest weekly metabolic equivalent hours values. Among women, the sense of coherence score was associated with the diet score when adjusted for age, socioeconomic status, received dietary guidance, and nephropathy status. The sense of coherence score independently predicted the metabolic equivalent hours value in men. CONCLUSIONS: A higher sense of coherence score predicted more prudent food choices in women and higher physical activity in men. In the future, the health consequences associated with a weak sense of coherence should be studied prospectively. Also, the possibility to use the sense of coherence questionnaire as a screening instrument to identify patients who could benefit from intensified counseling should be investigated.

Genetic variants and blood pressure in a population-based cohort: the Cardiovascular Risk in Young Finns study.

Clinical relevance of a genetic predisposition to elevated blood pressure was quantified during the transition from childhood to adulthood in a population-based Finnish cohort (N=2357). Blood pressure was measured at baseline in 1980 (age 3-18 years) and in follow-ups in 1983, 1986, 2001, and 2007. Thirteen single nucleotide polymorphisms associated with blood pressure were genotyped, and 3 genetic risk scores associated with systolic and diastolic blood pressures and their combination were derived for all of the participants. Effects of the genetic risk score were 0.47 mm Hg for systolic and 0.53 mm Hg for diastolic blood pressures (both P<0.01). The combination genetic risk score was associated with diastolic blood pressure from age 9 years onward (ß=0.68 mm Hg; P=0.015). Replications in 1194 participants of the Bogalusa Heart Study showed essentially similar results. The participants in the highest quintile of the combination genetic risk score had a 1.82-fold risk of hypertension in adulthood (P<0.0001) compared with the lowest quintile, independent of a family history of premature hypertension. These findings show that genetic variants are associated with preclinical blood pressure traits in childhood; individuals with several susceptibility alleles have, on average, a 0.5-mm Hg higher blood pressure, and this trajectory continues from childhood to adulthood.

Lifetime fruit and vegetable consumption and arterial pulse wave velocity in adulthood: the Cardiovascular Risk in Young Finns Study.

BACKGROUND: The relationships between childhood lifestyle risk factors and adulthood pulse wave velocity (PWV) have not been reported. We studied whether childhood and adulthood lifestyle risk factors are associated with PWV assessed in adulthood. METHODS AND RESULTS: The study cohort comprised 1622 subjects of the Cardiovascular Risk in Young Finns Study followed up for 27 years since baseline (1980; aged 3 to 18 years) with lifestyle risk factor data available since childhood. Arterial PWV was measured in 2007 by whole-body impedance cardiography device. Vegetable consumption in childhood was inversely associated with adulthood PWV (ß=-0.06, P=0.02), and this association remained significant (ß=-0.07, P=0.004) when adjusted for traditional risk factors (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, body mass index, and smoking). Vegetable consumption was also an independent predictor of PWV in adulthood when adjusted for lifestyle or traditional risk factors (ß=-0.08, P=0.002 and ß=-0.07, P=0.0007, respectively). Persistently high consumption of both fruits and vegetables from childhood to adulthood was associated with lower PWV compared with persistently low consumption (P=0.03 for both). The number of lifestyle risk factors (the lowest quintile for vegetable consumption, fruit consumption, physical activity, and smoking) in childhood was directly associated with PWV in adulthood (P=0.001). This association remained significant when adjusted for the number of lifestyle risk factors in adulthood (P=0.003). CONCLUSIONS: These findings suggest that lifetime lifestyle risk factors, with low consumption of fruits and vegetables in particular, are related to arterial stiffness in young adulthood.

Life-time risk factors and progression of carotid atherosclerosis in young adults: the Cardiovascular Risk in Young Finns study.

AIMS: The aim of this study is to evaluate whether childhood risk factors are associated with a 6-year change in carotid intima-media thickness (IMT) in young adulthood independent of the current risk factors. METHODS AND RESULTS: The Cardiovascular Risk in Young Finns cohort consisted of 1809 subjects who were followed-up for 27 years since baseline (1980, age 3-18 years) and having carotid IMT measured both in 2001 and 2007. Cardiovascular risk factors were assessed repeatedly since childhood. A genotype risk score was calculated using 17 newly identified genetic variants associating with cardiovascular morbidity. The number of childhood risk factors (high LDL-cholesterol, low HDL-cholesterol, high blood pressure, obesity, diabetes, smoking, low physical activity, infrequent fruit consumption) was associated with a 6-year change in adulthood IMT. In subjects with 0, 1, 2, and > or =3 childhood risk factors, IMT [mean (95% CI)) increased by 35 (28-42), 46 (40-52), 49 (41-57), and 61 (49-73) microm (P = 0.0001). This association remained significant when adjusted for adulthood risk score and genotype score (P = 0.007). Of the individual childhood variables, infrequent fruit consumption ((beta (95% CI) for 1-SD change -5(-9 to -1), P = 0.03) and low physical activity (-6(-10 to -2), P = 0.01) were associated with accelerated IMT progression after taking into account these variables assessed in adulthood. CONCLUSION: These findings indicate that children with risk factors have increased atherosclerosis progression rate in adulthood, and support the idea that the prevention of atherosclerosis by means of life style could be effective when initiated in childhood.

Major dietary patterns and cardiovascular risk factors from childhood to adulthood. The Cardiovascular Risk in Young Finns Study.

Studies on the impact of single nutrients on the risk of CVD have often given inconclusive results. Recent research on dietary patterns has offered promising information on the effects of diet as a whole on the risk of CVD. The Cardiovascular Risk in Young Finns Study is an ongoing, prospective cohort study with a 21-year follow-up to date. The subjects were children and adolescents at baseline (3-18 years, n 1768) and adults at the latest follow-up study (24-39 years, n 1037). We investigated the associations between two major dietary patterns and several risk factors for CVD. In longitudinal analyses with repeated measurements, using multivariate mixed linear regression models, the traditional dietary pattern (characterised by high consumption of rye, potatoes, butter, sausages, milk and coffee) was independently associated with total and LDL cholesterol concentrations, apolipoprotein B and C-reactive protein concentrations among both genders, and also with systolic blood pressure and insulin levels among women and concentrations of homocysteine among men (P < 0.05 for all). A dietary pattern reflecting more health-conscious food choices (such as high consumption of vegetables, legumes and nuts, tea, rye, cheese and other dairy products, and alcoholic beverages) was inversely, but less strongly associated with cardiovascular risk factors. Our results support earlier findings that dietary patterns have a role in the development of CVD.

Geographic origin as a determinant of carotid artery intima-media thickness and brachial artery flow-mediated dilation: the Cardiovascular Risk in Young Finns study.

OBJECTIVE: People living in eastern Finland have approximately 40% higher coronary heart disease mortality rates than western Finns. Whether this is because of genetic or environmental factors is unknown. We examined the effect of geographic family origin on subclinical atherosclerosis among young Finns. METHODS AND RESULTS: As part of a longitudinal follow-up study, we measured carotid intima-media thickness (IMT) in 2264 and brachial flow-mediated dilation (FMD) in 2109 white adults, aged 24 to 39 years. Subjects from eastern Finland had greater IMT and lower FMD compared with western subjects. These differences accentuated when the subjects' family origin (grandparents' birthplace) was taken into account and remained significant after adjusting for several environmental factors. Among subjects with all grandparents born in eastern or western Finland, IMTs were (mean+/-SEM) 0.592+/-0.003 versus 0.565+/-0.005 mm (P<0.0001), respectively. The corresponding FMD values were 7.61+/-0.15% versus 8.75+/-0.26%; P<0.01. The number of grandparents born in eastern Finland was directly related to IMT (P<0.0001) and inversely to FMD (P<0.05). CONCLUSIONS: Young adults originating from eastern Finland have greater carotid IMT and lower brachial FMD than western Finns. Consistent with a hereditable component predisposing to or protecting from atherosclerosis, these differences accentuated when subjects' family origin was taken into account. We studied whether an east-west difference exists in markers of subclinical atherosclerosis in 2264 Finns aged 24 to 39 years. Subjects with family origin in eastern Finland had greater carotid IMT and lower brachial FMD compared with western subjects, suggesting that hereditable factors play a role in excess atherosclerosis risk in eastern Finland.

Associates of obesity and weight dissatisfaction among Finnish adolescents.

OBJECTIVE: We investigated behavioural and socio-economic factors associated with obesity and weight dissatisfaction among Finnish adolescents. DESIGN: A total of 60,252 Finnish adolescents aged 14 to 16 years filled in a questionnaire about their health, health behaviour and socio-economic background. Food choices were obtained by using a short food-frequency questionnaire. Obesity was defined as a weight at least 120% of the sex- and height-specific mean weight for subjects. RESULTS: Of girls and boys, 54% and 66%, respectively, were satisfied with their weight. Among dissatisfied normal-weight adolescents, 81% of girls but only 48% of boys thought they were overweight. Of obese boys, 25% were satisfied with their weight. For both genders, obesity and weight dissatisfaction were associated with economic problems in the family. In girls, an association was also found with poor school performance, low educational level of parents and not having evening meals at home; and in boys, with physical inactivity and not eating school lunch. Smoking was more common among girls who were dissatisfied with their weight. Differences in food choices were small between different weight and weight satisfaction categories. CONCLUSIONS: Having normal weight and being satisfied with that weight are favourable for an adolescent. Obesity and weight dissatisfaction are associated mostly with disadvantageous health behaviours and low socio-economic status. Health behaviour seems to be associated more with weight satisfaction than with actual weight.