Diet and the development of atherosclerosis : a whole-diet approach from childhood to adulthood

Cardiovascular diseases (CVDs) are the leading cause of mortality in the world. Studies of the impact of single nutrients on the risk for CVD have often provided inconclusive results, and recent research in nutritional epidemiology with a more holistic whole-diet approach has proven fruitful. Moreover, dietary habits in childhood and adolescence may play a role in later health and disease, either independently or by tracking into adulthood. The main aims of this study were to find childhood and adulthood determinants of adulthood diet, to identify dietary patterns present among the study population and to study the associations between long-term food choices and cardiovascular health in young Finnish adults. The study is a part of the multidisciplinary Cardiovascular Risk in Young Finns study, which is an ongoing, prospective cohort study with a 21-year follow-up. At baseline in 1980, the subjects were children and adolescents aged 3 to 18 years (n included in this study = 1768), and young adults aged 24 to 39 years at the latest follow-up study in 2001 (n = 1037). Food consumption and nutrient intakes were assessed with repeated 48-hour dietary recalls. Other determinations have included comprehensive risk factor assessments using blood tests, physical measurements and questionnaires. In the latest follow-up, ultrasound examinations were performed to study early atherosclerotic vascular changes. The average intakes showed substantial changes since 1980. Intakes of fat and saturated fat had decreased, whereas the consumption of fruits and vegetables had increased. Intake of fat and consumption of vegetables in childhood and physical activity in adulthood were important health behavioural determinants of adult diet. Additionally, a principal component analysis was conducted to identify major dietary patterns at each study point. A similar set of two major patterns was recognised throughout the study. The traditional dietary pattern positively correlated with the consumption of traditional Finnish foods, such as rye, potatoes, milk, butter, sausages and coffee, and negatively correlated with fruit, berries and dairy products other than milk. This type of diet was independently associated with several risk factors of CVD, such as total and low-density lipoprotein cholesterol, apolipoprotein B and C-reactive protein concentrations among both genders, as well as with systolic blood pressure and insulin levels among women. The traditional pattern was also independently associated with intima media thickness (IMT), a subclinical predictor of CVD, in men but not in women. The health-conscious pattern, predominant among female subjects, non-smokers and urbanites, was characterised by more health-conscious food choices such as vegetables, legumes and nuts, tea, rye, fish, cheese and other dairy products, as well as by the consumption of alcoholic beverages. This pattern was inversely, but less strongly, associated with cardiovascular risk factors. Tracking of the dietary pattern scores was observed, particularly among subjects who were adolescents at baseline. Moreover, a long-term high intake of protein concurrent with a low intake of fat was positively associated with IMT. These findings suggest that food behaviour and food choices are to some extent established as early as in childhood or adolescence and may significantly track into adulthood. Long-term adherence to traditional food choices seems to increase the risk for developing CVD, especially among men. Those with intentional or unintentional low fat diets, but with high intake of protein may also be at increased risk for CVD. The findings offer practical, food-based information on the relationship between diet and CVD and encourage further use of the whole-diet approach in epidemiological research. The results support earlier findings that long-term food choices play a role in the development of CVD. The apparent influence of childhood habits is important to bear in mind when planning educational strategies for the primary prevention of CVD. Further studies on food choices over the entire lifespan are needed.Sepelvaltimotaudin kliiniset oireet tulevat useimmiten esiin vasta keski-iässä tai sen jälkeen. Siihen johtavat ateroskleroottiset muutokset verisuonissa saattavat kehittyä jo lapsuudesta tai nuoruudesta alkaen. Ravinto on eräs tärkeimmistä sepelvaltimotaudin riskitekijöiden tasoa selittävistä tekijöistä. Useilla ravintotekijöillä on arveltu olevan yhteisvaikutuksia toistensa kanssa. Siksi ruokavalioon kokonaisuutena on viime aikoina alettu kiinnittää kasvavaa huomiota. Tämä tutkimus on osa laajaa LASERI-hanketta, jossa suomalaisten lasten, nuorten ja nuorten aikuisten sepelvaltimotaudin riskitekijöitä ja niiden muovautumista lapsuudesta aikuisuuteen on kartoitettu koko maan kattavassa monikeskustutkimuksessa. Tämä kansainvälisestikin ainutlaatuinen hanke käynnistettiin vuonna 1980, jolloin tutkittavat olivat 3-18-vuotiaita. Tämän tutkimuksen aineistona käytettiin kaikkiaan 1037 tutkittavalta toistuvasti vuosina 1980-2001 kerättyjä tietoja ruokavaliosta ja sepelvaltimotaudin riskitekijöiden tasosta. Vuonna 2001 saatiin ultraäänimittauksella tietoja kaulasuonten rakenteesta. Pitkän seurannan ansiosta tässä tutkimuksessa oli ainutlaatuinen mahdollisuus selvittää lapsuudesta aikuisuuteen muovautuvien ruokatottumusten roolia ateroskleroosin kehittymisessä. Kun ruokavaliota tarkasteltiin kokonaisuutena, aineistossa oli koko 21 vuoden seurannan ajan havaittavissa kaksi toisistaan poikkeavaa ruokavaliotyyppiä. Perinteiseen ruokavaliotyyppiin kuului runsas rukiin, perunoiden, maidon, voin, makkaran ja kahvin käyttö. Terveystietoiseksi nimetty toinen ruokavalio sisälsi runsaasti kasviksia, juureksia, teetä, ruista, kalaa, juustoa sekä aikusiällä myös alkoholijuomia. Nämä ruokavaliotyypit näyttivät pysyvän pääpiirteissään samanlaisina lapsuudesta aikuisuuteen. Pitkäaikainen perinteinen ruokavalio oli yhteydessä useisiin sepelvaltimotaudin riskitekijöihin, kuten korkeisiin LDL-kolesterolin, apolipoproteiini B:n ja C-reaktiivisen proteiinin tasoihin sekä naisilla myös kohonneeseen verenpaineeseen ja insuliinitasoon. Niillä miehillä, jotka käyttivät runsaasti perinteiselle ruokavaliolle tyypillisiä elintarvikkeita, havaittiin muita enemmän sepelvaltimotaudin riskiä ennustavaa valtimon seinämän paksuuntumista. Tätä paksuuntumista esiintyi myös niillä tutkittavilla, joiden ruokavalio sisälsi keskimääräistä enemmän proteiinia ja vähemmän rasvaa. Tutkimuksen tulokset vahvistavat näkemystä siitä, että lapsuudessa muotoutuvat ruokatottumukset jatkuvat usein aikuisuuteen. Perinteisen ruokavalion pitkäaikainen noudattaminen saattaa johtaa kohonneeseen riskiin sairastua sepelvaltimotautiin. Myös proteiinipitoinen ruokavalio ja samanaikainen, usein tietoinen, rasvan välttäminen saattaa lisätä sepelvaltimotaudin kehittymisen riskiä. Tämä tutkimus tarkastelee ruokavaliota kokonaisuutena ja tarjoaa siten käytännönläheistä tietoa ravinnon merkityksestä sepelvaltimotaudin kehittymisessä

Dairy Consumption and Body Mass Index Among Adults : Mendelian Randomization Analysis of 184802 Individuals from 25 Studies

BACKGROUND: Associations between dairy intake and body mass index (BMI) have been inconsistently observed in epidemiological studies, and the causal relationship remains ill defined. METHODS: We performed Mendelian randomization (MR) analysis using an established dairy intake-associated genetic polymorphism located upstream of the lactase gene (LCT-13910 C/T, rs4988235) as an instrumental variable (IV). Linear regression models were fitted to analyze associations between (a) dairy intake and BMI, (b) rs4988235 and dairy intake, and (c) rs4988235 and BMI in each study. The causal effect of dairy intake on BMI was quantified by IV estimators among 184802 participants from 25 studies. RESULTS: Higher dairy intake was associated with higher BMI (beta = 0.03 kg/m(2) per serving/day; 95% CI, 0.00-0.06; P = 0.04), whereas the LCT genotype with 1 or 2 T allele was significantly associated with 0.20 (95% CI, 0.14-0.25) serving/day higher dairy intake (P = 3.15 x 10(-12)) and 0.12 (95% CI, 0.06-0.17) kg/m(2) higher BMI (P = 2.11 x 10(-5)). MR analysis showed that the genetically determined higher dairy intake was significantly associated with higher BMI (beta = 0.60 kg/m(2) per serving/day; 95% CI, 0.27-0.92; P = 3.0 x 10(-4)). CONCLUSIONS: The present study provides strong evidence to support a causal effect of higher dairy intake on increased BMI among adults. (c) 2017 American Association for Clinical ChemistryPeer reviewe

Higher step count is associated with greater bone mass and strength in women but not in men

In this cross-sectional study, peripheral bone traits were examined relative to total daily steps measured with pedometer. Higher number of steps was associated with greater bone values at the calcaneus and tibia in women, but not in men. In women, dose-dependent associations at the radius were congruent with the weight-bearing bones. Introduction Habitual physical activity measured as daily steps may contribute to bone density and strength at the calcaneus and other weight-bearing bones. Methods Subgroups of 705-837 women and 480-615 men aged 31-46 years from the Cardiovascular Risk in Young Finns Study participated in the present study. Participants were instructed to use pedometer for 1 week, and the total daily steps, divided into tertiles, were evaluated relative to quantitative ultrasound-measured bone traits at the calcaneus and peripheral quantitative computed tomography-measured bone traits at the tibia and radius. Analysis of covariance was used to examine the between-group differences. Results In women, significant dose-dependent between-group differences were found in the weight-bearing bones and in non-weight-bearing radius. The differences in broadband ultrasound attenuation and speed of sound at the calcaneus were 3.8 and 0.5% greater in women within the highest tertile of daily steps compared to the lowest tertile (p values for trend 8765 steps/day) had on average 1-5.4% greater bone cross-sectional area, bone mineral content (BMC), trabecular density, and bone strength index at the distal site and 1.6-2.7% greater bone areas, BMC and strength strain index (SSI) at the shaft compared to women with less daily steps (p values for trend Conclusion Observed significant positive associations between daily steps and various bone traits at the calcaneus, tibia, and radius in women suggest that habitual physical activity may benefit skeletal health in adulthood.Peer reviewe

Dairy Intake and Body Composition and Cardiometabolic Traits among Adults : Mendelian Randomization Analysis of 182041 Individuals from 18 Studies

BACKGROUND: Associations between dairy intake and body composition and cardiometabolic traits have been inconsistently observed in epidemiological studies, and the causal relationship remains ill-defined. METHODS: We performed Mendelian randomization analysis using an established genetic variant located upstream of the lactase gene (LCT- 13910 C/T, rs4988235) associated with dairy intake as an instrumental variable (IV). The causal effects of dairy intake on body composition and cardiometabolic traits (lipids, glycemic traits, and inflammatory factors) were quantified by IV estimators among 182041 participants from 18 studies. RESULTS: Each 1 serving/day higher dairy intake was associated with higher lean mass [beta (SE) = 0.117 kg (0.035); P = 0.001], higher hemoglobin A(1c) [0.009% (0.002); P <0.001], lower LDL [-0.014 mmol/L (0.006); P = 0.013], total cholesterol (TC) [-0.012 mmol/L (0.005); P = 0.023], and non-HDL [- 0.012 mmol/L (0.005); P = 0.028]. The LCT- 13910 C/T CT + TT genotype was associated with 0.214 more dairy servings/day (SE = 0.047; P = 0.001), 0.284 cm higher waist circumference (SE = 0.118; P = 0.017), 0.112 kg higher lean mass (SE = 0.027; P = 3.8 X 10(-5)), 0.032 mmol/L lower LDL (SE = 0.009; P = 0.001), and 0.032 mmol/L lower TC (SE = 0.010; P = 0.001). Genetically higher dairy intake was associated with increased lean mass [0.523 kg per serving/day (0.170); P = 0.002] after correction for multiple testing (0.05/18). However, we find that genetically higher dairy intake was not associated with lipids and glycemic traits. CONCLUSIONS: The present study provides evidence to support a potential causal effect of higher dairy intake on increased lean mass among adults. Our findings suggest that the observational associations of dairy intake with lipids and glycemic traits may be the result of confounding. (C) 2019 American Association for Clinical ChemistryPeer reviewe

A Protein Diet Score, Including Plant and Animal Protein, Investigating the Association with HbA1c and eGFR-The PREVIEW Project

Higher-protein diets have been advocated for body-weight regulation for the past few decades. However, the potential health risks of these diets are still uncertain. We aimed to develop a protein score based on the quantity and source of protein, and to examine the association of the score with glycated haemoglobin (HbA1c) and estimated glomerular filtration rate (eGFR). Analyses were based on three population studies included in the PREVIEW project (PREVention of diabetes through lifestyle Intervention and population studies in Europe and around the World): NQplus, Lifelines, and the Young Finns Study. Cross-sectional data from food-frequency questionnaires (n = 76,777 subjects) were used to develop a protein score consisting of two components: 1) percentage of energy from total protein, and 2) plant to animal protein ratio. An inverse association between protein score and HbA1c (slope -0.02 +/- 0.01 mmol/mol, p <0.001) was seen in Lifelines. We found a positive association between the protein score and eGFR in Lifelines (slope 0.17 +/- 0.02 mL/min/1.73 m(2), p <0.0001). Protein scoring might be a useful tool to assess both the effect of quantity and source of protein on health parameters. Further studies are needed to validate this newly developed protein score.Peer reviewe

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).Peer reviewe

Outdoor time and dietary patterns in children around the world

Abstract Background Whether outdoor time is linked to dietary patterns of children has yet to be empirically tested. The objective of this study was to examine the association between outdoor time and dietary patterns of children from 12 countries around the world. Methods This multinational, cross-sectional study included 6229 children 9–11 years of age. Children self-reported the time that they spent outside before school, after school and on weekends. A composite score was calculated to reflect overall daily outdoor time. Dietary patterns were assessed using a food frequency questionnaire, and two components were used for analysis: healthy and unhealthy dietary pattern scores. Results On average, children spent 2.5 h outside per day. After adjusting for age, sex, parental education, moderate-to-vigorous physical activity, screen time and body mass index z-score, greater time spent outdoors was associated with healthier dietary pattern scores. No association was found between outdoor time and unhealthy dietary pattern scores. Similar associations between outdoor time and dietary patterns were observed for boys and girls and across study sites. Conclusions Greater time spent outside was associated with a healthier dietary pattern in this international sample of children. Future research should aim to elucidate the mechanisms behind this association. </jats:sec

Association of circulating metabolites with healthy diet and risk of cardiovascular disease : analysis of two cohort studies

Diet may modify metabolomic profiles towards higher or lower cardiovascular disease (CVD) risk. We aimed to identify metabolite profiles associated with high adherence to dietary recommendations-the Alternative Healthy Eating Index (AHEI) - and the extent to which metabolites associated with AHEI also predict incident CVD. Relations between AHEI score and 80 circulating lipids and metabolites, quantified by nuclear magnetic resonance metabolomics, were examined using linear regression models in the Whitehall II study (n = 4824, 55.9 +/- 6.1 years, 28.0% women) and were replicated in the Cardiovascular Risk in Young Finns Study (n = 1716, 37.7 +/- 5.0 years, 56.3% women). We used Cox models to study associations between metabolites and incident CVD over the 15.8-year follow-up in the Whitehall II study. After adjustment for confounders, higher AHEI score (indicating healthier diet) was associated with higher degree of unsaturation of fatty acids (FA) and higher ratios of polyunsaturated FA, omega-3 and docosahexaenoic acid relative to total FA in both Whitehall II and Young Finns studies. A concordance of associations of metabolites with higher AHEI score and lower CVD risk was observed in Whitehall II. Adherence to healthy diet seems to be associated with specific FA that reduce risk of CVD.Peer reviewe

Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent

Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter‐individual variability in associations between body weight and dairy consumption. Methods and results: A genome‐wide interaction study to discover genetic variants that account for variation in BMI in the context of low‐fat, high‐fat and total dairy intake in cross‐sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta‐analyzed. Twenty‐six genetic variants reached the selected significance threshold (p‐interaction \u3c10−7), and six independent variants (LINC01512‐rs7751666, PALM2/AKAP2‐rs914359, ACTA2‐rs1388, PPP1R12A‐rs7961195, LINC00333‐rs9635058, AC098847.1‐rs1791355) were evaluated meta‐analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3’ of LINC00333) was replicated (p‐interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p‐interaction = 7.36 × 10−8) such that each serving of low‐fat dairy was associated with 0.225 kg m−2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2‐rs1388) approached interaction replication significance for low‐fat dairy exposure. Conclusion: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight