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1.
Clin Nutr ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32994068

RESUMO

BACKGROUND & AIMS: The influence of dietary calcium intake in childhood on adult cardiovascular health is unknown, particularly in those with long-term high intake. To examine both linear and non-linear associations of childhood and long-term (between childhood and adulthood) dietary calcium intake with adult cardiovascular risk outcomes. METHODS: A population-based prospective cohort study in Finland (n = 1029, aged 3-18 years at baseline). Dietary calcium intake was assessed in childhood (1980, baseline) and adulthood (mean of available data from 2001, 2007 and 2011). Long-term dietary calcium intake was calculated as the mean between childhood and adulthood. Outcomes were measured in 2001, 2007, and/or 2011, and the latest available data were used for analyses, including high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity (PWV), carotid artery compliance (CAC), Young's elastic modulus (YEM), and stiffness index (SI). RESULTS: There were no significant non-linear or linear associations between childhood or long-term dietary calcium intake with any adult cardiovascular outcomes, after adjustment for age, sex, and childhood and adulthood confounders (e.g., body mass index, systolic blood pressure, smoking, physical activity, fruit and vegetable consumption). CONCLUSIONS: Childhood or long-term dietary calcium intake that is higher than the recommended level is not associated with increased cardiovascular risk in adulthood.

2.
Hypertension ; 76(5): 1572-1579, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32921196

RESUMO

We examined whether success in achieving the key targets of an infancy-onset 20-year dietary intervention was associated with blood pressure (BP) from infancy to young adulthood. In the prospective randomized STRIP (Special Turku Coronary Risk Factor Intervention Project; n=877 children), dietary counseling was provided biannually based on the Nordic Nutrition Recommendations primarily to improve the quality of dietary fat in children's diets and secondarily to promote intake of vegetables, fruits, and whole grains. Dietary data and BP were accrued annually from the age of 13 months to 20 years. The dietary targets for fat quality were defined as the ratio of saturated fatty acids to monounsaturated and polyunsaturated fatty acids <1:2 and intake of saturated fatty acids <10 E%, dietary fiber intake in the top age-specific quintile, and dietary sucrose intake as being in the lowest age-specific quintile. Attaining a higher number of the dietary targets was associated with lower systolic BP (mean [SE] systolic BP, 107.3 [0.3], 107.6 [0.3], 106.8 [0.3], and 106.7 [0.5] mm Hg in participants meeting 0, 1, 2, and 3 to 4 targets, respectively; P=0.03) and diastolic BP (mean [SE] diastolic BP, 60.4 [0.2], 60.5 [0.2], 59.9 [0.2], and 59.9 [0.3] mm Hg; P=0.02). When the lowest age-specific quintile of dietary cholesterol was added as an additional target, the association with systolic BP remained significant (P=0.047), but the association with diastolic BP attenuated (P=0.13). Achieving the key targets of an infancy-onset 20-year dietary intervention, reflecting dietary guidelines, was favorably albeit modestly associated with systolic and diastolic BP from infancy to young adulthood. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00223600.

3.
J Am Heart Assoc ; 9(14): e015288, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32627629

RESUMO

Background Whether long-term exposure to overweight or obesity from early life to adulthood has a detrimental influence on health outcomes is unknown. We aimed to investigate whether duration of overweight or obesity from youth to adulthood is associated with adult cardiometabolic risk. Methods and Results A population-based cohort study was performed of 1268 youths, aged 3 to 18 years, with follow-ups at 3, 6, 9, 12, 21, 27, and 31 years. Duration of overweight or obesity over 31-year follow-up was calculated. Adulthood outcomes included type 2 diabetes mellitus, impaired fasting glucose, high insulin levels, high carotid intima-media thickness, hypertension, low high-density lipoprotein cholesterol, high low-density lipoprotein cholesterol and triglycerides, arterial pulse wave velocity, carotid artery compliance, Young elastic modulus, and stiffness index. Rates of overweight/obesity were 7.9% at baseline and 55.9% after 31 years. After adjustment for confounders, longer duration of overweight or obesity was associated with increased risk of all outcomes (relative risk ranged from 1.45-9.06 for type 2 diabetes mellitus, impaired fasting glucose, carotid intima-media thickness, hypertension, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides; ß from 0.370-0.543 m/s for pulse wave velocity; -0.193 to -0.237 %/10 mm Hg for carotid artery compliance; 52.1-136.8 mm Hg·mm for Young elastic modulus; and 0.554-0.882 for stiffness index). When body mass index was further adjusted, these associations disappeared or were substantially reduced. Detrimental associations of adult body mass index with all outcomes were robust to adjustment for confounders and duration of overweight or obesity. Conclusions Overweight or obesity in adulthood rather than childhood appears to be more important for adult cardiometabolic health.

4.
Int J Obes (Lond) ; 44(8): 1733-1742, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32494039

RESUMO

BACKGROUND: The role of genetic risk scores associated with adult body mass index (BMI) on BMI levels across the life course is unclear. We examined if a 97 single nucleotide polymorphism weighted genetic risk score (wGRS97) associated with age-related progression in BMI at different life stages and distinct developmental trajectories of BMI across the early life course. METHODS: 2188 Cardiovascular Risk in Young Finns Study participants born pre-1980 who had genotype data and objective measurements of height and weight collected up to 8 times from age 6 to 49 years. Associations were examined using Individual Growth Curve analysis, Latent Class Growth Mixture Modelling, and Poisson modified regression. RESULTS: The wGRS97 associated with BMI from age 6 years with peak effect sizes observed at age 30 years (females: 1.14 kg/m2; males: 1.09 kg/m2 higher BMI per standard deviation increase in wGRS97). The association between wGRS97 and BMI became stronger with age in childhood but slowed in adolescence, especially in females, and weakened at age 35-40 years. A higher wGRS97 associated with an increased BMI velocity in childhood and adulthood, but not with BMI change in adulthood. Compared with belonging to a 'normal stable' life-course trajectory group (normal BMI from childhood to adulthood), a one standard deviation higher wGRS97 associated with a 13-127% increased risk of belonging to a less favourable life-course BMI trajectory group. CONCLUSIONS: Individuals with genetic susceptibility to higher adult BMI have higher levels and accelerated rates of increase in BMI in childhood/adolescence, and are at increased risk of having a less favourable life-course BMI trajectory.

5.
Psychiatry Res ; 289: 112976, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32413709

RESUMO

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.

6.
Am J Epidemiol ; 189(7): 679-689, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239174

RESUMO

The association between socioeconomic disadvantage and increased risk of depressive symptoms in adulthood is well established. We tested 1) the contribution of early exposure to neighborhood socioeconomic disadvantage to later depressive symptoms throughout life, 2) the persistence of the potential association between early exposure and depressive symptoms, and 3) the contributions of other known risk factors to the association. Data were collected from the Young Finns Study, a prospective, population-based 32-year follow-up study that included participants aged 3-18 years at baseline in 1980. Participants were followed up with repeated measurements of depressive symptoms between 1992 and 2012 (n = 2,788) and linked to national grid data on neighborhood disadvantage via residential addresses. We examined the associations in mixed models separately for the 5-, 10-, 15-, and 20-year follow-ups. Living in a disadvantaged neighborhood during childhood and adolescence was associated with a higher level of depressive symptoms in adulthood during all follow-up periods (ß = 0.07, P = 0.001) than living in a nondisadvantaged area. Individual adulthood socioeconomic status mediated the associations. These findings suggest that living in a socioeconomically disadvantaged area during childhood and adolescence has a long-lasting negative association with mental health irrespective of family-related risks, partially due to socioeconomic adversity later in life.


Assuntos
Depressão/epidemiologia , Características de Residência/estatística & dados numéricos , Fatores Socioeconômicos , Populações Vulneráveis/psicologia , Adolescente , Adulto , Criança , Pré-Escolar , Depressão/etiologia , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
7.
J Am Heart Assoc ; 9(7): e014381, 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32264731

RESUMO

Background Despite declining US adolescent smoking prevalence from 40% among 12th graders in 1995 to around 10% in 2018, adolescent smoking is still a significant problem. Using the International Childhood Cardiovascular Cohort (i3C) Consortium, which includes 7 international cohorts recruited in childhood and followed into adulthood, the present study was designed to confirm the important relation between adolescent smoking and daily adult smoking and present new data on adult smoking into the forties and comparison of smoking in the United States, Finland, and Australia. Methods and Results Childhood smoking experience during ages 6 to 19 in the 1970s and 1980s was classifiable in 6687 i3C participants who also provided smoking status in their twenties and forties through 2011-2018. Prevalence of daily smoking in their twenties was directly related to degree of smoking during adolescence and inversely related to the age at which that smoking experience occurred (P trend, <0.001). Similar patterns were observed for prediction of smoking during age forties. Among the 2465 smokers in their twenties, cessation by their forties was generally inverse to degree of smoking in ages 6 to 19 (P trend, <0.001). Prevalence of smoking during adolescence and adulthood was similar among US, Finnish, and Australian participants. Conclusions These long-term follow-up data show that smoking intensity increased throughout adolescence. Prevalence of adult smoking and cessation by the forties were both correlated with levels of childhood smoking intensity. These data lend support to preventive strategies designed to reduce, delay, or eliminate any youth access to cigarettes.

8.
Lancet Child Adolesc Health ; 4(5): 359-369, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32333883

RESUMO

BACKGROUND: Primordial and primary prevention is the cornerstone for cardiometabolic health. In the randomised, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP; n=1116), a 20-year dietary counselling intervention was given to children biannually from infancy, and cardiometabolic health benefits had been observed among the participants in the intervention group. Here, we report on the key results of the first follow-up done 6 years after the end of the intervention, at age 26 years. METHODS: The randomised controlled STRIP study recruited children at age 5 months from well-baby clinics in Turku, Finland, and randomly assigned them to either an intervention or control group; group allocation was unmasked. The intervention introduced participants to a heart-healthy diet, characterised by low proportional intake of saturated fat and cholesterol, by dietary counselling and nutrition education sessions to parents and children from the age of 7 months to 20 years. Children in the control group received only the basic health education given at Finnish well-baby clinics and school health care. We assessed diet, lifestyle, and cardiometabolic risk factor data, including blood pressure, anthropometry, serum biochemistry (lipids, apolipoproteins, glucose, and insulin), and homoeostatic model assessment of insulin resistance (HOMA-IR) in the participants at age 26 years. FINDINGS: 1116 children were included in the original STRIP study, of whom 551 provided data at the age 26 years follow-up, and data for 507 participants were analysed (243 in the intervention group and 264 in the control group). At follow-up, those who had been in the intervention group had slightly lower mean intake of saturated fat as a proportion of total energy intake than the control group (13·0% [SD 3·3] vs 13·7% [3·6], p=0·049). A higher proportion of participants in the intervention group achieved the targeted monounsaturated and polyunsaturated fat to saturated fat ratio of more than 2:1 than the control group (78 [39%] of 200 vs 70 [30%] of 235; risk ratio [RR] 1·16 [95% CI 1·01-1·33]; p=0·035). A higher proportion of intervention group participants met the ideal total cholesterol concentration of less than 5·17 mmol/L (194 [81%] of 240 vs 187 [72%] of 261; RR 1·45 [1·05-2·01], p=0·024) and optimal LDL cholesterol concentration of less than 3·0 mmol/L (166 [69%] of 240 vs 158 [61%] of 251; RR 1·30 [1·03-1·66], p=0·031). Those who received the intervention had lower glucose (5·00 mmol/L [SD 0·43] vs 5·07 mmol/L [0·46], p=0·040) and HOMA-IR (median 1·44 [IQR 1·09-1·91] vs 1·62 [1·22-2·09], p=0·037) than the participants in the control group. INTERPRETATION: Previously observed intervention effects during the 20-year counselling were largely maintained into adulthood 6 years after the withdrawal of the intervention. Dietary counselling introduced in infancy thus provided a sustained benefit to diet quality and cardiometabolic risk factor levels. FUNDING: Academy of Finland, Juho Vainio Foundation, Finnish Foundation for Cardiovascular Research, Finnish Ministry of Education and Culture, Finnish Cultural Foundation, Sigrid Jusélius Foundation, Special Governmental grants for Health Sciences Research (Turku University Hospital), Yrjö Jahnsson Foundation, Finnish Medical Foundation, and Turku University Foundation.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Aconselhamento/métodos , Dieta Saudável/métodos , Síndrome Metabólica/prevenção & controle , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Doenças Cardiovasculares/metabolismo , Colesterol/metabolismo , Colesterol na Dieta , LDL-Colesterol/metabolismo , Gorduras na Dieta , Gorduras Insaturadas na Dieta , Ingestão de Energia , Feminino , Finlândia , Seguimentos , Humanos , Insulina/metabolismo , Resistência à Insulina , Estudos Longitudinais , Masculino , Síndrome Metabólica/metabolismo , Prevenção Primária/métodos , Fatores de Risco
9.
Appetite ; 151: 104681, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32251766

RESUMO

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<.001; B for linear association = 0.09, P = 0.58). Children in the negative/low regulation temperament group had a lower diet score (less healthy diet) across the 18 years compared to children in the neutral/average or in the positive/high regulation group. Temperament was not associated with the rate of change in diet over time. Temperament did not have any interactive effects with the intervention (F [2, 627], P = 0.72). CONCLUSION: Children with a temperament profile characterized by high negative mood, high irregularity and high intensity in emotion expression constitute a risk group for less healthy eating over the lifespan.

10.
Am J Epidemiol ; 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32242223

RESUMO

Acknowledging the lack of previous knowledge, we studied whether childhood/adolescent exposure to parental smoking associates with midlife cognitive function leveraging the data from the Cardiovascular Risk in Young Finns Study. A population-based cohort of 3,596 children/adolescents aged 3-18 years was followed-up between 1980-2011. Cognitive testing was performed in 2011 on 2,026 participants aged 34-49 years using a computerized test. Measures of childhood/adolescent second-hand smoke exposure were parental self-reports of smoking and participants' serum cotinine levels. Participants were classified into: 1)no exposure (non-smoking parents, cotinine<1.0ng/mL); 2)hygienic parental smoking (1-2 smoking parents, cotinine<1.0ng/mL); and 3)non-hygienic parental smoking (1-2 smoking parents, cotinine ≥1.0ng/mL). Analyses were adjusted for sex, age, family socio-economic status, polygenic risk score for cognitive function, adolescence/adulthood smoking, blood pressure and serum total cholesterol. Compared with non-exposed, participants exposed to non-hygienic parental smoking were at higher relative risk (RR) for poor (lowest quartile) midlife episodic memory and associative learning (RR=1.38, 95%CI=1.08-1.75) and a weak association was found for short term and spatial working memory (RR=1.25, 95%CI=0.98-1.58). The associations for those exposed to hygienic parental smoking were non-significant (episodic memory and associative learning: RR=1.19, 95%CI=0.92-1.54; short term and spatial working memory: RR=1.10, 95%CI=0.85-1.33). Avoiding childhood/adolescence second-hand smoking exposure promotes adulthood cognitive function.

11.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32209700

RESUMO

BACKGROUND: The association of dietary fat distribution with markers of subclinical atherosclerosis during early life is unknown. We examined whether success in achieving the main target of an infancy-onset dietary intervention based on the distribution of dietary fat was associated with aortic and carotid intima-media thickness (IMT) and distensibility from childhood to young adulthood. METHODS: In the prospective randomized controlled Special Turku Coronary Risk Factor Intervention Project trial, personalized dietary counseling was given biannually to healthy children from infancy to young adulthood. The counseling was based on Nordic Nutrition Recommendations, with the main aim of improving the distribution of dietary fat in children's diets. IMT and distensibility of the abdominal aorta and common carotid artery were measured repeatedly at ages 11 (n = 439), 13 (n = 499), 15 (n = 506), 17 (n = 477), and 19 years (n = 429). The targeted distribution of dietary fat was defined as a ratio of saturated fatty acids to monounsaturated and polyunsaturated fatty acids of <1:2 and as an intake of saturated fatty acids of <10% of energy intake. Participants who met ≥1 of these 2 criteria were defined to achieve the main intervention target. RESULTS: Individuals who achieved the main intervention target had lower aortic IMT (age- and sex-adjusted mean difference 10.4 µm; 95% confidence interval: 0.3 to 20.5 µm) and better aortic distensibility (0.13% per 10 mm Hg; 95% confidence interval: 0.00% to 0.26% per10 mm Hg) compared with their peers who did not meet the target. CONCLUSIONS: Achieving the main target of an infancy-onset dietary intervention, reflecting dietary guidelines, was favorably associated with aortic IMT and distensibility during the early life course. These data support the recommendation of favoring unsaturated fat to enhance arterial health.


Assuntos
Aterosclerose/prevenção & controle , Dieta com Restrição de Gorduras/métodos , Gorduras na Dieta/farmacologia , Ingestão de Energia/fisiologia , Adolescente , Aorta Torácica/diagnóstico por imagem , Aterosclerose/epidemiologia , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Criança , Aconselhamento , Progressão da Doença , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Incidência , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco , Adulto Jovem
12.
Pediatrics ; 145(4)2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32209701

RESUMO

BACKGROUND: Elevated non-high-density lipoprotein cholesterol (HDL-C) levels are used to identify children at increased cardiovascular risk, but the use of non-HDL-C in childhood to predict atherosclerosis is unclear. We examined whether the National Heart, Lung, and Blood Institute classification of youth non-HDL-C status predicts high common carotid artery intima-media thickness in adulthood. METHODS: We analyzed data from 4 prospective cohorts among 4582 children aged 3 to 19 years who were remeasured as adults (mean follow-up of 26 years). Non-HDL-C status in youth and adulthood was classified according to cut points of the National Heart, Lung, and Blood Institute and the National Cholesterol Education Program Adult Treatment Panel III. High carotid intima-media thickness (cIMT) in adulthood was defined as at or above the study visit-, age-, sex-, race-, and cohort-specific 90th percentile of intima-media thickness. RESULTS: In a log-binomial regression analysis adjusted with age at baseline, sex, cohort, length of follow-up, baseline BMI, and systolic blood pressure, children with dyslipidemic non-HDL-C were at increased risk of high cIMT in adulthood (relative risk [RR], 1.29; 95% confidence interval [CI], 1.07-1.55). Compared with the persistent normal group, the persistent dyslipidemia group (RR, 1.80; 95% CI, 1.37-2.37) and incident dyslipidemia (normal to dyslipidemia) groups (RR, 1.45; 95% CI, 1.07-1.96) had increased risk of high cIMT in adulthood, but the risk was attenuated for the resolution (dyslipidemia to normal) group (RR, 1.17; 95% CI, 0.97-1.41). CONCLUSIONS: Dyslipidemic non-HDL-C levels predict youth at risk for developing high cIMT in adulthood. Those who resolve their non-HDL-C dyslipidemia by adulthood have normalized risk of developing high cIMT in adulthood.


Assuntos
Aterosclerose/sangue , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Colesterol/sangue , Previsões , Medição de Risco/métodos , Adolescente , Adulto , Aterosclerose/diagnóstico , Aterosclerose/epidemiologia , Austrália/epidemiologia , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangue , Estados Unidos/epidemiologia , Adulto Jovem
14.
Atherosclerosis ; 299: 56-63, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32113648

RESUMO

BACKGROUND AND AIMS: Apolipoprotein A-I (apoA-I) infusions represent a potential novel therapeutic approach for the prevention of coronary artery disease (CAD). Although circulating apoA-I concentrations inversely associate with risk of CAD, the evidence base of this representing a causal relationship is lacking. The aim was to assess the causal role of apoA-I using human genetics. METHODS: We identified a variant (rs12225230) in APOA1 locus that associated with circulating apoA-I concentrations (p < 5 × 10-8) in 20,370 Finnish participants, and meta-analyzed our data with a previous GWAS 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. RESULTS: 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 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 from the observational association. Similar findings were observed using an independent ABCA1 variant in sensitivity analysis. CONCLUSIONS: Genetic evidence fails to support a cardioprotective role for apoA-I. This is in line with the cumulative evidence showing that HDL-related phenotypes are unlikely to have a protective role in CAD.

15.
J Pediatr ; 218: 198-203.e6, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31757470

RESUMO

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.

16.
Bone ; 131: 115160, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31759205

RESUMO

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 < 0.05) lipid species jointly associated with subclinical markers of both osteoporosis and atherosclerosis within the module were all triacylglycerols (TAGs) - TAG(18:0/18:0/18:1) with an adjusted p-value of 8.6 × 10-8, TAG(18:0/18:1/18:1) with an adjusted p-value of 3.7 × 10-6, and TAG(16:0/18:0/18:1) with an adjusted p-value of 8.5 × 10-6. 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.

17.
Atherosclerosis ; 293: 18-25, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31830725

RESUMO

BACKGROUND AND AIMS: Carotid plaque is a specific sign of atherosclerosis and adults with carotid plaque are at increased risk for cardiovascular outcomes. Atherosclerosis has roots in childhood and pediatric guidelines provide cut-off values for cardiovascular risk factors. However, it is unknown whether these cut-offs predict adulthood advanced atherosclerosis. METHODS: The Cardiovascular Risk in Young Finns Study is a follow-up of children that begun in 1980 when 2653 participants with data for the present analyses were aged 3-18 years. In 2001 and 2007 follow-ups, in addition to adulthood cardiovascular risk factors, carotid ultrasound data was collected. Long-term burden, as the area under the curve, was evaluated for childhood (6-18 years) risk factors. To study the associations of guideline-based cut-offs with carotid plaque, both childhood and adult risk factors were classified according to clinical practice guidelines. RESULTS: Carotid plaque, defined as a focal structure of the arterial wall protruding into lumen >50% compared to adjacent intima-media thickness, was present in 88 (3.3%) participants. Relative risk for carotid plaque, when adjusted for age and sex, was 3.03 (95% CI, 1.76-5.21) for childhood dyslipidemia, 1.51 (95% CI, 0.99-2.32) for childhood elevated systolic blood pressure, and 1.93 (95% CI, 1.26-2.94) for childhood smoking. Childhood dyslipidemia and smoking remained independent predictors of carotid plaque in models additionally adjusted for adult risk factors and family history of coronary heart disease. Carotid plaque was present in less than 1% of adults with no childhood risk factors. CONCLUSIONS: Findings reinforce childhood prevention efforts and demonstrate the utility of guideline-based cut-offs in identifying children at increased risk for adulthood atherosclerosis.

18.
Eur J Public Health ; 30(1): 195-199, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31169878

RESUMO

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 (<5.6 mmol l-1), triglycerides (<1.695 mmol l-1), high density lipoprotein cholesterol (≥1.295 mmol l-1 females, ≥1.036 mmol l-1 males), blood pressure (<130/85 mmHg) and no medications for these conditions. BMI trajectories were compared for adults with MHO and MUHO using multilevel mixed models adjusted for age, sex and follow-up time. RESULTS: Mean (SD) follow-up time was 29 (3) years. Five hundred and twenty-four participants were obese in adulthood, 66 (12.6%) had MHO. BMI was similar through childhood, adolescence and young adulthood. BMI trajectories diverged at age 33, when individuals with MHO had at least 1.0 kg m-2 lower BMI than those with MUHO, significantly lower at 36 (-2.1 kg m-2, P = 0.001) and 42 years (-1.7 kg m-2; P = 0.005). CONCLUSION: Adult MHO was characterized by lower adult BMI, not youth BMI. Preventing additional weight gain among adults who are obese may be beneficial for metabolic health.

19.
Hepatology ; 71(1): 67-75, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31169929

RESUMO

Fatty liver is a preventable cause of liver failure, but early risk factors for adulthood fatty liver are poorly understood. We examined the association of childhood socioeconomic disadvantage with adulthood fatty liver and tested adulthood risk factors of fatty liver as possible mediators of this link. The study population comprised 2,042 participants aged 3-18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns Study. Follow-up with repeated clinical examinations was 31 years. Childhood socioeconomic disadvantage was assessed using data from parents' socioeconomic position and socioeconomic circumstances in participants' residential neighborhoods, categorized as high versus low socioeconomic disadvantage. Fatty liver was determined by ultrasound during the last follow-up (2011) at ages 34-49 years. Childhood and adulthood risk factors, including metabolic biomarkers and lifestyle variables, were assessed in clinical examinations. A total of 18.9% of the participants had fatty liver in adulthood. High childhood socioeconomic disadvantage was associated with an increased risk of fatty liver (risk ratio [95% confidence interval], 1.42 [1.18-1.70]; P = 0.0002). This association was robust to adjustment for age, sex, and childhood risk factors of fatty liver, including high body mass index, elevated insulin, and low birth weight (1.33 [1.09-1.62]; P = 0.005). High childhood socioeconomic disadvantage was also associated with the development of risk factors of fatty liver in adulthood. Adulthood risk factors linking childhood socioeconomic disadvantage with fatty liver included waist circumference (proportion mediated of the total effect of childhood socioeconomic disadvantage, 45%), body mass index (40%), systolic blood pressure (29%), insulin (20%), physical activity (15%), triglycerides (14%), and red meat consumption (7%). Conclusion: Childhood socioeconomic disadvantage was associated with multiple risk factors of fatty liver and increased likelihood of fatty liver in adulthood.

20.
PLoS Biol ; 17(12): e3000572, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31860674

RESUMO

Cholesteryl ester transfer protein (CETP) inhibition reduces vascular event risk, but confusion surrounds its effects on low-density lipoprotein (LDL) cholesterol. Here, we clarify associations of genetic inhibition of CETP on detailed lipoprotein measures and compare those to genetic inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR). We used an allele associated with lower CETP expression (rs247617) to mimic CETP inhibition and an allele associated with lower HMGCR expression (rs12916) to mimic the well-known effects of statins for comparison. The study consists of 65,427 participants of European ancestries with detailed lipoprotein subclass profiling from nuclear magnetic resonance spectroscopy. Genetic associations were scaled to 10% reduction in relative risk of coronary heart disease (CHD). We also examined observational associations of the lipoprotein subclass measures with risk of incident CHD in 3 population-based cohorts totalling 616 incident cases and 13,564 controls during 8-year follow-up. Genetic inhibition of CETP and HMGCR resulted in near-identical associations with LDL cholesterol concentration estimated by the Friedewald equation. Inhibition of HMGCR had relatively consistent associations on lower cholesterol concentrations across all apolipoprotein B-containing lipoproteins. In contrast, the associations of the inhibition of CETP were stronger on lower remnant and very-low-density lipoprotein (VLDL) cholesterol, but there were no associations on cholesterol concentrations in LDL defined by particle size (diameter 18-26 nm) (-0.02 SD LDL defined by particle size; 95% CI: -0.10 to 0.05 for CETP versus -0.24 SD, 95% CI -0.30 to -0.18 for HMGCR). Inhibition of CETP was strongly associated with lower proportion of triglycerides in all high-density lipoprotein (HDL) particles. In observational analyses, a higher triglyceride composition within HDL subclasses was associated with higher risk of CHD, independently of total cholesterol and triglycerides (strongest hazard ratio per 1 SD higher triglyceride composition in very large HDL 1.35; 95% CI: 1.18-1.54). In conclusion, CETP inhibition does not appear to affect size-specific LDL cholesterol but is likely to lower CHD risk by lowering concentrations of other atherogenic, apolipoprotein B-containing lipoproteins (such as remnant and VLDLs). Inhibition of CETP also lowers triglyceride composition in HDL particles, a phenomenon reflecting combined effects of circulating HDL, triglycerides, and apolipoprotein B-containing particles and is associated with a lower CHD risk in observational analyses. Our results reveal that conventional composite lipid assays may mask heterogeneous effects of emerging lipid-altering therapies.


Assuntos
Proteínas de Transferência de Ésteres de Colesterol/antagonistas & inibidores , Doença das Coronárias/sangue , Hidroximetilglutaril-CoA Redutases/sangue , Lipoproteínas/sangue , Adolescente , Adulto , Alelos , Apolipoproteínas B/sangue , Proteínas de Transferência de Ésteres de Colesterol/sangue , Proteínas de Transferência de Ésteres de Colesterol/genética , LDL-Colesterol/sangue , Estudos de Coortes , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/etiologia , Doença das Coronárias/genética , Feminino , Seguimentos , Variação Genética , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipoproteínas/classificação , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue , Adulto Jovem
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