Publications by authors named "Olli Raitakari"

841 Publications

Cardiovascular risk factors before and during pregnancy: Does pregnancy unmask or initiate risk?

J Obstet Gynaecol Res 2021 Sep 5. Epub 2021 Sep 5.

Department of Medicine, University of Turku and Division of Medicine, Turku University Hospital, Turku, Finland.

Objectives: To understand if pregnancy unmasks previously silent cardiovascular (CV) adverse factors, or initiates lasting injury.

Methods: Pre-pregnancy and during pregnancy CV risk factors (blood pressure, fasting lipids, and glucose) from 296 women belonging to studies in the International Childhood Cardiovascular Cohort (i3C) Consortium, a group of studies assessing the relationship between child and adolescent CV risk factors and adult outcomes, were used. Correlation coefficients between the pre- and during pregnancy measures were calculated, and the mean difference between the measures was modeled with adjustment for age, body mass index, race, smoking, and study.

Results: Measures were strongly correlated at pre- and during-pregnancy visits (p < 0.01), with r of between 0.30 and 0.55. In most cases, the difference between pre-pregnancy and during-pregnancy did not differ significantly from 0 after adjustment for confounders. Stratification by gestational age indicated stronger correlations with measurements obtained during the first and second trimesters than the third. The correlation did not differ by the time elapsed between the pre-pregnancy and pregnancy visits.

Conclusions: Pre- and during-pregnancy CV risk factors are moderately well correlated. This may indicate that susceptible women enter pregnancy with higher risk rather than pregnancy inducing new vascular or metabolic effects.
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http://dx.doi.org/10.1111/jog.14971DOI Listing
September 2021

Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression.

Nat Genet 2021 Sep 2;53(9):1300-1310. Epub 2021 Sep 2.

Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.

Trait-associated genetic variants affect complex phenotypes primarily via regulatory mechanisms on the transcriptome. To investigate the genetics of gene expression, we performed cis- and trans-expression quantitative trait locus (eQTL) analyses using blood-derived expression from 31,684 individuals through the eQTLGen Consortium. We detected cis-eQTL for 88% of genes, and these were replicable in numerous tissues. Distal trans-eQTL (detected for 37% of 10,317 trait-associated variants tested) showed lower replication rates, partially due to low replication power and confounding by cell type composition. However, replication analyses in single-cell RNA-seq data prioritized intracellular trans-eQTL. Trans-eQTL exerted their effects via several mechanisms, primarily through regulation by transcription factors. Expression of 13% of the genes correlated with polygenic scores for 1,263 phenotypes, pinpointing potential drivers for those traits. In summary, this work represents a large eQTL resource, and its results serve as a starting point for in-depth interpretation of complex phenotypes.
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http://dx.doi.org/10.1038/s41588-021-00913-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432599PMC
September 2021

Genetic differential susceptibility to the parent-child relationship quality and the life span development of compassion.

Dev Psychobiol 2021 Sep 22;63(6):e22184. Epub 2021 Aug 22.

Division of Psychology, Faculty of Education, University of Oulu, Oulu, Finland.

The development of compassion for others might be influenced by the social experiences made during childhood and has a genetic component. No research has yet investigated whether the parent-child relationship quality interacts with genetic variation in the oxytocin and dopamine systems in predicting compassion over the life span. In the prospective Young Finns Study (N = 2099, 43.9% men), we examined the interaction between mother-reported emotional warmth and intolerance toward their child assessed in 1980 (age of participants, 3-18 years) and two established genetic risk scores for oxytocin levels and dopamine signaling activity. Dispositional compassion for others was measured with the Temperament and Character Inventory 1997, 2001, and 2012 (age of participants, 20-50 years). We found a gene-environment interaction (p = .031) that remained marginally significant after adjustment for multiple testing. In line with the differential susceptibility hypothesis, only participants who carry alleles associated with low dopamine signaling activity had higher levels of compassion when growing up with emotionally warm parents, whereas they had lower levels of compassion when their parents were emotionally cold. Children's genetic variability in the dopamine system might result in plasticity to early environmental influences that have a long-lasting effect on the development of compassion. However, our findings need replication.
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http://dx.doi.org/10.1002/dev.22184DOI Listing
September 2021

Within-visit SBP variability from childhood to adulthood and markers of cardiovascular end-organ damage in mid-life.

J Hypertens 2021 Sep;39(9):1865-1875

Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.

Background: Within-visit SBP variability is associated with age and SBP, but its long-term clinical significance is unknown. We examined the association between child, adult, and life-time within-visit SBP variability with markers of end-organ damage using data from a 31-year longitudinal study.

Methods: Within-visit SBP variability was calculated as the standard deviation of three sitting SBP readings among up to 3010 participants aged 6-18 years (childhood) who were re-measured up to seven times to mid-adulthood. Markers of cardiovascular end-organ damage in adulthood were carotid intima--media thickness, brachial flow-mediated dilatation, carotid distensibility, pulse wave velocity, left ventricular mass index, carotid plaque, and coronary artery calcification.

Results: The mean (standard deviation) cumulative within-visit SBP variability was 2.7 (1.5) mmHg in childhood, 3.9 (1.9) mmHg in adulthood and 3.7 (1.5) mmHg across the observed life-time. Childhood within-visit SBP variability was not correlated with its subsequent values measured from 3 to 31 years later. With adjustment for age, sex, cumulative SBP, BMI and serum lipids, neither child, adult, or life-time cumulative within-visit SBP variability associated with markers of cardiovascular end-organ damage. However, higher child, adult, and life-time cumulative SBP significantly associated with higher carotid intima--media thickness, higher pulse wave velocity, lower brachial flow-mediated dilatation, lower carotid distensibility in adulthood.

Conclusion: Within-visit SBP variability from childhood to adulthood does not provide additional predictive utility over SBP over the same period of the life course.
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http://dx.doi.org/10.1097/HJH.0000000000002855DOI Listing
September 2021

Genetic association study of childhood aggression across raters, instruments, and age.

Transl Psychiatry 2021 07 30;11(1):413. Epub 2021 Jul 30.

Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGG. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E-06), PCDH7 (P = 2.0E-06), and IPO13 (P = 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (r) among rater-specific assessment of AGG ranged from r = 0.46 between self- and teacher-assessment to r = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range [Formula: see text]: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r = ~-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range [Formula: see text]: 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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http://dx.doi.org/10.1038/s41398-021-01480-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324785PMC
July 2021

Fatty liver index predicts incident risk of prediabetes, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).

Ann Med 2021 12;53(1):1256-1264

Department of Medicine, University of Turku, Turku, Finland.

Aims: To investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up.

Methods: At baseline (in 2001) 2020 participants, males and females, aged 24-39 years, were stratified according to body mass index (BMI), normal weight (<25 kg/m), overweight (≥25-<30 kg/m), or obese (≥30 kg/m) and FLI (as high FLI ≥60 or low FLI <60). We examined the incidence of prediabetes/type 2 diabetes and NAFLD (ultrasound assessed) over 10 years to 2011 to determine the relative impact of FLI and BMI.

Results: 514 and 52 individuals developed prediabetes and type 2 diabetes during follow-up. Such individuals were older, with higher BMI, serum glucose, insulin, alanine aminotransferase (ALT) and triglyceride (TG) concentrations than those who did not develop prediabetes or type 2 diabetes ( = 1454). The additional presence of high FLI significantly increased the risk of developing prediabetes and type 2 diabetes above the risk of being overweight/obese. Compared with normal weight, low FLI participants, the odds of prediabetes were ∼2-fold higher and the odds of type 2 diabetes were 9-10-fold higher respectively in the overweight/obese, high FLI group. No difference was observed between normal weight, low FLI and overweight/obese and low FLI groups.

Conclusions: An increased FLI significantly increases the odds of incident prediabetes, type 2 diabetes and NAFLD in individuals with overweight/obese highlighting the contributory role of liver fat accumulation in the pathophysiology of prediabetes/type 2 diabetes.Key messagesObesity is a risk factor for non-alcoholic fatty liver disease (NAFLD), prediabetes and type 2 diabetes.Additionally, NAFLD is more prevalent in people with prediabetes and type 2 diabetes when compared to age- and BMI-matched individuals.The presence of a raised fatty liver index (FLI) confers a significantly increased risk of developing prediabetes, type 2 diabetes and NAFLD above that conferred by being overweight/obese.The degree of elevation of FLI can risk stratify for incident prediabetes and type 2 diabetes in people with obesity.
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http://dx.doi.org/10.1080/07853890.2021.1956685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317942PMC
December 2021

Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs.

Clin Epigenetics 2021 Jul 22;13(1):143. Epub 2021 Jul 22.

Department of Clinical Chemistry, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Pirkanmaa Hospital District and Fimlab Laboratories, Tampere, Finland.

Background: Non-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines.

Results: We confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual's methylation status is associated with the mother's age and socioeconomic status, but not with the individual's own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood.

Conclusions: These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.
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http://dx.doi.org/10.1186/s13148-021-01132-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296652PMC
July 2021

Sugar-Sweetened Beverage Consumption May Modify Associations Between Genetic Variants in the CHREBP (Carbohydrate Responsive Element Binding Protein) Locus and HDL-C (High-Density Lipoprotein Cholesterol) and Triglyceride Concentrations.

Circ Genom Precis Med 2021 Aug 16;14(4):e003288. Epub 2021 Jul 16.

Department of Clinical Epidemiology (R.L.G., D.O.M.-K., F.R.R., R.dM.), Leiden University Medical Center, the Netherlands.

Background: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the locus and dyslipidemia.

Methods: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.

Results: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; <0.0001), but not significantly among the lowest SSB consumers (=0.81; <0.0001). Similar results were observed for 2 additional variants (rs35709627 and rs71556736). For triglyceride, rs55673514 was positively associated with triglyceride concentrations only among the highest SSB consumers (β, 0.06 [95% CI, 0.02-0.09] ln-mg/dL per allele, =0.001) but not the lowest SSB consumers (=0.84; =0.0005).

Conclusions: Our results identified genetic variants in the locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005133, NCT00005121, NCT00005487, and NCT00000479.
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http://dx.doi.org/10.1161/CIRCGEN.120.003288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373451PMC
August 2021

Tracking and Changes in Daily Step Counts among Finnish Adults.

Med Sci Sports Exerc 2021 08;53(8):1615-1623

LIKES Research Centre for Physical Activity and Health, Jyväskylä, FINLAND.

Purpose: This study aimed to investigate the tracking and changes of steps per day in adults and their determinants over 13 yr.

Methods: A total of 2195 subjects (1236 women) 30-45 yr of age were randomly recruited from the ongoing Cardiovascular Risk in Young Finns Study in 2007 and were followed up in 2020. Steps per day, including both total and aerobic steps per day, were monitored for seven consecutive days with a pedometer in 2007-2008 and 2011-2012 and with an accelerometer in 2018-2020. Tracking was analyzed using Spearman's correlation. Stability and changes of steps per day over time in both low-active and high-active groups (based on median values) were described by percentage agreements, kappa statistics, and logistic regression. Associations of sex, age, and body mass index with the initial number and changes in steps per day were analyzed using linear growth curve modeling.

Results: Tracking correlations of total steps per day at 4-, 9-, and 13-yr intervals were 0.45-0.66, 0.33-0.70, and 0.29-0.60, while corresponding correlations for aerobic steps per day were 0.28-0.55, 0.23-0.52, and 0.08-0.55, respectively. Percentage agreements were higher than 54%, and kappa statistics ranged from slight to fair over time. Compared with the low-active group, the high-active group at baseline had a higher probability of being active later in adulthood. Female sex and higher age were associated directly with the initial number of steps per day and inversely with changes in the number of steps per day. Body mass index was inversely associated with the initial number of steps per day and changes in the number of total steps per day.

Conclusion: The 13-yr tracking of steps per day in adulthood was found to be low to moderately high. Daily ambulatory activity is essential to maintaining an active lifestyle throughout adulthood. Changes in the amount of adult steps per day vary by sex, age, and BMI.
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http://dx.doi.org/10.1249/MSS.0000000000002621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284380PMC
August 2021

Systematic evaluation of the association between hemoglobin levels and metabolic profile implicates beneficial effects of hypoxia.

Sci Adv 2021 Jul 14;7(29). Epub 2021 Jul 14.

Biocenter Oulu, 90014 Oulu, Finland.

Activation of the hypoxia-inducible factor (HIF) pathway reprograms energy metabolism. Hemoglobin (Hb) is the main carrier of oxygen. Using its normal variation as a surrogate measure for hypoxia, we explored whether lower Hb levels could lead to healthier metabolic profiles in mice and humans ( = 7175) and used Mendelian randomization (MR) to evaluate potential causality ( = 173,480). The results showed evidence for lower Hb levels being associated with lower body mass index, better glucose tolerance and other metabolic profiles, lower inflammatory load, and blood pressure. Expression of the key HIF target genes and in skeletal muscle and adipose tissue, respectively, associated with systolic blood pressure in MR analyses and body weight, liver weight, and adiposity in mice. Last, manipulation of murine Hb levels mediated changes to key metabolic parameters. In conclusion, low-end normal Hb levels may be favorable for metabolic health involving mild chronic activation of the HIF response.
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http://dx.doi.org/10.1126/sciadv.abi4822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279517PMC
July 2021

Birth weight and adult income: An examination of mediation through adult height and body mass.

Health Econ 2021 Sep 11;30(10):2383-2398. Epub 2021 Jul 11.

Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.

This paper examines the causal links between early human endowments and socioeconomic outcomes in adulthood. We use a genotyped longitudinal survey (Cardiovascular Risk in Young Finns Study) that is linked to the administrative registers of Statistics Finland. We focus on the effect of birth weight on income via two anthropometric mediators: body mass index (BMI) and height in adulthood. We find that (i) the genetic instruments for birth weight, adult height, and adult BMI are statistically powerful; (ii) there is a robust total effect of birth weight on income for men but not for women; (iii) the total effect of birth weight on income for men is partly mediated via height but not via BMI; and (iv) the share of the total effect mediated via height is substantial, of approximately 56%.
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http://dx.doi.org/10.1002/hec.4387DOI Listing
September 2021

The Timing and Sequence of Cardiovascular Health Decline.

Am J Prev Med 2021 Oct 6;61(4):545-553. Epub 2021 Jul 6.

Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Introduction: Childhood declines in cardiovascular health have been linked to the development of subclinical atherosclerosis; however, less is known about the timing and sequence of the decline of the specific cardiovascular health components. The study objective is to identify the patterns of decline and associations with adulthood subclinical atherosclerosis.

Methods: Data were pooled from 5 cardiovascular cohorts. Clinical components of cardiovascular health (BMI, blood pressure, cholesterol, and blood glucose) were categorized as ideal or nonideal using American Heart Association definitions. Multitrajectory models simultaneously fitted the probability ideal for each factor. Adjusted associations between trajectory groups and carotid intima-media thickness were modeled. Data were pooled from December 1, 2015 to June 1, 2019; statistical analysis occurred between June 1, 2019 and June 1, 2020.

Results: This study included 9,388 individuals (55% female, 66% White). A total of 5 distinct trajectory groups were created: 1 maintained the ideal levels of all the 4 health factors, 2 had risk onset of a single factor in childhood, 1 had risk onset of multiple factors in childhood, and 1 had risk onset in adulthood. Those with childhood multiple risk onset had 8.1% higher carotid intima-media thickness (95% CI=0.067, 0.095) than those in the ideal group, childhood cholesterol risk onset had 5.9% higher carotid intima-media thickness (95% CI=0.045, 0.072), childhood BMI risk onset had 5.5% higher carotid intima-media thickness (95% CI=0.041, 0.069), and early adulthood multiple risk onset had 2.7% higher carotid intima-media thickness (95% CI=0.013, 0.041).

Conclusions: Those who lost the ideal status of cardiovascular health in childhood and early adulthood had more subclinical atherosclerosis than those who retained the ideal cardiovascular health across the life course, underscoring the importance of preserving the ideal cardiovascular health beginning in childhood and continued into adulthood.
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http://dx.doi.org/10.1016/j.amepre.2021.04.010DOI Listing
October 2021

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging.

Genome Biol 2021 06 29;22(1):194. Epub 2021 Jun 29.

Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.

Background: Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field.

Results: Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels.

Conclusion: This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.
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http://dx.doi.org/10.1186/s13059-021-02398-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243879PMC
June 2021

Uncovering the shared lipidomic markers of subclinical osteoporosis-atherosclerosis comorbidity: The Young Finns Study.

Bone 2021 10 5;151:116030. Epub 2021 Jun 5.

Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Finnish Cardiovascular Research Centre, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.

Background: Osteoporosis and atherosclerosis are complex multifactorial diseases sharing common risk factors and pathophysiological mechanisms suggesting that these are comorbidities. Omics studies identifying joint molecular markers associated with these diseases are sparse.

Subjects And Methods: Using liquid chromatography-tandem mass spectrometry, we quantified 437 molecular lipid species from the Young Finns Study cohort (aged 30-45 years and 57% women) and performed lipidome-wide multivariate analysis of variance (MANOVA) with early markers for both diseases. Carotid intima-media thickness for atherosclerosis measured with ultrasound and bone mineral density from distal radius and tibia for osteoporosis measured with peripheral quantitative computed tomography were used as early markers of the diseases.

Results: MANOVA adjusted with age, sex and body mass index, identified eight statistically significant (adjusted p-value (p) < 0.05) and 15 suggestively significant (p < 0.25) molecular lipid species associated with the studied markers. Similar analysis adjusted additionally for smoking habit, physical activity and alcohol consumption identified four significant and six suggestively significant molecular lipid species. These most significant lipid classes/species jointly associated with the studied markers were glycerolipid/TAG(18:0/18:0/18:1), glycerophospholipid/PC(40:3), sphingolipid/Gb3(d18:1/22:0), and sphingolipid/Gb3(d18:1/24:0).

Conclusion: Our results support the osteoporosis-atherosclerosis comorbidity hypothesis and present potential new joint lipid biomarkers for these diseases.
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http://dx.doi.org/10.1016/j.bone.2021.116030DOI Listing
October 2021

Variants associated with expression have sex-differential effects on lung function.

Wellcome Open Res 2020 24;5:111. Epub 2021 May 24.

Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, EH4 2XU, UK.

Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10 ) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10 ). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV ) (P=3.15x10 ), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV more in males (untransformed FEV β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein ( ) gene and was previously associated with lung function and lung expression. We found expression was significantly different between the sexes (P=6.90x10 ), but we could not detect sex differential effects of rs7697189 on expression. We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the gene. Establishing the mechanism by which SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.
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http://dx.doi.org/10.12688/wellcomeopenres.15846.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938335.2PMC
May 2021

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness.

Eur J Epidemiol 2021 Jun 6. Epub 2021 Jun 6.

Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = -0.0264, p value = 3.5 × 10) in the discovery panel and was replicated in replication panel (beta = -0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.
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http://dx.doi.org/10.1007/s10654-021-00759-zDOI Listing
June 2021

Association between Number of Siblings and Cardiovascular Risk Factors in Childhood and in Adulthood: The Cardiovascular Risk in Young Finns Study.

J Pediatr 2021 Jun 1. Epub 2021 Jun 1.

Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Center for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland; Heart Center, Turku University Hospital and University of Turku, Turku, Finland.

Objective: To determine the association of number of siblings on cardiovascular risk factors in childhood and in adulthood.

Study Design: In total, 3554 participants (51% female) from the Cardiovascular Risk in Young Finns Study with cardiovascular disease risk factor data at baseline 1980 (age 3-18 years) and 2491 participants with longitudinal risk factor data at the 2011 follow-up. Participants were categorized by number of siblings at baseline (0, 1, or more than 1). Risk factors (body mass index, physical activity, hypertension, dyslipidemia, and overweight, and metabolic syndrome) in childhood and in adulthood were used as outcomes. Analyses were adjusted for age and sex.

Results: In childhood, participants without siblings had higher body mass index (18.2 kg/m, 95% CI 18.0-18.3) than those with 1 sibling (17.9 kg/m, 95% CI 17.8-18.0) or more than 1 sibling (17.8 kg/m, 95% CI 17.7-17.9). Childhood physical activity index was lower among participants without siblings (SD -0.08, 95% CI -0.16-0.00) compared with participants with 1 sibling (SD 0.06, 95%CI 0.01-0.11) or more than 1 sibling (SD -0.02, 95% CI -0.07-0.03). OR for adulthood hypertension was lower among participants with 1 sibling (OR 0.73, 95% CI 0.54-0.98) and more than 1 sibling (OR 0.71, 95% CI 0.52-0.97) compared with participants with no siblings. OR for obesity was lower among participants with 1 sibling (OR 0.72, 95% CI 0.54-0.95) and more than 1 sibling (OR 0.75, 95% CI 0.56-1.01) compared with those with no siblings.

Conclusions: Children without siblings had poorer cardiovascular risk factor levels in childhood and in adulthood. The number of siblings could help identify individuals at increased risk that might benefit from early intervention.
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http://dx.doi.org/10.1016/j.jpeds.2021.05.058DOI Listing
June 2021

Influential Periods in Longitudinal Clinical Cardiovascular Health Scores.

Am J Epidemiol 2021 May 20. Epub 2021 May 20.

Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low, and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. This study pools data from five longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults (CARDIA), Special Turku Coronary Risk Factor Intervention Project (STRIP)) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (body mass index, blood pressure, cholesterol, blood glucose) measured between ages 8 to 55 were included. These factors were categorized and summed into a clinical CVH score ranging from 0 (worst) to 8 (best). Adjusted segmented linear mixed models were used to estimate the change in CVH over time. Among the 18,343 participants, 9461(52%) were female and 12,346(67%) White. The baseline mean (SD) clinical CVH score was 6.9(1.2) at an average age of 17.6(8.1). Two inflection points were estimated, at 16.9 years (95% CI: 16.4, 17.4) and at 37.2 years (95% CI: 32.4, 41.9). Late adolescence and early middle age appear to be influential periods at which the loss of CVH accelerates.
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http://dx.doi.org/10.1093/aje/kwab149DOI Listing
May 2021

Cardiovascular Risk Factor Trajectories Since Childhood and Cognitive Performance in Midlife: The Cardiovascular Risk in Young Finns Study.

Circulation 2021 May 10;143(20):1949-1961. Epub 2021 May 10.

Research Centre of Applied and Preventive Cardiovascular Medicine (J.O.H., K.P., P.S., O.T.R., S.P.R.), University of Turku, Finland.

Background: Cardiovascular risk factors, such as high blood pressure, adverse serum lipids, and elevated body mass index in midlife, may harm cognitive performance. It is important to note that longitudinal accumulation of cardiovascular risk factors since childhood may be associated with cognitive performance already since childhood, but the previous evidence is scarce. We studied the associations of cardiovascular risk factors from childhood to midlife, their accumulation, and midlife cognitive performance.

Methods: From 1980, a population-based cohort of 3596 children (3-18 years of age) have been repeatedly followed up for 31 years. Blood pressure, serum lipids, and body mass index were assessed in all follow-ups. Cardiovascular risk factor trajectories from childhood to midlife were identified using latent class growth mixture modeling. Cognitive testing was performed in 2026 participants 34 to 49 years of age using a computerized test. The associations of the cardiovascular risk factor trajectories and cognitive performance were studied for individual cardiovascular risk factors and cardiovascular risk factor accumulation.

Results: Consistently high systolic blood pressure (β=-0.262 SD [95% CI, -0.520 to -0.005]) and serum total cholesterol (β=-0.214 SD [95% CI, -0.365 to -0.064]) were associated with worse midlife episodic memory and associative learning compared with consistently low values. Obesity since childhood was associated with worse visual processing and sustained attention (β=-0.407 SD [95% CI, -0.708 to -0.105]) compared with normal weight. An inverse association was observed for the cardiovascular risk factor accumulation with episodic memory and associative learning ( for trend=0.008; 3 cardiovascular risk factors: β=-0.390 SD [95% CI, -0.691 to -0.088]), with visual processing and sustained attention ( for trend<0.0001; 3 cardiovascular risk factors: β=-0.443 SD [95% CI, -0.730 to -0.157]), and with reaction and movement time ( for trend=0.048; 2 cardiovascular risk factors: β=-0.164 SD [95% CI, -0.318 to -0.010]).

Conclusions: Longitudinal elevated systolic blood pressure, high serum total cholesterol, and obesity from childhood to midlife were inversely associated with midlife cognitive performance. It is important to note that the higher the number of cardiovascular risk factors, the worse was the observed cognitive performance. Therefore, launching preventive strategies against cardiovascular risk factors beginning from childhood might benefit primordial promotion of cognitive health in adulthood.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052358DOI Listing
May 2021

Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health.

Sci Rep 2021 04 28;11(1):9203. Epub 2021 Apr 28.

Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and Finnish Cardiovascular Research Center, Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Preterm birth (PTB) is associated with increased risk of type 2 diabetes and neurocognitive impairment later in life. We analyzed for the first time the associations of PTB with blood miRNA levels in adulthood. We also investigated the relationship of PTB associated miRNAs and adulthood phenotypes previously linked with premature birth. Blood MicroRNA profiling, genome-wide gene expression analysis, computer-based cognitive testing battery (CANTAB) and serum NMR metabolomics were performed for Young Finns Study subjects (aged 34-49 years, full-term n = 682, preterm n = 84). Preterm birth (vs. full-term) was associated with adulthood levels of hsa-miR-29b-3p in a fully adjusted regression model (p = 1.90 × 10, FDR = 0.046). The levels of hsa-miR-29b-3p were down-regulated in subjects with PTB with appropriate birthweight for gestational age (p = 0.002, fold change [FC] = - 1.20) and specifically in PTB subjects with small birthweight for gestational age (p = 0.095, FC = - 1.39) in comparison to individuals born full term. Hsa-miR-29b-3p levels correlated with the expressions of its target-mRNAs BCL11A and CS and the gene set analysis results indicated a target-mRNA driven association between hsa-miR-29b-3p levels and Alzheimer's disease, Parkinson's disease, Insulin signaling and Regulation of Actin Cytoskeleton pathway expression. The level of hsa-miR-29b-3p was directly associated with visual processing and sustained attention in CANTAB test and inversely associated with serum levels of VLDL subclass component and triglyceride levels. In conlcusion, adult blood levels of hsa-miR-29b-3p were lower in subjects born preterm. Hsa-miR-29b-3p associated with cognitive function and may be linked with adulthood morbidities in subjects born preterm, possibly through regulation of gene sets related to neurodegenerative diseases and insulin signaling as well as VLDL and triglyceride metabolism.
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http://dx.doi.org/10.1038/s41598-021-88465-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080838PMC
April 2021

Evaluation of Shared Genetic Susceptibility to High and Low Myopia and Hyperopia.

JAMA Ophthalmol 2021 Jun;139(6):601-609

Cardiff University School of Optometry and Vision Sciences, Cardiff, United Kingdom.

Importance: Uncertainty currently exists about whether the same genetic variants are associated with susceptibility to low myopia (LM) and high myopia (HM) and to myopia and hyperopia. Addressing this question is fundamental to understanding the genetics of refractive error and has clinical relevance for genotype-based prediction of children at risk for HM and for identification of new therapeutic targets.

Objective: To assess whether a common set of genetic variants are associated with susceptibility to HM, LM, and hyperopia.

Design, Setting, And Participants: This genetic association study assessed unrelated UK Biobank participants 40 to 69 years of age of European and Asian ancestry. Participants 40 to 69 years of age living in the United Kingdom were recruited from January 1, 2006, to October 31, 2010. Of the total sample of 502 682 participants, 117 279 (23.3%) underwent an ophthalmic assessment. Data analysis was performed from December 12, 2019, to June 23, 2020.

Exposures: Four refractive error groups were defined: HM, -6.00 diopters (D) or less; LM, -3.00 to -1.00 D; hyperopia, +2.00 D or greater; and emmetropia, 0.00 to +1.00 D. Four genome-wide association study (GWAS) analyses were performed in participants of European ancestry: (1) HM vs emmetropia, (2) LM vs emmetropia, (3) hyperopia vs emmetropia, and (4) LM vs hyperopia. Polygenic risk scores were generated from GWAS summary statistics, yielding 4 sets of polygenic risk scores. Performance was assessed in independent replication samples of European and Asian ancestry.

Main Outcomes And Measures: Odds ratios (ORs) of polygenic risk scores in replication samples.

Results: A total of 51 841 unrelated individuals of European ancestry and 2165 unrelated individuals of Asian ancestry were assigned to a specific refractive error group and included in our analyses. Polygenic risk scores derived from all 4 GWAS analyses were predictive of all categories of refractive error in both European and Asian replication samples. For example, the polygenic risk score derived from the HM vs emmetropia GWAS was predictive in the European sample of HM vs emmetropia (OR, 1.58; 95% CI, 1.41-1.77; P = 1.54 × 10-15) as well as LM vs emmetropia (OR, 1.15; 95% CI, 1.07-1.23; P = 8.14 × 10-5), hyperopia vs emmetropia (OR, 0.83; 95% CI, 0.77-0.89; P = 4.18 × 10-7), and LM vs hyperopia (OR, 1.45; 95% CI, 1.33-1.59; P = 1.43 × 10-16).

Conclusions And Relevance: Genetic risk variants were shared across HM, LM, and hyperopia and across European and Asian samples. Individuals with HM inherited a higher number of variants from among the same set of myopia-predisposing alleles and not different risk alleles compared with individuals with LM. These findings suggest that treatment interventions targeting common genetic risk variants associated with refractive error could be effective against both LM and HM.
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http://dx.doi.org/10.1001/jamaophthalmol.2021.0497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033508PMC
June 2021

Evaluating the direct effects of childhood adiposity on adult systemic metabolism: a multivariable Mendelian randomization analysis.

Int J Epidemiol 2021 Mar 30. Epub 2021 Mar 30.

MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK.

Background: Individuals who are obese in childhood have an elevated risk of disease in adulthood. However, whether childhood adiposity directly impacts intermediate markers of this risk, independently of adult adiposity, is unclear. In this study, we have simultaneously evaluated the effects of childhood and adulthood body size on 123 systemic molecular biomarkers representing multiple metabolic pathways.

Methods: Two-sample Mendelian randomization (MR) was conducted to estimate the causal effect of childhood body size on a total of 123 nuclear magnetic resonance-based metabolic markers using summary genome-wide association study (GWAS) data from up to 24 925 adults. Multivariable MR was then applied to evaluate the direct effects of childhood body size on these metabolic markers whilst accounting for adult body size. Further MR analyses were undertaken to estimate the potential mediating effects of these circulating metabolites on the risk of coronary artery disease (CAD) in adulthood using a sample of 60 801 cases and 123 504 controls.

Results: Univariable analyses provided evidence that childhood body size has an effect on 42 of the 123 metabolic markers assessed (based on P < 4.07 × 10-4). However, the majority of these effects (35/42) substantially attenuated when accounting for adult body size using multivariable MR. We found little evidence that the biomarkers that were potentially influenced directly by childhood body size (leucine, isoleucine and tyrosine) mediate this effect onto adult disease risk. Very-low-density lipoprotein markers provided the strongest evidence of mediating the long-term effect of adiposity on CAD risk.

Conclusions: Our findings suggest that childhood adiposity predominantly exerts its detrimental effect on adult systemic metabolism along a pathway that involves adulthood body size.
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http://dx.doi.org/10.1093/ije/dyab051DOI Listing
March 2021

Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis in the Young Finns Study.

Sci Rep 2021 03 29;11(1):7111. Epub 2021 Mar 29.

Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the diseases was tested with multivariate analysis. Among the six modules significantly correlated with early traits of both the diseases, two had significant (adjusted p-values (p.adj) < 0.05) and another two had suggestively significant (p.adj < 0.25) joint association with the two diseases after adjusting for age, sex, body mass index, smoking habit, alcohol consumption, and physical activity. The three most significant member genes from the significant modules were NOSIP, GXYLT2, and TRIM63 (p.adj ≤ 0.18). Genes in the modules were enriched with biological processes that have separately been found to be involved in either bone metabolism or atherosclerosis. The gene modules and their most significant member genes identified in this study support the osteoporosis-atherosclerosis comorbidity hypothesis and can provide new joint biomarkers for both diseases and their dual prevention.
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http://dx.doi.org/10.1038/s41598-021-86536-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007808PMC
March 2021

Life-course leisure-time physical activity trajectories in relation to health-related behaviors in adulthood: the Cardiovascular Risk in Young Finns study.

BMC Public Health 2021 03 19;21(1):533. Epub 2021 Mar 19.

LIKES Research Centre for Physical Activity and Health, Jyväskylä, Finland.

Background: Evidence on whether leisure-time physical activity (LTPA) facilitates individuals' adoption of multiple healthy behaviors remains scarce. This study investigated the associations of diverse longitudinal LTPA trajectories from childhood to adulthood with diet, screen time, smoking, binge drinking, sleep difficulties, and sleep duration in adulthood.

Methods: Data were drawn from the Cardiovascular Risk in Young Finns Study. Participants were aged 9-18 years (N = 3553; 51% females) in 1980 and 33-49 years at the latest follow-up in 2011. The LTPA trajectories were identified using a latent profile analysis. Differences in self-reported health-related behaviors across the LTPA trajectories were studied separately for women and men by using the Bolck-Croon-Hagenaars approach. Models were adjusted for age, body mass index, education level, marital status, total energy intake and previous corresponding behaviors.

Results: Persistently active, persistently low-active, decreasingly and increasingly active trajectories were identified in both genders and an additional inactive trajectory for women. After adjusting the models with the above-mentioned covariates, the inactive women had an unhealthier diet than the women in the other trajectories (p <  0.01; effect size (ES) > 0.50). The low-active men followed an unhealthier diet than the persistently and increasingly active men (p <  0.01; ES > 0.50). Compared to their inactive and low-active peers, smoking frequency was lower in the increasingly active women and men (p <  0.01; ES > 0.20) and persistently active men (p <  0.05; ES > 0.20). The increasingly active men reported lower screen time than the low-active (p <  0.001; ES > 0.50) and persistently active (p <  0.05; ES > 0.20) men. The increasingly and persistently active women reported fewer sleep difficulties than the inactive (p <  0.001; ES > 0.80) and low-active (p <  0.05; ES > 0.50 and > 0.80, respectively) women. Sleep duration and binge drinking were not associated with the LTPA trajectories in either gender, nor were sleep difficulties in men and screen time in women.

Conclusions: Not only persistently higher LTPA but also an increasing tendency to engage in LTPA after childhood/adolescence were associated with healthier diet and lower smoking frequency in both genders, having less sleep difficulties in women and lower screen time in increasingly active men. Inactivity and low activity were associated with the accumulation of several unhealthy behaviors in adulthood. Associations were stronger in women.
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http://dx.doi.org/10.1186/s12889-021-10554-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977567PMC
March 2021

Early cardiovascular structural and functional abnormalities as a guide to future morbid events.

Eur J Prev Cardiol 2020 Mar 25. Epub 2020 Mar 25.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland.

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http://dx.doi.org/10.1177/2047487320908700DOI Listing
March 2020

Achievement of the Targets of the 20-Year Infancy-Onset Dietary Intervention-Association with Metabolic Profile from Childhood to Adulthood.

Nutrients 2021 Feb 6;13(2). Epub 2021 Feb 6.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520 Turku, Finland.

The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9-19 years ( = 549-338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) < 1:2, (2) intake of SAFA < 10% of total energy intake, (3) fiber intake ≥ 80th age-specific percentile, and (4) sucrose intake ≤ 20th age-specific percentile. Metabolic biomarkers were quantified by high-throughput nuclear magnetic resonance metabolomics. Better adherence to the dietary targets, regardless of study group allocation, was assoiated with higher serum proportion of PUFAs, lower serum proportion of SAFAs, and a higher degree of unsaturation of fatty acids. Achieving ≥ 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (≥2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health.
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http://dx.doi.org/10.3390/nu13020533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915301PMC
February 2021

Associations of Serum Fatty Acid Proportions with Obesity, Insulin Resistance, Blood Pressure, and Fatty Liver: The Cardiovascular Risk in Young Finns Study.

J Nutr 2021 04;151(4):970-978

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

Background: The links between fatty acids (FAs) and cardiometabolic outcomes are topics of debate.

Objective: Our aim was to investigate the associations between serum standardized FA percentages and cardiometabolic outcomes.

Methods: We used cross-sectional (n = 2187-2200 subjects, age 24-39 y, women 54%) and 10-year prospective data (n = 975-1414 subjects) from the Young Finns Study. Outcomes included prevalent and incident obesity, insulin resistance (HOMA-IR index in the upper quintile), elevated blood pressure (BP; taking medication, or diastolic or systolic BP in the upper quintile), and incident nonalcoholic fatty liver. Logistic regression models were used to calculate ORs per SD increase in fatty acids (FAs). The models were adjusted for age and sex, and additionally for other potential confounders.

Results: Several cross-sectional findings were also statistically significant in prospective models (Bonferroni corrected P < 0.003). In fully-adjusted models for obesity, these consisted of SFAs (OR: 1.28) and MUFAs (OR: 1.38), including palmitoleic (OR: 1.39) and oleic acids (OR: 1.37). Furthermore, PUFAs (OR: 0.70), including linoleic (OR: 0.67) and docosahexaenoic acids (OR: 0.75), were inversely related with obesity, whereas γ-linolenic acid (OR: 1.32) was positively associated with obesity. In age- and sex-adjusted models for insulin resistance, MUFAs (OR: 1.26) and oleic acid (OR: 1.25) were positively, and PUFAs (OR: 0.81), particularly linoleic acid (OR: 0.78), were inversely associated with HOMA-IR. Similarly with elevated BP, palmitic acid (OR: 1.22), MUFAs (OR: 1.28), and oleic acid (OR: 1.28) were positively associated with elevated BP, whereas PUFAs (OR: 0.77), n-6 (omega-6) PUFAs (OR: 0.79), and linoleic acid (OR: 0.77) were inversely associated. In fully-adjusted models for incident fatty liver, the most consistent predictors were high palmitic (OR: 1.61) and low linoleic acid (OR: 0.63) percentages. The n-6/n-3 (omega-3) PUFA ratio was not linked with any adverse outcomes.

Conclusions: High serum percentages of total SFAs and MUFAs and low PUFAs, but also several specific FAs, predict future unfavorable cardiometabolic outcomes in Finnish adults.
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http://dx.doi.org/10.1093/jn/nxaa409DOI Listing
April 2021

Fatty liver index and left ventricular mass: prospective associations from two independent cohorts.

J Hypertens 2021 05;39(5):961-969

Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, Louisiana, USA.

Objectives: Heart disease is the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD). Emerging data have shown that NAFLD may affect subclinical myocardial remodeling, mainly left ventricular hypertrophy; however, evidence from the prospective studies is still lacking.

Methods: Prospective analyses were performed to investigate the association of fatty liver index (FLI) with left ventricular mass (LVM) among 1962 participants from the Bogalusa Heart Study (BHS, 1995-2010) and 1547 participants from the Cardiovascular Risk in Young Finns Study (YFS, 2001-2011) free of cardiovascular diseases (CVD) at baseline. LVM was assessed by two-dimensional guided M-mode echocardiography and indexed (LVMI) to body height (m2.7). Multivariable regression models were applied after adjustment for traditional CVD risk factors.

Results: In both cohorts, we observed significant and positive associations between FLI and LVM (BHS: β=0.59, P < 0.001; YFS: β=0.41, P < 0.001) and LVMI (BHS: β=0.14, P < 0.001; YFS: β=0.09, P < 0.001). In addition, we found that the relationship between FLI and LVMI was stronger in women than men (BHS: P-interaction = 0.01; YFS: P-interaction < 0.01); and the relationship between FLI and LVM/LVMI was stronger in black than white individuals (LVM: P-interaction = 0.02; LVMI: P-interaction = 0.04). Moreover, we found that the associations of FLI with LVM and LVMI were attenuated by high physical activity, especially in BHS (P-interaction = 0.02).

Conclusion: Our findings from two independent prospective cohorts indicate that FLI is positively associated with LVM/LVMI, independent of traditional cardiovascular risk factors. Such relationships are more pronounced among women and black individuals and are attenuated by high physical activity.
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http://dx.doi.org/10.1097/HJH.0000000000002716DOI Listing
May 2021

Cardiovascular Risk Factors in Childhood and Left Ventricular Diastolic Function in Adulthood.

Pediatrics 2021 03 8;147(3). Epub 2021 Feb 8.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.

Background And Objectives: Cardiovascular risk factors, such as obesity, blood pressure, and physical inactivity, have been identified as modifiable determinants of left ventricular (LV) diastolic function in adulthood. However, the links between childhood cardiovascular risk factor burden and adulthood LV diastolic function are unknown. To address this lack of knowledge, we aimed to identify childhood risk factors associated with LV diastolic function in the participants of the Cardiovascular Risk in Young Finns Study.

Methods: Study participants ( = 1871; 45.9% men; aged 34-49 years) were examined repeatedly between the years 1980 and 2011. We determined the cumulative risk exposure in childhood (age 6-18 years) as the area under the curve for systolic blood pressure, adiposity (defined by using skinfold and waist circumference measurements), physical activity, serum insulin, triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterols. Adulthood LV diastolic function was defined by using E/é ratio.

Results: Elevated systolic blood pressure and increased adiposity in childhood were associated with worse adulthood LV diastolic function, whereas higher physical activity level in childhood was associated with better adulthood LV diastolic function ( < .001 for all). The associations of childhood adiposity and physical activity with adulthood LV diastolic function remained significant (both < .05) but were diluted when the analyses were adjusted for adulthood systolic blood pressure, adiposity, and physical activity. The association between childhood systolic blood pressure and adult LV diastolic function was diluted to nonsignificant ( = .56).

Conclusions: Adiposity status and the level of physical activity in childhood are independently associated with LV diastolic function in adulthood.
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http://dx.doi.org/10.1542/peds.2020-016691DOI Listing
March 2021
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