Publications by authors named "Britt-Marie Loo"

34 Publications

Physical inactivity from youth to adulthood and adult cardiometabolic risk profile.

Prev Med 2021 Apr 23;145:106433. Epub 2021 Jan 23.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland; Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.

Adults with a low physical activity (PA) level are at increased risk for cardiometabolic diseases, but little is known on the association between physical inactivity since youth and cardiometabolic health in adulthood. We investigated the association of persistent physical inactivity from youth to adulthood with adult cardiometabolic risk factors. Data were drawn from the ongoing Cardiovascular Risk in Young Finns Study with seven follow-ups between 1980 and 2011 (baseline age 3-18 years, n = 1961). Physical activity data from a standardized questionnaire was expressed as a PA-index. Using the PA-index, four groups were formed: 1)persistently physically inactive (n = 246), 2)decreasingly active (n = 305), 3)increasingly active (n = 328), and 4)persistently active individuals (n = 1082). Adulthood cardiometabolic risk indicators included waist circumference, body mass index (BMI), blood pressure, and fasting lipids, insulin, and glucose. Clustered cardiometabolic risk was defined using established criteria for metabolic syndrome. Persistently physically inactive group was used as a reference. Compared to the persistently physically inactive group, those who were persistently active had lower risk for adult clustered cardiometabolic risk (RR = 0.67;CI95% = 0.53-0.84; Harmonized criteria), obesity (BMI > 30 kg/m, RR = 0.76;CI95% = 0.59-0.98), high waist circumference (RR = 0.82;CI95% = 0.69-0.98), and high triglyceride (RR = 0.60;CI95% = 0.47-0.75), insulin (RR = 0.58;CI95% = 0.46-0.74) and glucose (RR = 0.77;CI95% = 0.62-0.96) concentrations as well as low high-density lipoprotein cholesterol (HDLC) concentration (RR = 0.78;CI95% = 0.66-0.93). Comparable results were found when persistently physically inactive individuals were compared with those who increased PA. The results remained essentially similar after adjustment for education, diet, smoking, and BMI. Persistently physically inactive lifestyle since youth is associated with an unfavorable cardiometabolic risk profile in adulthood. Importantly, even minor increase in PA lowers the cardiometabolic risk.
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http://dx.doi.org/10.1016/j.ypmed.2021.106433DOI Listing
April 2021

Effects of 20-year infancy-onset dietary counselling on cardiometabolic risk factors in the Special Turku Coronary Risk Factor Intervention Project (STRIP): 6-year post-intervention follow-up.

Lancet Child Adolesc Health 2020 05;4(5):359-369

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Centre for Population Health Research, Turku University Hospital, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, University of Turku, Turku, Finland.

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.
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http://dx.doi.org/10.1016/S2352-4642(20)30059-6DOI Listing
May 2020

Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes.

Sci Rep 2019 06 20;9(1):8887. Epub 2019 Jun 20.

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

We analyzed the associations between whole blood microRNA profiles and the indices of glucose metabolism and impaired fasting glucose and examined whether the discovered microRNAs correlate with the expression of their mRNA targets. MicroRNA and gene expression profiling were performed for the Young Finns Study participants (n = 871). Glucose, insulin, and glycated hemoglobin (HbA1c) levels were measured, the insulin resistance index (HOMA2-IR) was calculated, and the glycemic status (normoglycemic [n = 534]/impaired fasting glucose [IFG] [n = 252]/type 2 diabetes [T2D] [n = 24]) determined. Levels of hsa-miR-144-5p, -122-5p, -148a-3p, -589-5p, and hsa-let-7a-5p associated with glycemic status. hsa-miR-144-5p and -148a-3p associated with glucose levels, while hsa-miR-144-5p, -122-5p, -184, and -339-3p associated with insulin levels and HOMA2-IR, and hsa-miR-148a-3p, -15b-3p, -93-3p, -146b-5p, -221-3p, -18a-3p, -642a-5p, and -181-2-3p associated with HbA1c levels. The targets of hsa-miR-146b-5p that correlated with its levels were enriched in inflammatory pathways, and the targets of hsa-miR-221-3p were enriched in insulin signaling and T2D pathways. These pathways showed indications of co-regulation by HbA1c-associated miRNAs. There were significant differences in the microRNA profiles associated with glucose, insulin, or HOMA-IR compared to those associated with HbA1c. The HbA1c-associated miRNAs also correlated with the expression of target mRNAs in pathways important to the development of T2D.
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http://dx.doi.org/10.1038/s41598-019-43793-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586838PMC
June 2019

Childhood Exposure to Passive Smoking and Bone Health in Adulthood: The Cardiovascular Risk in Young Finns Study.

J Clin Endocrinol Metab 2019 06;104(6):2403-2411

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

Context: Passive smoke exposure has been linked to the risk of osteoporosis in adults.

Objective: We examined the independent effects of childhood passive smoke exposure on adult bone health.

Design/setting: Longitudinal, the Cardiovascular Risk in Young Finns Study.

Participants: The study cohort included 1422 individuals followed for 28 years since baseline in 1980 (age 3 to 18 years). Exposure to passive smoking was determined in childhood. In adulthood, peripheral bone traits were assessed with peripheral quantitative CT (pQCT) at the tibia and radius, and calcaneal mineral density was estimated with quantitative ultrasound. Fracture data were gathered by questionnaires.

Results: Parental smoking in childhood was associated with lower pQCT-derived bone sum index in adulthood (β± SE, -0.064 ± 0.023 per smoking parent; P = 0.004) in multivariate models adjusted for age, sex, active smoking, body mass index, serum 25-OH vitamin D concentration, physical activity, and parental socioeconomic position. Similarly, parental smoking was associated with lower heel ultrasound estimated bone mineral density in adulthood (β± SE, -0.097 ± 0.041 per smoking parent; P = 0.02). Parental smoking was also associated with the incidence of low-energy fractures (OR, 1.28; 95% CI, 1.01 to 1.62). Individuals with elevated cotinine levels (3 to 20 ng/mL) in childhood had lower bone sum index with pQCT (β± SE, -0.206 ± 0.057; P = 0.0003). Children whose parents smoked and had high cotinine levels (3 to 20 ng/mL) had significantly lower pQCT-derived bone sum index compared with those with smoking parents but had low cotinine levels (<3 ng/mL) (β± SE, -0.192 ± 0.072; P = 0.008).

Conclusions And Relevance: Children of parents who smoke have evidence of impaired bone health in adulthood.
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http://dx.doi.org/10.1210/jc.2018-02501DOI Listing
June 2019

Blood hsa-miR-122-5p and hsa-miR-885-5p levels associate with fatty liver and related lipoprotein metabolism-The Young Finns Study.

Sci Rep 2016 12 5;6:38262. Epub 2016 Dec 5.

Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, and University of Tampere, School of Medicine, Tampere, Finland.

MicroRNAs are involved in disease development and may be utilized as biomarkers. We investigated the association of blood miRNA levels and a) fatty liver (FL), b) lipoprotein and lipid pathways involved in liver lipid accumulation and c) levels of predicted mRNA targets in general population based cohort. Blood microRNA profiling (TaqMan OpenArray), genome-wide gene expression arrays and nuclear magnetic resonance metabolomics were performed for Young Finns Study participants aged 34-49 years (n = 871). Liver fat status was assessed ultrasonographically. Levels of hsa-miR-122-5p and -885-5p were up-regulated in individuals with FL (fold change (FC) = 1.55, p = 1.36 * 10 and FC = 1.25, p = 4.86 * 10, respectively). In regression model adjusted with age, sex and BMI, hsa-miR-122-5p and -885-5p predicted FL (OR = 2.07, p = 1.29 * 10 and OR = 1.41, p = 0.002, respectively). Together hsa-miR-122-5p and -885-5p slightly improved the detection of FL beyond established risk factors. These miRNAs may be associated with FL formation through the regulation of lipoprotein metabolism as hsa-miR-122-5p levels associated with small VLDL, IDL, and large LDL lipoprotein subclass components, while hsa-miR-885-5p levels associated inversely with XL HDL cholesterol levels. Hsa-miR-885-5p levels correlated inversely with oxysterol-binding protein 2 (OSBPL2) expression (r = -0.143, p = 1.00 * 10) and suppressing the expression of this lipid receptor and sterol transporter could link hsa-miR-885-5p with HDL cholesterol levels.
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http://dx.doi.org/10.1038/srep38262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137183PMC
December 2016

Consumption of chokeberry (Aronia mitschurinii) products modestly lowered blood pressure and reduced low-grade inflammation in patients with mildly elevated blood pressure.

Nutr Res 2016 11 14;36(11):1222-1230. Epub 2016 Sep 14.

Department of Health, National Institute for Health and Welfare, Turku, Finland; Department of Medicine, University of Turku, Turku, Finland. Electronic address:

Previous studies suggest that consumption of chokeberries may improve cardiovascular disease risk factor profiles. We hypothesized that chokeberries (Aronia mitschurinii) have beneficial effects on blood pressure, low-grade inflammation, serum lipids, serum glucose, and platelet aggregation in patients with untreated mild hypertension. A total of 38 participants were enrolled into a 16-week single blinded crossover trial. The participants were randomized to use cold-pressed 100% chokeberry juice (300 mL/d) and oven-dried chokeberry powder (3 g/d), or matched placebo products in random order for 8 weeks each with no washout period. The daily portion of chokeberry products was prepared from approximately 336 g of fresh chokeberries. Urinary excretion of various polyphenols and their metabolites increased during the chokeberry period, indicating good compliance. Chokeberries decreased daytime blood pressure and low-grade inflammation. The daytime ambulatory diastolic blood pressure decreased (-1.64 mm Hg, P = .02), and the true awake ambulatory systolic (-2.71 mm Hg, P = .077) and diastolic (-1.62 mm Hg, P = .057) blood pressure tended to decrease. The concentrations of interleukin (IL) 10 and tumor necrosis factor α decreased (-1.9 pg/mL [P = .008] and -0.67 pg/mL [P = .007], respectively) and tended to decrease for IL-4 and IL-5 (-4.5 pg/mL [P = .084] and -0.06 pg/mL [P = .059], respectively). No changes in serum lipids, lipoproteins, glucose, and in vitro platelet aggregation were noted with the chokeberry intervention. These findings suggest that inclusion of chokeberry products in the diet of participants with mildly elevated blood pressure has minor beneficial effects on cardiovascular health.
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http://dx.doi.org/10.1016/j.nutres.2016.09.005DOI Listing
November 2016

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

J Hepatol 2016 10 24;65(4):784-790. Epub 2016 May 24.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland; Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.

Background & Aims: Fatty liver is a potentially preventable cause of serious liver diseases. This longitudinal study aimed to identify childhood risk factors of fatty liver in adulthood in a population-based group of Finnish adults.

Methods: Study cohort included 2,042 individuals from the Cardiovascular Risk in Young Finns Study aged 3-18years at baseline in 1980. During the latest follow-up in 2011, the liver was scanned by ultrasound. In addition to physical and environmental factors related to fatty liver, we examined whether the genetic risk posed by a single nucleotide polymorphism in the patatin-like phospholipase domain-containing protein 3 gene (PNPLA3) (rs738409) strengthens prediction of adult fatty liver.

Results: Independent childhood predictors of adult fatty liver were small for gestational age, (odds ratio=1.71, 95% confidence interval=1.07-2.72), variant in PNPLA3 (1.63, 1.29-2.07 per one risk allele), variant in the transmembrane 6 superfamily 2 gene (TM6SF2) (1.57, 1.08-2.30), BMI (1.30, 1.07-1.59 per standard deviation) and insulin (1.25, 1.05-1.49 per standard deviation). Childhood blood pressure, physical activity, C-reactive protein, smoking, serum lipid levels or parental lifestyle factors did not predict fatty liver. Risk assessment based on childhood age, sex, BMI, insulin levels, birth weight, TM6SF2 and PNPLA3 was superior in predicting fatty liver compared with the approach using only age, sex, BMI and insulin levels (C statistics, 0.725 vs. 0.749; p=0.002).

Conclusions: Childhood risk factors on the development of fatty liver were small for gestational age, high insulin and high BMI. Prediction of adult fatty liver was enhanced by taking into account genetic variants in PNPLA3 and TM6SF2 genes.

Lay Summary: The increase in pediatric obesity emphasizes the importance of identification of children and adolescents at high risk of fatty liver in adulthood. We used data from the longitudinal Cardiovascular Risk in Young Finns Study to examine the associations of childhood (3-18years) risk variables with fatty liver assessed in adulthood at the age of 34-49years. The findings suggest that a multifactorial approach with both lifestyle and genetic factors included would improve early identification of children with a high risk of adult fatty liver.
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http://dx.doi.org/10.1016/j.jhep.2016.05.020DOI Listing
October 2016

Determinants of serum 25(OH)D concentration in young and middle-aged adults. The Cardiovascular Risk in Young Finns Study.

Ann Med 2015 May 23;47(3):253-62. Epub 2015 Apr 23.

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

Introduction: We studied prevalence of hypovitaminosis D, its determinants, and whether achievement of recommended dietary vitamin D intake (10 μg/d) is associated with absence of hypovitaminosis D in adults.

Methods: The study is part of the Cardiovascular Risk in Young Finns Study. We collected serum samples of 25-hydroxyvitamin D as part of the 27-year follow-up (994 men and 1,210 women aged 30-45 years). Hypovitaminosis was defined as vitamin D concentration ≤ 50 nmol/L.

Results: Hypovitaminosis D was found in 38% of men and 34% of women. Dietary vitamin D intake (OR 0.90, 95% CI 0.86-0.93), use of vitamin-mineral supplements (0.66, 0.51-0.85), sunny holiday (0.55, 0.41-0.75), and oral contraceptive use in women (0.45, 0.27-0.75) were independently associated with reduced odds of hypovitaminosis. Increase in body mass index (1.06, 1.03-1.09), being a smoker (1.36, 0.97-1.92), investigation month (December versus other) (1.35, 1.12-1.61), and risk alleles in genotypes rs12785878 (1.31, 1.00-1.70) and rs2282679 (2.08, 1.66-2.60) increased odds of hypovitaminosis. Hypovitaminosis D was common also when recommended dietary intake was obtained (men 29%, women 24%).

Conclusion: Several factors were associated with hypovitaminosis D. The condition was common even when recommended vitamin D intake was reported. The results support the importance of vitamin D fortification and nutrient supplement use.
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http://dx.doi.org/10.3109/07853890.2015.1020860DOI Listing
May 2015

Childhood 25-OH vitamin D levels and carotid intima-media thickness in adulthood: the cardiovascular risk in young Finns study.

J Clin Endocrinol Metab 2015 Apr 10;100(4):1469-76. Epub 2015 Feb 10.

Research Centre of Applied and Preventive Cardiovascular Medicine (M.J., A.V., K.P., C.G.M., O.T.R.) and the Departments of Medicine (M.J., J.S.A.V.), University of Turku, 20520 Turku, Finland; Division of Medicine (M.J., J.S.A.V.) and Department of Clinical Physiology and Nuclear Medicine (O.T.R.), Turku University Hospital, 20520 Turku, Finland; Murdoch Children's Research Institute and Royal Children's Hospital (M.J., D.B., M.A.S.), 3052 Parkville, Victoria, Australia; Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Physical Activity and Health (K.P.), University of Turku and Turku University Hospital, 20520 Turku, Finland; Department of Food and Environmental Sciences (V.M.) and Hospital for Children and Adolescents (E.J.), University of Helsinki, 00014 Helsinki, Finland; Departments of Clinical Physiology (M.K.) and Pediatrics (N.H-K.), University of Tampere and Tampere University Hospital, 33520 Tampere, Finland; National Institute of Health and Welfare, Department of Chronic Disease Prevention (A.J., J.M., B-M.L.), 20720 Turku, Finland; Department of Paediatrics (D.B., M.A.S.), University of Melbourne, 3010 Melbourne, Victoria, Australia; Department of Paediatrics (D.B.), Monash University, 3800 Clayton, Victoria, Australia; Department of Pediatrics (L.T.), Vaasa Central Hospital, 65130 Vaasa, Finland; Department of Pediatrics (L.T.), University of Oulu, 90014 Oulu, Finland; Department of Clinical Physiology, University of Eastern Finland and Kuopio University Hospital (T.L.), 70029 Kuopio, Finland; and Menzies Research Institute (C.G.M.), 7000 Hobart, Tasmania, Australia.

Context: Low vitamin D levels in adulthood have been associated with cardiovascular disease.

Objective: To investigate if low vitamin D levels in childhood are related with increased carotid artery intima-media thickness (IMT) in adulthood.

Design, Setting, And Participants: The analyses included 2148 subjects from the Cardiovascular Risk in Young Finns Study, aged 3-18 years at baseline (in 1980). Subjects were re-examined at age 30-45 years (in 2007). Childhood levels of 25-hydroxy-vitamin D were measured from stored serum in 2010.

Main Outcome Measure: The carotid artery IMT from 2007 was used.

Results: When adjusted for age, sex, and childhood risk factors, continuous data of childhood 25-OH vitamin was inversely associated with adulthood carotid IMT levels among females (β ± SE -0.006 ± 0.003, P = 0.03), but not among males (0.001 ± 0.004, P = 0.88). Children with 25-OH vitamin D levels in the lowest quartile (<40 nmol/L) had significantly increased odds of having high-risk IMT (highest decile of common carotid or carotid bulb IMT or carotid plaque) as adults, in analyses adjusted for age, sex and either childhood risk factors (odds ratio 1.70 [95 % CI 1.15-2.31], P = 0.0007) or adult risk factors, including adult vitamin D levels (odds ratio 1.80 [1.30-2.48], P = 0.0004). In sex-specific analyses, these associations were significant both in females and males (P always <0.05). In sensitivity analyses, those with childhood vitamin D levels in the lowest quintile (<37 nmol/L), gave similar results to those using a quartile cut-point.

Conclusions: Low 25-OH vitamin D levels in childhood were associated with increased carotid IMT in adulthood.
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http://dx.doi.org/10.1210/jc.2014-3944DOI Listing
April 2015

Insulin and BMI as predictors of adult type 2 diabetes mellitus.

Pediatrics 2015 Jan 22;135(1):e144-51. Epub 2014 Dec 22.

Research Centre of Applied and Preventive Cardiovascular Medicine, and Departments of Clinical Physiology and Nuclear Medicine, and.

Background And Objectives: Fasting insulin concentrations are increasingly being used as a surrogate for insulin resistance and risk for type 2 diabetes (T2DM), although associations with adult outcomes are unclear. Our objective was to determine whether fasting insulin concentrations in childhood associate with later T2DM.

Methods: Fasting insulin values were available from 2478 participants in the longitudinal Cardiovascular Risk in Young Finns Study at baseline age 3 to 18 years, along with data on adult T2DM (N = 84, mean age = 39.6 years).

Results: Among 3- to 6-year-olds, a 1-SD increase in fasting insulin was associated with a relative risk (RR) of 2.04 (95% confidence interval [CI], 1.54-2.70) for later T2DM, which remained significant after we adjusted for BMI and parental history of T2DM. For those aged 9 to 18 years, a 1-SD increase in insulin was associated with an RR of 1.32 (95% CI, 1.06-1.65) for T2DM, but this became nonsignificant after we adjusted for BMI and parental history of T2DM. In the latter age group, a 1-SD increase in BMI was associated with an RR of 1.45 (95% CI, 1.21-1.73) for T2DM, with adjustment for insulin and parental history of T2DM not improving this association. BMI in younger children was not associated with later T2DM. In life course analyses, those with T2DM had higher fasting insulin levels in early childhood and later adulthood but not in peripubertal years.

Conclusions: Elevated fasting insulin concentrations in early childhood, but not adolescence, are independently associated with an elevated risk of T2DM in adulthood.
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http://dx.doi.org/10.1542/peds.2014-1534DOI Listing
January 2015

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

Ann Med 2015 Feb 21;47(1):40-6. Epub 2014 Oct 21.

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

Background And Aims: Fatty liver may have different determinants in normal-weight and in obese individuals. We measured factors associated with fatty liver in 863 normal-weight (BMI < 25) and 1135 overweight/obese (BMI ≥ 25) young and middle-aged adults (45% male, age 34-49 years) in the population-based Cardiovascular Risk in Young Finns Study.

Methods And Results: The prevalence of fatty liver detected with ultrasound was 29% in overweight/obese and 5% in normal-weight participants. In overweight/obese, the independent correlates were waist circumference (odds ratio for 1 standard deviation increase = 3.78), alanine transaminase (2.11), BMI (2.00), male sex (1.74), triglycerides (1.44), systolic blood pressure (1.31), fasting insulin (1.23), and physical activity (0.76). In normal weight, the independent correlates included alanine transaminase (3.05), smoking (2.56), systolic blood pressure (1.54), and alcohol intake (1.41). In normal-weight participants, the associations with fatty liver were stronger for alcohol intake and smoking, and weaker for triglycerides, than in overweight/obese participants (P for interaction < 0.05).

Conclusion: Prevalence of fatty liver was 29% in overweight/obese and 5% in normal-weight adults. Differences in factors associated with fatty liver were seen between these two groups: alcohol intake and smoking were more strongly and triglycerides more weakly associated in normal-weight than in overweight/obese participants.
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http://dx.doi.org/10.3109/07853890.2014.966752DOI Listing
February 2015

Cardiovascular risk factors in 2011 and secular trends since 2007: the Cardiovascular Risk in Young Finns Study.

Scand J Public Health 2014 Nov 22;42(7):563-71. Epub 2014 Jul 22.

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

Aims: Cardiovascular risk factor levels in 2011 and 4-year changes between 2007 and 2011 were examined using data collected in follow-ups of the Cardiovascular Risk in Young Finns Study.

Methods: The study population comprised 2063 Finnish adults aged 34-49 years (45% male). Lipid and blood pressure levels, glucose and anthropometry were measured and life style risk factors examined with questionnaires.

Results: Mean total cholesterol level in 2011 was 5.19 mmol/l, low density lipoprotein (LDL)-cholesterol 3.27 mmol/l, high density lipoprotein (HDL)-cholesterol 1.33 mmol/l, and triglycerides 1.34 mmol/l. Using American Diabetes Association criteria, Type 2 diabetes (T2D) was observed in 4.1% and prediabetes (fasting glucose 5.6-6.9 mmol/l or glycated hemoglobin 5.7-6.4%) diagnosed for 33.8% of the participants. Significant changes (P < 0.05) between 2007 and 2011 included an increase in waist circumference (3.3%) in women. In both sexes, systolic (-3.0% in women, -4.0% in men) and diastolic (-3.0% in women, -3.3% in men) blood pressure and triglycerides (-3.4% in women, -6.5% in men) decreased during follow-up.

Conclusions: Previously observed favorable trends in ldl-cholesterol levels have leveled off among a sample of young and middle-aged adults in finland triglyceride and blood pressure levels have decreased over one-third of the study population had prediabetes and may be at increased risk for T2D:
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http://dx.doi.org/10.1177/1403494814541597DOI Listing
November 2014

Blood microRNA profile associates with the levels of serum lipids and metabolites associated with glucose metabolism and insulin resistance and pinpoints pathways underlying metabolic syndrome: the cardiovascular risk in Young Finns Study.

Mol Cell Endocrinol 2014 Jun 28;391(1-2):41-9. Epub 2014 Apr 28.

Department of Clinical Chemistry, Pirkanmaa Hospital District, Fimlab Laboratories, University of Tampere, School of Medicine, Tampere, Finland.

Since metabolic syndrome (MetS) is a collection of cardiovascular risk factors involving multiple signaling systems, we related the metabolic abnormalities associated with MetS with circulating microRNA profiles to pinpoint the affected signaling pathways. The blood microRNA profile, genome wide gene expression and serum NMR metabolomics were analyzed from 71 participants of the Young Finns Study. We found nine microRNAs that associated significantly with metabolites connected to MetS. MicroRNA-144-5p concentration correlated with glucose levels, hsa-1207-5p with glycosylated hemoglobin and hsa-miR-484 with metabolites related to insulin resistance. Hsa-miR-625-3p correlated with cholesterol levels, hsa-miR-1237-3p and hsa-miR-331-3p expression with certain fatty acids levels and hsa-miR-129-1-3p, -129-2-3p, and -1288-3p with glycerol levels. The down-regulated targets of miR-1207-5p and -129-2-3p were enriched in PI3K and MAPK pathways and 8 out of the 12 enriched pathways were down-regulated in individuals with MetS. In conclusion microRNAs associated with several aspects of MetS, possibly regulating glucose and lipid metabolism.
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http://dx.doi.org/10.1016/j.mce.2014.04.013DOI Listing
June 2014

Associations of the Baltic Sea diet with obesity-related markers of inflammation.

Ann Med 2014 Mar 22;46(2):90-6. Epub 2014 Jan 22.

Department of Chronic Disease Prevention, National Institute for Health and Welfare , Helsinki and Turku , Finland.

Introduction: Inflammation is an important contributor to the development of chronic diseases. We examined whether a healthy Nordic diet, also called the Baltic Sea diet, associates with lower concentrations of inflammatory markers.

Methods: We used two independent cross-sectional studies: the DILGOM study including Finnish participants aged 25-74 years (n = 4579), and the Helsinki Birth Cohort Study including individuals born at Helsinki University Central Hospital between 1934 and 1944 and who participated in a clinical examination in 2001-2004 (n = 1911). Both studies measured anthropometrics, drew blood, and assessed concentrations of leptin, high-molecular-weight adiponectin, tumor necrosis factor α, interleukin 6, and high-sensitivity C-reactive protein (hs-CRP). A food frequency questionnaire was used to measure dietary intake over the past year and calculate the Baltic Sea Diet Score (BSDS).

Results: In both studies, linear regression adjusting for age, sex, energy intake, lifestyle factors, obesity, statin medication, and upstream inflammatory markers revealed an inverse association between the BSDS and hs-CRP concentrations (P < 0.01). Especially, high intake of Nordic fruits and cereals, low intake of red and processed meat, and moderate intake of alcohol contributed to the emerged association (P < 0.05). The BSDS did not associate with other inflammatory markers.

Conclusion: The Baltic Sea diet is associated with lower hs-CRP concentrations.
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http://dx.doi.org/10.3109/07853890.2013.870020DOI Listing
March 2014

Infancy-onset dietary counseling of low-saturated-fat diet improves insulin sensitivity in healthy adolescents 15-20 years of age: the Special Turku Coronary Risk Factor Intervention Project (STRIP) study.

Diabetes Care 2013 Oct 25;36(10):2952-9. Epub 2013 Jun 25.

Corresponding author: Olli Oranta,

Objective: We reported previously that low-saturated-fat dietary counseling started in infancy improves insulin sensitivity in healthy children 9 years of age. The aim of this study was to evaluate the effect of lifelong dietary counseling on insulin sensitivity in healthy adolescents between 15 and 20 years of age. In addition, we examined dietary fiber intake and the polyunsaturated fatty acid (PUFA)+monounsaturated (MUFA)-to-saturated fatty acid (SFA) ratio in the intervention and control adolescents and the association of these dietary factors with homeostasis model of insulin resistance (HOMA-IR).

Research Design And Methods: The study comprised adolescents participating in the randomized, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP) study, which aims to guide the study participants toward a diet beneficial for cardiovascular health. HOMA-IR was assessed annually between 15 and 20 years of age (n=518; intervention, n=245; control, n=273), along with diet, BMI, pubertal status, serum cotinine concentrations, and physical activity. Dietary counseling was given biannually during the follow-up.

Results: HOMA-IR was lower (7.5% on average) in the intervention group than in the control group between 15 and 20 years of age (P=0.0051). The intervention effect was similar in girls and boys. The PUFA+MUFA-to-SFA ratio was higher (P<0.0001) and the dietary fiber (g/MJ) intake was higher (P=0.0058) in the intervention group compared with the control group. There was no association between the PUFA+MUFA-to-/SFA ratio and HOMA-IR, whereas dietary fiber intake (g/MJ) was associated with HOMA-IR in girls (P<0.0001).

Conclusions: Dietary counseling initiated in infancy and maintained until 20 years of age was associated with improved insulin sensitivity in adolescents.
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http://dx.doi.org/10.2337/dc13-0361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781523PMC
October 2013

Computationally estimated apolipoproteins B and A1 in predicting cardiovascular risk.

Atherosclerosis 2013 Jan 2;226(1):245-51. Epub 2012 Nov 2.

Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland.

Objective: Apolipoproteins B (apoB) and A1 (apoA1) may be better markers of atherosclerosis than serum lipids. We used computational methods to estimate apoB and apoA1 from serum total cholesterol, HDL-cholesterol and triglycerides and tested their clinical value in comparison to measured apoB and apoA1 values.

Methods: ApoB and apoA1 were measured with standard methods and estimated based on neural network regression models in 2166 young adult with data on carotid artery intima-media thickness (cIMT).

Results: Correlations between estimated and measured apoB and apoA1 were r = 0.98 and r = 0.95, respectively. ApoB/apoA1-ratio (both measured and estimated) associated with cIMT in multivariable models, and predicted cIMT at all levels of LDL-cholesterol concentration. Strong correlations between the estimated apolipoproteins and those measured from fasting samples were replicated in over 15,000 Caucasian subjects (r = 0.93-0.96 for apoB and r = 0.91-0.92 for apoA1). Correlations with cIMT were replicated in over 2000 individuals. Estimated apoB/apoA1-ratio calculated from non-fasting lipids in over 20,000 individuals in the INTERHEART study was better than any of the cholesterol measures for estimation of the myocardial risk.

Conclusions: Serum cholesterol, HDL-cholesterol and triglycerides can be used to compute clinically useful estimates of apoB and apoA1. Using this methodology, estimates of apolipoproteins could be routinely added to laboratory reports to complement lipoprotein lipids in risk assessment.
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http://dx.doi.org/10.1016/j.atherosclerosis.2012.10.049DOI Listing
January 2013

Plasminogen activator inhitor-1 associates with cardiovascular risk factors in healthy young adults in the Cardiovascular Risk in Young Finns Study.

Atherosclerosis 2012 Sep 16;224(1):208-12. Epub 2012 Jul 16.

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

Aims: Hypofibrinolysis displayed by elevated serum plasminogen activator inhibitor 1 (PAI-1) level has been associated with cardiovascular disease (CVD) and its risk factors such as obesity and insulin resistance. However, no studies have examined associations between PAI-1 and CVD risk factors in healthy subjects. We examined associations between serum PAI-1, ultrasound markers of atherosclerosis and CVD risk factors and whether PAI-1 improves prediction of atherosclerosis over known risk factors in a cohort of asymptomatic adults.

Methods: We analyzed PAI-1 and CVD risk factors and assessed carotid intima-media thickness (cIMT), distensibility (CDist) and the presence of a carotid atherosclerotic plaque and flow-mediated dilation (FMD) ultrasonographically for 2202 adults (993 men and 1,209 women, aged 30-45 years) participating in the ongoing longitudinal cohort study, The Cardiovascular Risk in Young Finns Study. High cIMT was defined as >90th percentile and/or carotid plaque and low CDist and low FMD as <20th percentile.

Results: In bivariate analyses, PAI-1 correlated directly with cIMT and the risk factors: blood pressure, BMI, waist and hip circumference, alcohol use, total and LDL-cholesterol, triglycerides, glomerular filtration rate, high-sensitivity CRP and glucose (all P<0.005). PAI-1 was higher in men and increased with age. Inverse correlation was observed with CDist, HDL-cholesterol and adiponectin in both sexes, with testosterone and sex hormone binding globulin in men and with creatinine and oral contraceptive use in women (P<0.005). Independent direct associations were observed between PAI-1 and waist circumference, serum triglycerides, insulin, alcohol use and age and inverse with serum creatinine, HDL-cholesterol and adiponectin. PAI-1 did not improve estimation of high cIMT, low CDist and low FMD over conventional risk factors (P for difference in area under curve ≥ 0.37).

Conclusion: PAI-1 was independently associated with several known CVD risk factors, especially obesity markers, in both men and women. However, addition of PAI-1 to known risk factors did not improve cross-sectional prediction of high cIMT, low CDist and low FMD suggesting that PAI-1 is not a clinically important biomarker in early atherosclerosis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2012.06.062DOI Listing
September 2012

Associations between serum uric acid and markers of subclinical atherosclerosis in young adults. The cardiovascular risk in Young Finns study.

Atherosclerosis 2012 Aug 7;223(2):497-503. Epub 2012 Jun 7.

The Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 10, P.O. Box 52, FI-20520 Turku, Finland.

Background And Methods: Serum uric acid (SUA) is a suggested biomarker for established coronary artery disease, but the role of SUA in early phases of atherosclerosis is controversial. The relations of SUA with vascular markers of subclinical atherosclerosis, including carotid artery intima-media thickness (cIMT), carotid plaque, carotid distensibility (Cdist) and brachial flow-mediated dilatation (FMD) were examined in 1985 young adults aged 30-45 years. In addition to ordinary regression, we used Mendelian randomization techniques to infer causal associations.

Results: In women, the independent multivariate correlates of SUA included BMI, creatinine, alcohol use, triglycerides, glucose and adiponectin (inverse association) (Model R(2) = 0.30). In men, the correlates were BMI, creatinine, triglycerides, C-reactive protein, alcohol use, total cholesterol and adiponectin (inverse) (Model R(2) = 0.33). BMI alone explained most of the variation of SUA levels both in women and men (Partial R(2) ∼ 0.2). When SUA was modeled as an explanatory variable for vascular markers, it directly associated with cIMT and inversely with Cdist in age- and sex-adjusted analysis. After further adjustments for BMI or glomerular filtration rate, these relations were reduced to non-significance. No associations were found between SUA and FMD or the presence of a carotid plaque. Mendelian randomization analyses using known genetic variants for BMI and SUA confirmed that BMI is causally linked to SUA and that BMI is a significant confounder in the association between SUA and cIMT.

Conclusion: SUA is associated with cardiovascular risk markers in young adults, especially BMI, but we found no evidence that SUA would have an independent role in the pathophysiology of early atherosclerosis.
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http://dx.doi.org/10.1016/j.atherosclerosis.2012.05.036DOI Listing
August 2012

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Authors:
Zari Dastani Marie-France Hivert Nicholas Timpson John R B Perry Xin Yuan Robert A Scott Peter Henneman Iris M Heid Jorge R Kizer Leo-Pekka Lyytikäinen Christian Fuchsberger Toshiko Tanaka Andrew P Morris Kerrin Small Aaron Isaacs Marian Beekman Stefan Coassin Kurt Lohman Lu Qi Stavroula Kanoni James S Pankow Hae-Won Uh Ying Wu Aurelian Bidulescu Laura J Rasmussen-Torvik Celia M T Greenwood Martin Ladouceur Jonna Grimsby Alisa K Manning Ching-Ti Liu Jaspal Kooner Vincent E Mooser Peter Vollenweider Karen A Kapur John Chambers Nicholas J Wareham Claudia Langenberg Rune Frants Ko Willems-Vandijk Ben A Oostra Sara M Willems Claudia Lamina Thomas W Winkler Bruce M Psaty Russell P Tracy Jennifer Brody Ida Chen Jorma Viikari Mika Kähönen Peter P Pramstaller David M Evans Beate St Pourcain Naveed Sattar Andrew R Wood Stefania Bandinelli Olga D Carlson Josephine M Egan Stefan Böhringer Diana van Heemst Lyudmyla Kedenko Kati Kristiansson Marja-Liisa Nuotio Britt-Marie Loo Tamara Harris Melissa Garcia Alka Kanaya Margot Haun Norman Klopp H-Erich Wichmann Panos Deloukas Efi Katsareli David J Couper Bruce B Duncan Margreet Kloppenburg Linda S Adair Judith B Borja James G Wilson Solomon Musani Xiuqing Guo Toby Johnson Robert Semple Tanya M Teslovich Matthew A Allison Susan Redline Sarah G Buxbaum Karen L Mohlke Ingrid Meulenbelt Christie M Ballantyne George V Dedoussis Frank B Hu Yongmei Liu Bernhard Paulweber Timothy D Spector P Eline Slagboom Luigi Ferrucci Antti Jula Markus Perola Olli Raitakari Jose C Florez Veikko Salomaa Johan G Eriksson Timothy M Frayling Andrew A Hicks Terho Lehtimäki George Davey Smith David S Siscovick Florian Kronenberg Cornelia van Duijn Ruth J F Loos Dawn M Waterworth James B Meigs Josee Dupuis J Brent Richards Benjamin F Voight Laura J Scott Valgerdur Steinthorsdottir Christian Dina Ryan P Welch Eleftheria Zeggini Cornelia Huth Yurii S Aulchenko Gudmar Thorleifsson Laura J McCulloch Teresa Ferreira Harald Grallert Najaf Amin Guanming Wu Cristen J Willer Soumya Raychaudhuri Steve A McCarroll Oliver M Hofmann Ayellet V Segrè Mandy van Hoek Pau Navarro Kristin Ardlie Beverley Balkau Rafn Benediktsson Amanda J Bennett Roza Blagieva Eric Boerwinkle Lori L Bonnycastle Kristina Bengtsson Boström Bert Bravenboer Suzannah Bumpstead Noël P Burtt Guillaume Charpentier Peter S Chines Marilyn Cornelis Gabe Crawford Alex S F Doney Katherine S Elliott Amanda L Elliott Michael R Erdos Caroline S Fox Christopher S Franklin Martha Ganser Christian Gieger Niels Grarup Todd Green Simon Griffin Christopher J Groves Candace Guiducci Samy Hadjadj Neelam Hassanali Christian Herder Bo Isomaa Anne U Jackson Paul R V Johnson Torben Jørgensen Wen H L Kao Augustine Kong Peter Kraft Johanna Kuusisto Torsten Lauritzen Man Li Aloysius Lieverse Cecilia M Lindgren Valeriya Lyssenko Michel Marre Thomas Meitinger Kristian Midthjell Mario A Morken Narisu Narisu Peter Nilsson Katharine R Owen Felicity Payne Ann-Kristin Petersen Carl Platou Christine Proença Inga Prokopenko Wolfgang Rathmann N William Rayner Neil R Robertson Ghislain Rocheleau Michael Roden Michael J Sampson Richa Saxena Beverley M Shields Peter Shrader Gunnar Sigurdsson Thomas Sparsø Klaus Strassburger Heather M Stringham Qi Sun Amy J Swift Barbara Thorand Jean Tichet Tiinamaija Tuomi Rob M van Dam Timon W van Haeften Thijs van Herpt Jana V van Vliet-Ostaptchouk G Bragi Walters Michael N Weedon Cisca Wijmenga Jacqueline Witteman Richard N Bergman Stephane Cauchi Francis S Collins Anna L Gloyn Ulf Gyllensten Torben Hansen Winston A Hide Graham A Hitman Albert Hofman David J Hunter Kristian Hveem Markku Laakso Andrew D Morris Colin N A Palmer Igor Rudan Eric Sijbrands Lincoln D Stein Jaakko Tuomilehto Andre Uitterlinden Mark Walker Richard M Watanabe Goncalo R Abecasis Bernhard O Boehm Harry Campbell Mark J Daly Andrew T Hattersley Oluf Pedersen Inês Barroso Leif Groop Rob Sladek Unnur Thorsteinsdottir James F Wilson Thomas Illig Philippe Froguel Cornelia M van Duijn Kari Stefansson David Altshuler Michael Boehnke Mark I McCarthy Nicole Soranzo Eleanor Wheeler Nicole L Glazer Nabila Bouatia-Naji Reedik Mägi Joshua Randall Paul Elliott Denis Rybin Abbas Dehghan Jouke Jan Hottenga Kijoung Song Anuj Goel Taina Lajunen Alex Doney Christine Cavalcanti-Proença Meena Kumari Nicholas J Timpson Carina Zabena Erik Ingelsson Ping An Jeffrey O'Connell Jian'an Luan Amanda Elliott Steven A McCarroll Rosa Maria Roccasecca François Pattou Praveen Sethupathy Yavuz Ariyurek Philip Barter John P Beilby Yoav Ben-Shlomo Sven Bergmann Murielle Bochud Amélie Bonnefond Knut Borch-Johnsen Yvonne Böttcher Eric Brunner Suzannah J Bumpstead Yii-Der Ida Chen Peter Chines Robert Clarke Lachlan J M Coin Matthew N Cooper Laura Crisponi Ian N M Day Eco J C de Geus Jerome Delplanque Annette C Fedson Antje Fischer-Rosinsky Nita G Forouhi Maria Grazia Franzosi Pilar Galan Mark O Goodarzi Jürgen Graessler Scott Grundy Rhian Gwilliam Göran Hallmans Naomi Hammond Xijing Han Anna-Liisa Hartikainen Caroline Hayward Simon C Heath Serge Hercberg David R Hillman Aroon D Hingorani Jennie Hui Joe Hung Marika Kaakinen Jaakko Kaprio Y Antero Kesaniemi Mika Kivimaki Beatrice Knight Seppo Koskinen Peter Kovacs Kirsten Ohm Kyvik G Mark Lathrop Debbie A Lawlor Olivier Le Bacquer Cécile Lecoeur Yun Li Robert Mahley Massimo Mangino María Teresa Martínez-Larrad Jarred B McAteer Ruth McPherson Christa Meisinger David Melzer David Meyre Braxton D Mitchell Sutapa Mukherjee Silvia Naitza Matthew J Neville Marco Orrù Ruth Pakyz Giuseppe Paolisso Cristian Pattaro Daniel Pearson John F Peden Nancy L Pedersen Andreas F H Pfeiffer Irene Pichler Ozren Polasek Danielle Posthuma Simon C Potter Anneli Pouta Michael A Province Nigel W Rayner Kenneth Rice Samuli Ripatti Fernando Rivadeneira Olov Rolandsson Annelli Sandbaek Manjinder Sandhu Serena Sanna Avan Aihie Sayer Paul Scheet Udo Seedorf Stephen J Sharp Beverley Shields Gunnar Sigurðsson Eric J G Sijbrands Angela Silveira Laila Simpson Andrew Singleton Nicholas L Smith Ulla Sovio Amy Swift Holly Syddall Ann-Christine Syvänen Anke Tönjes André G Uitterlinden Ko Willems van Dijk Dhiraj Varma Sophie Visvikis-Siest Veronique Vitart Nicole Vogelzangs Gérard Waeber Peter J Wagner Andrew Walley Kim L Ward Hugh Watkins Sarah H Wild Gonneke Willemsen Jaqueline C M Witteman John W G Yarnell Diana Zelenika Björn Zethelius Guangju Zhai Jing Hua Zhao M Carola Zillikens Ingrid B Borecki Pierre Meneton Patrik K E Magnusson David M Nathan Gordon H Williams Kaisa Silander Stefan R Bornstein Peter Schwarz Joachim Spranger Fredrik Karpe Alan R Shuldiner Cyrus Cooper Manuel Serrano-Ríos Lars Lind Lyle J Palmer Frank B Hu Paul W Franks Shah Ebrahim Michael Marmot W H Linda Kao Peter Paul Pramstaller Alan F Wright Michael Stumvoll Anders Hamsten Thomas A Buchanan Timo T Valle Jerome I Rotter Brenda W J H Penninx Dorret I Boomsma Antonio Cao Angelo Scuteri David Schlessinger Manuela Uda Aimo Ruokonen Marjo-Riitta Jarvelin Leena Peltonen Vincent Mooser Robert Sladek Kiran Musunuru Albert V Smith Andrew C Edmondson Ioannis M Stylianou Masahiro Koseki James P Pirruccello Daniel I Chasman Christopher T Johansen Sigrid W Fouchier Gina M Peloso Maja Barbalic Sally L Ricketts Joshua C Bis Mary F Feitosa Marju Orho-Melander Olle Melander Xiaohui Li Mingyao Li Yoon Shin Cho Min Jin Go Young Jin Kim Jong-Young Lee Taesung Park Kyunga Kim Xueling Sim Rick Twee-Hee Ong Damien C Croteau-Chonka Leslie A Lange Joshua D Smith Andreas Ziegler Weihua Zhang Robert Y L Zee John B Whitfield John R Thompson Ida Surakka Tim D Spector Johannes H Smit Juha Sinisalo James Scott Juha Saharinen Chiara Sabatti Lynda M Rose Robert Roberts Mark Rieder Alex N Parker Guillaume Pare Christopher J O'Donnell Markku S Nieminen Deborah A Nickerson Grant W Montgomery Wendy McArdle David Masson Nicholas G Martin Fabio Marroni Gavin Lucas Robert Luben Marja-Liisa Lokki Guillaume Lettre Lenore J Launer Edward G Lakatta Reijo Laaksonen Kirsten O Kyvik Inke R König Kay-Tee Khaw Lee M Kaplan Åsa Johansson A Cecile J W Janssens Wilmar Igl G Kees Hovingh Christian Hengstenberg Aki S Havulinna Nicholas D Hastie Tamara B Harris Talin Haritunians Alistair S Hall Leif C Groop Elena Gonzalez Nelson B Freimer Jeanette Erdmann Kenechi G Ejebe Angela Döring Anna F Dominiczak Serkalem Demissie Panagiotis Deloukas Ulf de Faire Gabriel Crawford Yii-der I Chen Mark J Caulfield S Matthijs Boekholdt Themistocles L Assimes Thomas Quertermous Mark Seielstad Tien Y Wong E-Shyong Tai Alan B Feranil Christopher W Kuzawa Herman A Taylor Stacey B Gabriel Hilma Holm Vilmundur Gudnason Ronald M Krauss Jose M Ordovas Patricia B Munroe Jaspal S Kooner Alan R Tall Robert A Hegele John J P Kastelein Eric E Schadt David P Strachan Muredach P Reilly Nilesh J Samani Heribert Schunkert L Adrienne Cupples Manjinder S Sandhu Paul M Ridker Daniel J Rader Sekar Kathiresan

PLoS Genet 2012 29;8(3):e1002607. Epub 2012 Mar 29.

Department of Epidemiology, Biostatistics, and Occupational Health, Jewish General Hospital, Lady Davis Institute, McGill University, Montreal, Canada.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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http://dx.doi.org/10.1371/journal.pgen.1002607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315470PMC
September 2012

Relation of total and free testosterone and sex hormone-binding globulin with cardiovascular risk factors in men aged 24-45 years. The Cardiovascular Risk in Young Finns Study.

Atherosclerosis 2012 May 21;222(1):257-62. Epub 2012 Feb 21.

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

Background: Total and free testosterone decrease gradually in men with advancing age but it is not completely known how lower levels of testosterone are related with various cardiovascular risk factors. We studied the levels of total testosterone, calculated free testosterone and sex hormone-binding globulin (SHBG), and their relations with cardiovascular risk factors in young Finnish men.

Methods: The study cohort consisted of 24-45-year-old men participating the Cardiovascular Risk in Young Finns Study in the follow-up surveys performed in 2001 (N=1024) and 2007 (N=991). Levels of total testosterone, SHBG, lipids, glucose, insulin, blood pressure and anthropometric factors were measured and free testosterone was calculated.

Results: In multivariable analyses adjusted for age, body mass index and life-style factors (alcohol consumption, smoking and physical activity), total and calculated free testosterone were inversely correlated with triglycerides (both P<0.0001), insulin (P=0.0004 and P=0.01), systolic blood pressure (P=0.007 and P=0.01), and directly with high-density lipoprotein (HDL) cholesterol (P<0.0001 and P=0.003). SHBG was inversely correlated with triglycerides and insulin, and directly with HDL-cholesterol (all P<0.001). In longitudinal analyses, lower levels of testosterone and SHBG were associated with higher levels of triglycerides and insulin six years later (all P<0.01). Baseline level of SHBG was directly associated with HDL-cholesterol (P<0.0001).

Conclusion: In young and middle-aged men, higher levels of testosterone and SHBG are associated with favourable cardiovascular risk profile characterized by lower levels of triglycerides, insulin and systolic blood pressure, and higher levels of HDL-cholesterol.
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http://dx.doi.org/10.1016/j.atherosclerosis.2012.02.020DOI Listing
May 2012

Socioeconomic status, cardiovascular risk factors, and subclinical atherosclerosis in young adults: the cardiovascular risk in Young Finns Study.

Arterioscler Thromb Vasc Biol 2012 Mar 5;32(3):815-21. Epub 2012 Jan 5.

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

Objective: The goal of this study was to investigate the extent to which socioeconomic status (SES) in young adults is associated with cardiovascular risk factor levels and carotid intima-media thickness (IMT) and their changes over a 6-year follow-up period.

Methods And Results: The study population included 1813 subjects participating in the 21- and 27-year follow-ups of the Cardiovascular Risk in Young Finns Study (baseline age 24-39 years in 2001). At baseline, SES (indexed with education) was inversely associated with body mass index (P=0.0002), waist circumference (P<0.0001), glucose (P=0.01), and insulin (P=0.0009) concentrations; inversely associated with alcohol consumption (P=0.02) and cigarette smoking (P<0.0001); and directly associated with high-density lipoprotein cholesterol levels (P=0.05) and physical activity (P=0.006). Higher SES was associated with a smaller 6-year increase in body mass index (P=0.001). Education level and IMT were not associated (P=0.58) at baseline, but an inverse association was observed at follow-up among men (P=0.004). This became nonsignificant after adjustment with conventional risk factors (P=0.11). In all subjects, higher education was associated with a smaller increase in IMT during the follow-up (P=0.002), and this association remained after adjustments for conventional risk factors (P=0.04).

Conclusion: This study shows that high education in young adults is associated with favorable cardiovascular risk factor profile and 6-year change of risk factors. Most importantly, the progression of carotid atherosclerosis was slower among individuals with higher educational level.
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http://dx.doi.org/10.1161/ATVBAHA.111.241182DOI Listing
March 2012

Plasma osteopontin is not associated with vascular markers of subclinical atherosclerosis in a population of young adults without symptoms of cardiovascular disease. The Cardiovascular Risk in Young Finns Study.

Scand J Clin Lab Invest 2011 Dec 21;71(8):683-9. Epub 2011 Oct 21.

Department of Clinical Physiology, Turku University Hospital, Turku, Finland.

Objective: Osteopontin is used as a biomarker for measuring the severity of atherosclerosis, but the role of osteopontin in the pathogenesis of atherosclerosis is not clear.

Methods: The distribution and determinants of osteopontin were studied in a randomized cohort of 1,817 young adults (aged 30–45 years) without clinical symptoms of atherosclerosis.

Results: The mean ± SD osteopontin concentration was 60.7 ± 15.6 μg/mL in men and 51.7 ± 16.0 μg/mL in women. In multivariable models the correlates of osteopontin explained 6.9% (Model R² of the total variation in osteopontin in men, including CRP (β = 3.02, p < 0.0001), SHBG (β = 0.21, p < 0.0001), total cholesterol (β = − 1.78, p = 0.002), age (β = − 0.26, p = 0.02) and alcohol use (β = 0.57, p = 0.04) and of these CRP had the greatest influence (Partial R² = 2.1%). In women, multivariable correlates of osteopontin included CRP (β = 2.90, p < 0.0001), total cholesterol (β = − 1.99, p = 0.002), insulin (β = − 1.76, p = 0.001), physical activity (β = 0.66, p = 0.03), adiponectin (β = 0.25, p = 0.008) and diastolic blood pressure (β = 0.14, p = 0.003). These five variables explained 6.7% (Model R²) of the total variation in osteopontin, with CRP (Partial R² = 2.7%) having the greatest influence. Osteopontin was not associated with carotid intima-media thickness, carotid elasticity, brachial endothelial function or the presence of a carotid plaque in either sex.

Conclusion: We found no evidence of association between osteopontin levels and early vascular markers of atherosclerosis in asymptomatic young adults, suggesting that osteopontin is not implicated in the preclinical atherosclerotic changes in vascular structure and function.
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http://dx.doi.org/10.3109/00365513.2011.621027DOI Listing
December 2011

Apolipoprotein B, oxidized low-density lipoprotein, and LDL particle size in predicting the incidence of metabolic syndrome: the Cardiovascular Risk in Young Finns study.

Eur J Prev Cardiol 2012 Dec 29;19(6):1296-303. Epub 2011 Sep 29.

Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 10, Turku, Finland.

Objective: To test whether serum apolipoprotein B (apoB) and low-density lipoprotein (LDL) particle characteristics (oxidation and mean particle size) predict the incidence of metabolic syndrome (MetS).

Methods: The 6-year follow-up study included 1429 adults (baseline mean age 31.5). Lipids, apoB, and apoA1 were measured at baseline in 2001. LDL oxidation was measured with monoclonal antibody-based enzyme-linked immunosorbent assay (oxLDL-prot) and with a method measuring oxidized lipids in LDL (oxLDL-lipids). Mean LDL particle size was calculated from proton nuclear magnetic resonance spectroscopy data.

Results: Increased concentrations of both oxLDL-measures were associated with increased apoB levels but not with LDL particle size. The odds ratios (95% confidence intervals) for MetS incidence during a 6-year follow up by quartiles of apoB were 2.0 (1.0-3.8) for the second quartile, 3.1 (1.7-5.7) for the third quartile, and 4.2 (2.3-7.6) for the fourth quartile. This association remained after adjusting for age, sex, body mass index, homeostasis model assessment for insulin resistance, C-reactive protein, smoking, LDL cholesterol, oxidized LDL measures (p ≤ 0.01) in addition to risk factors comprising the MetS (p = 0.03). OxLDL-prot and oxLDL-lipids levels were not independently associated with incident MetS after adjusting for apoB. Mean LDL particle size was not associated with the incidence of MetS.

Conclusion: ApoB is associated with increased risk of MetS incidence. We found no clear evidence to suggest that increased LDL oxidation or small mean LDL particle size would facilitate the development of MetS.
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http://dx.doi.org/10.1177/1741826711425343DOI Listing
December 2012

Inflammation in psychotic disorders: a population-based study.

Psychiatry Res 2011 Sep 27;189(2):305-11. Epub 2011 Jul 27.

Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland.

We investigated inflammatory markers in psychotic disorders and their association with metabolic comorbidity, antipsychotic medication, smoking, alcohol use, physical condition, and mood. From the population-based Finnish Health 2000 study, we identified all persons with schizophrenia (n=45), other nonaffective psychosis (ONAP) (n=57), affective psychosis (n=37) and chose controls matched by age, sex, and region of residence. We found that persons with schizophrenia had significantly higher sIL-2Rα, IL-1RA and C-reactive protein (CRP), persons with ONAP significantly higher IL-1RA and CRP and persons with affective psychosis almost significantly higher TNF-α compared to their matched controls. Current antipsychotic use was associated with elevated IL-1RA and CRP. After taking metabolic and lifestyle-related variables that associated with inflammatory markers into account, only antipsychotic medication remained associated with elevated IL-1RA and TNF-α which are markers related to the activation of innate immune system. CRP was influenced by both antipsychotic medication and nonaffective psychosis. sIL-2Rα, a marker of T-cell activation, was associated with depressive symptoms, schizophrenia, and affective psychosis. We conclude that in persons with psychotic disorders, activation of mononuclear phagocyte system was mostly related to metabolic comorbidity and antipsychotic medication use, whereas T-cell activation had a more direct relationship with both psychotic disorders and depressive symptoms.
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http://dx.doi.org/10.1016/j.psychres.2011.07.006DOI Listing
September 2011

Evaluation of multiplex immunoassays, used for determination of adiponectin, resistin, leptin, and ghrelin from human blood samples, in comparison to ELISA assays.

Scand J Clin Lab Invest 2011 May 3;71(3):221-6. Epub 2011 Feb 3.

National Institute for Health and Welfare, Department of Chronic Disease Prevention, Turku, Finland.

Background: Many different multiplex biomarker immunoassays based on Luminex®-technology have been developed during recent years. We have evaluated the performance of two multiplex immunoassays for determination of adiponectin, resistin, ghrelin and leptin in comparison to corresponding, conventional ELISA assays.

Methods: Human serum or plasma samples were analysed by commercially available multiplex and ELISA immunoassays manufactured by Millipore Corp.

Results: The correlation between tested multiplex and ELISA immunoassays was good, r > 0.9 for all analytes. The agreement between the methods was acceptable but there were differences in analytical levels. Intra- and inter-assay variation was comparable between both assays. The coefficient of variation for all analytes, independent of method, was ≤15% and for most of them <10%.

Conclusion: The performance of the tested multiplex assays was reasonable and they can be considered as valid options to the conventional ELISA assays. However, results obtained with the two different techniques are not necessarily interchangeable due to differences in the concentration levels.
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http://dx.doi.org/10.3109/00365513.2011.554996DOI Listing
May 2011

Association of liver enzymes with metabolic syndrome and carotid atherosclerosis in young adults. The Cardiovascular Risk in Young Finns Study.

Ann Med 2012 Mar 24;44(2):187-95. Epub 2011 Jan 24.

Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Kiinamyllynkatu 10, Turku, Finland.

Objective: We examined whether metabolic syndrome (MetS) predicts increased alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) levels in young adults, whether spontaneous recovery from MetS has a favorable effect on liver enzyme activities, and whether these enzymes contribute to the atherogenicity of MetS (assessed by carotid intima-media thickness (IMT)).

Methods: The study included 1,553 subjects (base-line age 31.5 ± 5.0 years). ALT and GGT were measured in 2007. MetS was diagnosed by the new Joint Interim Societies definition.

Results: ALT and GGT levels were higher in subjects with MetS compared to those without in 2007. The association was independent of alcohol intake and BMI. In multivariable models adjusted for base-line age, LDL cholesterol, CRP, alcohol intake, and adiponectin, MetS in 2001 predicted increased ALT (β ± SEM = 0.320 ± 0.062, P < 0.0001 in men; 0.134 ± 0.059, P = 0.02 in women) and GGT (β ± SEM = 0.222 ± 0.067, P < 0.0001 in men; 0.236 ± 0.060, P < 0.0001 in women) levels after 6 years. Subjects with MetS only at base-line (2001) had lower ALT levels after 6 years compared to subjects with persistent and incident MetS. No statistically significant interaction for MetS*ALT (P = 0.81) or MetS*GGT (P = 0.92) on IMT was observed.

Conclusion: In young adults MetS may induce liver enzyme changes that indicate increased risk of non-alcoholic fatty liver disease, but we found no evidence that increased enzyme levels would amplify the atherogenicity of MetS.
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http://dx.doi.org/10.3109/07853890.2010.532152DOI Listing
March 2012

Conventional and Mendelian randomization analyses suggest no association between lipoprotein(a) and early atherosclerosis: the Young Finns Study.

Int J Epidemiol 2011 Apr 14;40(2):470-8. Epub 2010 Nov 14.

Department of Epidemiology, University College London, London, UK.

Background: Lipoprotein(a) [Lp(a)] is an established risk factor for coronary disease and stroke, but mechanisms underlying this association are unknown. We examined the association of Lp(a) with early atherosclerosis by using conventional epidemiologic analysis and a Mendelian randomization analysis. The latter utilized genetic variants that are associated with Lp(a) to estimate causal effect.

Methods: A prospective population-based cohort study of 939 men and 1141 women was conducted. Lp(a) was measured repeatedly at mean ages 17 and 38 years. Measurements of carotid intima-media thickness (IMT) and brachial flow-mediated dilation (FMD) at mean ages 32 and 38 years were used to determine the level and 6-year progression of subclinical atherosclerosis. Lp(a)-related genetic variant, rs783147, was identified by a genome wide association analysis (P = 3.1 × 10⁻⁵⁸), and a genetic score was constructed based on 10 Lp(a)-related variants. Mendelian randomization test was performed using a two-stage instrumental variables analysis.

Results: rs783147 and the genetic score were strong instruments for nonconfounded Lp(a) levels (F-statistics 269.6 and 446.0 in the first-stage instrumental variable analysis). However, Lp(a) levels were not associated with the levels of or change in IMT or FMD in any of the conventional and instrumental variables tests. The null finding was observed both with rs783147 and the genetic score as instruments and remained unchanged after adjustment for clinical characteristics, such as age, sex, HDL and LDL cholesterol, ApoB, systolic and diastolic blood pressure, diabetes and smoking.

Conclusions: Data from conventional and Mendelian randomization analyses provide no support for early atherogenic effects of increased Lp(a) levels.
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http://dx.doi.org/10.1093/ije/dyq205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3106966PMC
April 2011

Cardiovascular risk scores in the prediction of subclinical atherosclerosis in young adults: evidence from the cardiovascular risk in a young Finns study.

Eur J Cardiovasc Prev Rehabil 2010 Oct;17(5):549-55

Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku and Turku University Hospital dFinnish Institute of Occupational Health, Helsinki, Finland.

Aim: To study the utility of risk scores in the prediction of subclinical atherosclerosis in young adults.

Methods And Results: Participants were 2204 healthy Finnish adults aged 24-39 years in 2001 from a population-based follow-up study Cardiovascular Risk in Young Finns. We examined the performance of the Framingham, Reynolds, Systematic Coronary Risk Evaluation (SCORE), PROCAM, and Finrisk cardiovascular risk scores to predict subclinical atherosclerosis, that is carotid artery intima-media thickness (IMT) and plaque, carotid artery distensibility (CDist), and brachial artery flow-mediated dilatation (FMD) 6 years later. In a 6-year prediction of high IMT (highest decile or plaque), areas under the receiver operating characteristic curves (AUC) for baseline Finrisk (0.733), SCORE (0.726), PROCAM (0.712), and Reynolds (0.729) risk scores were similar as for Framingham risk score (0.728, P always ≥0.15). All risk scores had a similar discrimination in predicting low CDist (lowest decile) (0.652, 0.642, 0.639, 0.658, 0.652 respectively, P always ≥0.41). In the prediction of low FMD (lowest decile), Finrisk, PROCAM, Reynolds, and Framingham scores had similar AUCs (0.578, 0.594, 0.582, 0.568, P always ≥0.08) and SCORE discriminated slightly better (AUC=0.596, P<0.05). The prediction of subclinical outcomes was consistent when estimated from other statistical measures of discrimination, reclassification, and calibration.

Conclusion: Cardiovascular disease risk scores had equal value in predicting subclinical atherosclerosis measured by IMT and CDist in young adults. SCORE was more accurate in predicting low FMD than Framingham risk score.
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http://dx.doi.org/10.1097/HJR.0b013e3283386419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907448PMC
October 2010

Genetic variation of the interleukin-1 family and nongenetic factors determining the interleukin-1 receptor antagonist phenotypes.

Metabolism 2010 Oct 23;59(10):1520-7. Epub 2010 Feb 23.

Department of Medicine, HUCH-Helsinki University Central Hospital, Box 340 HUS, FI-00029 Helsinki, Finland.

The natural anti-inflammatory protein interleukin-1 receptor antagonist (IL-1Ra) inhibits the activity of IL-1 and is associated with vascular injury and metabolic disorders. We analyzed genetic and nongenetic determinants of the IL-1Ra phenotype. Fifteen haplotype-tagging single nucleotide polymorphisms (SNPs) in the IL-1α (IL1A), IL-1β (IL1B), and IL-1 receptor antagonist (IL-1RN) genes were determined in the Health 2000 survey (n = 6771) and European myocardial infarction (MI) survivors (n = 972). Three SNPs were genotyped in the FINRISK97 (FR97) study (n = 7222). We found 3 IL1RN variants that were associated with the IL-1Ra phenotype in the study populations and remained significant after Bonferroni correction with increasing significance in meta-analysis (P values for rs3213448,rs315952, rs315949, respectively: 5.5 x 10(-11), 1.5 x 10(-11), and 4.0 x 10(-14)). Minor allele of the rare IL1B variant rs1143642 was associated with decreased IL-1Ra levels in the Health 2000 and FR97 populations, and the association strengthened in the meta-analysis (P = 9.4 x 10(-7)). The proportion of variance explained by the IL1RN variant was larger in MI survivors (5.0%) than in the unselected population (0.5%). Body mass index was the strongest nongenetic predictor of the IL-1Ra phenotype, explaining 11.8% of the variance in Health 2000, 18.1% in FR97, and 25% in MI survivors. In conclusion, 3 IL1RN SNPs and 1 IL1B variant were determining IL-1Ra phenotype independently of body mass index and other metabolic phenotypes. The proportion of phenotypic variation in IL-1Ra explained by the genetic variants was, however, modest compared with the proportion explained by the body mass index.
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http://dx.doi.org/10.1016/j.metabol.2010.01.017DOI Listing
October 2010

Alcohol consumption is directly associated with carotid intima-media thickness in Finnish young adults: the Cardiovascular Risk in Young Finns Study.

Atherosclerosis 2009 Jun 30;204(2):e93-8. Epub 2008 Nov 30.

University of Turku, Department of Medicine, Finland.

Objectives: There is substantial epidemiological data suggesting a J- or U-shaped association between alcohol consumption and coronary events. However, some studies in experimental animals suggest that alcohol may increase atherosclerosis. Therefore, our aim was to study whether alcohol consumption is associated with carotid intima-media thickness (IMT), marker of subclinical atherosclerosis, in young, healthy adults.

Methods: Alcohol consumption, carotid IMT and conventional cardiovascular risk factors were investigated in 2074 subjects, aged 24-39 years.

Results: In subjects consuming none, >0 to <2, 2 to <4 or >or=4 units of alcohol per day, the respective carotid IMT values were 0.57+/-0.004, 0.59+/-0.003, 0.59+/-0.006, and 0.60+/-0.012 mm (mean+/-S.E.M., P<0.0001 for increasing IMT trend across alcohol consumption categories). This direct association between alcohol consumption and IMT was independent of age, sex and several cardiovascular risk factors, e.g. blood pressure, LDL-cholesterol, HDL-cholesterol, BMI, smoking, CRP and insulin (P=0.008 in multivariable regression model). The frequencies of drinking wine or strong alcohol beverages (respective P-values 0.03 and 0.01 for increasing IMT trend across beverage consuming frequency) were directly correlated with carotid IMT in models adjusted for age, sex and risk factors.

Conclusions: We found a direct relationship between alcohol consumption and carotid IMT in young adults. This association was independent of cardiovascular risk factors suggesting that in young healthy adults alcohol consumption may have pro-atherogenic effects.
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http://dx.doi.org/10.1016/j.atherosclerosis.2008.11.021DOI Listing
June 2009