Association of tobacco smoke exposure with metabolic profile from childhood to early adulthood: the Special Turku Coronary Risk Factor Intervention Project.

AIMS: To investigate the associations between passive tobacco smoke exposure and daily smoking with a comprehensive metabolic profile, measured repeatedly from childhood to adulthood. METHODS AND RESULTS: Study cohort was derived from the Special Turku Coronary Risk Factor Intervention Project (STRIP). Smoking status was obtained by questionnaire, while serum cotinine concentrations were measured using gas chromatography. Metabolic measures were quantified by nuclear magnetic resonance metabolomics at 9 (n = 539), 11 (n = 536), 13 (n = 525), 15 (n = 488), 17 (n = 455), and 19 (n = 409) years. Association of passive tobacco smoke exposure with metabolic profile compared participants who reported less-than-weekly smoking and had serum cotinine concentration <1 ng/mL (no exposure) with those whose cotinine concentration was ≥10 ng/mL (passive tobacco smoke exposure). Associations of daily smoking with metabolic profile in adolescence were analysed by comparing participants reporting daily smoking with those reporting no tobacco use and having serum cotinine concentrations <1 ng/mL. Passive tobacco smoke exposure was directly associated with the serum ratio of monounsaturated fatty acids to total fatty acids [ß = 0.34 standard deviation (SD), (0.17-0.51), P < 0.0001] and inversely associated with the serum ratios of polyunsaturated fatty acids. Exposure to passive tobacco smoke was directly associated with very-low-density lipoprotein particle size [ß = 0.28 SD, (0.12-0.45), P = 0.001] and inversely associated with HDL particle size {ß = -0.21 SD, [-0.34 to -0.07], P = 0.003}. Daily smokers exhibited a similar metabolic profile to those exposed to passive tobacco smoke. These results persisted after adjusting for body mass index, STRIP study group allocation, dietary target score, pubertal status, and parental socio-economic status. CONCLUSION: Both passive and active tobacco smoke exposures during childhood and adolescence are detrimentally associated with circulating metabolic measures indicative of increased cardio-metabolic risk.

A substantial proportion of children are affected by tobacco smoke exposure worldwide, and early life exposure to passive tobacco smoke may be even more harmful than active smoking in terms of cardiovascular disease risk. Our study suggests the following: Passive tobacco smoke exposure during childhood is associated with metabolic measures indicative of increased cardio-metabolic risk and that the association profile is similar with active daily smoking during adolescence.Reducing both active and passive tobacco smoke exposures during childhood and adolescence could reduce the risk of future cardio-metabolic disease.

Use of antibiotics and risk of type 2 diabetes, overweight and obesity: the Cardiovascular Risk in Young Finns Study and the national FINRISK study.

PURPOSE: To investigate whether exposure to systemic antibiotics influences the risk of developing type 2 diabetes and overweight/obesity. METHODS: The study sample comprised 2209 (110 with incident diabetes) participants from the population-based Cardiovascular Risk in Young Finns Study (YFS) aged 24-39 years in 2001. The exposure was national linked register data on purchased antibiotic courses between 1993 and 2001. Clinical examinations including BMI were conducted in 2001, 2007 and 2011. Participants with prevalent diabetes in 2001 were excluded. Data on type 2 diabetes was also obtained from two national registers until 2017. Data from four population-based National FINRISK studies were used for replication (N = 24,674, 1866 with incident diabetes). RESULTS: Prior antibiotic exposure (> 5 versus 0-1 antibiotic courses) was associated with subsequent type 2 diabetes in both YFS (OR 2.29; 95%CI 1.33-3.96) and FINRISK (HR 1.73; 95%CI 1.51-1.99). An increased risk for type 2 diabetes was observed in YFS (OR 1.043; 95%CI 1.013-1.074) and FINRISK (HR 1.022; 95%CI 1.016-1.029) per course. Exposure to antibiotics increased the risk of overweight/obesity (BMI > 25 kg/m2) after a 10-year follow-up in YFS (OR 1.043; 95%CI 1.019-1.068) and in FINRISK (OR 1.023; 95%CI 1.018-1.029) at baseline per antibiotic course. Adjustments for confounders from early life in YFS and at baseline in FINRISK, including BMI, socioeconomic status, smoking, insulin, blood pressure, and physical activity, did not appreciably alter the findings. CONCLUSION: Our results show that exposure to antibiotics was associated with increased risk for future type 2 diabetes and overweight/obesity and support judicious antibiotic prescribing.

Effects of Randomized Controlled Infancy-Onset Dietary Intervention on Leukocyte Telomere Length-The Special Turku Coronary Risk Factor Intervention Project (STRIP).

Reduced telomere length (TL) is a biological marker of aging. A high inter-individual variation in TL exists already in childhood, which is partly explained by genetics, but also by lifestyle factors. We examined the influence of a 20-year dietary/lifestyle intervention on TL attrition from childhood to early adulthood. The study comprised participants of the longitudinal randomized Special Turku Coronary Risk Factor Intervention Project (STRIP) conducted between 1990 and 2011. Healthy 7-month-old children were randomized to the intervention group (n = 540) receiving dietary counseling mainly focused on dietary fat quality and to the control group (n = 522). Leukocyte TL was measured using the Southern blot method from whole blood samples collected twice: at a mean age of 7.5 and 19.8 years (n = 232; intervention n = 108, control n = 124). Yearly TL attrition rate was calculated. The participants of the intervention group had slower yearly TL attrition rate compared to the controls (intervention: mean = -7.5 bp/year, SD = 24.4 vs. control: mean = -15.0 bp/year, SD = 30.3; age, sex and baseline TL adjusted ß = 0.007, SE = 0.004, p = 0.040). The result became stronger after additional adjustments for dietary fat quality and fiber intake, serum lipid and insulin concentrations, systolic blood pressure, physical activity and smoking (ß = 0.013, SE = 0.005, p = 0.009). A long-term intervention focused mainly on dietary fat quality may affect the yearly TL attrition rate in healthy children/adolescents.

Childhood and long-term dietary calcium intake and adult cardiovascular risk in a population with high calcium intake.

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

Childhood exposure to parental smoking and life-course overweight and central obesity.

OBJECTIVE: To evaluate the association between childhood parental smoking exposure and the risk of overweight/obesity from childhood to adulthood. METHODS: This study leverages the data from two longitudinal population based cohort studies, the Cardiovascular Risk in Young Finns Study between years 1980-2011/2012 (YFS; N = 2,303; baseline age 3-18 years) and the Special Turku Coronary Risk Factor Intervention Project between years 1989-2009/2010 (STRIP; N = 632; baseline age 7 months). Weight, height and waist circumference were measured from childhood to adulthood. Overweight/obesity was defined as body mass index ≥25 kg/m2 in adults and using the Cole criteria in children. Central obesity was defined as waist circumference > 100/90 cm in men/women and as a waist-to-height ratio > 0.50 in children. Statistical analyses were adjusted for age, sex, socioeconomic status, smoking, birth weight, parental ages, diet and physical activity. RESULTS: Childhood parental smoking exposure was associated with increased risk for life-course overweight/obesity (YFS: RR1.13, 95%CI 1.02-1.24; STRIP: RR1.57, 95%CI 1.10-2.26) and central obesity (YFS: RR1.18, 95%CI 1.01-1.38; STRIP: RR1.45, 95%CI 0.98-2.15). CONCLUSIONS: Childhood exposure to parental smoking is associated with increased risk of overweight/obesity over the life-course. KEY MESSAGES Exposure to parental smoking in childhood was associated with increased risk of overweight/obesity, central obesity and adiposity measured by skinfold thickness from childhood to adulthood.

Weight gain and body composition during pregnancy: a randomised pilot trial with probiotics and/or fish oil.

We evaluated the effects of fish oil and/or probiotic supplementation in a randomised placebo-controlled intervention pilot trial on gestational weight gain (GWG) and body composition. Additionally, the influence of gestational diabetes (GDM) on GWG and body composition was assessed. We randomised 439 overweight women into intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics and placebo + placebo (fish oil: 1·9 g DHA and 0·22 g EPA and probiotics: Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each). GDM was diagnosed with oral glucose tolerance test. Body composition was measured with air displacement plethysmography at randomisation (mean 13·9) and in late pregnancy (mean 35·2 gestational weeks). Intervention did not influence mean GWG or change in body fat mass/percentage (P > 0·17). Body composition in early pregnancy did not differ between the women who did or did not develop GDM (adjusted P > 0·23). Compared with the normoglycaemic women (n 278), women diagnosed with GDM (n 119) gained less weight (7·7 (sd 0·4) v. 9·3 (sd 0·4) kg, adjusted mean difference -1·66 (95 % CI -2·52, -0·80) and fat mass (0·4 (sd 0·4) v. 1·8 (sd 0·3) kg, adjusted mean difference -1·43 (95 % CI -2·19, -0·67) during the follow-up. In conclusion, adiposity of pregnant overweight women was not affected by supplementation with fish oil and/or probiotics, nor did it predict the development of GDM. However, adiposity was reduced in women with GDM compared with normoglycaemic women irrespective of the dietary intervention.

Efficacy of Fish Oil and/or Probiotic Intervention on the Incidence of Gestational Diabetes Mellitus in an At-Risk Group of Overweight and Obese Women: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

OBJECTIVE: To assess whether the risk of gestational diabetes mellitus (GDM) may be lowered and glucose metabolism improved by daily administration of fish oil and/or probiotic supplements in overweight and obese pregnant women. RESEARCH DESIGN AND METHODS: We randomized in a double-blind manner 439 women (mean 13.9 ± 2.1 gestational weeks [gw]) into four intervention groups: fish oil + placebo, probiotics + placebo, fish oil + probiotics, and placebo + placebo. Fish oil (1.9 g docosahexaenoic acid and 0.22 g eicosapentaenoic acid) and probiotic supplements (Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420, 1010 colony-forming units each) were provided for daily consumption from randomization beyond delivery. Primary outcomes were the incidence of GDM diagnosed with oral glucose tolerance test targeted at 24-28 gw and the change in fasting glucose between randomization and late pregnancy (mean 35.2 ± 0.9 gw). Insulin concentration, insulin resistance HOMA2-IR index, and pregnancy outcomes were determined, as were adverse effects related to the intervention. Analyses were by intent to treat. RESULTS: No differences were found among the intervention groups in the maternal and neonatal pregnancy outcomes or side effects related to the intervention (P > 0.05). The proportion of women with GDM (94 of 377; fish oil + placebo, 23 of 96, 24.0%; probiotics + placebo, 25 of 99, 25.3%; fish oil + probiotics, 26 of 91, 28.6%; and placebo + placebo, 20 of 91, 22.0%) and the change in glucose, insulin, or HOMA2-IR (n = 364) did not differ among the intervention groups (P > 0.11 for all comparisons). CONCLUSIONS: An intervention with fish oil and/or probiotics during pregnancy seemed to be both safe and well tolerated but conferred no benefits in lowering the risk of GDM or improving glucose metabolism in overweight and obese women.

Body composition measurement by air displacement plethysmography in pregnancy: Comparison of predicted versus measured thoracic gas volume.

OBJECTIVES: Body composition measurements with air displacement plethysmography (ADP) define body volume, which must be corrected for thoracic gas volume (TGV). We hypothesized that physiologic changes owing to pregnancy could affect the accuracy of predicted TGV and introduce errors into body composition measurements. METHODS: We investigated the effect of measuring versus predicting TGV on the accuracy of body composition calculations measured with ADP in overweight and obese pregnant women. The fat and fat-free masses of 110 women were determined with ADP with predicted and measured TGV. RESULTS: Measured TGV decreased from early to late pregnancy (P = 0.0002). Compared with measured TGV, predicted TGV was 6.3% higher during early gestation and 12.6% higher during late gestation (both P ≤ 0.001). The use of predicted instead of measured TGV in body composition calculations resulted in an overestimation of fat mass by 0.8% during the early stage, and 2.6% during the late stage of pregnancy (both P ≤ 0.001). CONCLUSIONS: Measuring TGV increases the accuracy of body composition measurement by ADP in overweight and obese women, particularly during the late stage of pregnancy.

Low childhood high density lipoprotein cholesterol levels and subsequent risk for chronic inflammatory bowel disease.

BACKGROUND AND AIMS: Several genetic and environmental risk factors have been linked to chronic inflammatory bowel disease (IBD). The incidence of IBD has significantly increased in developed countries during last decades. The aim of the present study was to examine childhood risk factors for subsequent IBD diagnosis in a longitudinal cohort study of children and adolescents. METHODS: A Finnish study population consisting of 3551 children and adolescents originally evaluated as part of the Cardiovascular Risk in Young Finns study in 1980. At baseline, participant BMI, insulin, lipid, C-reactive protein and blood pressure levels, socioeconomic position, dietary habits, and physical activity, were evaluated. In addition, information was gathered on rural residency, severe infections, breast feeding, parental smoking and birth weight. Subsequent IBD diagnosis status was evaluated based on nationwide registries on hospitalisations and drug imbursement decisions. RESULTS: Altogether, 49 participants (1.4%) had IBD diagnosed during the 34 years of register follow-up, of which 31 had ulcerative colitis, 12 Crohn's disease and 6 undetermined colitis. In univariate analyses, significant correlations were observed between childhood HDL-cholesterol (risk ratio (95% CI) for 1-SD change (0.58 (0.42-0.79)) and CRP concentrations (1.20 (1.01-1.43)) with IBD. The inverse association between HDL-cholesterol and IBD remained significant (0.57 (0.39-0.82)) in a multivariable model including data on age, sex and CRP. In addition, a weighted genetic z-score of 71 single nucleotide polymorphisms associated with elevated HDL-cholesterol levels was significantly lower in IBD patients, P=0.01). CONCLUSION: Low childhood HDL-cholesterol levels are associated with subsequent IBD diagnosis. In addition, a genetic risk score associated with low HDL-cholesterol levels predict later IBD suggesting that HDL-cholesterol metabolism might have a role in the pathogenesis of IBD.

Blood pathway analyses reveal differences between prediabetic subjects with or without dyslipidaemia. The Cardiovascular Risk in Young Finns Study.

BACKGROUND: Prediabetes often occurs together with dyslipidaemia, which is paradoxically treated with statins predisposing to type 2 diabetes mellitus. We examined peripheral blood pathway profiles in prediabetic subjects with (PRD ) and without dyslipidaemia (PR0 ) and compared these to nonprediabetic controls without dyslipidaemia (C0 ). METHODS: The participants were from the Cardiovascular Risk in Young Finns Study, including 1240 subjects aged 34 to 49 years. Genome-wide expression data of peripheral blood and gene set enrichment analysis were used to investigate the differentially expressed genes and enriched pathways between different subtypes of prediabetes. RESULTS: Pathways for cholesterol synthesis, interleukin-12-mediated signalling events, and downstream signalling in naïve CD8+ T-cells were upregulated in the PR0 group in comparison with controls (C0 ). The upregulation of these pathways was independent of waist circumference, blood pressure, smoking status, and insulin. Adjustment for CRP left the CD8+ T-cell signalling and interleukin-12-mediated signalling event pathway upregulated. The cholesterol synthesis pathway was also upregulated when all prediabetic subjects (PR0 and PRD ) were compared with the nonprediabetic control group. No pathways were upregulated or downregulated when the PRD group was compared with the C0 group. Five genes in the PR0 group and 1 in the PRD group were significantly differentially expressed in comparison with the C0 group. CONCLUSIONS: Blood cell gene expression profiles differ significantly between prediabetic subjects with and without dyslipidaemia. Whether this classification may be used in detection of prediabetic individuals at a high risk of cardiovascular complications remains to be examined.

Cardiorespiratory Fitness and Risk of Fatty Liver: The Young Finns Study.

PURPOSE: Fatty liver is an expanding health concern associated with metabolic disturbances and increased risk of cardiovascular disease. Experimental studies in animals have shown associations between fatty liver and cardiorespiratory fitness but limited data exist in humans. The aim of this study was to analyze the links between cardiorespiratory fitness and fatty liver in a population-based sample of adults. METHODS: Participants were 463 adults (48% men) from the Cardiovascular Risk in Young Finns Study. Cardiorespiratory fitness was measured with a cycle ergometer exercise test as peak oxygen uptake (V˙O2peak [mL·kg·min]) in 2008 to 2009. Hepatic ultrasonographic imaging was performed in 2011 to determine fatty liver. RESULTS: Cardiorespiratory fitness was associated with lower risk of fatty liver (1 mL·kg·min increase in V˙O2peak: risk ratio, 0.90; 95% confidence interval, 0.88-0.93, P < 0.0001; adjusted for age and sex). This association remained significant after further adjustments with physical activity, adiposity, smoking, alcohol consumption, serum lipids, insulin, glucose, and C-reactive protein. Participants who were obese (waist circumference, >80 cm in women and >94 cm in men) but fit (V˙O2peak in the upper age- and sex-specific median) had lower prevalence of fatty liver than participants who were obese and unfit (below median), (11.7% vs 34.8%, P = 0.0003). CONCLUSIONS: In a population-based sample of adults, cardiorespiratory fitness is strongly, inversely and independently related with the risk of fatty liver. Importantly, the association is evident also among obese.

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

Nonalcoholic fatty liver is associated with obesity-related metabolic disturbances, but little is known about the metabolic perturbations preceding fatty liver disease. We performed comprehensive metabolic profiling to assess how circulating metabolites, such as lipoprotein lipids, fatty acids, amino acids, and glycolysis-related metabolites, reflect the presence of and future risk for fatty liver in young adults. Sixty-eight lipids and metabolites were quantified by nuclear magnetic resonance metabolomics in the population-based Young Finns Study from serum collected in 2001 (n = 1,575), 2007 (n = 1,509), and 2011 (n = 2,002). Fatty liver was diagnosed by ultrasound in 2011 when participants were aged 34-49 years (19% prevalence). Cross-sectional associations as well as 4-year and 10-year risks for fatty liver were assessed by logistic regression. Metabolites across multiple pathways were strongly associated with the presence of fatty liver (P < 0.0007 for 60 measures in age-adjusted and sex-adjusted cross-sectional analyses). The strongest direct associations were observed for extremely large very-low-density lipoprotein triglycerides (odds ratio [OR] = 4.86 per 1 standard deviation, 95% confidence interval 3.48-6.78), other very-low-density lipoprotein measures, and branched-chain amino acids (e.g., leucine OR = 2.94, 2.51-3.44). Strong inverse associations were observed for high-density lipoprotein measures, e.g., high-density lipoprotein size (OR = 0.36, 0.30-0.42) and several fatty acids including omega-6 (OR = 0.37, 0.32-0.42). The metabolic associations were attenuated but remained significant after adjusting for waist, physical activity, alcohol consumption, and smoking (P < 0.0007). Similar aberrations in the metabolic profile were observed already 10 years before fatty liver diagnosis. CONCLUSION: Circulating lipids, fatty acids, and amino acids reflect fatty liver independently of routine metabolic risk factors; these metabolic aberrations appear to precede the development of fatty liver in young adults. (Hepatology 2017;65:491-500).

Role of Conventional Childhood Risk Factors Versus Genetic Risk in the Development of Type 2 Diabetes and Impaired Fasting Glucose in Adulthood: The Cardiovascular Risk in Young Finns Study.

OBJECTIVE: We examined whether the addition of novel genetic risk variant data to conventional childhood risk factors improves risk assessment of impaired fasting glucose (IFG) and type 2 diabetes in adulthood. RESEARCH DESIGN AND METHODS: An association of a weighted genetic risk score (wGRS) based on 73 risk variants with IFG and type 2 diabetes was analyzed in 2,298 participants of the Cardiovascular Risk in Young Finns Study who were followed for 24-31 years from childhood to adulthood. In addition, the value of the wGRS in pediatric prediction of type 2 diabetes was examined. RESULTS: Of the 2,298 participants, 484 (21.8%) and 79 (3.4%) had IFG or type 2 diabetes in adulthood, respectively. Adjusting for age, sex, baseline BMI, parental diabetes, mother's BMI, fasting insulin concentration, systolic blood pressure, and smoking status, wGRS was associated with an increased risk of IFG (odds ratio 1.64 [95% CI 1.33-2.01] per unit increase in the wGRS) and type 2 diabetes (2.22 [1.43-3.44]). Incorporating wGRS into pediatric risk models improved model discrimination and reclassification properties. Area under the receiver operating curve improved for IFG (from 0.678 to 0.691, P = 0.015), combined IFG and type 2 diabetes outcome (from 0.678 to 0.692, P = 0.007), and type 2 diabetes (from 0.728 to 0.749, P = 0.158). The net reclassification improvement and integrated discrimination improvement were significant for all outcomes. CONCLUSIONS: A multifactorial approach combining genetic and clinical risk factors may be useful in identifying children at high risk for adult IFG and type 2 diabetes.

Psychological wellbeing in 20-year-old adults receiving repeated lifestyle counselling since infancy.

AIM: This study examined whether there was an association between a repeated dietary and lifestyle intervention that began in infancy and participants' psychological wellbeing at the age of 20. METHODS: We examined the psychological wellbeing of 457 young adults participating in the Special Turku Coronary Risk Factor Intervention Project (STRIP), a randomised controlled trial conducted in Finland between 1989 and 2011. We assessed potential differences in psychological wellbeing between the intervention and control groups by examining participants' satisfaction with life, how they rated their health, their experiences of stress and the consequences of experiencing stress and symptoms of depression at the age of 20. We also assessed socio-economic status during childhood as a potential confounding factor. RESULTS: We found no association between the long-term dietary and lifestyle intervention and participants' psychological wellbeing in adulthood. Adjusting for sex and childhood socio-economic status did not affect the results and socio-economic status did not moderate the association between the intervention and psychological wellbeing. CONCLUSION: Our findings showed no association between intensive dietary and lifestyle counselling that was initiated in infancy with psychological wellbeing in adulthood and the initiative did not appear to pose any psychological risks.

High lipoprotein(a) concentrations are associated with impaired endothelial function in children.

OBJECTIVE: To examine the association between familial high lipoprotein(a), or Lp(a), concentrations and endothelial function in children participating in the Special Turku Coronary Risk Factor Intervention Project study. STUDY DESIGN: Seven-month-old children (n = 1062) with their families were randomized to a risk intervention group or to a control group. The intervention group received individualized dietary counseling to reduce the total cholesterol concentration. Children's Lp(a) and lipid values were measured repeatedly. At age 11 years, children were recruited to an ultrasound study of the flow-mediated dilation (FMD) of the brachial artery. The association between relative peak FMD and Lp(a) concentration was examined in 198 control and 193 intervention group children by linear regression analyses adjusted for sex, total cholesterol concentration, and basal artery diameter. The analyses were made in both the control and intervention groups and in the familial risk children who had a parent with Lp(a) concentration greater than 250 mg/l. RESULTS: Lp(a) concentrations were similar at age 11 years in the intervention and control groups. In all control children, FMD (%) associated inversely with Lp(a) concentration: (ß [%/1000 mg/L] = -3.74, 95% CI [-6.43, -1.45]; P = .007) and in 68 familial risk children (ß = -4.92, 95% CI [-8.18, -1.66]; P = .0037). In the intervention group the associations were lacking (P > .5), and FMD in the children with high Lp(a) concentrations (>500 mg/L, n = 12) had no attenuation (P = .027). CONCLUSIONS: Familial high Lp(a) concentration is associated with attenuated endothelial function. This association may be mitigated by an early lifestyle intervention. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00223600.

Association of physical activity in childhood and early adulthood with carotid artery elasticity 21 years later: the cardiovascular risk in Young Finns Study.

BACKGROUND: Decreased arterial elasticity is a risk factor for several cardiovascular outcomes. Longitudinal data on the effect of physical activity in youth on adult arterial elasticity are limited. The aim of this study was to determine the long-term effects of physical activity in children and young adults on carotid artery elasticity after 21 years of follow-up. METHODS AND RESULTS: Participants were 1417 children (aged 9 to 15 years) and 999 young adults (aged 18 to 24 years) from the prospective Cardiovascular Risk in Young Finns Study. Participants had questionnaire measures of leisure-time physical activity available from 1986 and ultrasound-derived indices of carotid artery elasticity measured in 2007. Carotid artery elasticity indices were distensibility (%/10 mm Hg), Young's elastic modulus (kPa), and stiffness index (unitless). Physical activity at age 18 to 24 years was directly associated with distensibility (ß=0.068, P=0.014) and inversely with Young's elastic modulus (ß=-0.057, P=0.0037) and indirectly with stiffness index (ß=-0.050, P=0.0028) 21 years later in males and females. The associations remained after adjustment for age, sex, body mass index, smoking, systolic blood pressure, serum lipids and insulin, and 21-year change in physical activity. At age 9 to 15 years, the favorable association, remaining after adjustment, was found in males (distensibility [ß=0.097, P=0.010], Young's elastic modulus [ß=-0.060, P=0.028], and stiffness index [ß=-0.062, P=0.007]) but not in females (P=0.70, P=0.85, and P=0.91, respectively). CONCLUSIONS: Leisure-time physical activity in boys and young adults is associated with carotid artery elasticity later in life, suggesting that higher levels of physical activity in youth may benefit future cardiovascular health.

Association of fitness with vascular intima-media thickness and elasticity in adolescence.

OBJECTIVES: Vascular intima-media thickness (IMT) and elasticity are surrogate markers of atherosclerosis. Data on the effect of cardiorespiratory fitness on these measures of vascular health in adolescence are scarce. The aim was to examine the association of fitness with aortic and carotid artery IMT and elasticity in adolescents. METHODS: Aortic (n = 449) and carotid (n = 467) IMT and elasticity were measured ultrasonographically in 17-year-old adolescents participating in a prospective, longitudinal atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project). Distensibility and Young's elastic modulus (YEM) were used as measures of arterial elasticity. Cardiorespiratory fitness (maximum oxygen uptake, mL/kg/min) was measured with a maximal cycle ergometer test. Data on fitness were available for 341 of adolescents with aortic and 355 with carotid ultrasound measures. RESULTS: Fitness was inversely associated with aortic IMT (ß[SE] = -0.0029[0.0013]; P = .031) and YEM (ß[SE] = -0.012[0.0053]; P = .025) after adjusting for gender, physical activity, high-density lipoprotein/total cholesterol, triglycerides, high-sensitivity C-reactive protein, homeostasis model of assessment-insulin resistance, BMI, systolic blood pressure, and smoking. Risk of having low aortic distensibility (≤10th percentile) decreased with increasing fitness (odds ratio = 0.89, 95% confidence interval 0.82-0.98); P = .014). The increase in aortic IMT and YEM between ages 11 and 17 years was smaller in adolescents who were fit at age 17 compared with adolescents who had the lowest fitness level (P for IMT = .015, P for YEM = .0072). Fitness was not associated with carotid IMT or elasticity. Lifestyle counseling given in the Special Turku Coronary Risk Factor Intervention Project was not associated with fitness. CONCLUSIONS: Fitness was favorably associated with aortic IMT and elasticity in adolescents. No association of fitness with the respective carotid indices was found. These data suggest that fitness in part enhances vascular health in healthy adolescents.

Cross-sectional associations between physical activity and selected coronary heart disease risk factors in young adults. The Cardiovascular Risk in Young Finns Study.

OBJECTIVE: Physical activity (PA) may reduce the risk of coronary heart disease (CHD) by inducing beneficial changes in several risk factors. We studied the associations between PA and a range of risk markers of CHD in young adults. METHODS AND RESULTS: We measured serum lipoproteins, oxidized LDL, adipokines, inflammatory markers, metabolic markers, and arginine metabolites in 2,268 individuals (age 24-39 y). Participants were asked frequency, duration, and intensity of PA in leisure time. In addition, commuting to work was assessed. In both sexes, PA was inversely associated with waist circumference (all P < 0.0001). After controlling for sex, age, and waist circumference, PA was directly associated with HDL-cholesterol and apolipoprotein A1, and inversely with heart rate, smoking, oxidized LDL, apolipoprotein B, insulin, glucose, C-reactive protein, leptin, L-arginine, and phospholipase A2 activity (all P < 0.05). CONCLUSION: These population-based data are consistent with the idea that the beneficial effects of PA on CHD risk are mediated by favorable influences on several risk factors, as judged by independent relations to markers of lipoprotein metabolism, glucose metabolism, and inflammation. These associations reflect beneficial effects on cardiovascular health in both sexes and may offer mechanistic insights for the inverse association between PA and CHD.

Clustered metabolic risk and leisure-time physical activity in adolescents: effect of dose?

OBJECTIVES: The authors studied the association of leisure-time physical activity (LTPA) with clustered and individual metabolic risk factors in adolescents taking into account diet and pubertal status. The authors also studied whether screen time was associated with clustered risk. METHODS: Self-reported LTPA and screen time, lipids, lipoproteins, apolipoproteins, high-sensitivity C reactive protein, blood pressure, body mass index (BMI), pubertal status and diet were assessed in 13-year-old adolescents (n=542) participating in an atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children). Activity groups were formed according to sex-specific LTPA index tertile cut-off points. BMI, high-density lipoprotein cholesterol (HDL-C), triglycerides and blood pressure comprised the cluster. RESULTS: An increase in LTPA was associated with a decreased risk for clustered metabolic risk in girls. When sedentary and highly active adolescents were compared, an increase in LTPA decreased clustering of risk factors in boys as well. Little extra benefit on clustered risk was obtained by increasing LTPA from 30 MET h/week (eg, 4-5 h/week bicycling or playing soccer) to 50 MET h/week (eg, 7-8 h/week bicycling or playing soccer). LTPA was beneficially associated with BMI, HDL-C, systolic blood pressure and HDL-C/total cholesterol in girls and HDL-C in boys. Diet and pubertal status were similar in all activity groups. In girls, screen time >2 h/day was associated with an increased risk for clustered risk, independent of LTPA. CONCLUSION: Sedentary adolescents had an increased risk for clustered metabolic risk compared with physically more active peers. Only minor extra benefit was obtained when LTPA increased over 30 MET h/week. Focus in the prevention of clustered risk should especially be on avoiding sedentary lifestyle.

Association of physical activity with vascular endothelial function and intima-media thickness.

BACKGROUND: Impairment of vascular endothelial function and increased intima-media thickness (IMT) are important early steps in atherogenesis. Longitudinal data on the effect of physical activity on endothelial function and IMT in healthy adolescents are lacking. We investigated prospectively the association of leisure-time physical activity with endothelial function (brachial artery flow-mediated dilatation; FMD) and aortic IMT in adolescents. METHODS AND RESULTS: FMD and IMT were measured with ultrasonography at 13 (n=553), 15 (n=531), and 17 (n=494) years of age in adolescents participating in a longitudinal atherosclerosis prevention study (Special Turku Coronary Risk Factor Intervention Project for Children). Mean aortic IMT, maximum FMD, and total FMD response (area under the dilatation curve 40 to 180 seconds after hyperemia) were calculated. Leisure-time physical activity was assessed with a questionnaire, and metabolic equivalent (MET) hours per week of leisure-time physical activity were calculated by multiplying weekly mean exercise intensity, duration, and frequency. Leisure-time physical activity was directly associated with endothelial function (P for maximum FMD=0.0021, P for total FMD response=0.0036) and inversely with IMT (P=0.011) after adjustment for age, sex, body mass index, high-density lipoprotein/total cholesterol, systolic blood pressure, and C-reactive protein and regarding FMD brachial artery diameter. Sedentary adolescents who increased their leisure-time physical activity from <5 to >5 (IMT) or >30 (maximum FMD) MET h/wk between 13 and 17 years of age had an increased maximum FMD (P=0.031) and decreased progression of IMT (P=0.047) compared with adolescents who remained sedentary. IMT progression was attenuated in persistently active adolescents compared with those who became sedentary (P=0.0072). CONCLUSIONS: Physical activity is favorably associated with endothelial function and IMT in adolescents. Importantly, a moderate increase in physical activity is related to decreased progression of IMT. A physically active lifestyle seems to prevent the development of subclinical atherosclerotic vascular changes in healthy adolescents. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00223600 (STRIP19902010).