Cardiovascular risk factors and cardiovascular risk prediction from childhood to adulthood. The Cardiovascular Risk in Young Finns Study

Background: In the late 1960s, Finland had the world’s highest coronary heart disease mortality. Atherosclerosis has its roots in childhood. Childhood risk factors are associated with risk factors in adulthood that predict arterial changes, surrogate markers for atherosclerosis. Since the 1960s, coronary heart disease mortality has decreased over 80%. Over two thirds of the reduction in mortality can be explained by change in risk factor levels. Nevertheless, atherosclerotic cardiovascular diseases are still the leading cause of death and disability in Finland and worldwide. Aims: The aims of this thesis were to: study risk factor levels and their changes in Finnish adult population; investigate how many childhood measurements of lipids and blood pressure are needed to optimize the prediction of adult risk factor levels and arterial changes; and determine if adding information on genetic variants to child lipid levels improves prediction of adulthood dyslipidemia. Participants and methods: This thesis uses data from the Cardiovascular Risk in Young Finns Study, a prospective cohort of Finnish children initiated in 1980. Over 31 years, cardiovascular risk factors were measured from participants at several follow-ups. In the most recent follow-up performed in 2011, 57% of the original study population participated. Results: In 2011, the previously observed favorable trends in cholesterol levels had leveled off and over one-third of participants had prediabetes. Two lipid and blood pressure measures in childhood significantly improved prediction of adult dyslipidemia and hypertension over one measurement. Use of genetic risk score approach combined to traditional risk factors significantly enhanced the prediction of adulthood dyslipidemia over conventional childhood risk factors. Conclusions: Favorable trends in cardiovascular risk factor levels appear to be leveling off in Finland. At least two measures of blood pressure and lipids should be used in childhood assessment for future cardiovascular disease risk. Genetic information can help identify children at risk for adult dyslipidemia.Valtimotaudin riskitekijät ja niiden ennustaminen lapsuuden havaintojen perusteella (LASERI-tutkimus) Tausta: Suomessa oli 1960-luvulla maailman korkein sepelvaltimotautikuolleisuus. Valtimotauti alkaa lapsuudessa. Lapsuuden riskitekijät ovat yhteydessä aikuisiän riskitekijöihin, jotka taas ennustavat valtimomuutoksia. Sepelvaltimotautikuolleisuus on laskenut Suomessa yli 80 %:lla 1960-luvulta lähtien. Yli kaksi kolmasosaa kuolleisuuden vähentymisestä selittyy riskitekijätasojen muutoksilla. Valtimotauti on yhä yleisin kuolinsyy sekä toimintakyvyn menetyksen aiheuttaja Suomessa ja maailmalla. Tavoite: Väitöskirjatyön tavoitteena oli tutkia valtimotaudin riskitekijätasoja ja niiden muutoksia suomalaisessa aikuisväestössä. Toisena tavoitteena on ollut selvittää, kuinka monella lapsuuden aikaisella kolesteroli- tai verenpainemittauksella voidaan tehokkaasti ennustaa aikuisiän riskitekijätasoja ja valtimomuutoksia, sekä tutkia parantaako geneettinen tieto aikuisiän rasva-aineenvaihdunnan häiriöiden ennustamista. Menetelmät: Väitöskirjatutkimus on osa vuonna 1980 aloitettua Lasten Sepelvaltimotaudin Riskitekijät (LASERI) – seurantatutkimusta. Koko tutkimuksen ajan tutkittavilta on mitattu sydän- ja verisuonitautien riskitekijöitä kattavasti. Vuonna 2011, yli 30 vuoden seurannan jälkeen, oli mukana edelleen 57 % alkuperäisestä tutkimusväestöstä. Tulokset: Vuonna 2011 todettiin vuosikymmeniä jatkuneen myönteisen trendin veren kolesteroliarvoissa tasoittuneen. Lisäksi kolmanneksella väestöstä oli diabeteksen esiaste. Kahdella lapsuuden aikaisella mittauksella saatiin luotettava ennuste aikuisiän rasva-aineenvaihdunnan häiriöistä ja kohonneesta verenpaineesta, kolmannesta mittauksesta saatava hyöty jäi vaatimattomaksi. Geneettinen tieto alttiudesta rasva-aineenvaihdunnan häiriöille paransi merkittävästi aikuisiän rasva-aineenvaihdunnan häiriöiden ennustamisen tarkkuutta. Johtopäätökset: Suomalaisten sydän- ja verisuonitautien riskitekijätasojen myönteinen kehitys näyttää tasoittuvan. Lapsuuden verenpaine- ja kolesterolitasojen arvioinnissa on syytä käyttää vähintään kahdesti toistettua mittausta. Geneettistä tietoa käyttämällä voidaan tarkemmin tunnistaa jo lapsena henkilöt, joilla on kohonnut riski rasva-aineenvaihdunnan häiriöihin aikuisena.Siirretty Doriast

Mistä ero sepelvaltimotaudissa idän ja lännen välillä johtuu?

Sepelvaltimotautisairastavuus ja -kuolleisuus on ollut vuosikymmeniä suurempaa Koillis-Suomessa kuin Lounais-Suomessa (niin sanottu itä-länsiero). Viime vuosikymmeninä työikäisten sepelvaltimotautikuolleisuus on vähentynyt yli 80 %, ja samalla itä-länsierokin on kaventunut. Itäsuomalaisten riski menehtyä sepelvaltimotautiin on kuitenkin edelleen noin viidenneksen suurempi kuin länsisuomalaisten. Itä-länsiero ei ole selitettävissä pelkästään sepelvaltimotaudin tunnetuilla vaaratekijöillä. Yleisesti hyväksyttyä selitystä tälle erolle ei runsaasta tutkimuksesta huolimatta ole onnistuttu löytämään. Todennäköisesti kyseessä ovat joko perinnölliset erot tai vaihtoehtoisesti ympäristön tai käyttäytymisen erot, jotka jo lapsuudessa vaikuttavat peruuttamattomasti aikuisiän sepelvaltimotautiriskiin. Geneettisten tutkimusmenetelmien kehitys tuonee tulevaisuudessa lisätietoa perimän merkityksestä eron taustalla

Longitudinal blood pressure patterns and cardiovascular disease risk

Observational and interventional studies have unequivocally demonstrated that "present", i.e. single-occasion, blood pressure is one of the key determinants of cardiovascular disease risk. Over the past two decades, however, numerous publications have suggested that longitudinal blood pressure data and assessment of long-term blood pressure exposure provide incremental prognostic value over present blood pressure. These studies have used several different indices to quantify the overall exposure to blood pressure, such as time-averaged blood pressure, cumulative blood pressure, blood pressure trajectory patterns, and age of hypertension onset. This review summarises existing research on the association between these indices and hard cardiovascular outcomes, outlines the strengths and weaknesses of these indices, and provides an overview of how longitudinal blood pressure changes can be measured and used to improve cardiovascular disease risk prediction.KEY MESSAGES Numerous recent publications have examined the relation between cardiovascular disease and long-term blood pressure (BP) exposure, quantified using indices such as time-averaged BP, cumulative BP, BP trajectory patterns, and age of hypertension onset. This review summarises existing research on the association between these indices and hard cardiovascular outcomes, outlines the strengths and weaknesses of these indices, and provides an overview of how longitudinal BP changes can be measured and used to improve cardiovascular disease risk prediction. Although longitudinal BP indices seem to predict cardiovascular outcomes better than present BP, there are considerable differences in the clinical feasibility of these indices along with a limited number of prospective data.</p

CVD risk factors and surrogate markers-Urban-rural differences

Aims: Disparity in cardiovascular disease (CVD) mortality and risk factor levels between urban and rural regions has been confirmed worldwide. The aim of this study was to examine how living in different community types (urban-rural) in childhood and adulthood are related to cardiovascular risk factors and surrogate markers of CVD such as carotid intima-media thickness (IMT) and left ventricular mass (LVM). Methods: The study population comprised 2903 participants (54.1% female, mean age 10.5 years in 1980) of the Cardiovascular Risk in Young Finns Study who had been clinically examined in 1980 (age 3-18 years) and had participated in at least one adult follow-up (2001-2011). Results: In adulthood, urban residents had lower systolic blood pressure (-1 mmHg), LDL-cholesterol (-0.05 mmol/l), lower body mass index (-1.0 kg/m(2)) and glycosylated haemoglobin levels (-0.05 mmol/mol), and lower prevalence of metabolic syndrome (19.9 v. 23.7%) than their rural counterparts. In addition, participants continuously living in urban areas had significantly lower IMT (-0.01 mm), LVM (1.59 g/m(2.7)) and pulse wave velocity (-0.22 m/s) and higher carotid artery compliance (0.07%/10 mmHg) compared to persistently rural residents. The differences in surrogate markers of CVD were only partially attenuated when adjusted for cardiovascular risk factors. Conclusions: Participants living in urban communities had a more favourable cardiovascular risk factor profile than rural residents. Furthermore, participants continuously living in urban areas had less subclinical markers related to CVD compared with participants living in rural areas. Urban-rural differences in cardiovascular health might provide important opportunities for optimizing prevention by targeting areas of highest need.Peer reviewe

Lower grip strength in youth with obesity identifies those with increased cardiometabolic risk

Background: We examined whether grip strength differentiates youth with obesity with increased cardiometabolic risk.Methods: The sample comprised 43 youth with severe obesity (mean age 14.8, standard deviation 3.0 years) enrolled in the Childhood Overweight BioRepository of Australia. Grip strength was normalized to body mass and categorized as low and moderate/high.Results: Youth with low grip strength had higher systolic blood pressure (mean difference 13 mmHg), lowdensity lipoprotein cholesterol (0.26 mmol/l), continuous metabolic syndrome score (0.36), and carotid intima-media thickness (0.05 mm) compared with those with moderate/high grip strength.Conclusions: Low grip strength may differentiate youth with obesity with increased cardiometabolic risk.</p

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/m(2)) 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.Peer reviewe

Decreasing severity of obesity from early to late adolescence and young adulthood associates with longitudinal metabolomic changes implicated in lower cardiometabolic disease risk

Background Obesity in childhood is associated with metabolic dysfunction, adverse subclinical cardiovascular phenotypes and adult cardiovascular disease. Longitudinal studies of youth with obesity investigating changes in severity of obesity with metabolomic profiles are sparse. We investigated associations between (i) baseline body mass index (BMI) and follow-up metabolomic profiles; (ii) change in BMI with follow-up metabolomic profiles; and (iii) change in BMI with change in metabolomic profiles (mean interval 5.5 years). Methods Participants (n = 98, 52% males) were recruited from the Childhood Overweight Biorepository of Australia study. At baseline and follow-up, BMI and the % >95th BMI-centile (percentage above the age-, and sex-specific 95th BMI-centile) indicate severity of obesity, and nuclear magnetic resonance spectroscopy profiling of 72 metabolites/ratios, log-transformed and scaled to standard deviations (SD), was performed in fasting serum. Fully adjusted linear regression analyses were performed.Results Mean (SD) age and % >95th BMI-centile were 10.3 (SD 3.5) years and 134.6% (19.0) at baseline, 15.8 (3.7) years and 130.7% (26.2) at follow-up. Change in BMI over time, but not baseline BMI, was associated with metabolites at follow-up. Each unit (kg/m2) decrease in sex- and age-adjusted BMI was associated with change (SD; 95% CI; p value) in metabolites of: alanine (-0.07; -0.11 to -0.04; p p p p p = 0.003), monounsaturated fatty acids (-0.04; -0.07 to -0.01; p = 0.004), ratio of ApoB/ApoA1 (-0.05; -0.07 to -0.02; p = 0.001), VLDL-cholesterol (-0.04; -0.06 to -0.01; p = 0.01), HDL cholesterol (0.05; 0.08 to 0.1; p = 0.01), pyruvate (-0.08; -0.11 to -0.04; p p = 0.005) and 3-hydroxybuturate (0.07; 0.02 to 0.11; p = 0.01). Results using the % >95th BMI-centile were largely consistent with age- and sex-adjusted BMI measures.Conclusions In children and young adults with obesity, decreasing the severity of obesity was associated with changes in metabolomic profiles consistent with lower cardiovascular and metabolic disease risk in adults.</p

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

The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9-19 years (n = 549-338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) = 80th age-specific percentile, and (4) sucrose intake = 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (>= 2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health

Modest decrease in severity of obesity in adolescence associates with low arterial stiffness

Background and aimsChildhood obesity is associated with cardiovascular risk factors (CVRF), subclinical cardiovascular phenotypes (carotid intima-media thickness, cIMT; pulse-wave velocity, PWV; and carotid elasticity), and adult cardiovascular disease (CVD) mortality. In youth with obesity (body mass index, BMI ≥95th centile), we investigated associations between changes in adiposity and CVRF in early adolescence and subclinical cardiovascular phenotypes in late adolescence.MethodsParticipants had adiposity measures (the severity of obesity in percentage >95th BMI-centile (%>95th BMI-centile)), waist circumference (WC), percentage total body fat (%BF) and CVRF (systolic blood pressure, SBP; glycoprotein acetyls, GlycA; and low-density lipoprotein cholesterol) assessed in early (mean age 10.2 ± 3.5y) and late (15.7 ± 3.7y) adolescence. Subclinical cardiovascular phenotypes were assessed in late adolescence. Multivariable regression analysis was performed.ResultsDecreasing the %>95th BMI-centile was associated with carotid elasticity (0.945%/10 mmHg, p = 0.002) in females, and with PWV in males (−0.75 m/s, p p p μmol-increase) were associated with elasticity (−0.162%/10 mmHg, p = 0.042), and changes in SBP (per 10 mmHg-increase) were associated with PWV (0.260 m/s, p μm, p = 0.006).ConclusionsIn youth with obesity, decreasing or maintaining the severity of obesity, and decreasing the levels of SBP and GlycA from early to late adolescence was associated with low arterial stiffness.</p

Childhood Socioeconomic Disadvantage and Risk of Fatty Liver in Adulthood: The Cardiovascular Risk in Young Finns Study

Fatty liver is a preventable cause of liver failure, but early risk factors for adulthood fatty liver are poorly understood. We examined the association of childhood socioeconomic disadvantage with adulthood fatty liver and tested adulthood risk factors of fatty liver as possible mediators of this link. The study population comprised 2,042 participants aged 3-18 years at baseline (1980) from the longitudinal Cardiovascular Risk in Young Finns Study. Follow-up with repeated clinical examinations was 31 & x202f;years. Childhood socioeconomic disadvantage was assessed using data from parents' socioeconomic position and socioeconomic circumstances in participants' residential neighborhoods, categorized as high versus low socioeconomic disadvantage. Fatty liver was determined by ultrasound during the last follow-up (2011) at ages 34-49 years. Childhood and adulthood risk factors, including metabolic biomarkers and lifestyle variables, were assessed in clinical examinations. A total of 18.9% of the participants had fatty liver in adulthood. High childhood socioeconomic disadvantage was associated with an increased risk of fatty liver (risk ratio [95% confidence interval], 1.42 [1.18-1.70]; P = 0.0002). This association was robust to adjustment for age, sex, and childhood risk factors of fatty liver, including high body mass index, elevated insulin, and low birth weight (1.33 [1.09-1.62]; P = 0.005). High childhood socioeconomic disadvantage was also associated with the development of risk factors of fatty liver in adulthood. Adulthood risk factors linking childhood socioeconomic disadvantage with fatty liver included waist circumference (proportion mediated of the total effect of childhood socioeconomic disadvantage, 45%), body mass index (40%), systolic blood pressure (29%), insulin (20%), physical activity (15%), triglycerides (14%), and red meat consumption (7%). Conclusion: Childhood socioeconomic disadvantage was associated with multiple risk factors of fatty liver and increased likelihood of fatty liver in adulthood