Markus Juonala

Cohort Profile: The Cardiovascular Risk in Young Finns Study

In Finland, coronary heart disease (CHD) incidence was very high in the 1960s and 1970s. In line with this high incidence, the Seven Countries Study showed that the level of serum cholesterol in Finns was also the highest among the investigated countries in the 1960s. Because several studies indicated that the atherosclerotic process starts early in life, and in accord with the World Health Organization Recommendation of 1978 which stated that studies assessing atherosclerosis precursors in children should be initiated, a program was launched in Finland in the late 1970s to study cardiovascular risk in the youth. The Cardiovascular Risk in Young Finns Study was designed as a collaborative effort between five university departments of medical schools (i.e. in Helsinki, Kuopio, Oulu, Tampere and Turku) and several other institutions in Finland. The aim was to study the levels of CHD risk factors and their determinants in children and adolescents of various ages in different parts of the country. Two pilot studies were carried out in 1978 (N1⁄4 264, age 8 years) and in 1979 (N1⁄4 634, aged 3, 12 and 17 years). The first main cross-sectional (baseline) study was performed in 1980. The baseline study included 3596 children and adolescents aged 3, 6, 9, 12, 15 and 18 years. Between 1980 and 1992, these cohorts were followed up at 3-year intervals. The latest examination of the Cardiovascular Risk in Young Finns Study was performed in 2001, when the participants were young adults, aged 24–39 years. At the time of writing, the 27-year (i.e. 27 years since the start of the study when the participants are aged 30–45 years) follow-up field studies are being conducted, and will be completed in the beginning of 2008.

Interrelations Between Brachial Endothelial Function and Carotid Intima-Media Thickness in Young Adults The Cardiovascular Risk in Young Finns Study

Background—Endothelial vasodilator dysfunction and carotid intima-media thickening (IMT) are 2 indicators of subclinical cardiovascular disease. We examined their correlation and interaction with risk factors in a large, community-based cohort of young adults. Methods and Results—As part of the longitudinal Cardiovascular Risk in Young Finns Study, we measured endothelium-dependent brachial artery flow–mediated dilatation (FMD) and carotid artery IMT by ultrasound in 2109 healthy adults aged 24 to 39 years. FMD was inversely associated with IMT (P≤0.001) in a multivariate model adjusted for age, sex, brachial vessel size, and several risk variables. The subjects with age- and sex-specific FMD values in the extreme deciles were classified into groups of impaired (n=204, FMD=1.1±1.4%, mean±SD) and enhanced (n=204, FMD=16.3±2.9%) FMD response. The number of risk factors was correlated with increased IMT in subjects with an impaired FMD response (P<0.05) but not in subjects with an enhanced FMD response (P>0.2). Conclusions—Brachial FMD is inversely associated with carotid IMT. The number of risk factors in young adults is correlated with increased IMT in subjects with evidence of endothelial dysfunction, but not in subjects with preserved endothelial function. These observations suggest that endothelial dysfunction is an early event in atherosclerosis and that the status of systemic endothelial function may modify the association between risk factors and atherosclerosis.

Risk Factors Identified in Childhood and Decreased Carotid Artery Elasticity in Adulthood The Cardiovascular Risk in Young Finns Study

Background—Exposure to risk factors in childhood may have long-term influences on vascular function. We examined the relationship between risk factors identified in childhood and arterial elasticity assessed in adulthood. Methods and Results—Carotid artery compliance (CAC), Young’s elastic modulus (YEM), and stiffness index (SI), 3 measures of large-artery elasticity, were assessed with noninvasive ultrasound in 2255 healthy white adults aged 24 to 39 years participating in a population-based cohort study and who had risk factor data available since childhood. In multivariate models, childhood obesity (skinfold thickness) predicted decreased CAC (P<0.001), increased YEM (P<0.01), and increased SI (P<0.01) in adulthood. Childhood blood pressure was inversely associated with CAC (P<0.001) and directly associated with YEM (P<0.001). The number of risk factors identified in childhood, which included high LDL cholesterol (at or above 80th percentile), elevated blood pressure, skinfold thickness, low HDL cholesterol (at or below 20th percentile), and smoking, was related inversely with CAC (P<0.001) and directly with YEM (P<0.001). These associations remained highly significant after adjustment for the number of risk factors identified in adulthood (P=0.005 for CAC and P<0.001 for YEM). Conclusions—Cardiovascular risk factors identified in childhood and adolescence predict decreased carotid artery elasticity in adulthood. These data suggest that risk factors operating in early life may have sustained deleterious effects on arterial elasticity.

Tracking of Serum Lipid Levels, Blood Pressure, and Body Mass Index from Childhood to Adulthood: The Cardiovascular Risk in Young Finns Study.

OBJECTIVES To examine tracking and predictiveness of childhood lipid levels, blood pressure, and body mass index for risk profile in adulthood and the best age to measure the childhood risk factor levels. STUDY DESIGN Study subjects were participants of the longitudinal Cardiovascular Risk in Young Finns Study, started in 1980 (age 3, 6, 9, 12, 15, and 18 years). A total of 2204 subjects participated to the 27-year follow-up in 2007 (age, 30 to 45 years). RESULTS In both sex groups and in all age groups, childhood risk factors were significantly correlated with levels in adulthood. The correlation coefficients for cholesterol levels and body mass index were 0.43 to 0.56 (P < .0001), and for blood pressure and triglyceride levels, they were 0.21 to 0.32 (P < .0001). To recognize children with abnormal adult levels, the National Cholesterol Education Program and the National High Blood Pressure Education Program cutoff points for lipid and blood pressure values and international cutoff points for overweight and obesity were used. Age seemed to affect associations. The best sensitivity and specificity rates were observed in 12- to 18-year-old subjects. CONCLUSIONS Childhood blood pressure, serum lipid levels, and body mass index correlate strongly with values measured in middle age. These associations seemed to be stronger with increased age at measurements.

Influence of Age on Associations Between Childhood Risk Factors and Carotid Intima-Media Thickness in Adulthood The Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium

Background— Atherosclerosis has its roots in childhood. Therefore, defining the age when childhood risk exposure begins to relate to adult atherosclerosis may have implications for pediatric cardiovascular disease prevention and provide insights about the early determinants of atherosclerosis development. The aim of this study was to investigate the influence of age on the associations between childhood risk factors and carotid artery intima-media thickness, a marker of subclinical atherosclerosis. Methods and Results— We used data for 4380 members of 4 prospective cohorts—Cardiovascular Risk in Young Finns Study (Finland), Childhood Determinants of Adult Health study (Australia), Bogalusa Heart Study (United States), and Muscatine Study (United States)—that have collected cardiovascular risk factor data from childhood (age 3 to 18 years) and performed intima-media thickness measurements in adulthood (age 20 to 45 years). The number of childhood risk factors (high [highest quintile] total cholesterol, triglycerides, blood pressure, and body mass index) was predictive of elevated intima-media thickness (highest decile) on the basis of risk factors measured at age 9 years (odds ratio [95% confidence interval] 1.37 [1.16 to 1.61], P =0.0003), 12 years (1.48 [1.28 to 1.72], P <0.0001), 15 years (1.56 [1.36 to 1.78], P <0.0001), and 18 years (1.57 [1.31 to 1.87], P <0.0001). The associations with risk factors measured at age 3 years (1.17 [0.80 to 1.71], P =0.42) and 6 years (1.20 [0.96 to 1.51], P =0.13) were weaker and nonsignificant. Conclusions— Our analyses from 4 longitudinal cohorts showed that the strength of the associations between childhood risk factors and carotid intima-media thickness is dependent on childhood age. On the basis of these data, risk factor measurements obtained at or after 9 years of age are predictive of subclinical atherosclerosis in adulthood. # Clinical Perspective {#article-title-31}

The 21‐year follow‐up of the Cardiovascular Risk in Young Finns Study: risk factor levels, secular trends and east–west difference

Objectives.  The Cardiovascular Risk in Young Finns Study is an on‐going multicentre study of atherosclerosis precursors in Finnish children and young adults. We have collected risk factor data in the 21‐year follow‐up performed in 2001. The aims of this analysis were to examine the levels, secular trends and east–west difference in risk factors amongst young adults.

Pediatric Metabolic Syndrome Predicts Adulthood Metabolic Syndrome, Subclinical Atherosclerosis, and Type 2 Diabetes Mellitus but Is No Better Than Body Mass Index Alone The Bogalusa Heart Study and the Cardiovascular Risk in Young Finns Study

Background— The clinical utility of identifying pediatric metabolic syndrome (MetS) is controversial. This study sought to determine the status of pediatric MetS as a risk factor for adult subclinical atherosclerosis (carotid intima-media thickness [cIMT]) and type 2 diabetes mellitus (T2DM) and compare and contrast this prediction with its individual components. Methods and Results— Using data from the population-based, prospective, observational Bogalusa Heart and Cardiovascular Risk in Young Finns studies, we examined the utility of 4 categorical definitions of youth MetS and their components in predicting adult high cIMT and T2DM among 1781 participants aged 9 to 18 years at baseline (1984 to 1988) who were then examined 14 to 27 years later (2001–2007) when aged 24 to 41 years. Youth with MetS were at 2 to 3 times the risk of having high cIMT and T2DM as adults compared with those free of MetS at youth. Risk estimates with the use of high body mass index were similar to those of MetS phenotypes in predicting adult outcomes. Comparisons of area under the receiver operating characteristic curve and net reclassification index suggested that prediction of adult MetS, high cIMT, and T2DM in adulthood with the use of youth MetS was either equivalent or inferior to classification based on high body mass index or overweight and obesity. Conclusions— Youth with MetS are at increased risk of meaningful adult outcomes; however, the simplicity of screening for high BMI or overweight and obesity in the pediatric setting offers a simpler, equally accurate alternative to identifying youth at risk of developing adult MetS, high cIMT, or T2DM.

Childhood C-reactive protein in predicting CRP and carotid intima-media thickness in adulthood: The cardiovascular Risk in Young Finns Study

Background—Atherosclerosis begins in childhood, and inflammation may contribute to its pathophysiology. The value of measuring inflammatory markers in the pediatric risk assessment, however, is uncertain. We examined whether childhood C-reactive protein (CRP) levels predict CRP and carotid intima-media thickness (IMT) in adulthood. Methods and Results—Study cohort included 1617 subjects, aged 3 to 18 years at baseline in 1980. These subjects were reexamined in 2001 at ages 24 to 39 years. In 2001, CRP was measured from fresh samples, and the subjects underwent carotid IMT study to evaluate subclinical atherosclerosis. Baseline (1980) CRP concentrations were measured from frozen samples in 2005. A significant tracking was observed between childhood and adult CRP levels. The age- and sex-specific correlations were the highest in the age group of 18 years at baseline (r=0.47 in females, r=0.32 in males, P<0.0001). The association between childhood and adult CRP levels was independent of serum lipids, blood pressure, smoking, obesity indices, and insulin. In multivariate analysis, childhood risk factors that independently associated with increased adult IMT included elevated systolic blood pressure (P<0.0001), high low-density lipoprotein-cholesterol (P=0.01) and smoking (P=0.049), but not CRP (P=0.95). Conclusions—Childhood CRP values predict weakly but significantly adult CRP, and this association is independent of other metabolic risk factors. Unlike conventional risk factors, however, childhood CRP does not predict adult IMT.

Obesity in childhood and vascular changes in adulthood : insights into the Cardiovascular Risk in Young Finns Study

AIMS:Exposure to risk factors in childhood may have long-term influences on vascular structure and function. This paper reviews recent findings from the Cardiovascular Risk in Young Finns Study looking at the relationships between risk factors identified in childhood, including obesity, and arterial structure/function assessed in adulthood.METHODS:The Young Finns Study is a longitudinal study from childhood to adulthood. The baseline study was carried out in 1980 and included 3.596 children and adolescents aged 3–18 y. Regular follow-up examinations of this cohort have included comprehensive data collection, including obesity indices (body mass index (BMI, kg/m2) and skinfolds in childhood), serum lipoproteins, insulin, glucose, blood pressure, family risk, lifestyle factors, smoking status, alcohol use, physical activity, psychological factors, diet and socioeconomic status. The latest follow-up was carried out in 2001 (N=2283, ages 24–39 y). In addition to the usual protocol, this 21-y follow-up study included ultrasound measurements of carotid artery intima–media thickness (IMT) and carotid artery elasticity.RESULTS:In this cohort, BMI measured in youth is significantly associated with BMI measured in adulthood. The correlation coefficient for 21-y tracking between childhood and adulthood BMI is r=0.45 (P<0.0001). In multivariate analysis, childhood LDL-cholesterol, systolic blood pressure, BMI and smoking were all significantly associated with adult IMT. The effects of childhood LDL-cholesterol and systolic blood pressure remained independently associated with carotid IMT when adjusted for the current risk factor values (P<0.01 for both). However, when adulthood BMI was entered into the model, the effect of childhood BMI became nonsignificant. The age- and sex-adjusted multivariate correlates of carotid artery elasticity included childhood skinfold thickness (sum of biceps, triceps and subscabular) and childhood systolic blood pressure. Childhood systolic blood pressure remained borderline significantly (P=0.08) associated with carotid elasticity when the effect of current blood pressure was taken into account. However, the effect of childhood skinfold thickness on carotid artery elasticity became nonsignificant (P=0.16) when adjusted with adult BMI.CONCLUSIONS:The data from the Cardiovascular Risk in Young Finns Study suggest that obesity indices measured in youth are significantly associated with increased carotid artery IMT and decreased elasticity in adulthood. These relations are, at least, partly explained by significant tracking of obesity from youth to adulthood. These findings emphasize the importance of maintaining ideal weight from youth to adulthood in cardiovascular risk reduction.

Ideal Cardiovascular Health in Childhood and Cardiometabolic Outcomes in Adulthood: The Cardiovascular Risk in Young Finns Study

Background— The American Heart Association (AHA) defined a new concept, cardiovascular health, and determined metrics needed to monitor it over time as part of its 2020 Impact Goal definition. Ideal cardiovascular health is defined by the presence of both ideal health behaviors and ideal health factors. The applicability of this concept to a cohort of children and its relationship with cardiometabolic outcomes in adulthood has not been reported. Methods and Results— The sample comprised 856 participants aged 12 to 18 years (mean age 15.0 years) from the Cardiovascular Risk in Young Finns Study cohort. Participants were followed up for 21 years since baseline (1986) and had data available concerning health factors and behaviors in childhood and cardiometabolic outcomes in adulthood (2007). The number of ideal cardiovascular health metrics present in childhood was associated with reduced risk of hypertension (odds ratio [95% confidence interval] 0.66 [0.52–0.85], P<0.001), metabolic syndrome (0.66 [0.52–0.77], P<0.001), high low-density lipoprotein cholesterol (0.66 [0.52–0.85], P=0.001), and high-risk carotid artery intima-media thickness (0.75 [0.60–0.94], P=0.01) in adulthood. All analyses were age and sex adjusted, and the results were not altered after additional adjustment with socioeconomic status. Conclusions— The number of ideal cardiovascular health metrics present in childhood predicts subsequent cardiometabolic health in adulthood. Our findings suggest that pursuit of ideal cardiovascular health in childhood is important to prevent cardiometabolic outcomes in adulthood.