Leena Taittonen

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.

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.

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.

Conventional Cardiovascular Risk Factors and Metabolic Syndrome in Predicting Carotid Intima-Media Thickness Progression in Young Adults: The Cardiovascular Risk in Young Finns Study

Background— Conventional risk factors and metabolic syndrome (MetS) are cross-sectionally associated with subclinical atherosclerosis in young adults. We evaluated the relations of conventional risk factors and MetS to the 6-year progression of carotid intima-media thickness (IMT) in a population of young adults. Results and Methods— The study included 1809 subjects (aged 32±5 years) who had IMT measured in 2001 and 2007. Risk factor measurements included low-density lipoprotein cholesterol, body mass index, C-reactive protein, smoking, and family history of coronary disease in addition to MetS components. We used European Group for the Study of Insulin Resistance, revised National Cholesterol Education Program, and International Diabetes Federation definitions to diagnose MetS in 2001. Waist circumference (P<0.0001), low-density lipoprotein cholesterol (P=0.01), and insulin (P=0.003) were directly associated with IMT progression in a multivariable model adjusted for age, sex, and baseline IMT (model R2=24%). When the MetS/European Group for the Study of Insulin Resistance definition was included in the model, it was directly associated with IMT progression (P=0.03), but its inclusion did not improve the model’s predictive value. IMT increased 79±7 &mgr;m (mean±SEM) in subjects with MetS according to the MetS/European Group for the Study of Insulin Resistance definition and 42±2 &mgr;m in subjects without MetS (P<0.0001). In addition, the number of MetS components was linearly associated with IMT progression (P<0.0001). Similar results were seen with MetS/revised National Cholesterol Education Program and MetS/International Diabetes Federation definitions. Conclusions— Obesity, high low-density lipoprotein cholesterol, and high insulin level predicted IMT progression in young adults. All MetS definitions identified young adults with accelerated IMT progression, but we found no evidence that MetS would predict IMT progression more than expected from the sum of its risk components.

Life-time risk factors and progression of carotid atherosclerosis in young adults: the Cardiovascular Risk in Young Finns study

AIMS The aim of this study is to evaluate whether childhood risk factors are associated with a 6-year change in carotid intima-media thickness (IMT) in young adulthood independent of the current risk factors. METHODS AND RESULTS The Cardiovascular Risk in Young Finns cohort consisted of 1809 subjects who were followed-up for 27 years since baseline (1980, age 3-18 years) and having carotid IMT measured both in 2001 and 2007. Cardiovascular risk factors were assessed repeatedly since childhood. A genotype risk score was calculated using 17 newly identified genetic variants associating with cardiovascular morbidity. The number of childhood risk factors (high LDL-cholesterol, low HDL-cholesterol, high blood pressure, obesity, diabetes, smoking, low physical activity, infrequent fruit consumption) was associated with a 6-year change in adulthood IMT. In subjects with 0, 1, 2, and > or =3 childhood risk factors, IMT [mean (95% CI)) increased by 35 (28-42), 46 (40-52), 49 (41-57), and 61 (49-73) microm (P = 0.0001). This association remained significant when adjusted for adulthood risk score and genotype score (P = 0.007). Of the individual childhood variables, infrequent fruit consumption ((beta (95% CI) for 1-SD change -5(-9 to -1), P = 0.03) and low physical activity (-6(-10 to -2), P = 0.01) were associated with accelerated IMT progression after taking into account these variables assessed in adulthood. CONCLUSION These findings indicate that children with risk factors have increased atherosclerosis progression rate in adulthood, and support the idea that the prevention of atherosclerosis by means of life style could be effective when initiated in childhood.

Childhood Levels of Serum Apolipoproteins B and A-I Predict Carotid Intima-Media Thickness and Brachial Endothelial Function in Adulthood : The Cardiovascular Risk in Young Finns Study

OBJECTIVES The aim of this study was to determine whether apolipoproteins (apo) B and A-I measured in childhood and adolescence predict atherosclerosis in adulthood. BACKGROUND Exposure to dyslipidemia in childhood predicts the development of atherosclerosis. Apolipoproteins B and A-I might be good markers of atherogenic dyslipidemia, but there is a paucity of information concerning their importance in childhood. METHODS Apolipoproteins B and A-I, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, blood pressure, obesity, insulin, C-reactive protein, and smoking were assessed in 1980 and 2001 among 879 subjects in the Cardiovascular Risk in Young Finns Study (ages 3 to 18 years at baseline). Carotid artery intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) were measured in 2001 at the age of 24 to 39 years. RESULTS In subjects ages 12 to 18 years at baseline, apoB and apoB/apoA-I ratio were directly (p < 0.001) related and apoA-I was inversely (p = 0.01) related with adulthood IMT. In subjects ages 3 to 18 years at baseline, apoB (p = 0.02) and the apoB/apoA-I ratio (p < 0.001) were inversely related and apoA-I (p = 0.003) was directly related to adulthood FMD. These relations were not altered when the effects of nonlipid risk factors and adulthood apolipoproteins were taken into account. The apoB/apoA-I ratio measured in adolescence was superior to LDL/HDL ratio (c-values, 0.623 vs. 0.569, p = 0.03) in predicting increased IMT in adulthood (IMT >or=90th percentile and/or carotid plaque). CONCLUSIONS Apolipoproteins B and A-I measured in children and adolescents reflect a lipoprotein profile predisposing to the development of subclinical atherosclerosis in adulthood. These markers might have value in pediatric lipid risk assessment.