In Finland, coronary heart disease (CHD) incidence was very high in the 1960s and 1970s . In line, the Seven Countries Study showed that the level of serum cholesterol in Finns was also the highest among the investigated countries in the 1960s . With reference to the studies indicating that atherosclerosis starts early and in accord with the WHO Recommendation of 1978 , 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 universities with medical schools and several other institutions in Finland. The main 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 (N = 264, age 8 years) and in 1979 (N = 634, aged 3, 12, and 17 years) [4,5]. The first large-scale cross-sectional study was performed in 1980. This baseline study included 3596 children and adolescents aged 3, 6, 9, 12, 15, and 18 years . Thereafter this cohort has been followed up with 3–9-year intervals. The study participants are now in middle age, and at the moment, the main aim is to investigate the effects of childhood, environmental, physical, and genetic factors on the later risk of cardiometabolic disease. Since 2007, Young Finns Study group has been actively participating in a collaborative effort between several longitudinal cohort studies initiated in childhood. This International Childhood Cardiovascular Cohort (i3C) Consortium enables the pooling of data to increase power, most importantly for the follow-up of clinical cardiovascular events in adulthood .
The Cardiovascular Risk in Young Finns Study has been carried out in all five Finnish university cities with medical schools (Helsinki, Kuopio, Oulu, Tampere, and Turku) and their rural surroundings. The first cross-sectional study was conducted in 1980 . Altogether, 4320 children and adolescents aged 3, 6, 9, 12, 15, and 18 years were randomly chosen from the population register of these areas to produce a representative sample of Finnish children. In practice, girls and boys of each age cohort in each study community were separately placed in random order on the basis of the unique personal identification number. The final sample was designed to apply the following two considerations: children and adolescents from different parts (east and west) of Finland with varying CHD risk in adults should be studied; their socioeconomic background and living conditions should vary, so as to represent reasonably well all Finnish children and adolescents and allow comparisons of urban and rural and different socioeconomic groups.
After the first cross-sectional study in 1980, follow-up studies have been conducted 3–9 years apart (Fig. 1). In adulthood, field studies have been conducted in 2001, 2007, and 2010–2012. The participation rates in follow-up studies have been satisfactory. In childhood, in 1983 and 1986, a total of 2991 (83.2%) and 2799 (78.3%) individuals participated. In 2001, 2283 individuals (63.5%) of the original cohort participated in clinical examinations, and 2620 (72.9%) individuals returned questionnaires. In 2007, a total of 2204 individuals participated and in 2010–2012, there were 2063 participants. So far, 76 participants have deceased, two of them due to cardiovascular disease. We have examined the representativeness of the remaining cohort on several occasions. Early in the study, those lost during the follow-up tended to be older, more often men, and more often smokers [8,9]. Detailed analyses of nonparticipants were done in adult follow-ups. Interestingly, the participation has been dynamic, so that many patients lost to follow-up early in the study have actually returned to the study later on . When we tested the representativeness of the participants in adult follow-up by comparing their baseline characteristics with those of the nonparticipants [10,11], we found that the participants were more often women and older than nonparticipants. Otherwise, comparing nonparticipants and participants using age-adjusted analysis, there were no significant differences in either men or women in total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, blood pressure (BP), physical activity, or parents’ education [10,11]. In 2007, BMI was higher in female nonparticipants than in participants .
The main study variables are shown in Table 1. In the first cross-sectional study in 1980, a comprehensive data collection was performed using questionnaires, physical measurements, and blood tests, including general health status, serum lipids, insulin, obesity indices, BP, lifestyle factors, smoking status, alcohol use, food consumption, dietary intakes, food behavior, physical activity, psychological and behavioral factors, and socioeconomic status. In the follow-ups, serial information concerning these risk factors has been gathered. In addition, several novel risk factors, including C-reactive protein (CRP), homocysteine, asymmetric dimethlyarginine, adiponectin, leptin, and a comprehensive set of metabonomic variables have been analyzed. In addition, heart rate variability measurements to study autonomic nervous system function have been collected in adulthood.
To assess subclinical atherosclerosis, carotid artery intima–media thickness (IMT), carotid elasticity, and brachial flow-mediated dilatation (FMD) were measured in the 21-year and 27-year follow-ups in 2001 and 2007 [11–13]. These noninvasive vascular markers were chosen because they can be measured quickly and with relative ease in large population studies. During the latest follow-up in 2010–2012, cardiac ultrasound examinations were performed to study especially left ventricular mass, and liver ultrasound measures to assess fat content. In addition, cognitive testing was done.
In adult follow-ups, genomic DNA was extracted from peripheral blood leukocytes. Genome-wide single-nucleotide polymorphisms (SNPs) data were obtained with a custom-built Illumina BeadChip Human670K.
By far, the main issues addressed in the Young Finns Study have considered the associations between child and adult risk factors and the effect of childhood factors on subclinical markers of atherosclerosis.
The associations of child and adult risk factors
Important for strategies of primary prevention among children and adolescents is the question whether risk factors measured at one time point are predictive of risk factor values years later. Interestingly, concerning lipid measurements, in a subcohort of 57 individuals, the greatest relative decrease in correlations took place during the determination periods of 2 and 7 days, whereafter the decline was much slower . In the 12-year follow-up between 1980 and 1992, significant tracking was found for each of the serum lipid variables . The range of 12-year correlation was 0.48–0.58 for serum cholesterol levels and 0.33–0.37 for triglycerides. Twenty-seven-year correlations were of comparable level : 0.51–0.56 for cholesterol levels, 0.46 for BMI, and 0.27 for SBP and triglycerides. In addition, elevated childhood risk factors were strongly associated with respective adult abnormalities. Children with overweight/obesity had 6–14 times increased risk of adult obesity, and those with elevated childhood LDL-cholesterol levels had over four times increased risk of adult hypercholesterolemia. Our studies have also shown that lifestyle adopted in childhood is clearly predictive of diet and physical activity in adulthood [17,18]. Dietary patterns are established already in childhood, persist into adulthood, and are significantly associated with CHD risk factors [19,20].
The Young Finns data have allowed comprehensive analyses of childhood predictors of adult cardiovascular risk factors. It has been observed that in addition to BMI, childhood levels of CRP, family income (inverse association), mother's BMI, and polymorphisms near genes TFAP2B, LRRN6C, and FLJ35579 are independently associated with the risk of adult obesity [21▪]. Moreover, a risk assessment based on childhood BMI, mother's BMI, and family income was superior in predicting obesity compared with the approach using data only on BMI. Childhood BP, parental hypertension, childhood overweight/obesity, low parental occupational status, and a genetic risk score based on 29 newly identified SNPs for elevated BP predicted adult hypertension [22▪]. For lipids, a risk score based on previously identified loci for high triglycerides improved the risk discrimination over childhood lipid measurement for adult hypertriglyceridemia . Concerning the clustering of adult risk factors, it has been found that high levels of BMI, triglycerides, and insulin, low frequency of vegetable consumption, family history of hypertension, and family history of type 2 diabetes predict the occurrence of metabolic syndrome in adulthood [24,25▪]. In childhood, several risk habits, such as aggressiveness, past unemployment, and a low sense of responsibility also clustered and were associated with several metabolic risk factors . Suggesting the importance of dietary fatty acid intake, serum cholesterol ester fraction in childhood is independently associated with adulthood BP .
Regarding risk factor trends over time, we observed a rapid decrease in total cholesterol levels between 1980 and 1986, whereas the decrease was slower between 1986 and 2001 . At the same time, a clear increase in BMI and triglycerides levels, and a decrease in HDL-cholesterol and BP levels were observed. Between 2001 and 2007 LDL-cholesterol levels decreased, whereas waist circumference, glucose, and BP levels increased .
Childhood risk factors and subclinical atherosclerosis in adulthood
At present, there are no prospective long-term data available that could be used to test the hypothesis that exposure to risk factors in childhood influence cardiovascular morbidity or mortality. Therefore, within the Young Finns Study, ultrasound measures of carotid and brachial arteries have been used as surrogate measures of atherosclerosis. In line with other longitudinal studies, such as Bogalusa Heart Study  and Muscatine Study , we have observed that several conventional cardiovascular risk factors measured in childhood are predictive of subclinical atherosclerosis later in life. Childhood cholesterol and apolipoprotein levels have been associated with increased carotid IMT, decreased carotid elasticity, and impaired brachial endothelial function in adulthood [12,31,32]. Childhood BP and adiposity measures predict high IMT and low elasticity, and among 12–18-year olds, BP levels were also associated with lower brachial FMD values [12,31,33,34▪▪]. In a collaborative effort between Young Finns and the Bogalusa Heart Study, pediatric metabolic syndrome was predictive of adult IMT but did not provide any additional information when compared with using only data on childhood BMI levels . Adolescent smoking has been associated with increased carotid IMT . Concerning clinical aspects, one important question concerning childhood risk factor measurements is the effect of age. This issue was studied within the i3C consortium . The results suggest that the child's overall risk factor profile is predictive of adult atherosclerosis from the age of 9 onwards. However, BMI levels were informative already at the age of 3 years.
In addition to conventional risk factors, childhood lifestyle has been shown to have an important effect on subsequent arterial health. Infrequent fruit consumption and low physical activity in childhood were associated with accelerated 6-year IMT progression in adulthood . Importantly, these associations remained significant after taking into account these variables assessed in adulthood. In addition, persistently high consumption of both fruits and vegetables from childhood to adulthood was associated with improved arterial elasticity . In line, a traditional dietary pattern, characterized by low intakes of fruits and vegetables was associated with elevated increased adulthood IMT especially in men . In January 2010, the American Heart Association released its 2020 Impact Goals . In order to improve the prevention of cardiovascular disease, a new definition of ideal cardiovascular health was published. In these criteria, there are four ideal health behaviors (nonsmoking, ideal BMI, physical activity at goal levels, and diet consistent with current guideline recommendations) and three ideal health factors (ideal levels of total cholesterol, BP, and fasting blood glucose). Using the Young Finns data from the field study in 1986 (first time glucose levels were measured), we observed that the number of ideal cardiovascular health metrics present in childhood was associated with lower risk of high carotid IMT in adulthood [40▪]. Importantly, this association was not altered after adjustment for change in the ideal cardiovascular health index between childhood and adulthood. In addition to individual's own lifestyle, it seems that also parental behaviors have long-term consequences. In joint analyses between Young Finns Study and the Childhood Determinants of Adult Health study in Australia, it was found that parental smoking during offspring's childhood was associated with impaired brachial endothelial function over 20 years later [41▪▪]. This association was independent of individual's smoking status and several other possible confounding factors in adulthood. In addition, the findings were consistent in several sensitivity analyses performed according to study cohort, sex, BMI, smoking status, and socioeconomic status. Suggesting the importance of prebirth circumstances, recent analyses from the Young Finns Study showed that preterm birth and impaired fetal growth are associated with increased carotid IMT and decreased brachial FMD .
Genetic and metabonomic risk factors
During recent years, genetic analyses and metabonomic analyses have been an active part of the Young Finns study. By far, it seems that genetic risk scores for cardiovascular disease derived from genome-wide association studies do not provide appreciable additional information over conventional risk factors in risk prediction [11,43]. However, a predictive modeling framework with machine learning-based SNP selection, improved the prediction of the extreme classes of atherosclerosis risk and progression over a 6-year period . Detailed metabolic profiling performed during adult follow-ups seems also to provide additional information for risk stratification of subclinical atherosclerosis .
Reversibility of cardiovascular risk
From a clinical point of view, it is essential to know whether the associations between childhood risk factors and adult outcomes are only due to tracking of risk factors (e.g., childhood obesity leads to adult obesity) or whether childhood circumstances have permanent deleterious effects, irrespective of later risk factor status. Concerning continuous measures of adolescent LDL-cholesterol and BP, as well as smoking, it has been observed that their associations with adult carotid IMT are independent of respective adult risk factors . In addition, clustering of these adolescent risk factors was predictive of IMT in stratified analyses among adults with a different amount of concurrent risk factors.
Instead, the effects of childhood overweight/obesity or metabolic syndrome seem to be reversible. In a collaborative analysis within the i3C consortium, the risks of several cardiometabolic outcomes were increased only among those overweight/obese children who became obese adults, whereas the risks were completely normalized among those overweight/obese children who became nonobese adults [34▪▪]. However, the risk of adult obesity and associated cardiometabolic abnormalities was strongly dependent on childhood adiposity status, as only 15% of normal-weight children became obese adults, whereas of overweight/obese children, 65% were obese at follow-up. Favorable changes in obesity status from childhood to adulthood are also associated with improved arterial elasticity in adulthood . Moreover, in the Young Finns cohort, individuals recovering from metabolic syndrome during a 6-year follow-up in young adulthood had smaller carotid IMT and higher carotid distensibility values, both absolute and 6-year change, compared with those with persistent metabolic syndrome .
The existing results from the prospective Cardiovascular Risk in Young Finns Study have shown that several childhood cardiovascular risk factors and lifestyle are associated with the risk of subclinical atherosclerosis in adulthood (Fig. 2). Recent encouraging findings suggest that obesity-associated risks can be reversed if adverse childhood adiposity status can be reversed by adulthood. In the future, with extending follow-up, the main aim is to investigate the influences of childhood factors on the risk of clinical cardiovascular events.
The Young Finns Study has been financially supported by the Academy of Finland: grants 126925, 121584, 124282, 129378, 117797, and 41071, the Social Insurance Institution of Finland, Kuopio, Tampere and Turku University Hospital Medical Funds, Juho Vainio Foundation, Paavo Nurmi Foundation, Finnish Foundation of Cardiovascular Research and Finnish Cultural Foundation, Sigrid Juselius Foundation, Emil Aaltonen Foundation and the Research foundation of Orion Corporation.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
- ▪ of special interest
- ▪▪ of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 92).
1. Pyörälä K, Salonen JT, Valkonen T. Trends in coronary heart disease mortality and morbidity and related factors in Finland. Cardiology 1985; 72:35–51.
2. Keys A, Aravanis C, Blackburn HW, et al. Epidemiological studies related to coronary heart disease: characteristics of men aged 40–59 in seven countries. Acta Med Scand 1966; 460 (Suppl):1–392.
3. WHO. Study of the precursors of atherosclerosis. Protocol of a WHO collaborative project. Geneva: World Health Organization; 1978.
4. Viikari JS, Åkerblom HK, Nikkari T, et al. Multicenter study of atherosclerosis precursors in Finnish children: pilot study of 8-year-old boys. Ann Clin Res 1982; 14:103–110.
5. Åkerblom H, Viikari J, Uhari M, et al. A study of cardiovascular risk factors and their determinants in Finnish children. Ann Clin Res 1984; 16:23–33.
6. Åkerblom HK, Viikari J, Uhari M, et al. Atherosclerosis precursors in Finnish children and adolescents. I. General description of the cross-sectional study of 1980, and an account of the children's and families’ state of health. Acta Paediatr Scand Suppl 1985; 318:49–63.
7. Dwyer T, Sun C, Magnussen CG, et al.
Cohort Profile: The International Childhood Cardiovascular Cohort (i3C) Consortium. Int J Epidemiol 2012 [Epub ahead of print].
8. Raitakari OT, Porkka KV, Rasanen L, et al. Clustering and six year cluster-tracking of serum total cholesterol, HDL-cholesterol and diastolic blood pressure in children and young adults. The Cardiovascular Risk in Young Finns Study. J Clin Epidemiol 1994; 47:1085–1093.
9. Porkka KV, Raitakari OT, Leino A, et al. Trends in serum lipid levels during 1980–1992 in children and young adults. The Cardiovascular Risk in Young Finns Study. Am J Epidemiol 1997; 146:64–77.
10. Juonala M, Viikari JSA, Hutri-Kähönen N, et al. The 21-year follow-up of the Cardiovascular Risk in Young Finns Study: risk factor
levels, secular trends and east-west difference. J Intern Med 2004; 255:457–468.
11. Juonala M, Viikari JSA, Kähönen M, et al. Life-time risk factors and progression of carotid atherosclerosis in young adults. The Cardiovascular Risk in Young Finns Study. Eur Heart J 2010; 31:1745–1751.
12. Raitakari OT, Juonala M, Kähönen M, et al. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: The Cardiovascular Risk in Young Finns Study. JAMA 2003; 290:2277–2283.
13. Juonala M, Kähönen M, Laitinen T, et al. Effect of age and sex on carotid intima-media thickness, elasticity and brachial endothelial function in healthy adults: The Cardiovascular Risk in Young Finns Study. Eur Heart J 2008; 29:1198–1206.
14. Porkka KV, Viikari JS, Åkerblom HK. Short-term intra-individual variation and long-term tracking of serum lipid levels in children: the Cardiovascular Risk in Young Finns Study. Atherosclerosis 1994; 105:63–69.
15. Porkka KVK, Viikari JSA, Taimela S, et al. Tracking and predictiveness of serum lipid and lipoprotein measurements in childhood: A 12-year follow-up – the Cardiovascular Risk in Young Finns Study. Am J Epidemiol 1994; 140:1096–1110.
16. Juhola J, Magnussen CG, Viikari JS, et al. Tracking of serum lipid levels, blood pressure, and body mass index from childhood to adulthood: the Cardiovascular Risk in Young Finns Study. J Pediatr 2011; 159:584–590.
17. Mikkilä V, Räsänen L, Raitakari OT, et al. Longitudinal changes in diet from childhood into adulthood with respect to risk of cardiovascular diseases: The Cardiovascular Risk in Young Finns Study. Eur J Clin Nutr 2004; 58:1038–1045.
18. Telama R, Yang X, Viikari J, et al. Physical activity from childhood to adulthood: a 21-year tracking study. Am J Prev Med 2005; 28:267–273.
19. Mikkilä V, Räsänen L, Raitakari OT, et al. Consistent dietary patterns identified from childhood to adulthood: the cardiovascular risk in Young Finns Study. Br J Nutr 2005; 93:923–931.
20. Mikkilä V, Räsänen L, Raitakari OT, et al. Major dietary patterns and cardiovascular risk factors from childhood to adulthood. The Cardiovascular Risk in Young Finns Study. Br J Nutr 2007; 98:218–225.
21▪. Juonala M, Juhola J, Magnussen CG, et al. Childhood environmental and genetic predictors of adulthood obesity: the cardiovascular risk in young Finns study. J Clin Endocrinol Metab 2011; 96:E1542–E1549.
This study examined the associations between childhood risk factors and adult obesity. The main finding was that children at high risk of adult obesity can be identified using a simple nonlaboratory-based risk assessment (own BMI, parental BMI, socioeconomic status).
22▪. Juhola J, Oikonen M, Magnussen CG, et al. Childhood physical, environmental, and genetic predictors of adult hypertension: the cardiovascular risk in young Finns study. Circulation 2012; 126:402–409.
This study suggests that among children, the prediction of adult hypertension can be improved by utilizing data on parental hypertension and genetic variants associated with elevated BP.
23. Tikkanen E, Tuovinen T, Widen E, et al. Association of known loci with lipid levels among children and prediction of dyslipidemia in adults. Circ Cardiovasc Genet 2011; 4:673–680.
24. Mattsson N, Rönnemaa T, Juonala M, et al. Childhood predictors of the metabolic syndrome in adulthood. The Cardiovascular Risk in Young Finns Study. Ann Med 2008; 40:542–552.
25▪. Jääskeläinen P, Magnussen CG, Pahkala K, et al.
Childhood Nutrition in Predicting Metabolic Syndrome in Adults: The Cardiovascular Risk in Young Finns Study. Diabetes Care 2012; 35:1937–1943.
On the basis of this study, childhood vegetable consumption is associated with smaller later risk of metabolic syndrome. Those children eating at least one daily serving of vegetables had significantly decreased occurrence of metabolic syndrome in adulthood.
26. Raitakari OT, Leino M, Räikkönen K, et al. Clustering of risk habits in young adults: the Cardiovascular Risk in Young Finns Study. Am J Epidemiol 1995; 142:36–44.
27. Kaikkonen JE, Jula A, Mikkilä V, et al. Childhood serum cholesterol ester fatty acids are associated with blood pressure 27 y later in the Cardiovascular Risk in Young Finns Study. Am J Clin Nutr 2012; 95:1422–1431.
28. Raiko JRH, Viikari JSA, Ilmanen A, et al. Follow-ups of the Cardiovascular Risk in Young Finns Study in 2001 and 2007: Levels and 6-year changes in risk factors. J Intern Med 2010; 267:370–384.
29. Li S, Chen W, Srinivasan SR, et al. Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart Study. JAMA 2003; 290:2271–2276.
30. Davis PH, Dawson JD, Riley WA, Lauer RM. Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: The Muscatine Study. Circulation 2001; 104:2815–2819.
31. Juonala M, Järvisalo MJ, Mäki-Torkko N, et al. Risk factors identified in childhood and decreased carotid artery elasticity in adulthood. The Cardiovascular Risk in Young Finns Study. Circulation 2005; 112:1489–1496.
32. Juonala M, Viikari JSA, Kähönen M, et al. 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. J Am Coll Cardiol 2008; 52:293–299.
33. Juonala M, Viikari JSA, Rönnemaa T, et al. Elevated blood pressure in adolescent boys predicts endothelial dysfunction: The Cardiovascular Risk in Young Finns Study. Hypertension 2006; 48:424–430.
34▪▪. Juonala M, Magnussen CG, Berenson GS, et al. Childhood adiposity, adult adiposity, and cardiovascular risk factors. N Engl J Med 2011; 365:1876–1885.
The joint analyses in four longitudinal cohorts studies suggest that cardiometabolic risk associated with childhood overweight/obesity is reversible. Those overweight/obese children who became nonobese adults had normalized their risks of dyslipidemia, hypertension, and subclinical atherosclerosis in adulthood.
35. Magnussen CG, Koskinen J, Chen W, et al. 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. Circulation 2010; 122:1604–1611.
36. Juonala M, Magnussen CG, Venn A, et al. The 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. Circulation 2010; 122:2514–2520.
37. Aatola H, Koivistoinen T, Hutri-Kähönen N, et al. Lifetime fruit and vegetable consumption and arterial pulse wave velocity in adulthood: the Cardiovascular Risk in Young Finns Study. Circulation 2010; 122:2521–2528.
38. Mikkilä V, Räsänen L, Laaksonen MM, et al. Long-term dietary patterns and carotid artery intima media thickness: the Cardiovascular Risk in Young Finns Study. Br J Nutr 2009; 102:1507–1512.
39. Lloyd-Jones DM, Hong Y, Labarthe D, et al. American Heart Association Strategic Planning Task Force and Statistics CommitteeDefining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association's strategic Impact Goal through 2020 and beyond. Circulation 2010; 121:586–613.
40▪. Laitinen TT, Pahkala K, Magnussen CG, et al. Ideal cardiovascular health in childhood and cardiometabolic outcomes in adulthood: the Cardiovascular Risk in Young Finns Study. Circulation 2012; 125:1971–1978.
The number of ideal cardiovascular health metrics (as defined by American Heart Association) present in childhood was associated with reduced risks of hypertension, metabolic syndrome, high LDL cholesterol, and high-risk carotid artery IMT in adulthood.
41▪▪. Juonala M, Magnussen CG, Venn A, et al. Parental smoking in childhood and brachial artery flow-mediated dilatation in young adults: the Cardiovascular Risk in Young Finns Study and the Childhood Determinants of Adult Health (CDAH) Study. Arterioscler Thromb Vasc Biol 2012; 32:1024–1031.
The joint analyses in two independent cohorts showed that parental smoking in youth is associated with reduced brachial FMD measured over 20 years later. Importantly, these associations were not altered after adjustments with classical cardiovascular risk factors. Therefore, these data suggest that passive exposure to cigarette smoke among children might cause irreversible impairment in endothelium-dependent vasodilation.
42. Skilton MR, Viikari JS, Juonala M, et al. Fetal growth and preterm birth influence cardiovascular risk factors and arterial health in young adults: the Cardiovascular Risk in Young Finns Study. Arterioscler Thromb Vasc Biol 2011; 31:2975–2981.
43. Hernesniemi JA, Seppälä I, Lyytikäinen LP, et al. Genetic profiling using genome-wide significant coronary artery disease risk variants does not improve the prediction of subclinical atherosclerosis: the Cardiovascular Risk in Young Finns Study, the Bogalusa Heart Study and the Health 2000 Survey: a meta-analysis of three independent studies. PLoS One 2012; 7:e28931.
44. Okser S, Lehtimäki T, Elo LL, et al. Genetic variants and their interactions in the prediction of increased preclinical carotid atherosclerosis: the cardiovascular risk in young Finns study. Plos Genet 2010; 6:e1001146.
45. Würtz P, Raiko JR, Magnussen CG, et al.
High-throughput quantification of circulating metabolites improves prediction of subclinical atherosclerosis. Eur Heart J 2012; 33:2307–2316.
46. Aatola H, Hutri-Kähönen N, Juonala M, et al. Lifetime risk factors and arterial pulse wave velocity in adulthood: the cardiovascular risk in young Finns study. Hypertension 2010; 55:806–811.
47. Koskinen J, Magnussen CG, Taittonen L, et al. Arterial structure and function after recovery from the metabolic syndrome: the Cardiovascular risk in Young Finns Study. Circulation 2010; 121:392–400.