CLB-08734; No. of pages: 2; 4C: Clinical Biochemistry xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem
Short Communication
Cardiovascular risk prediction in children and adolescents Olli T. Raitakari Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
Atherosclerosis starts at a young age. The Landmark study by Dr Enos and colleagues [1] who performed autopsy studies in 300 young soldiers killed in action in the Korean War is often cited as one of first studies demonstrating that atherosclerosis begins at an early age. They observed that about 80% of the young soldiers had some indications of coronary atherosclerosis, and a small proportion (3%) had occlusions of more than 50% in some of their coronary arteries. Previously, however, similar findings were reported by the German pathologist Mönckeberg already in 1915 who reported autopsy findings in 140 soldiers who were killed in action during the First World War, and observed that about 46% had had atherosclerotic plaques in the coronary arteries [2]. Thus, by the 1970s it had become evident that the development of atherosclerosis starts at an early age. Therefore, in the 1970s and 1980s, several cohort studies world-wide were initiated to examine atherosclerotic risk factors in children. Some of the largest studies include the Muscatine and Bogalusa studies in the US, the Young Finns Study in Finland, and the CDAH study in Australia. The participants in these cohorts were recruited between the ages 3 and 20 in the 70s and early 80s, and have now reached adulthood. The mean age of the cohort members is approximately 50 years. By advancing age, these individuals are beginning to develop cardio-metabolic outcomes. At present it is possible to study endpoints like type 2 diabetes, hypertension, markers of subclinical atherosclerosis, and dyslipidemias in these cohorts [3]. The collection of follow-up data on mortality and morbidity in these cohorts has also been initiated. Therefore, for the first time in the history of cardiovascular disease epidemiology, it is now possible to study the relations between childhood risk exposures and adulthood cardio-metabolic outcomes. Many of these cohort studies have provided insights on how childhood risk factors contribute to the development of atherosclerosis. In the Bogalusa Heart Study, the investigators have performed autopsies on young persons, who had died from various causes, principally accidents and suicide, and for whom they had data on antemortem risk factors [4]. The observations made in the Bogalusa study replicated the findings seen in soldiers showing that histological atherosclerotic changes in arteries are frequently present at a young age. In addition, the observations demonstrated the links of these vascular changes to ante-mortem levels of risk markers, such as elevated body mass index, systolic blood pressure, triglycerides and LDL-cholesterol.
All these longitudinal cohorts have made an effort to study the effects of risk factors on vascular structure by using non-invasive imaging studies, for example, by measuring carotid artery intima–media thickness (IMT) by ultrasound in adult participants and linking these findings to childhood risk factor measurements. Increased carotid intima–media thickness is an established marker of subclinical atherosclerosis that has been shown to predict vascular events in population studies in adults. The Muscatine study was the first to demonstrate a link between exposure to adverse levels of lipids and blood pressure in childhood and subsequently increased carotid IMT in adulthood, and these results have been replicated in the Bogalusa and Young Finns studies [5–7]. The data published from the Young Finns Study demonstrated that the effect of childhood risk factor exposure to adult carotid IMT was independent of the effect of contemporary adult risk factors, thus suggesting that both childhood and adult risk factor burdens independently contribute to the intima–media thickness [7]. By pooling the data in these three studies it has been possible to examine the influence of age in more detail. Juonala et al. [8] attempted to ask the question from what age we start to see the associations between childhood risk exposures and high adult IMT. The effect seems to become stronger by age, and from the age of 9 years onwards this relation becomes statistically significant. This may therefore suggest that by measuring risk factors in children after the age of 9 years may help to identify individuals who are at increased risk for development of subclinical atherosclerosis in adulthood. Other childhood exposures, apart from the classical risk factors, that have been associated with increased adult IMT include low fruit and vegetable intakes, exposure to parental smoking, low socioeconomic position, and impaired fetal growth. These observations highlight potentially important areas for primary prevention. Furthermore, the links between childhood risk exposures and adult subclinical changes are not limited to carotid IMT. Youth risk factors are also predictive of coronary calcification at middle age. The data from the Young Finns study demonstrated that male sex, adolescent LDL-cholesterol and systolic blood pressure independently predict coronary calcification measured in adulthood [9]. One explanation why childhood risk factors predict risk in adulthood relates to tracking, which simply means that risk factor values predict their own levels in the future or tend to maintain the rank order. The levels of conventional risk variables, such as serum lipids, body mass index and systolic blood pressure are relatively stable
http://dx.doi.org/10.1016/j.clinbiochem.2014.05.028 0009-9120/© 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Please cite this article as: Raitakari OT, Cardiovascular risk prediction in children and adolescents, Clin Biochem (2014), http://dx.doi.org/10.1016/ j.clinbiochem.2014.05.028
2
O.T. Raitakari / Clinical Biochemistry xxx (2014) xxx–xxx
from childhood to adulthood. Childhood overweight and obesity are especially important risk factors for adult obesity. The pooled data from the Bogalusa, Muscatine, Young Finns and CDAH studies showed that out of 6328 children examined at baseline in late 70s and early 80s, 12% were overweight or obese according to the international criteria and 88% were normal weight. After a mean followup of 23 years, a large majority 65% of the initially overweight or obese children became obese adults having BMI of 30 kg/m 2 or greater. In contrast, only 15% of the initially normal weight children were classified as obese adults [3]. This highlights that the tracking of increased childhood adiposity is relatively strong, and most overweight and obese children end up being obese as adults. Furthermore, childhood obesity is not only a risk factor of adult obesity, but it is also significantly linked with other adulthood outcomes such type 2 diabetes, hypertension, increased carotid artery intima–media thickness, and dyslipidemia. However, the future risk associated with childhood obesity seems to become lower in those individuals who recover from increased adiposity and end-up being non-obese as adults. Current data thus suggest that several childhood risk factors are associated with higher risk of cardio-metabolic outcomes in adulthood. Future studies among aging cohorts followed since childhood will provide data on their influence on clinical cardiovascular outcomes.
References [1] Landmark article, July 18, 1953: Coronary disease among United States soldiers killed in action in Korea. Preliminary report. By William F. Enos, Robert H. Holmes and James BeyerEnos WF, Holmes RH, Beyer J. JAMA Nov 28 1986;256(20):2859–62. [2] Über die Atherosklerose der Kombattanten (nach Obduktionsbefunden)Mönckeberg JG. Zentralbl Herz Gefässkrankheiten 1915;7:10–22. [3] Childhood adiposity, adult adiposity, and cardiovascular risk factorsJuonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA, et al. NEJM 2011;365: 1876–85. [4] Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart StudyBerenson GS, Srinivasan SR, Bao W, Newman III WP, Tracy RE, Wattigney WA. NEJM 1998;338:1650–6. [5] Carotid intimal–medial thickness is related to cardiovascular risk factors measured from childhood through middle age: The Muscatine Study.Davis PH, Dawson JD, Riley WA, Lauer RM. Circulation 2001;104:2815–9. [6] Cardiovascular risk factors in childhood and carotid artery intima–media thickness in adulthood: the Cardiovascular Risk in Young Finns StudyRaitakari OT, Juonala M, Kähönen M, Taittonen L, Laitinen T, Mäki-Torkko N, et al. JAMA 2003;290:2277–83. [7] Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart StudyLi S, Chen W, Srinivasan SR, Bond MG, Tang R, Urbina EM, et al. JAMA 2003;290:2271–6. [8] 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.Juonala M, Magnussen CG, Venn A, Dwyer T, Burns TL, Davis PH, et al. Circulation 2010;122:2514–20. [9] Adolescence risk factors are predictive of coronary artery calcification at middle age: the cardiovascular risk in young Finns study.Hartiala O, Magnussen CG, Kajander S, Knuuti J, Ukkonen H, Saraste A, et al. J Am Coll Cardiol 2012;60:1364–70.
Please cite this article as: Raitakari OT, Cardiovascular risk prediction in children and adolescents, Clin Biochem (2014), http://dx.doi.org/10.1016/ j.clinbiochem.2014.05.028
Contents lists available at ScienceDirect
Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem
Short Communication
Cardiovascular risk prediction in children and adolescents Olli T. Raitakari Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland
Atherosclerosis starts at a young age. The Landmark study by Dr Enos and colleagues [1] who performed autopsy studies in 300 young soldiers killed in action in the Korean War is often cited as one of first studies demonstrating that atherosclerosis begins at an early age. They observed that about 80% of the young soldiers had some indications of coronary atherosclerosis, and a small proportion (3%) had occlusions of more than 50% in some of their coronary arteries. Previously, however, similar findings were reported by the German pathologist Mönckeberg already in 1915 who reported autopsy findings in 140 soldiers who were killed in action during the First World War, and observed that about 46% had had atherosclerotic plaques in the coronary arteries [2]. Thus, by the 1970s it had become evident that the development of atherosclerosis starts at an early age. Therefore, in the 1970s and 1980s, several cohort studies world-wide were initiated to examine atherosclerotic risk factors in children. Some of the largest studies include the Muscatine and Bogalusa studies in the US, the Young Finns Study in Finland, and the CDAH study in Australia. The participants in these cohorts were recruited between the ages 3 and 20 in the 70s and early 80s, and have now reached adulthood. The mean age of the cohort members is approximately 50 years. By advancing age, these individuals are beginning to develop cardio-metabolic outcomes. At present it is possible to study endpoints like type 2 diabetes, hypertension, markers of subclinical atherosclerosis, and dyslipidemias in these cohorts [3]. The collection of follow-up data on mortality and morbidity in these cohorts has also been initiated. Therefore, for the first time in the history of cardiovascular disease epidemiology, it is now possible to study the relations between childhood risk exposures and adulthood cardio-metabolic outcomes. Many of these cohort studies have provided insights on how childhood risk factors contribute to the development of atherosclerosis. In the Bogalusa Heart Study, the investigators have performed autopsies on young persons, who had died from various causes, principally accidents and suicide, and for whom they had data on antemortem risk factors [4]. The observations made in the Bogalusa study replicated the findings seen in soldiers showing that histological atherosclerotic changes in arteries are frequently present at a young age. In addition, the observations demonstrated the links of these vascular changes to ante-mortem levels of risk markers, such as elevated body mass index, systolic blood pressure, triglycerides and LDL-cholesterol.
All these longitudinal cohorts have made an effort to study the effects of risk factors on vascular structure by using non-invasive imaging studies, for example, by measuring carotid artery intima–media thickness (IMT) by ultrasound in adult participants and linking these findings to childhood risk factor measurements. Increased carotid intima–media thickness is an established marker of subclinical atherosclerosis that has been shown to predict vascular events in population studies in adults. The Muscatine study was the first to demonstrate a link between exposure to adverse levels of lipids and blood pressure in childhood and subsequently increased carotid IMT in adulthood, and these results have been replicated in the Bogalusa and Young Finns studies [5–7]. The data published from the Young Finns Study demonstrated that the effect of childhood risk factor exposure to adult carotid IMT was independent of the effect of contemporary adult risk factors, thus suggesting that both childhood and adult risk factor burdens independently contribute to the intima–media thickness [7]. By pooling the data in these three studies it has been possible to examine the influence of age in more detail. Juonala et al. [8] attempted to ask the question from what age we start to see the associations between childhood risk exposures and high adult IMT. The effect seems to become stronger by age, and from the age of 9 years onwards this relation becomes statistically significant. This may therefore suggest that by measuring risk factors in children after the age of 9 years may help to identify individuals who are at increased risk for development of subclinical atherosclerosis in adulthood. Other childhood exposures, apart from the classical risk factors, that have been associated with increased adult IMT include low fruit and vegetable intakes, exposure to parental smoking, low socioeconomic position, and impaired fetal growth. These observations highlight potentially important areas for primary prevention. Furthermore, the links between childhood risk exposures and adult subclinical changes are not limited to carotid IMT. Youth risk factors are also predictive of coronary calcification at middle age. The data from the Young Finns study demonstrated that male sex, adolescent LDL-cholesterol and systolic blood pressure independently predict coronary calcification measured in adulthood [9]. One explanation why childhood risk factors predict risk in adulthood relates to tracking, which simply means that risk factor values predict their own levels in the future or tend to maintain the rank order. The levels of conventional risk variables, such as serum lipids, body mass index and systolic blood pressure are relatively stable
http://dx.doi.org/10.1016/j.clinbiochem.2014.05.028 0009-9120/© 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Please cite this article as: Raitakari OT, Cardiovascular risk prediction in children and adolescents, Clin Biochem (2014), http://dx.doi.org/10.1016/ j.clinbiochem.2014.05.028
2
O.T. Raitakari / Clinical Biochemistry xxx (2014) xxx–xxx
from childhood to adulthood. Childhood overweight and obesity are especially important risk factors for adult obesity. The pooled data from the Bogalusa, Muscatine, Young Finns and CDAH studies showed that out of 6328 children examined at baseline in late 70s and early 80s, 12% were overweight or obese according to the international criteria and 88% were normal weight. After a mean followup of 23 years, a large majority 65% of the initially overweight or obese children became obese adults having BMI of 30 kg/m 2 or greater. In contrast, only 15% of the initially normal weight children were classified as obese adults [3]. This highlights that the tracking of increased childhood adiposity is relatively strong, and most overweight and obese children end up being obese as adults. Furthermore, childhood obesity is not only a risk factor of adult obesity, but it is also significantly linked with other adulthood outcomes such type 2 diabetes, hypertension, increased carotid artery intima–media thickness, and dyslipidemia. However, the future risk associated with childhood obesity seems to become lower in those individuals who recover from increased adiposity and end-up being non-obese as adults. Current data thus suggest that several childhood risk factors are associated with higher risk of cardio-metabolic outcomes in adulthood. Future studies among aging cohorts followed since childhood will provide data on their influence on clinical cardiovascular outcomes.
References [1] Landmark article, July 18, 1953: Coronary disease among United States soldiers killed in action in Korea. Preliminary report. By William F. Enos, Robert H. Holmes and James BeyerEnos WF, Holmes RH, Beyer J. JAMA Nov 28 1986;256(20):2859–62. [2] Über die Atherosklerose der Kombattanten (nach Obduktionsbefunden)Mönckeberg JG. Zentralbl Herz Gefässkrankheiten 1915;7:10–22. [3] Childhood adiposity, adult adiposity, and cardiovascular risk factorsJuonala M, Magnussen CG, Berenson GS, Venn A, Burns TL, Sabin MA, et al. NEJM 2011;365: 1876–85. [4] Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart StudyBerenson GS, Srinivasan SR, Bao W, Newman III WP, Tracy RE, Wattigney WA. NEJM 1998;338:1650–6. [5] Carotid intimal–medial thickness is related to cardiovascular risk factors measured from childhood through middle age: The Muscatine Study.Davis PH, Dawson JD, Riley WA, Lauer RM. Circulation 2001;104:2815–9. [6] Cardiovascular risk factors in childhood and carotid artery intima–media thickness in adulthood: the Cardiovascular Risk in Young Finns StudyRaitakari OT, Juonala M, Kähönen M, Taittonen L, Laitinen T, Mäki-Torkko N, et al. JAMA 2003;290:2277–83. [7] Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa Heart StudyLi S, Chen W, Srinivasan SR, Bond MG, Tang R, Urbina EM, et al. JAMA 2003;290:2271–6. [8] 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.Juonala M, Magnussen CG, Venn A, Dwyer T, Burns TL, Davis PH, et al. Circulation 2010;122:2514–20. [9] Adolescence risk factors are predictive of coronary artery calcification at middle age: the cardiovascular risk in young Finns study.Hartiala O, Magnussen CG, Kajander S, Knuuti J, Ukkonen H, Saraste A, et al. J Am Coll Cardiol 2012;60:1364–70.
Please cite this article as: Raitakari OT, Cardiovascular risk prediction in children and adolescents, Clin Biochem (2014), http://dx.doi.org/10.1016/ j.clinbiochem.2014.05.028
