Matti Pietikäinen

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.

Cardiovascular Risk in Young Finns

This report describes the general outline and progress of a multicentre study on risk factors of coronary heart disease and their determinants in children and adolescents. Cardiovascular Risk in Young Finns comprises a cross-sectional study of 3 to 18-year old subjects in 1980, and follow-up studies in 1983 and 1986 in various parts of Finland, and in 1989 in one of the study areas (Turku). The number of participants in 1980 was 3596 (83.1%) of those invited. In 1983 and 1986 83.2% and 77.8% of them, respectively, participated. The study programme has comprised questionnaire data on, for example, general health and living conditions, physical activity, eating habits, smoking, and psychological variables. The physical examination covered height, weight, skinfold thickness, pubertal stages and blood pressure. Blood specimens were obtained to assess concentrations of serum lipids and insulin, and in 1986 also for possible genetic markers of hypercholesterolemia. A 48 hour recall on nutrient intake was obtained from some of the subjects. The follow-up studies have enabled a study of the tracking phenomenon. Other important questions under study include, for example, the possible clustering of risk factors and their determinants. The cohorts studied provide a valuable research basis for the future, with emphasis on enabling a long-term follow-up of the subjects.

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

OBJECTIVESnTo 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.nnnSTUDY DESIGNnStudy 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).nnnRESULTSnIn 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.nnnCONCLUSIONSnChildhood 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.

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

Objectives.u2002 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.

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

AIMSnThe 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.nnnMETHODS AND RESULTSnThe 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.nnnCONCLUSIONnThese 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.

Serum Insulin and Other Cardiovascular Risk Indicators in Children, Adolescents and Young Adults

We wanted to determine the levels of fasting serum insulin during growth, the tracking of serum insulin, and the correlation of serum insulin with other coronary heart disease risk indicators in children and young adults. In 1986 2433 subjects, aged nine to 24 were studied, and insulin data were available from the same population in 1980 and 1983. Serum insulin levels showed a peak during puberty in both sexes and the decline in insulin continued after the age of 21. Tracking of serum insulin was only moderate, especially in females and young boys. Serum insulin correlated positively with body mass index, concentrations of serum triglycerides, and blood pressure, and inversely with the concentration of high density lipoprotein cholesterol. High triglycerides, high systolic blood pressure, and low level of high density lipoprotein cholesterol clustered among subjects within the highest insulin quartile. Our results suggest that the insulin resistance phenomenon, caused mainly by obesity and leading to unfavourable levels of other coronary heart disease risk indicators, is already developing in children and young adults. This suggests that preventing obesity in early life is important.

Serum Lipids and Lipoproteins in Children, Adolescents and Young Adults in 1980–1986

A multicentre study on atherosclerosis precursors in young Finns aged three to 18 years was started in 1980 (3596 subjects) serum lipid concentrations (cholesterol, HDL (high density lipoprotein) cholesterol and triglycerides) were determined (n = 3554) and the apolipoproteins A-I and B measured (n = 1355). Two follow-up studies were carried out in 1983 (n = 2851) and 1986 (n = 2489), when HDL-subfractions (HDL-2-cholesterol and HDL-3-cholesterol) were also determined. Apolipoproteins A-I and B were measured again in 1986 (n = 1202). Serum total cholesterol concentration has fallen by about 1% annually during the 1980s from 5.07 mmol/l (1980) to 4.79 mmol/l (1986) in 9- to 18-year old children and adolescents. Mean values of serum triglycerides have slightly increased during the follow-up from 0.79 mmol/l to 0.84 mmol/l, respectively. In children and young adults (3-24 years) the mean cholesterol concentration was highest at the age of six and lowest during puberty. Concentrations of serum cholesterol, LDL (low density lipoprotein) cholesterol apoprotein B and triglycerides were higher in eastern than in western Finland in 1980 and 1983, but these differences were smaller in 1986, with the exception of serum triglycerides. Both in 1983 and in 1986 HDL-2-cholesterol was lower in the west than in the east, whereas HDL-3-cholesterol was higher in the former. The favourable changes in lipid levels should be reflected in future morbidity and mortality rates from coronary heart disease in Finland.

Follow‐ups of the Cardiovascular Risk in Young Finns Study in 2001 and 2007: Levels and 6‐year changes in risk factors

Abstract.u2002 Raiko JRH, Viikari JSA, Ilmanen A, Hutri‐Kähönen N, Taittonen L, Jokinen E, Pietikäinen M, Jula A, Loo B.‐M, Marniemi J, Lehtimäki T, Kähönen M, Rönnemaa T, Raitakari OT, Juonala M (University of Turku; University of Tampere and Tampere University Hospital, Tampere; University of Oulu, Oulu; Vaasa Central Hospital, Vaasa; University of Helsinki, Helsinki; and Center of Social and Health Services, Kuopio; Finland). 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.

Young Adults With Family History of Coronary Heart Disease Have Increased Arterial Vulnerability to Metabolic Risk Factors The Cardiovascular Risk in Young Finns Study

Objective—Subjects with family history for coronary heart disease (CHD) may be more susceptible to the adverse effects of risk factors than subjects without family history. We investigated the occurrence of subclinical atherosclerosis in young adults with family history of CHD and tested the hypothesis that their arteries are more vulnerable to the proatherogenic effects of metabolic risk factors. Methods and Results—Carotid artery intima-media thickness (IMT), carotid artery compliance (CAC), and brachial artery flow-mediated dilation (FMD) were measured in the 21-year follow-up of the Cardiovascular Risk in Young Finns Study in 2265 white adults 24 to 39 years of age. Subjects with positive family history of CHD had greater IMT compared with those with negative history (mean±SEM; 0.600±0.006 versus 0.578±0.002 mm; P=0.003, respectively). No differences were observed in CAC or FMD (both P>0.2). The difference in IMT remained similar after adjustment with current risk factors (P=0.008) or childhood risk factors measured 21 years earlier (P=0.002). The number of metabolic risk factors (components of the NCEP metabolic syndrome) correlated more strongly with IMT in subjects with family history of CHD than those without (P=0.007 for interaction). Conclusions—Young healthy adults with family history of CHD have increased carotid IMT. This is partly explained by their increased vulnerability to metabolic risk factors.