Nina Hutri-Kähönen

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.

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.

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.

Lifetime Risk Factors and Arterial Pulse Wave Velocity in Adulthood The Cardiovascular Risk in Young Finns Study

Limited and partly controversial data are available regarding the relationship of arterial pulse wave velocity and childhood cardiovascular risk factors. We studied how risk factors identified in childhood and adulthood predict pulse wave velocity assessed in adulthood. The study cohort consisted of 1691 white adults aged 30 to 45 years who had risk factor data available since childhood. Pulse wave velocity was assessed noninvasively by whole-body impedance cardiography. The number of conventional childhood and adulthood risk factors (extreme quintiles for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, body mass index, and smoking) was directly associated with pulse wave velocity in adulthood (P=0.005 and P<0.0001, respectively). In multivariable regression analysis, independent predictors of pulse wave velocity were sex (P<0.0001), age (P<0.0001), childhood systolic blood pressure (P=0.002) and glucose (P=0.02), and adulthood systolic blood pressure (P<0.0001), insulin (P=0.0009), and triglycerides (P=0.003). Reduction in the number of risk factors (P<0.0001) and a favorable change in obesity status (P=0.0002) from childhood to adulthood were associated with lower pulse wave velocity in adulthood. Conventional risk factors in childhood and adulthood predict pulse wave velocity in adulthood. Favorable changes in risk factor and obesity status from childhood to adulthood are associated with lower pulse wave velocity in adulthood. These results support efforts for a reduction of conventional risk factors both in childhood and adulthood in the primary prevention of atherosclerosis.

Coronary Artery Disease–Associated Locus on Chromosome 9p21 and Early Markers of Atherosclerosis

Background—Genome-wide association studies have recently identified a locus on chromosome 9p21 that influences risk of coronary artery disease (CAD). The effect of the locus on early markers of atherosclerosis is unknown. We examined its association with carotid intima-media thickness (CIMT) and brachial flow-mediated dilatation (FMD). Methods and Results—We genotyped 2277 individuals, age 24 to 39 years, from the Cardiovascular Risk in Young Finns Study with CIMT and FMD measurements and 1295 individuals, age 46 to 76 years, from the Health 2000 Survey with CIMT for rs1333049, the chromosome 9p21 variant showing the strongest association with CAD. Both mean and maximum CIMT were significantly higher (P<0.001) in the older subjects of the Health 2000 Survey compared with the Young Finns Study. However, there was no association of the rs1333049 genotype with either mean or maximum CIMT at either age (P=0.959 and 0.977 for the 2 phenotypes in the Young Finns Study and P=0.714 and 0.725 in the Health 2000 Survey). Similarly, there was no association of the locus with variation in FMD in the Young Finns cohort (P=0.521). Conclusions—The chromosome 9p21 locus does not influence CAD risk through a mechanism that also affects CIMT or induces early changes in FMD.

Adolescence risk factors are predictive of coronary artery calcification at middle age: the Cardiovascular Risk in Young Finns Study

OBJECTIVES The purpose of this study was to examine the roles of adolescence risk factors in predicting coronary artery calcium (CAC). BACKGROUND Elevated coronary heart disease risk factor levels in adolescence may predict subsequent CAC independently of change in risk factor levels from adolescence to adulthood. METHODS CAC was assessed in 589 subjects 40 to 46 years of age from the Cardiovascular Risk in Young Finns Study. Risk factor levels were measured in 1980 (12 to 18 years) and in 2007. RESULTS The prevalence of any CAC was 19.2% (27.9% in men and 12.2% in women). Age, levels of systolic blood pressure (BP), total cholesterol, and low-density lipoprotein cholesterol (LDL-C) in adolescence, as well as systolic BP, total cholesterol, diastolic BP, and pack-years of smoking in adulthood were higher among subjects with CAC than those without CAC. Adolescence LDL-C and systolic BP levels predicted CAC in adulthood independently of 27-year changes in these risk factors. The multivariable odds ratios were 1.34 (95% confidence interval: 1.05 to 1.70; p=0.02) and 1.38 (95% confidence interval: 1.08 to 1.77; p=0.01), for 1-SD increase in adolescence LDL-C and systolic BP, respectively. Exposure to both of these risk factors in adolescence (defined as values at or above the age- and sex-specific 75th percentile) substantially increased the risk of CAC (multivariable odds ratio: 3.5 [95% confidence interval: 1.7 to 7.2; p=0.007]) between groups with no versus both risk factors. CONCLUSIONS Elevated adolescence LDL-C and systolic BP levels are independent predictors of adulthood CAC, indicating that adolescence risk factor levels play an important role in the pathogenesis of coronary heart disease.

Lifetime Fruit and Vegetable Consumption and Arterial Pulse Wave Velocity in Adulthood The Cardiovascular Risk in Young Finns Study

Background— The relationships between childhood lifestyle risk factors and adulthood pulse wave velocity (PWV) have not been reported. We studied whether childhood and adulthood lifestyle risk factors are associated with PWV assessed in adulthood. Methods and Results— The study cohort comprised 1622 subjects of the Cardiovascular Risk in Young Finns Study followed up for 27 years since baseline (1980; aged 3 to 18 years) with lifestyle risk factor data available since childhood. Arterial PWV was measured in 2007 by whole-body impedance cardiography device. Vegetable consumption in childhood was inversely associated with adulthood PWV (&bgr;=−0.06, P=0.02), and this association remained significant (&bgr;=−0.07, P=0.004) when adjusted for traditional risk factors (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure, body mass index, and smoking). Vegetable consumption was also an independent predictor of PWV in adulthood when adjusted for lifestyle or traditional risk factors (&bgr;=−0.08, P=0.002 and &bgr;=−0.07, P=0.0007, respectively). Persistently high consumption of both fruits and vegetables from childhood to adulthood was associated with lower PWV compared with persistently low consumption (P=0.03 for both). The number of lifestyle risk factors (the lowest quintile for vegetable consumption, fruit consumption, physical activity, and smoking) in childhood was directly associated with PWV in adulthood (P=0.001). This association remained significant when adjusted for the number of lifestyle risk factors in adulthood (P=0.003). Conclusions— These findings suggest that lifetime lifestyle risk factors, with low consumption of fruits and vegetables in particular, are related to arterial stiffness in young adulthood.