Eero Jokinen

Prospective randomised trial in 1062 infants of diet low in saturated fat and cholesterol

Interventions to avoid atherosclerosis might be more successful if launched early in life when eating and life-style patterns are formed, but dietary interventions have been limited by fears of diet-induced growth failure. We investigated the effects of a diet low in saturated fat and cholesterol on serum lipid concentrations and growth in 1062 healthy 7-month-old infants in a randomised study. Every 1-3 months, families in the intervention group received dietary advice aimed at adequate energy supply, with low fat intake (30-35% energy, polyunsaturated/monounsaturated/saturated fatty acid ratio 1/1/1, and cholesterol intake < 200 mg daily). Infants in control families consumed an unrestricted diet. 3-day food records were collected at ages 8 and 13 months. Growth was carefully monitored. Between 7 and 13 months serum cholesterol and non-high-density-lipoprotein cholesterol concentrations did not change significantly in the intervention group (mean change -0.03 [SD 0.72] mmol/L and 0.01 [0.67] mmol/L) but increased substantially in the control group (0.24 [0.64] mmol/L and 0.23 [0.60] mmol/L; p for difference in mean changes between groups < 0.001). Daily intakes of energy and saturated fat were lower in the intervention than in the control group at 13 months (4065 [796] vs 4370 [748] kJ, p = 0.033, and 9.3 [3.5] vs 14.5 [4.8] g, p < 0.001, respectively), and intake of polyunsaturated fat was higher (5.8 [2.2] vs 4.4 [1.4] g, p < 0.001). Growth did not differ between the groups and was as expected for children at this age. Serum cholesterol concentrations fell significantly in parents of intervention-group infants. The increases in serum cholesterol and non-high-density-lipoprotein cholesterol concentration that occur in infants between the ages of 7 and 13 months can be avoided by individualised diets, with no effect on the childrens growth.

Impact of Repeated Dietary Counseling Between Infancy and 14 Years of Age on Dietary Intakes and Serum Lipids and Lipoproteins The STRIP Study

Background— Atherosclerosis development might be delayed or prevented by dietary measures. The aims of the present study were to evaluate the effect of low-saturated-fat, low-cholesterol dietary counseling on fat intakes, growth, serum cholesterol values, and pubertal development in children and adolescents. Methods and Results— In the randomized prospective Special Turku Coronary Risk Factor Intervention Project (STRIP), a low-saturated-fat, low-cholesterol diet was introduced to intervention infants (n=540) at 7 months of age, and control children (n=522) received an unrestricted diet. Dietary intakes, serum cholesterol values, somatic growth, and development were followed up throughout childhood and adolescence. Saturated fat intakes, serum total cholesterol, and low-density lipoprotein cholesterol values were lower (P<0.001) in the intervention than in control children during the 14 years, whereas high-density lipoprotein cholesterol values in the 2 study groups showed no difference. Boys had lower total and low-density lipoprotein cholesterol concentrations than girls throughout childhood (P<0.001), and the intervention effect on serum cholesterol concentration was larger in boys than girls. The 2 study groups showed no difference in growth, body mass index, pubertal development, or age at menarche (median, 13.0 and 12.8 years in the intervention and control girls, respectively; P=0.52). The cholesterol values decreased as puberty progressed. Mean concentrations of total and high-density lipoprotein cholesterol decreased from ≈4.5 and ≈1.4 mmol/L, respectively, in Tanner stage 1 (prepubertal) boys to ≈3.9 and ≈1.1 mmol/L in Tanner stage 4 (late pubertal) boys. Conclusions— Repeated dietary counseling remains effective in decreasing saturated fat and cholesterol intake and serum cholesterol values at least until 14 years of age. Puberty markedly influences serum cholesterol concentrations.

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.

Idiopathic Dilated Cardiomyopathy in Children: Prognostic Indicators and Outcome

Objective. To determine the outcome of Finnish children and adolescents with idiopathic dilated cardiomyopathy (IDCM) and factors that might be useful as prognostic indicators. Methodology. The clinical profile and course of 62 Finnish children and adolescents (median age, 13 months; range, 1 day to 20 years) with IDCM in 1980 to 1991 were evaluated to detect factors that might predict outcome. Factors studied included age, gender, family history, previous viral illness, and symptoms and signs at presentation. Furthermore, data on serial electrocardiographic, echocardiographic, and chest x-ray examinations, histologic findings, and treatments were analyzed. Results. During a mean (±SD) follow-up of 3.9 ± 4.5 years (range, 1 day to 25 years), 10 patients (16%) recovered, 17 (27%) had residual disease, 4 (6.4%) underwent heart transplantation, and 31 (50%) died. Infants (<1 year of age) and adolescent (≥15 years of age) male patients with progressing symptoms of left ventricular failure after initiation of medical therapy tended to have the poorest outcome. However, in multivariate analysis, only histologic evidence of endocardial fibroelastosis, clinical signs of right ventricular failure at presentation, and the need for anticoagulative therapy during follow-up, the last an expression of a severely impaired left ventricular systolic function, appeared to be significant predictors of long-term outcome. Conclusions. Our study confirms that the outcome of children with IDCM still remains poor. However, a group of patients, mainly infants, make a full recovery. Adolescent male patients as well as infants suffering from endocardial fibroelastosis with persisting symptoms of congestive heart failure after initiation of medical therapy tend to have the poorest outcome. These patients need a careful follow-up at short time intervals and, in the case of lacking response to medical treatment with resulting growth failure and/or poor quality of life, should be offered urgent heart transplantation.

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.

Prospective Randomized Trial of Low-Saturated-Fat, Low-Cholesterol Diet During the First 3 Years of Life The STRIP Baby Project

BACKGROUND The long-term consequences of modified fat intake in early childhood are poorly known. The randomized prospective STRIP baby project evaluates the effects of repeated dietary counseling on nutrient intakes and serum lipid values in children 7 months to 3 years old. METHODS AND RESULTS One thousand sixty-two infants were randomized to intervention and control groups at 7 months of age. The families of the 540 intervention children were counseled to reduce the childs intake of saturated fat and cholesterol but to ensure adequate energy intake. Five hundred twenty-two control children consumed an unrestricted diet. Food records were kept, and serum lipids were measured at 5- to 12-month intervals. Intakes of saturated fat, fat as proportion of energy (E%), and cholesterol were lower in the intervention children than in control children at 13, 24, and 36 months of age. Fat intake by the intervention children decreased from 29 +/- 5 E% at 8 months of age to 26 +/- 6 E% at 13 months and then increased to 30 +/- 5 E% at 24 months and to 31 +/- 5 E% at 36 months. The control children consumed 29 +/- 4 E%, 28 +/- 5 E%, 33 +/- 5 E%, and 33 +/- 5 E% of fat at 8, 13, 24, and 36 months, respectively. The ratio of dietary poly-unsaturated to saturated fats of the intervention children was consistently higher than that of the control children (P < .0001). Baseline adjusted mean serum cholesterol concentration was lower in the intervention children than control children between 13 and 36 months (P < .0001; 95% confidence interval of the difference between the group means, -0.27 to -0.12 mmol/L). The effect was significant only in boys (95% confidence interval, -0.39 to -0.20 mmol/L in boys; -0.21 to 0.01 mmol/L in girls). CONCLUSIONS Repeated individualized dietary counseling markedly reduces the increase in serum cholesterol concentration that occurs in control children during the first years of life.

Development of overweight in an atherosclerosis prevention trial starting in early childhood. The STRIP study

Context:Recent data indicate a marked increase in the prevalence of obesity among school-aged children. Thus, efficacious programmes that prevent overweight development in children are urgently needed.Objective:To evaluate the impact of repeatedly given, individualised dietary and lifestyle counselling on the prevalence of overweight during the first 10 years of life.Design and participants:This study was a part of the Special Turku Coronary Risk Factor Intervention Project for Children (STRIP), which is a prospective, randomised trial aimed at reducing the exposure of the intervention children to the known risk factors of atherosclerosis. At the childs age of 7 months, 1062 children were assigned to an intervention group (n=540) or to a control group (n=522). The intervention children received individualised counselling focused on healthy diet and physical activity biannually. Height and weight of the children were measured at least once a year.Main outcome measure:Prevalence of overweight and obesity among the intervention and control children by sex and age. Children were classified as overweight or obese if their weight for height was >20% or ⩾40% above the mean weight for height of healthy Finnish children, respectively.Results:After the age of 2 years, there were continuously fewer overweight girls in the intervention group than in the control group. At the age of 10 years, 10.2% of the intervention girls and 18.8% of the control girls were overweight (P=0.0439), whereas 11.6% of the intervention boys and 12.1% of the control boys were overweight (P≈1.00). Only three children in the intervention group were obese at some age point, whereas 14 control children were classified as obese at some age point.Conclusion:Individualised dietary and lifestyle counselling given twice a year since infancy decreases prevalence of overweight in school-aged girls even without any primary energy restrictions.

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.

Effect of 7-Year Infancy-Onset Dietary Intervention on Serum Lipoproteins and Lipoprotein Subclasses in Healthy Children in the Prospective, Randomized Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) Study

Background—We previously showed that low-saturated-fat dietary intervention from infancy until 5 years of age safely and effectively reduced serum cholesterol concentration. We now report how such intervention influenced serum lipids, LDL particle size, and HDL subfractions in children when they reached the age of 7 years. Methods and Results—Healthy 7-month-old infants (n=1062) were randomized to the intervention (n=540) and control (n=522) groups. Each year, two individualized counseling sessions were organized to the intervention families. Serum lipid values were measured annually. The intervention boys had 0.20 to 0.39 mmol/L lower serum cholesterol values than the control boys throughout the follow-up (always P <0.05), but the values of the intervention and control girls did not differ. The LDL particle sizes and HDL subfractions were determined in a random subgroup of 96 intervention and 101 control children at the age of 7 years. The mean particle diameter of major LDL peak was 262.6 Å in the intervention boys and 258.5 Å in the control boys (P =0.05), and 259.2 Å in the intervention girls and 261.3 Å in the control girls (P =0.30). HDL2 and HDL3 cholesterol concentrations did not differ between the intervention and control children or between the two genders. Conclusions—The 7-year intervention favorably influenced not only the serum total and LDL cholesterol concentrations but also the LDL particle size in boys. LDL particle size remained unchanged in girls, as did HDL2 and HDL3 concentrations in both genders.