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Background: Atherosclerosis begins in childhood, and inflammation may contribute to its pathophysiology. The value of measuring inflammatory markers in the pediatric risk assessment, however, is uncertain. We examined whether childhood C-reactive protein (CRP) levels predict CRP and carotid intima-media thickness (IMT) in adulthood., Methods and Results: Study cohort included 1617 subjects, aged 3 to 18 years at baseline in 1980. These subjects were reexamined in 2001 at ages 24 to 39 years. In 2001, CRP was measured from fresh samples, and the subjects underwent carotid IMT study to evaluate subclinical atherosclerosis. Baseline (1980) CRP concentrations were measured from frozen samples in 2005. A significant tracking was observed between childhood and adult CRP levels. The age- and sex-specific correlations were the highest in the age group of 18 years at baseline (r=0.47 in females, r=0.32 in males, P<0.0001). The association between childhood and adult CRP levels was independent of serum lipids, blood pressure, smoking, obesity indices, and insulin. In multivariate analysis, childhood risk factors that independently associated with increased adult IMT included elevated systolic blood pressure (P<0.0001), high low-density lipoprotein-cholesterol (P=0.01) and smoking (P=0.049), but not CRP (P=0.95)., Conclusions: Childhood CRP values predict weakly but significantly adult CRP, and this association is independent of other metabolic risk factors. Unlike conventional risk factors, however, childhood CRP does not predict adult IMT.

The common apolipoprotein E (apoE) gene (APOE) epsilon2/epsilon3/epsilon4 polymorphism explains part of serum lipid variation, and polymorphisms in the APOE promoter region have been proposed to participate in the regulation of serum lipid levels within the most common APOE epsilon3/epsilon3 genotype group. We determined APOE -219G/T and +113G/C promoter genotypes and estimated APOE haplotypes in 525 participants of the Cardiovascular Risk in Young Finns Study. We studied the associations of the APOE promoter polymorphisms and their haplotypes with cross-sectional and longitudinal serum lipid and apolipoprotein concentrations as well as with flow-mediated dilatation (FMD), carotid artery compliance (CAC), and intima-media thickness (IMT) within the APOE epsilon3/epsilon3 carriers. We found no significant association between the APOE promoter genotypes and serum lipids [low density lipoprotein-cholesterol (LDL-C), HDL-C, and triglycerides], apolipoproteins (apoA-I and apoB), or brachial artery FMD, CAC, or carotid IMT in either men or women. In longitudinal analyses in males, the carriers of heterozygous genotypes (-219G/T or +113G/C) and, furthermore, carriers of the -219T/+113C/epsilon3 haplotype had significantly higher LDL-C and total cholesterol concentrations throughout the 21 year follow-up period compared with homozygous G allele carriers or noncarriers of the -219T/+113C/epsilon3 haplotype. Such associations were not found in females. In summary, the APOE promoter polymorphisms -219G/T and +113G/C as well as their haplotype are associated with longitudinal changes in LDL-C and total cholesterol concentrations in young Finnish males but do not seem to be major determinants for FMD, CAC, or carotid IMT in males or females.

Brachial artery FMD (flow-mediated dilatation) is widely used as a marker of systemic arterial endothelial function. FMD, however, shows considerable 25% day-to-day variation that hinders its clinical use. The reasons for this variability are poorly characterized. Therefore the present study was designed to clarify factors responsible for the hourly variation in endothelial function, including consuming a low-fat meal and circadian rhythms in endogenous hormonal levels. Brachial artery FMD, along with serum glucose, triacylglycerols (triglycerides) and levels of several hormones were measured six times per day on two separate days 1 week apart. On one day, the subjects (healthy males: n=12, mean age, 24 years) ate a light breakfast and a standardized lunch (23.5% fat, 48.7% carbohydrate and 27.8% protein). On the other day, they had a similar breakfast after which they fasted. Postprandial FMD values (both after breakfast and after lunch) were similar to baseline FMD. FMD showed a 28% hourly variation and 27% weekly variation. Variation in plasma levels of insulin (P=0.02) associated negatively and DHPG (3,4-dihydroxyphenylglycol) (P=0.001), a marker of sympathetic nervous activation, associated positively with variation in FMD. The effects of DHPG and insulin on FMD were independent of changes in baseline brachial artery diameter, although DHPG was also inversely associated with baseline diameter. Eating a regular low-fat meal does not have any measurable effects on brachial artery endothelial function. These data suggest that strict requirements for fasting conditions may be unnecessary when measuring peripheral endothelial function using the ultrasound technique. Circadian variation in serum insulin and sympathetic tone are physiological determinants of endothelial function.

Objective: The relationship between Chlamydia pneumoniae (Cpn) infection and arterial measures of preclinical atherosclerosis has remained controversial. Because atherogenesis begins in early life, we examined whether carotid and aortic intima-media thickness (IMT) and brachial artery endothelial function are associated with Cpn seropositivity in children., Methods and Results: Cpn-specific IgG and IgA antibodies were assessed by enzyme immunoassay in 199 healthy children followed-up annually from 7 to 11 years of age. Carotid (cIMT) and aortic IMT (aIMT), and brachial artery flow-mediated dilatation (FMD) were measured in 137 of the 199 children at the age of 11 years using high-resolution ultrasound. Children with persistent IgG and/or IgA seropositivity to Cpn had significantly increased aIMT compared with seronegative children (IgG< or =45 and IgA< or =12 enzyme immunounits) or children with transient Cpn seropositivity (seronegative, 0.496 [0.054]; transient, 0.494 [0.061]; and persistent, 0.532 [0.086] mm; P<0.05 for trend). This trend was not explained by traditional atherosclerotic risk factors or pubertal stage. cIMT and FMD were not associated with Cpn seropositivity., Conclusions: Eleven-year-old children with persistent Cpn seropositivity show increased aIMT but not cIMT, suggesting that Cpn may affect the aortic wall, the site where the earliest atherosclerotic lesions are known to occur, in otherwise healthy children.

Objective: Silent coeliac disease is reported in 1% of Caucasian populations, but there is a lack of knowledge of its natural course and the risk of complications. The need for population screening is debated. We sought for complications of untreated coeliac disease in a well-defined cohort of Finnish adults., Material and Methods: Subjects (n=2427, ages 24-39 years) attending the 21-year follow-up visit of the study "Cardiovascular Risk in Young Finns" completed an extensive questionnaire on their health, diet, social situation and family life, and were given a medical examination. Measurement of serum IgA-transglutaminase and IgA-endomysium antibodies identified 21 subjects with silent coeliac disease., Results: The subjects with silent coeliac disease did not differ from the rest of the cohort in age, gender, stature, weight, medical diagnoses (autoimmune, malignant), health concerns, use of alternative medications, physical activity, or in the cause of death their parents. They had lower serum HDL-cholesterol (1.12 versus 1.29 mmol/L; p=0.015), as described for active coeliac disease. Fewer (5.3% versus 22.8%; p=0.047) had a university or college degree or worked in managerial or professional positions (28% versus 45%; p=0.112)., Conclusions: The underachievement in education and working life observed in subjects with silent coeliac disease is a new and intriguing finding and may be related to the increased prevalence of depressive and disruptive behavioural disorders described in teenagers with untreated coeliac disease. Our findings add a new ingredient to the ongoing discussion regarding the need for population screening for silent coeliac disease.

Aim: The aim of this study was to investigate the role of skeletal muscle fibre type in the regulation of glucose metabolism in middle-aged obese subjects with impaired glucose tolerance (IGT) during a 2-year exercise and dietary intervention., Methods: Muscle biopsies (musculus vastus lateralis) were taken from 22 subjects belonging to the intervention group of the Finnish Diabetes Prevention Study [1]. According to their myosin heavy chain (MHC) profile at the baseline, the subjects were divided into two groups: IGT(slow) (n=10) with a high proportion of MHC I isoforms and IGT(fast) (n=12) with a high proportion of MHC II isoforms in the vastus lateralis muscle. The intervention consisted of dietary counselling, strength and power training and/or aerobic exercise. The amount of exercise was the same in both groups; the exercise frequency was 5.1+/-2.7 h/week in the IGT(slow) and 5.1+/-2.8 h/week in the IGT(fast) group., Results: Fasting glucose (p<0.05), 2-h glucose (p<0.05), fasting insulin (p<0.05), haemoglobin A1c (HbA(1c)) (p<0.01) and insulin resistance (p<0.05) [homeostasis model assessment for insulin resistance (HOMA-IR)] decreased in the IGT(fast) group, whereas only the 2-h glucose and HbA(1c) concentrations decreased in the IGT(slow) group. The amount of the glycogen synthase kinase-3-alphabeta (GSK-3-alphabeta) decreased in the IGT(fast) group (p<0.05). Exercise training increased the lactate dehydrogenase (LDH) (p<0.01), LDH-1 (p<0.05) and citrate synthase (CS) (p<0.05) activities in the vastus lateralis muscle in the IGT(slow) group, but only the CS activity (p<0.05) in the IGT(fast) group., Conclusions: The glucose metabolism improved both in the IGT(slow) and IGT(fast) group during the 2-year exercise and dietary intervention. The change was more prominent in the IGT(fast) group than in the IGT(slow) group, associated with the decrease of the GSK-alphabeta protein expression in skeletal muscle. The exercise training improved both glycolytic and oxidative capacity in the vastus lateralis muscle. The glycolytic capacity improved in the IGT(slow) group and the oxidative capacity in both groups.

Objectives: Elevated C-reactive protein (CRP) is a suggested risk marker for cardiovascular disease. We aimed at investigating the distribution and determinants of CRP levels in young adults., Design: Population-based study., Subjects: A total of 2,120 participants aged 24-39 years. Main outcome measures. Distribution of CRP, and the relationship between CRP and risk factors., Results: CRP concentration (mean+/-SD) was 1.43+/-3.26 mg L(-1) in men, 1.36+/-2.36 mg L(-1) in women who did not use oral contraceptives (OC) and 3.69+/-6.01 mg L(-1) in women who used OCs. In total, 8.8% of men, 10.3% of non-OC user women and 35.3% of OC user women had CRP concentration >3 mg L(-1) (recommended cut-off point of high risk for cardiovascular disease). In univariate analysis, CRP was associated with obesity indices and physical activity amongst both sexes. In men, the multivariate correlates of CRP included waist circumference (P<0.0001), smoking (<0.0001) and HDL cholesterol (P=0.024) (inverse association). These three variables explained 21.9% (model R(2)) of the total variation in CRP, waist circumference having the greatest influence (partial R(2)=19.6%). In women, the multivariate correlates of CRP included OC use (P<0.0001), body mass index (BMI) (P<0.0001), triglycerides (<0.0001) and physical activity (P=0.025) (inverse association). These four variables explained 38.2% (model R(2)) of the total variation in CRP, with OC use (partial R(2)=18.4%) and BMI (partial R(2)=18.0%) having the greatest influence., Conclusions: The determinants of CRP level include obesity and smoking in men, and obesity, OC use and physical activity in women. About one in three of healthy women who use OCs have CRP concentration exceeding 3 mg L(-1).

Objective: To explore the separate and combined effects of simvastatin and a low-saturated diet rich in alpha-linolenic acid on serum fatty acids., Methods and Results: 120 hypercholesterolemic men were randomly allocated to a habitual diet or dietary treatment group and to receive, in random order, simvastatin 20 mg/d or placebo, each for 12 weeks, in a double-blind manner. Dietary treatment decreased proportions from total fatty acids of palmitic acid (C16:0) by 3.3% (P<0.05), stearic acid (C18:0) by 3.7% (P<0.05) and increased proportions of oleic acid (C18:1n-9) by 4.2% (P<0.01), and alpha-linolenic acid (C18:3n-3) by 29.8% (P<0.001). Simvastatin decreased proportions from total fatty acids of palmitic acid by 2.0% (P<0.01), linoleic acid (C18:2n-6) by 5.3% (P<0.001), and alpha-linolenic acid by 6.8% (P<0.05), and increased proportions of gamma-linolenic acid (C18:3n-6) by 11.1% (P<0.001), dihomo-gamma-linolenic acid (C20:3n-6) by 4.2% (P<0.01), arachidonic acid (C20:4n-6) by 14.2% (P<0.001), and the sum of long-chain polyunsaturated fatty acids (C20-22) by 9.0% (P<0.001). Simvastatin increased ratios of stearic to palmitic, gamma-linolenic to linoleic, and arachidonic to dihomo-gamma-linolenic acid by 7.6%, 17.0%, and 10.0% (P<0.001 for all), respectively, suggesting increased fatty acid elongase and Delta6- and Delta5-desaturase enzyme activities., Conclusions: Increased formation of long-chain polyunsaturated fatty acids and their metabolites may contribute a substantial part of the pleiotropic effects of simvastatin.

Background and Aim: According to a widespread hypothesis, antioxidative vitamins and trace elements may protect the body against atherosclerotic diseases, especially in the elderly. We assessed dietary and serum vitamins and minerals for prediction of acute myocardial infarction (AMI) and stroke in elderly subjects., Methods and Results: In a population-based health survey with special emphasis on the diet, subjects aged 65-99 years were followed up for up to 10 years. The study population consisted of 361 men and 394 women. Information on individual food consumption was elicited by means of dietary history interviews. Serum vitamins and mineral elements were analysed utilizing commonly applied biochemical methods. Prediction analyses were based on 130 cases accumulated in the AMI group, 70 subjects in the stroke group, and corresponding control subjects. The cases were determined on the basis of revised information from the National Register of Cases of Death, and from the National Hospital Discharge Register. Low intake of vitamin D (p = 0.011) and low serum levels of 1,25-dihydroxy-vitamin D (p = 0.0053) were significantly predictive of stroke when adjusted for age, gender, smoking and functional capacity. On the other hand, high dietary intakes of two flavonoids, luteolin (p = 0.0096) and kaempferol (p = 0.002) were associated with lowered risk of AMI. Furthermore, low serum levels of iron predicted both AMI (p = 0.013) and stroke (p = 0.019). The results remained essentially unchanged when adjusted for additional major risk factors of atherosclerosis., Conclusions: From the items in the dietary interview, low intakes of vitamin D and certain flavonoids emerged as the sole predictors of AMI and stroke. In biochemical analyses, on the other hand, these disorders were predicted only by low levels of 1,25-dihydroxy-vitamin D and iron in the serum.

Apolipoprotein A-I/C-III/A-IV (apoA-I/C-III/A-IV) SstI and apolipoprotein B (apoB) XbaI polymorphisms have been shown to affect serum low-density lipoprotein (LDL) cholesterol concentrations in a sample of Finnish children. We studied whether these polymorphism are associated with carotid artery intima-media thickness (IMT), a marker of pre-clinical atherosclerosis, measured in the same subjects during their adulthood. A random sub-sample of 214 individuals from the "Cardiovascular Risk in Young Finns" study, for whom genotypes, cardiovascular risk factor data and carotid artery IMT measured in 2001 were available, were studied. Mean carotid IMT values increased according to the apoA-I/C-III/A-IV SstI genotype groups in the order of S1S1 (0.58+/-0.08 mm), S1S2 (0.61+/-0.08 mm), and S2S2 (0.70+/-0.16 mm, p=0.02, ANOVA). In multiple linear regression analysis after adjusting for age, sex and body mass index the mean IMT thickness among the S2 allele carriers was higher (p=0.02) compared to non-carriers. In logistic regression analysis the frequency of S2 allele carriers was higher among the high IMT group compared to the low IMT group (OR=4.02, CI: 1.68-9.61, p=0.002). No significant association between apoB XbaI polymorphism and carotid IMT was found. However, serum total and LDL cholesterol and apoB concentrations were significantly different among apoB genotype groups (p<0.001 for all traits). The apoA-I/C-III/A-IV SstI polymorphism is associated with carotid IMT in young Finns.

Objectives: Smoking is associated with false-positive rheumatoid factor (RF). We explored the dose-response relationship of this association, using smoking history and serum cotinine and thiocyanate concentrations as measures of tobacco exposure., Methods: A total of 6947 men and women aged 30 yr or over and free of clinical arthritis were included in the Mini-Finland Health Survey carried out between 1978 and 1980. Detailed histories of smoking and RF (sensitized sheep cell agglutination test) were obtained in the basic examination. In 2000, serum cotinine and thiocyanate were determined from serum samples collected at baseline and stored at -20 degrees C. A cut-off point of 100 microg/l was used for serum cotinine and 10 micromol/l for thiocyanate to indicate active smoking., Results: There was a close association between smoking and strongly positive RF. After adjustment for age, sex, coffee consumption and region, the odds ratios (95% confidence intervals in brackets) in current smokers and in those who had quit smoking were 3.94 (2.04-7.61) and 2.71 (1.33-5.53), respectively, compared with those who had never smoked. Among current smokers, the intensity, duration or tertiles of pack-years of smoking were not related to RF. No relationship between serum cotinine or thiocyanate and RF positivity was observed within the subgroups of current smokers and those who had quit. Among those who reported that they had never smoked but who nevertheless had serum cotinine levels at least 100 microg/l, the adjusted odds ratio of strongly positive RF was 4.48 (1.48-13.50) compared with people who had never smoked and whose serum cotinine levels were less than 100 microg/l., Conclusions: The results are not in line with the hypothesis of a dose-response relationship between smoking exposure and RF positivity.

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., Design: Population based follow-up study., Subjects: A total of 2283 participants aged 24-39 years in 2001 (63.5% of the original cohort)., Main Outcome Measures: Levels of serum lipids, apolipoproteins, blood pressure and smoking., Results: The mean serum total cholesterol, low density lipoprotein cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations in 24-39-year-old adults were 5.16, 3.27, 1.29 and 1.34 mmol L(-1), respectively. Total cholesterol (5.21 vs. 5.12 mmol L(-1), P = 0.046), HDL cholesterol (1.31 vs. 1.28 mmol L(-1), P = 0.027), systolic blood pressure (118 vs. 115 mmHg, P < 0.0001) and diastolic blood pressure (72 vs. 70 mmHg, P < 0.0001) were higher in subjects originating from eastern Finland compared with those from western Finland. Significant secular trends between 1986 and 2001 in 24-year-old subjects (n = 783) included an increase in serum triglycerides and body mass index (BMI), a decrease in blood pressure and HDL cholesterol and a modest 5% decrease in total cholesterol levels., Conclusions: During the past 15 years, BMI and triglyceride levels have increased in young adults in Finland. At the same time, the reduction in cholesterol concentration has been slow. Consistent with persistent regional differences in cardiovascular morbidity within Finland, our data demonstrate significant differences in the levels of cardiovascular risk factors between subjects originating from eastern and western Finland.

Background: High plasma homocysteine level has been associated with increased risk for coronary heart disease (CHD) events in nondiabetic individuals, especially in those with previously diagnosed CHD. In persons with type 2 diabetes mellitus, the association between homocysteine level and cardiovascular disease may be stronger than that in nondiabetic individuals, but no large prospective studies have examined the relationship between homocysteine level and CHD mortality in persons with type 2 diabetes., Objective: To investigate whether moderately elevated plasma homocysteine levels are independently related to increased incidence of fatal and nonfatal CHD events in persons with type 2 diabetes., Design: Prospective study., Setting: Finnish sample of patients with type 2 diabetes., Patients: 462 men and 368 women who were 45 to 64 years of age at baseline., Measurements: Coronary heart disease mortality and incidence of nonfatal myocardial infarction during the 7-year follow-up., Results: Participants with plasma homocysteine levels of 15 micromol/L or more at baseline had a higher risk for CHD death than those with plasma homocysteine levels less than 15 micromol/L (26.1% and 13.5%, respectively; P = 0.005). The risks for all CHD events were 36.2% and 22.6%, respectively (P = 0.011). In Cox regression analyses, elevated plasma homocysteine level was significantly associated with CHD mortality (P < 0.001) and all CHD events (P = 0.002) even after adjustment for confounding variables, including creatinine clearance. In participants without myocardial infarction at baseline, moderate hyperhomocysteinemia was also associated with CHD mortality and all CHD events in univariate (P < 0.001 and P = 0.006, respectively) and multivariate Cox regression analyses (P < 0.001 and P = 0.004, respectively)., Conclusions: In this large cohort of patients with type 2 diabetes, plasma homocysteine level was a strong and independent risk factor for CHD events.

Mortality rates from coronary heart disease are lower in Swedish men and among Finnish migrants who have lived in Sweden for over 20 years than in men living in Finland. Sero-epidemiological studies, investigations of atheromatous plaque specimens, in vitro animal models and anti-chlamydial antibiotic trials have given support to the hypothesis that Chlamydia pneumoniae (Cpn) has a role in atherosclerosis. We investigated whether men with a similar genetic background but living permanently in Finland or Sweden have differences in the prevalence of Cpn seropositivity, and whether chronic Cpn infection is associated with markers of subclinical atherosclerosis. We measured anti-Cpn antibodies and ultrasonographic markers of subclinical atherosclerosis, including carotid intima-media thickness, carotid artery compliance and brachial artery flow-mediated dilatation, in a population of 76 migrant-discordant male twin pairs (152 men). The number of men with seropositivity to Cpn infection (defined as IgA>/=1:64 and IgG>/=1:128) was greater in Finland than in Sweden (21.5% compared with 10.5%; P =0.046). Cpn seropositivity accompanied by elevated C-reactive protein (CRP) levels (>1 mg/l) was associated with attenuated brachial artery flow-mediated dilatation (3.3+/-0.3%, compared with 5.5+/-0.4% in men with no signs of Cpn infection; P <0.001).Thus, among Finnish twin brothers discordant for migration to Sweden, the prevalence of Cpn seropositivity is higher for those living in Finland, and men with Cpn seropositivity combined with elevated CRP levels had attenuated endothelial function. These findings offer insight into the mechanism whereby chronic Cpn infection may increase the risk of coronary heart disease.

Neuropeptide Y (NPY) is a molecule that may have both vasoconstrictive and vasodilatory actions. A common polymorphism in the human NPY gene that results in the Leucine7 to Proline7 substitution (Leu7Pro) in the signal peptide part of the NPY was recently identified. This substitution has been associated with elevated serum cholesterol levels and with slightly accelerated progression rate of carotid intima-media thickness, thus suggesting increased risk of atherosclerosis in carriers of Pro7 substitution. Recent data also indicate that subjects with Pro7 substitution may have increased endothelial release of NPY. This study was undertaken to elucidate the effects of Leu7Pro polymorphism on arterial endothelial function. We measured flow-mediated endothelial-dependent dilatation (FMD) of the brachial artery in two separate populations: in 152 middle-aged men and in 95 prepubertal children. In both study populations, subjects with Pro7 substitution had 48-52% higher FMD compared with subjects having the wildtype (Leu7/Leu7) signal peptide sequence. We conclude that Pro7 substitution in signal peptide of the NPY is associated with enhanced endothelial-dependent vasodilation. Prospective studies are needed to determine whether Pro7 substitution is associated with increased or decreased risk of cardiovascular morbidity and mortality.

Objective: To study serum quercetin concentrations of subjects consuming berries or habitual Finnish diets., Design: Randomized parallel dietary intervention., Subjects: Forty healthy men (age 60 y)., Intervention: Twenty subjects consumed 100 g/day of berries (black currants, lingonberries and bilberries) for 8 weeks. Twenty subjects consuming their habitual diets served as controls. Fasting blood samples were obtained 2 weeks prior to the study, at baseline, and at 2, 4 and 8 weeks. Intake of quercetin was assessed from 3 day food records collected at baseline and at 8 weeks., Results: The serum quercetin concentrations were significantly higher in the subjects consuming berries compared to the control group (P=0.039 ANCOVA with repeated measures). During the berry consumption period the mean serum concentrations of quercetin ranged between 21.4 and 25.3 micro g/l in the berry group, which was 32-51% higher compared with the control group. According to 3 day food records, there was no difference in quercetin intake at baseline, but at 8 weeks the intake was 12.3+/-1.4 mg/day (mean+/-s.e.m.) in the berry group and 5.8+/-0.6 mg/day in the control group (P=0.001)., Conclusions: The results indicate that the berries used in this study are a good source of bioavailable quercetin.

Background: Self-reported information on alcohol from questionnaires is generally assumed to introduce misclassification of consumption, mainly in the direction of underestimation. The aim of this study was to evaluate self-reported information on alcohol consumption from a mailed questionnaire by comparing to a dietary history interview and biochemical markers of alcohol intake., Subjects and Methods: For 76 male twin pairs of the Finnish Twin Cohort Study aged 40-70 years information on self-reported alcohol consumption was collected through mailed questionnaire and dietary history interview. Carbohydrate-deficient transferrin (CDT), Gamma-glutamyltransferase (Gamma-GT) and mean corpuscular volume (MCV) were determined from blood samples., Results: Mean levels of CDT, gamma-GT and MCV showed a rise with increased self-reported alcohol consumption already at low levels of reported consumption (<20 g alcohol/day). There was a positive correlation between reported amount alcohol intake per day and levels of CDT (r = 0.46), gamma-GT (r = 0.32) and MCV (r = 0.36) but within the high consumption group (> or = 30 g/day) there was no such correlation. The questionnaire had sensitivity of 28-43% and specificity of 89% for identification of high consumers of alcohol using the biochemical markers as reference and sensitivity 41% and specificity 94% using the dietary history interview as reference. Sensitivity was improved when information on binge drinking (82%) or possible drinking problems (73%) was considered., Conclusion: Comparison to dietary history interview as well as to biochemical markers indicate that self-reported information on alcohol consumption from a mailed questionnaire may be used to distinguish between groups with different levels of alcohol consumption. The suggested misclassification of high consumers implies that only strong associations between high alcohol intake and disease are likely to be detected in studies based on questionnaire data.

Finnish men have higher coronary heart disease (CHD) mortality than Swedish men do. To assess the impact of migration to a country with lower CHD mortality on subclinical atherosclerosis, we measured early functional and structural atherosclerotic vascular changes in twins discordant for migration from Finland to Sweden. Conventional CHD risk factors, flow-mediated dilatation (FMD) of the brachial artery, carotid intima-media thickness, and carotid artery compliance were measured in 74 male twin pairs (20 monozygous, 54 dizygous), aged 42 to 69 years, in which co-one twin had migrated more than 20 years ago permanently to Sweden. There were no significant differences in CHD risk factors except for diastolic blood pressure and body fat percentage, which were higher in Sweden. In all subjects, mean FMD was non-significantly higher in Sweden (5.7+/-4.3% vs 4.9+/-4.2%, P=0.22), but in monozygous twins the difference in FMD was highly significant (7.2+/-4.4 vs 3.7+/-2.9%, P=0.003). There was no significant difference in intima-media thickness or carotid artery compliance between Sweden and Finland. We conclude that in Finnish monozygous twins the endothelial function is better among the twins that have migrated to a country with lower CHD prevalence.

The effects of dietary intervention, sex, and apolipoprotein E phenotype on tracking of serum lipid values in young children have remained poorly characterized. We investigated these associations in 1062 infants who were randomized into control and intervention groups (n=522 and n=540, respectively) at age 7 months; the intervention group received counseling aimed at maintaining a low-saturated fat, low-cholesterol diet. In 519 children in the control (n=254) and intervention (n=265) groups, serum lipid values were studied annually between 13 months and 5 years of age. In all children, tracking was strongest for the ratio of high density lipoprotein (HDL) cholesterol to total cholesterol; when a 13-month-old child belonged to the lowest quartile of the distribution, the odds ratio for belonging to the same quartile at older ages was 39.0 (95% CI 23.1 to 66.0). Dietary intervention did not influence the tracking of serum lipids. Tracking of HDL cholesterol was stronger in the boys than in the girls (P=0.018). Tracking of non-HDL cholesterol and apolipoprotein B in the children with phenotypes E2/3 or E3/3 was stronger than that in the other children (P=0.031 and P=0.014, respectively). In conclusion, the apolipoprotein E phenotype strongly influences tracking of non-HDL cholesterol and apolipoprotein B values in early childhood, whereas dietary intervention had no effect on tracking of any of the lipids. A child's sex influenced tracking only of HDL cholesterol, with boys showing stronger tracking.

Aim: To evaluate the effects of gender, apolipoprotein E phenotype and cholesterol absorption and synthesis (estimated as serum plant sterol and cholesterol precursor sterol concentrations) on the cholesterol-lowering effect of plant stanol esters in children., Methods: Eighty-one healthy, normocholesterolaemic 6-y-old children (45 boys) were recruited from the Special Turku Coronary Risk Factor Intervention Project (STRIP), a randomized prospective trial aiming at atherosclerosis prevention in childhood. This placebo-controlled, double-blind, cross-over study comprised two 3-mo study periods and a 6-wk wash-out period. During the study periods, 20 g of the children's daily dietary fat intake was replaced with plant stanol ester margarine or control margarine., Results: In boys, plant stanol esters reduced serum total and low-density lipoprotein cholesterol concentrations by 6% (0.09 to 0.42 mmol/L) and 9% (0.09 to 0.36 mmol/L), respectively (p < 0.01 for both). In girls, the decreases in concentrations were 4% (0.03 to 0.38 mmol/L) and 6% (0.02 to 0.32 mmol/l) (p < 0.05 for both). The response rate did not differ between the genders. Serum total and low-density lipoprotein cholesterol concentrations decreased by 6% and 8% (p < 0.01 for both), respectively, in both children with the apolipoprotein E 3/4 or 4/4 (apoE4+) phenotype and the apolipoprotein E 2/3 or 3/3 (apoE4-) phenotype. Cholesterol absorption decreased both in the apoE4+ children and in the apoE4- children, but cholesterol synthesis consistently increased in the apoE4+ children only., Conclusion: Plant stanol esters reduce serum cholesterol concentration in healthy children irrespective of their gender or apoE4 phenotype.

Background: There is a clear east-west difference in coronary heart disease (CHD) mortality and incidence in Finland, people living in east Finland having higher CHD rate. A study of Finnish immigrants to Sweden has suggested that a long stay in Sweden would be associated with reduced CHD risk., Aim: To determine whether structural and functional markers of subclinical atherosclerosis differ between men originating from east and west Finland, and whether migration to Sweden influences subclinical atherosclerosis., Method: Carotid intima-media thickness (IMT) and brachial artery flow-mediated dilatation (FMD) with high-resolution ultrasound and a set of cardiovascular risk factors were measured in 76 middle-aged male twin pairs (55 pairs from east and 21 pairs from west Finland) discordant for migration to Sweden., Results: Among men living in Finland, IMT was significantly higher in men originating from east Finland compared to those from west Finland (0.796 +/- 0.212 versus 0.704 +/- 0.123 mm, P = 0.02). A similar east-west difference was observed in men who had migrated to Sweden (0.766 +/- 0.220 versus 0.686 +/- 0.089 mm, P = 0.03). The east-west difference in IMT persisted after adjustment for the major traditional cardiovascular risk factors. No east-west difference was seen in FMD. Smoking, Framingham risk score and physical activity had a greater impact on IMT in men originating from east compared to west Finland., Conclusions: Men originating from east Finland, irrespective of their current residence, have a greater degree of subclinical atherosclerosis and they may be more susceptible to the impact of conventional cardiovascular risk factors than men originating from west Finland.

Objectives: Accumulation of intra-abdominal fat has been suggested, but not yet proved, to be basically as a result of chronic psychosocial stress causing arousal of hypothalamic-pituitary-adrenal cortex axis. Our objectives were to study the association between psychosocial stress, obesity and body fat distribution when genetic factors are identical., Design: Monozygotic twins discordant for obesity were examined in an in-patient setting., Subjects: Adult monozygotic twin pairs (12 female, 8 male) with an average intrapair difference of 17 kg in body weight. They were divided into two groups: in group A the visceral fat area of the obese cotwin was higher and, in group B, lower than the gender-specific median value., Main Measures: Hormonal, physiological and psychological distress indicators, and sleep measures., Results: Daily urinary cortisol and noradrenaline excretion were higher in the obese cotwins when compared with the nonobese cotwins in group A but not in group B (P=0.026 and 0.020 when intrapair differences were compared between groups A and B, respectively). In serum cortisol, ACTH and CBG concentrations a similar trend was not statistically significant. In group A, the obese cotwins consumed almost 2.5 times as much alcohol as their lean cotwins, whilst in group B the situation was the opposite. The mean amount of active sleep was significantly higher and that of quiet sleep significantly lower in the obese than the lean cotwins only in group A. Intrapair differences in emotional reactions indicating distress and lack of subjective energy were seen only in group A., Conclusion: When genetic factors are identical, visceral fat accumulation, rather than obesity in general, is associated with increased psychosocial stress and concomitant hormonal changes.

Objectives: To study serum homocysteine concentration for its prediction of major coronary heart disease events amongst women., Design: A case-control study nested within a follow-up study. Subjects. A total of 74 and 75 major coronary events (coronary deaths or nonfatal myocardial infarction) which occurred in women with and without known heart disease, respectively, during a 13-year follow-up and two individually matched controls per case. Main outcome measure. Major coronary event., Results: Amongst women with baseline heart disease, the relative risk (95% CI) of such events, adjusted for age, smoking, hypertension, diabetes, serum cholesterol and body mass index, was 3.32 (1.05-10.5) in the highest homocysteine quintile compared with the lowest quintile. Amongst women free of heart disease at baseline, the corresponding relative risk value was 0.77 (0.24-2.45)., Conclusions: This prospective study support the hypothesis that homocysteine is a risk factor for coronary events in women with heart disease.

Background and Aim: The health-promoting effects of fruit- and vegetable-based diets are known to be associated with their antioxidative components. We found in our preliminary in vitro laboratory tests that extracts of many common Finnish edible berries are potent scavengers of peroxyl radicals and inhibitors of lipid peroxidation. We therefore designed the current study to evaluate both the long-term (8 weeks) and short-term (5 hours) effects of increased intake of three berries on antioxidant potential and lipid peroxidation., Methods and Results: Healthy 60-year-old men were randomized to berry, supplement and control groups (20 men in each group). The berry group ate, in addition to their normal diet, a 100 g portion of deep-frozen berries (bilberries, lingonberries, or black currants) daily for 8 weeks. The other groups ingested daily 100 mg of alpha-tocopherol and 500 mg of ascorbic acid (supplement group) or 500 mg of calcium gluconate (control group). In the short-term experiment 6 men ate 80 g of each of the three berries in one go. Serum ascorbate concentrations increased significantly in both the berry and the supplement group. Serum alpha-tocopherol levels and the antioxidant potential (TRAP) in low density lipoprotein (LDL) increased in the supplement group only. In the berry group, slightly lowered LDL diene conjugation (p = 0.074) and slightly increased total serum TRAP (p = 0.084) values were observed. No changes were found in these measures in the supplement or the control group. In the short-term experiment, LDL TRAP showed a small increase (about 10%, p = 0.039) during five hours after the intake of 240 g berries., Conclusions: The effects of consumption of berries on antioxidant potential and diene conjugation in LDL particles in vivo appear to be small.

Background: It has been hypothesized that high androgen levels are determinants of prostate carcinoma., Methods: Serum concentrations of testosterone, sex hormone-binding globulin (SHBG), and androstenedione were analyzed to determine their role as predictors of prostate carcinoma in a longitudinal, population-based, nested case-control study. The serum concentrations of testosterone, SHBG, and androstenedione were determined from serum samples collected by the Finnish Mobile Clinic Health Examination Survey between 1968-1972 and stored at -20 degrees C. During a follow-up period of 24 years, a total of 166 prostate carcinoma cases occurred among men who originally were cancer free. Two controls (matched for age and municipality) were chosen., Results: There was no association between serum testosterone, SHBG, or androstenedione concentrations and the occurrence of subsequent prostate carcinoma in the total study population or in subgroups determined based on age or body mass index. The association was not strengthened by simultaneous adjustment for the hormonal variables., Conclusions: The results of the current study do not appear to corroborate the hypothesis that serum testosterone, SHBG, or androstenedione are determinants of the subsequent occurrence of prostate carcinoma.

Objectives: To study the association of vitamin E status with occurrence of insulin-dependent diabetes mellitus (IDDM)., Design: A case-control study nested within a 21-year follow-up study., Subjects: Nineteen incident IDDM patients with an average age of 28 years and three individually matched controls per patient., Main Outcome Measure: Serum concentrations of alpha-tocopherol., Results: Serum alpha-tocopherol concentration at the baseline examination was inversely associated with IDDM occurring 4-14 years later. The cholesterol-adjusted relative risk of IDDM between the highest and lowest thirds of the vitamin concentration was 0.12 (95% confidence interval = 0.02-0.85)., Conclusions: The finding corroborates the hypothesis of a protective effect of vitamin E against development of IDDM. Because of the relatively old age of the patients in the present population, further epidemiological studies on the topic are warranted.

The hypothesis that low selenium may in some circumstances be a risk factor for lung cancer was investigated in a case-control study nested within a longitudinal study. Serum samples from 9,101 cancer-free individuals were collected and stored at -20 degrees C by the Finnish Mobile Clinic in 1968-1971 and 1973-1976. During follow-up until the end of 1991, 95 cases of lung cancer were diagnosed. Selenium concentrations were determined from the serum samples of the cases and 190 controls, individually matched for sex, age, and place of residence. Mean levels of serum selenium in cases and controls were 53.2 microg/liter and 57.8 microg/liter, respectively. The relative risk of lung cancer between the highest and lowest tertiles of serum selenium, adjusted for smoking, serum alpha-tocopherol, serum cholesterol, serum copper, serum orosomucoid, and body mass index (kg/m2), was 0.41 (95% confidence interval (CI) 0.17-0.94). The association was stronger at lower levels (<5.9 mg/liter) of alpha-tocopherol (relative risk=0.24, 95% CI 0.07-0.85). The association was also pronounced among current smokers and at higher levels of serum orosomucoid and serum copper. The relative risk for smokers who were twice ranked in higher selenium tertiles, at an interval of 4-7 years, in comparison with smokers who remained in the lowest tertile was 0.16 (95% CI 0.04-0.74). In accordance with the hypothesis, the findings suggest that very low selenium status may contribute to the risk of lung cancer.

Obesity is associated with adverse changes in plasma lipoprotein metabolism, but it is not known completely how this association is modified by genetic factors. We assessed the contribution of obesity to serum lipid and lipoprotein levels and lipid metabolizing enzyme activities by examining 23 identical twin pairs (9 male, 14 female) who had, on the average, an 18-kg intrapair difference in BW. Compared with lean co-twins, obese co-twins had approximately 20% higher low-density lipoprotein (LDL) cholesterol (P < 0.01), 20% lower high-density lipoprotein2 cholesterol (P = 0.010), and 90% (men) or 35% (women) higher (P < or = 0.06) total, very-low-density lipoprotein and LDL triglycerides. The pairs were divided into subgroups by the gender-specific median value of abdominal visceral fat (AVF) area in the obese co-twin and by apolipoprotein E 4 phenotype. The intrapair differences in serum cholesterol fractions were similar in twin pairs with high or low AVF, whereas only high AVF pairs showed significant differences in triglyceride fractions. The greatest intrapair differences in total, very-low-density lipoprotein and LDL triglycerides were observed in apolipoprotein E 4-positive pairs expressing high AVF. Compared with lean co-twins, lecithin cholesterol acyltransferase activity was 18% higher (P < 0.001) and hepatic lipase activity was 38% higher (P = 0.016) in obese co-twins with high AVF. When genetic factors are identical, obesity is associated with an atherogenic lipid profile, especially in subjects with high visceral fat accumulation.

Obesity, especially intraabdominally deposited fatness, is associated with reduced insulin sensitivity. However, it is not well established whether this association is confounded by genetic factors. We studied 23 monozygous twin pairs (14 female, 9 male), 33-59 yr old, who had, on the average, 18 kg intrapair difference in body weight. A 75-g oral glucose tolerance test with glucose and insulin measurements at 30-min intervals was performed, and fat distribution was determined with magnetic resonance imaging. The pairs were divided into two groups by the gender-specific median of the abdominal visceral fat area (AVF) in the obese co-twins. In the high-AVF pairs, the mean area under curve (AUC) for glucose (mmol x min/L) was 758 vs. 968 (P = 0.001), AUC for insulin (mU x min/L) was 4320 vs. 8741 (P = 0.001), and insulin sensitivity index (mg x L x L/mmol x mU x min) was 71.5 vs. 45.9 (P < 0.001) in the lean and obese co-twins, respectively. In the low AVF pairs, the mean AUC for glucose was 669 vs. 706 (not significant), AUC for insulin was 3323 vs. 4241 (not significant), and the sensitivity index was 85.2 vs. 73.7 (P = 0.04) in the lean and obese co-twins, respectively. In subjects who are genetically identical but who are discordant for body mass, only those who differ most in visceral fat level are characterized by major alterations in insulin sensitivity and glucose tolerance.

Background: The inherited apolipoprotein E (apoE) phenotype may determine effectiveness of dietary atherosclerosis prevention. This study analyzes the effects of apoE phenotypes on changes in serum lipid concentrations in a 6-month prospective, randomized trial of a low-saturated-fat, low-cholesterol diet in infancy., Patients and Methods: One thousand sixty-two healthy infants were randomized to intervention and control groups at the age of 7 months. Counseling was provided to the intervention families when the children's ages were 7, 8, and 10 months. Dietary goals were the child's intake of energy ad libitum, fat at 30% to 35% of energy, cholesterol at less than 200 mg/d, and saturated, monounsaturated, and polyunsaturated fatty acids at a 1:1:1 ratio. Control families consumed an unrestricted diet. The apoE phenotype of 846 of the infants was determined; serum lipid and lipoprotein concentrations were measured at 7 and 13 months of age; and nutrient intakes were analyzed using 3-day food records at 8 and 13 months of age., Results: At 7 months of age, serum cholesterol concentration was higher in apoE4-positive infants (E2/E4, E3/E4, and homozygous E4) than in apoE4-negative infants (159 +/- 31 mg/dL [4.10 +/- 0.81 mmol/L] vs 150 +/- 29 mg/dL [3.89 +/- 0.74 mmol/L]). The high-density lipoprotein cholesterol concentration was slightly lower in apoE4-positive infants than in apoE4-negative infants (34 +/- 8 mg/dL [0.88 +/- 0.20 mmol/L] vs 35 +/- 7 mg/dL [0.91 +/- 0.19 mmol/L]). Between 7 and 13 months of age, the serum cholesterol concentration in infants in the intervention group was unchanged, apoB concentration increased slightly, and apoA1 concentration decreased. In the control infants, serum cholesterol concentration increased 9 +/- 25 mg/dL (0.24 +/- 0.65 mmol/L), apoB concentration increased markedly, and apoA1 concentration was stable. Changes in serum lipid and apo concentrations that resulted from the dietary intervention were independent of the apoE phenotype., Conclusions: The apoE phenotype influenced serum cholesterol concentration markedly by 7 months of age. Between the ages of 7 and 13 months, a reduced saturated fat and cholesterol diet effectively prevented the age-associated increases in serum cholesterol and non-high-density cholesterol concentrations that were obvious in the control infants. The effects of the diet occurred in the infants independently of the apoE phenotype.

Objective: To study the association of serum calcium, magnesium, copper and zinc concentrations with cardiovascular mortality., Design: A nested case-control study within a prospective population study., Subjects and Methods: 230 men dying from cardiovascular diseases and 298 controls matched for age, place of residence, smoking and follow-up time. Mean follow-up time was 10 years. Serum calcium, magnesium, copper and zinc concentrations were determined from samples kept frozen at -20 degrees C., Results: High serum copper and low serum zinc concentrations were significantly associated with an increased mortality from all cardiovascular diseases and from coronary heart disease in particular. The relative risk of coronary heart disease mortality between the highest and lowest tertiles of serum copper and zinc were 2.86 (P = 0.03) and 0.69 (P = 0.04), respectively. Adjustment for social class, serum cholesterol, body mass index, hypertension and known heart disease at baseline examination did not materially alter the results. No significant differences were observed in concentrations of serum calcium and magnesium between cases and controls., Conclusions: High serum copper and low serum zinc are associated with increased cardiovascular mortality whereas no association was found with serum calcium and magnesium and mortality risk.

Hyperapobetalipoproteinemia (hyperapoB) is one of the most common phenotypes in patients with premature coronary heart disease. In this study the factors that affect the expression of the hyperapoB phenotype were evaluated in young individuals. A cohort of 1125 children and young adults aged 9-24 years was classified into three groups by sex: (1) normal serum apolipoprotein B (apoB), (2) high apoB (> or = 90th percentile) and normal low density lipoprotein cholesterol (LDL-C < 90th), (3) high apoB and high LDL-C (> or = 90th percentile). In females, alcohol use (11, 33, 0%, in groups 1-3, P < 0.05) and oral contraceptive use (35, 83, 47%, P < 0.01) were significantly different between the groups and the highest frequencies were seen in the hyperapoB group (group 2). In both sexes smoking tended to be more common in the hyperapoB group (29, 43, 18%, P < 0.14). The two hyperapoB definition criteria (high apoB and low LDL-C/apoB ratio) were studied with multiple linear regression analyses. Oral contraceptive use correlated positively with apoB values (coefficient beta = 0.101, R2 = 2.1%, P < 0.01) and negatively with LDL-C/apoB ratio (beta = -0.134, R2 = 3.3%, P < 0.001). Alcohol use (beta = -0.072, R2 = 2.9%, P < 0.001) and smoking (beta = -0.050, R2 = 1.0%, P < 0.05) correlated negatively with LDL-C/apoB ratio. Prevalence of the hyperapoB phenotype was 4.4%. According to the results, the expression of the hyperapoB phenotype may be influenced by common lifestyle habits. This should be considered if high risk young individuals are identified through the expression of the hyperapoB phenotype.

It recently has been hypothesized that increased plasma plasminogen activator inhibitor-1 (PAI-1) activity could be a possible link between insulin resistance and coronary heart disease. However, it is not known whether insulin sensitivity per se is a determinant of plasma PAI-1 activity or whether other intermediates could explain this association. We investigated the relationship between plasma PAI-1 activity and insulin sensitivity, obesity, distribution of body fat, blood pressure, plasma insulin concentration, and serum lipid levels in normoglycemic men (n = 61) and women (n = 77) 53 to 61 years old who participated in a previous population-based study. Insulin sensitivity was estimated by the minimal model from a frequently sampled intravenous glucose tolerance test. In univariate analyses, PAI-1 correlated positively with body mass index, waist-to-hip ratio (WHR), fasting and 2-hour insulin levels, and triglyceride level in both men and women. Furthermore, in women PAI-1 correlated inversely with high-density lipoprotein (HDL) cholesterol level. There was an inverse relationship between PAI-1 and insulin sensitivity (r = -.39, P < .01 in men; r = -.38, P < .001 in women). In multivariate analyses in men, insulin sensitivity failed to show any significant association with PAI-1. In contrast, triglyceride level and body mass index were independently associated with PAI-1. Also in women, insulin sensitivity was not independently associated with PAI-1. In women, WHR and HDL cholesterol concentration or WHR and 2-hour insulin concentration were independently related to PAI-1.(ABSTRACT TRUNCATED AT 250 WORDS)

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 1980's 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.

Both exercise and high ambient temperatures stimulate the secretion of counterregulatory hormones which can change glucose homeostasis. We studied whether in diabetic patients there are any differences in the hormonal response to exercise performed at cool or warm ambient temperatures. A study was performed on eight male insulin-dependent patients at rest and during exercise at +10 degrees C and +30 degrees C. Exercise consisted of three consecutive 15-min periods at 60% of maximal aerobic capacity. The concentrations of plasma lactate and counterregulatory hormones at rest were similar at warm and cool temperature, whereas prolactin concentration was higher (P less than 0.01) at +30 degrees C. Exercise resulted in an increase in noradrenaline, growth hormone and prolactin (P less than 0.01), prevented the diurnal decrease in cortisol, but had no effect on glucagon. Hormone responses to exercise were similar at +10 degrees C and at +30 degrees C, except for cortisol and noradrenaline which showed greater responses at warm than at cool temperatures. This may have been due to the higher relative work load at warm compared to cool temperatures as suggested by the higher heart rate and greater increase of lactate at +30 degrees C. These data indicate that within a range of ambient temperatures commonly occurring in sports, the response of counterregulatory hormones is largely independent of ambient temperature in insulin-dependent diabetic patients.

The effects of two dietary weight reduction programmes (1200 kcal/day) on lipid metabolism were followed for one year in moderately obese subjects. The groups consisted of lactovegetarian (n = 31), mixed diet (n = 37) and control (n = 42) groups. Serum triglyceride levels decreased rapidly during the first two weeks (46 per cent on average) especially in the mixed diet group, and this change was still statistically significant at 6 and 12 months after the beginning of the study. Serum total cholesterol levels also decreased rapidly in the beginning, but at 6 and 12 months the change was no longer statistically significant. After a small initial decrease HDL cholesterol levels appeared to increase towards the end of the study year. This increase was more marked in men (18.6 per cent at 6 months) than in women, and in the mixed diet group than in the lactovegetarian group (P less than 0.05 between the groups). The HDL/total cholesterol ratio increased rapidly in the beginning of the weight reduction and practically remained at the elevated (12-16 per cent) level during the whole follow-up. This increase was also more apparent in men than in women, and in the mixed diet group than in the lactovegetarian group. The changes in HDL subfractions, HDL2 and HDL3, paralleled those seen in the HDL cholesterol levels. Similarly the alterations in apolipoproteins A-I and B resembled those of the HDL and total cholesterol levels. The activity of adipose tissue lipoprotein lipase decreased drastically (about 50 per cent) at the beginning of the weight reduction, while at 6 and 12 months the mean activities were higher than the initial levels. This was also seen in the LPL activity when measured in post-heparin plasma. The activity of post-heparin plasma hepatic lipase decreased clearly at both 6 (P less than 0.001) and 12 months (P less than 0.01) in the mixed diet group, whereas no change was found in the lactovegetarian group. The ratio of subscapular to triceps skinfold reduced significantly (P less than 0.01) in women but not in men during the intervention period. Our study shows that in moderately overweight subjects weight reduction with the aid of a low-calorie dietary programme results in favourable responses in lipid metabolism many months after the cessation of the weight reduction programme. These responses appear to be stronger in subjects following mixed diet than in those attempting to follow a lactovegetarian diet.

Serum high density lipoprotein (HDL) subfractions HDL2 and HDL3, apolipoproteins, and plasma antipyrine clearance (AP-CL) rate, an index of liver microsomal enzyme activity, were determined in 21 healthy subjects. High HDL cholesterol and HDL2 cholesterol concentrations and HDL cholesterol/cholesterol and HDL2/HDL3 cholesterol ratios were associated with high AP-CL. Phenobarbital enhanced antipyrine elimination and increased the apolipoprotein A-I/A-II ratio. Subjects who had high AP-CL had a more antiatherogenic HDL subfraction and apolipoprotein profile than those with low AP-CL.

The effect on plasma apoproteins A-I and B and HDL cholesterol subfractions of acebutolol given orally over a 6-month period to 18 patients with essential hypertension was studied. The concentration of apoprotein A-I decreased during acebutolol treatment: statistical significance was reached at 3 (p less than 0.05) and 6 months (p less than 0.01). The level of apoprotein B increased slightly but not significantly. The ratio of apo A-I to apo B decreased significantly during acebutolol treatment. The concentration of total HDL cholesterol tended to be slightly but not significantly higher during therapy than before it. This increase was due to the increase of HDL3 cholesterol and this increase was significant (p less than 0.05) at 3 months. The level of HDL2 cholesterol did not change significantly during acebutolol therapy.

The effect of large-dose short-term administration of Max-Epa fish oil on serum lipoproteins in elderly people was studied. 17 elderly (aged 61-96 years) hospital patients were given an isocaloric diet which contained 70-80 ml (14-16 g of eicosapentaenoate) of Max-Epa fish oil for 3 weeks. The concentration of plasma total cholesterol and LDL cholesterol decreased significantly during the diet with fish oil. The levels of plasma VLDL cholesterol, HDL cholesterol and triglycerides decreased slightly (p less than 0.05). The concentration of apoprotein A decreased significantly (p less than 0.001) during the fish oil diet but the plasma level of apoprotein B did not change significantly. The ratio of apoprotein B to LDL cholesterol increased significantly (p less than 0.01) during the period with Max-Epa fish oil. The results show that marked changes in the lipoproteins of the elderly people occur when diet contains large doses of fish oil.

In 32 women of normal body weight who volunteered to participate in the study, the effect of rapid weight reduction by a low-calorie liquid diet on serum lipids and lecithin:cholesterol acyltransferase (LCAT) enzyme activity was studied. Women were on this 400 kJ/day diet for 7 days and fasting blood samples were drawn before and immediately after the diet. Serum cholesterol decreased from 5.7 +/- 1.0 to 5.2 +/- 1.1 mmol/l and high density lipoprotein cholesterol from 1.77 +/- 0.43 to 1.50 +/- 0.35 mmol/l. The serum LCAT activity decreased significantly during the weight reduction period. When serum LCAT activity was correlated to lipid parameters, a positive correlation was found with total cholesterol and triglyceride concentrations before weight reduction and also between changes in LCAT activity and total cholesterol concentration. The data suggest that serum LCAT activity might have a prominent role in the regulation of serum lipid levels.

Male Wistar rats were treated daily by gavage with two phenoxy herbicides, 2,4-dichlorophenoxyacetic acid (2,4-D)(100-200 mg/kg body wt) and 4-chloro-2-methylphenoxyacetic acid (MCPA) (100-200 mg/kg body wt), and with the chemically different glyphosate N-phosphonomethyl glycine (300 mg/kg body wt) 5 days per week for 2 weeks. A hypolipidemic drug, clofibrate [ethyl-2-(4-chlorophenoxy)-2-methylpropionate], which is structurally related to phenoxy acids, was used as a positive control (200 mg/kg body wt). 2,4-D and MCPA had several effects similar to those of clofibrate: all three compounds induced proliferation of hepatic peroxisomes, decreased serum lipid levels, and increased hepatic carnitine acetyltransferase and catalase activities. 2,4-D and MCPA, but not clofibrate, decreased lipoprotein lipase activity in the adipose tissue to about a third of the control value but did not change the lipoprotein lipase activity in the heart muscle. The data suggest that these compounds cause hypolipidemia not by enhancing the storage of peripheral lipids in adipose tissue but by preferentially increasing lipid utilization in the liver. Glyphosate caused no peroxisome proliferation or hypolipidemia, suggesting that these effects are associated with the structural similarity between phenoxy acid herbicides and clofibrate.

Adipose tissue lipoprotein lipase and postheparin plasma triglyceride lipase activities were measured in 28 men differing in their physical training activity. They were divided into 4 subclasses based on their training intensity. The two most active classes (17 subjects) having regular heavy exercise at least 4 times a week were considered as the actively training group, and the other two (11 subjects) classes not training regularly as the control group. In postheparin plasma, the lipoprotein lipase activities were not different between the two groups, whereas training subjects had significantly (P less than 0.02) lower hepatic lipase activities. Adipose tissue lipoprotein lipase activity was in the training group at about 70% higher level on an average than in the controls (P less than 0.10). A significant positive correlation (r = 0.38, P less than 0.05) was obtained between the adipose tissue lipoprotein lipase activity and the level of physical activity. Our data suggest that even moderate inter-group differences in the physical training activity are reflected as measurable alterations in the adipose tissue lipoprotein lipase activity in man.

The effects of inhalation and cutaneous exposure to styrene on the drug metabolizing enzymes were studied in the rat. Rats were exposed eight hours per day, for seven successive days to 450 ppm concentration of styrene or received one cutaneous dose of styrene daily for seven consecutive days (0.5 and 3.0 g/kg). The animals were killed one day after the last dose. Styrene inhalation increased the activities of epoxide hydrase and UDPglucuronosyltransferase (4-methylumbelliferone as substrate) in liver (1.5- and 1.7-fold, respectively). Ethoxycoumarin deethylation was enhanced 1.7-fold in the kidney. The content of cytochrome P-450 in the liver and the activities of NADPH cytochrome c-reductase, benzpyrene hydroxylase and glutathione S-transferase in the liver and kidney were not altered. No changes in the enzyme activities were detected in the lung. Styrene depressed the epoxide hydrase activity in liver when administered cutaneously. No signs of enzyme induction could be seen after cutaneous administration.