Decreased thioredoxin-1 and increased HSP90 expression in skeletal muscle in subjects with type 2 diabetes or impaired glucose tolerance.

In diabetes, the endogenous defence systems are overwhelmed, causing various types of stress in tissues. In this study, newly diagnosed or diet-treated type 2 diabetics (T2D) (n = 10) were compared with subjects with impaired glucose tolerance (IGT) (n = 8). In both groups, at resting conditions, blood samples were drawn for assessing metabolic indices and skeletal muscle samples (m. vastus lateralis) were taken for the measurements of cellular defence markers: thioredoxin-1 (TRX-1) and stress proteins HSP72, HSP90. The protein level of TRX-1 was 36.1% lower (P = 0.031) and HSP90 was 380% higher (P < 0.001) in the T2D than in the IGT subjects, with no significant changes in HSP72. However, after the adjustment of both analyses with HOMA-IR only HSP90 difference remained significant. In conclusion, level of TRX-1 in skeletal muscle tissue was lower while that of HSP90 was higher in T2D than in IGT subjects. This may impair antioxidant defence and lead to disruptions of protein homoeostasis and redox regulation of cellular defences. Because HSP90 may be involved in sustaining functional insulin signalling pathway in type 2 diabetic muscles and higher HSP90 levels can be a consequence of type 2 diabetes, our results are potentially important for the diabetes research.

Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis.

BACKGROUND: Fish consumption and omega-3 polyunsaturated fatty acid (PUFA) intake are shown to protect from cardiovascular diseases (CVD). However, most fish contain environmental contaminants such as dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and methylmercury (MeHg) that may have adverse effects on cardiovascular health. OBJECTIVE: Our aim was to elucidate the associations of fish consumption, omega-3 PUFAs, environmental contaminants with low-grade inflammation, early atherosclerosis, and traditional CVD risk factors. METHODS: The Health 2000 survey participants (n=1173) represented the general Finnish population and the Fishermen study participants (n=255) represented a population with high fish consumption and high exposure to environmental contaminants. Model-adjusted geometric means and tests for linear trend were calculated for CVD risk factors by tertiles of fish consumption and serum omega-3 PUFAs, and additionally in the Fishermen study only, by tertiles of serum PCDD/F+PCB, and blood MeHg. RESULTS: Serum triglyceride decreased across omega-3 PUFA tertiles in both sexes and studies. Insulin resistance, C-reactive protein, tumour necrosis factor α, and interleukin 6 decreased across omega-3 PUFA tertiles among the Health 2000 survey participants. Among the Fishermen study men, insulin resistance and arterial stiffness indicated by ß-stiffness index tended to increase and the RR estimate for carotid artery plaque tended to decrease across tertiles of PCDD/F+PCB and MeHg. CONCLUSION: Previously established hypotriglyceridemic and anti-inflammatory effects of omega-3 PUFAs were seen also in this study. The hypothesised favourable effect on insulin sensitivity and arterial elasticity was suggested to be counteracted by high exposure to environmental contaminants but the effect on plaque prevalence appeared not to be harmful.

Association of 25-hydroxyvitamin D with the incidence of knee and hip osteoarthritis: a 22-year follow-up study.

OBJECTIVE: In the light of conflicting results from previous studies on the role of vitamin D, we studied serum 25-hydroxyvitamin D [25(OH)D] with regard to its prediction of incident knee and hip osteoarthritis (OA). METHODS: The study population (n = 805) consisted of participants of a national health examination survey who had undergone baseline and follow-up clinical examinations at intervals of 20-23 years. Knee and hip OA were diagnosed on the basis of a standardized clinical examination by physicians with the same diagnostic criteria at baseline and follow-up. Information on covariates, including age, sex, season of blood draw, education, body mass index (BMI), physical workload, leisure time physical activity, smoking history, and previous injuries, was collected at baseline. Serum 25(OH)D concentrations were determined from baseline serum samples kept frozen at -20°C. RESULTS: We found no significant association between serum 25(OH)D level and the risk of incident knee or hip OA. However, a statistically significant interaction between season of blood draw and serum 25(OH)D emerged when predicting the development of definite knee OA (p = 0.004). After adjusting for all the covariates, the relative odds (95% confidence interval) of developing definite knee OA per increment of 1 SD (20.7 ng/mL) in winter season 25(OH)D was 1.57 (1.10-2.27), whereas for summer season sera the corresponding rate was 0.53 (0.28-1.00). CONCLUSION: The results do not support the hypothesis that a low level of serum 25(OH)D contributes to the development of OA. Instead, our study suggests that season is a potent effect modifier of 25(OH)D, which merits attention in future research.

Dioxins, polychlorinated biphenyls, methyl mercury and omega-3 polyunsaturated fatty acids as biomarkers of fish consumption.

BACKGROUND/OBJECTIVES: To assess biomarkers and frequency questions as measures of fish consumption. SUBJECTS/METHODS: Participants in the Fishermen substudy numbered 125 men and 139 women (aged 22-74), and in the Health 2000 substudy, 577 men and 712 women (aged 45-74) participated. The aim of the Fishermen study was to examine the overall health effect of fish consumption in a high-consumption population, whereas the aim of the Health 2000 substudy was to obtain in-depth information on cardiovascular diseases and diabetes. Fish consumption was measured by the same validated food frequency questionnaire (FFQ) in both the studies, with a further two separate frequency questions used in the Fishermen substudy. Dioxins, polychlorinated biphenyls (PCBs) and methyl mercury (MeHg) (in the Fishermen substudy alone), and omega-3 polyunsaturated fatty acids (omega-3 PUFAs) (in both studies) were analyzed from fasting serum/blood samples. RESULTS: The Spearman's correlation coefficients between FFQ fish consumption and dioxins, PCBs, MeHg and omega-3 PUFAs were respectively 0.46, 0.48, 0.43 and 0.38 among the Fishermen substudy men, and 0.28, 0.36, 0.45 and 0.31 among women. Similar correlation coefficients were observed between FFQ fish consumption and serum omega-3 PUFAs in the Health 2000 substudy, and also between FFQ fish consumption and the frequency questions on fish consumption in the Fishermen substudy. According to multiple regression modeling and LMG metrics, the most important fish consumption biomarkers were dioxins and PCBs among the men and MeHg among the women. CONCLUSIONS: Environmental contaminants seemed to be slightly better fish consumption biomarkers than omega-3 PUFAs in the Baltic Sea area. The separate frequency questions measured fish consumption equally well when compared with the FFQ.

Follow-ups of the Cardiovascular Risk in Young Finns Study in 2001 and 2007: levels and 6-year changes in risk factors.

OBJECTIVES: To examine cardiovascular risk factor levels in 2007 and their 6-year changes between 2001 and 2007 using the data collected in the follow-ups of the Cardiovascular Risk in Young Finns Study. DESIGN: Population-based follow-up study. SUBJECTS: A total of 2204 healthy Finnish adults aged 30-45 years (1210 women; 994 men). MAIN OUTCOME MEASURES: Levels in 2007 and changes between 2001 and 2007 of lipids, insulin, glucose, blood pressure, smoking, body mass index, alcohol consumption, waist and hip circumferences. RESULTS: The mean serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations in 30- to 45-year-old adults were 5.05, 3.09, 1.34 and 1.40 mmol L(-1), respectively. Significant changes (P < 0.05) between 2001 and 2007 in 30- to 39-year-old subjects included a decrease in total cholesterol (-6.6% in men, -5.8% in women), LDL-cholesterol (-10.2% and -11.6%) and an increase in diastolic blood pressure (3.5% and 3.9%). Waist circumference (1.8% and 5.5%) and systolic blood pressure increased in 36-39 year olds (2.3% and 2.3%). HDL-cholesterol increased in 30- to 33-year-old women (5.8%) Glucose levels increased in 30- to 39-year-old women (3.7%) and 36- to 39-year-old men (3.6%). Smoking prevalence decreased in 36- to 39-year-old men from 29.8% to 22.2%. CONCLUSIONS: The 6-year changes in total cholesterol, LDL-cholesterol and HDL-cholesterol in young Finns were favourable between 2001 and 2007. However, waist circumference, glucose and blood pressure levels increased. Therefore, continuous efforts are still needed in fighting against cardiovascular risk factors.

Hepatic lipase promoter C-480T polymorphism is associated with serum lipids levels, but not subclinical atherosclerosis: the Cardiovascular Risk in Young Finns Study.

The common C-480T polymorphism (rs1800588) of the hepatic lipase gene (LIPC) has been associated with high-density lipoprotein (HDL) cholesterol, atherosclerosis, and coronary artery disease. In this study, we examined whether the polymorphism is associated with serum lipid and lipoprotein concentrations, as well as with subclinical atherosclerosis in Young Finns. The participants comprised 2041 men and women (aged 24-39 years) enrolled in the Cardiovascular Risk in Young Finns Study with complete data concerning the rs1800588 polymorphism and serum lipids concentration. All participants underwent an ultrasound examination for brachial artery flow-mediated vasodilatation (FMD) and carotid artery intima-media thickness (IMT) measurement. The marker of arterial elasticity, carotid artery compliance (CAC), was also calculated by means of ultrasound and concomitant brachial blood pressure measurements. In all subjects, serum total cholesterol (p < 0.001), HDL cholesterol (p = 0.006), apolipoprotein AI (apoAI, p < 0.001), and triglyceride (p = 0.009) concentrations increased according to rs1800588 genotype in the order CC, CT, and TT. The same order applied only to apoAI after adjustment for age, body mass index, systolic and diastolic blood pressure, smoking, alcohol consumption, physical activity, diabetes, hypertension, contraceptive hormone use in women, and concentrations of glucose, insulin and C-reactive protein in men and women separately (p = 0.007 and p = 0.003, respectively). The polymorphism was also associated with HDL cholesterol, total cholesterol, and triglyceride levels in women (adjusted p = 0.004, p = 0.007 and 0.02, respectively), but not in men (p was not significant for all). No significant association between the rs1800588 and brachial FMD, carotid IMT, or CAC was found among the entire study population or among women or men separately, with or without adjustment for the above-mentioned factors. The rs1800588 is associated with serum lipid and apolipoprotein concentrations, especially in women, but does not seem to be a determinant of brachial artery FMD, carotid IMT, or CAC in young healthy adults.

Migration at early age from a high to a lower coronary heart disease risk country lowers the risk of subclinical atherosclerosis in middle-aged men.

BACKGROUND: Study of migrants offers a natural model to assess environmental risk of coronary heart disease (CHD) in countries differing in CHD occurrence. In Sweden, CHD risk has been markedly lower than in Finland from where a large migration occurred in the 1970s. OBJECTIVES: To study the structural and functional markers of subclinical atherosclerosis in twin pairs discordant for migration with the main focus on age at migration, length of residence and integration into Swedish society after migration from a high to a lower CHD risk country. METHODS: Carotid intima-media thickness (IMT) and brachial artery endothelial function (EF) were assessed with high-resolution ultrasound and a set of cardiovascular, socio-economic and psychosocial risk factors were estimated in 76 middle-aged male twin pairs discordant for migration from Finland to Sweden. RESULTS: Men who had migrated in adolescence had lower IMT values compared with their co-twins living in Finland (0.665 +/- 0.114 vs. 0.802 +/- 0.167 mm, P = 0.009). Also men who integrated well to Swedish society had lower (0.720 +/- 0.154 vs. 0.799 +/- 0.207 mm, P = 0.013) IMT values than their twin brothers living in Finland. Associations between IMT and migration age and between IMT and integration remained significant in multivariate analyses of several CHD risk factors. The intrapair difference in IMT was significantly associated with immigration age and integration (ANOVA, P = 0.0082), the difference being greatest among pairs where the brother living in Sweden had migrated at early age and integrated well to Swedish society. EF was better in men who had migrated to Sweden before the age of 21 years, but not later, compared with their co-twins in Finland (6.4 +/- 4.6% vs. 3.8 +/- 3.6%, P = 0.025). CONCLUSIONS: Migration at an early age and good integration are beneficial to vascular health associated with moving from a high to a lower CHD risk country, suggesting that an environment-sensitive period influences atherogenesis before adulthood.

Associations of methylenetetrahydrofolate reductase C677T polymorphism with markers of subclinical atherosclerosis: the Cardiovascular Risk in Young Finns Study.

OBJECTIVE: To study whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism or serum homocysteine concentration is associated with carotid artery intima media thickness (IMT), carotid artery compliance (CAC) or brachial artery flow mediated dilatation (FMD) in a healthy Finnish adult population. METHODS: Cross-sectional data obtained in 2001 for the Cardiovascular Risk in Young Finns Study were used. Carotid artery IMT, CAC and brachial FMD were measured by ultrasound and serum homocysteine concentrations using a commercial immunoassay kit. We studied 1,440 subjects (aged 24-39 years). Genotyping was performed using the 5' nuclease TaqMan assay. RESULTS: Homocysteine values differed between genotypes in women and men (ANOVA, p<0.001 for both sex groups): the genotype raised values in the order of CC, CT, TT. There was a significant difference in CAC values between the MTHFR genotypes in men (ANOVA, p = 0.008), and the CC genotype had the lowest values. In multivariate linear regression analysis adjusted for other major coronary risk factors (e.g. age, smoking, body mass index, systolic blood pressure, C-reactive protein), the association remained significant (R (2) = 25.8 %, beta = 0.091; p = 0.02). Homocysteine level was directly associated with CAC in the whole population (R (2) = 18.0 %, beta = 0.012; p = 0.014) and in women (R (2) = 9.3%, beta = 0.02; p = 0.013), but not in men (R (2) = 15.2 %, beta = 0.004; p = 0.444). We found no association between homocysteine level or the MTHFR polymorphism and carotid IMT or brachial artery FMD. CONCLUSIONS: The findings suggest that the MTHFR polymorphism does not influence IMT or FMD, but that the T allele may have an effect on CAC in men.

C-reactive protein genetics is associated with carotid artery compliance in men in The Cardiovascular Risk in Young Finns Study.

Although C-reactive protein (CRP) is known to predict cardiovascular events, its status as a causal risk factor is still controversial. CRP gene single nucleotide polymorphisms (SNPs) have been shown to associate with CRP concentration, but no direct independent effect on early atherosclerotic changes has been demonstrated. We aimed to determine if CRP gene polymorphisms or haplotypes are associated with CRP concentration or carotid artery compliance (CAC), an indicator of subclinical atherosclerosis. We genotyped CRP gene polymorphisms -717A>G, -286C>T>A, +1059G>C, +1444C>T and +1846G>A and measured CRP concentration and CAC in 2283 young adults participating in The Cardiovascular Risk in Young Finns Study. A strong association was found between CRP genotypes and CRP concentration, which was also seen at the haplotype level. Linear regression analysis showed an independent effect of each SNP on CRP concentration after adjustment for risk factors, except for +1444 in males. Moreover, -286C>T>A, +1444C>T and +1846G>A were associated with CAC in males, but not in females. Men carrying the SNP -286 allele C had increased CAC after adjusting for risk factors. These data suggest that the presence of high producer CRP genotype is deleterious to carotid elasticity in men.

When do social inequalities in C-reactive protein start? A life course perspective from conception to adulthood in the Cardiovascular Risk in Young Finns Study.

BACKGROUND: It is unclear when in the life course do social inequalities in inflammation emerge. We examined whether the association between socioeconomic position (SEP) and C-reactive protein (CRP) is determined at conception, in childhood, adolescence or adulthood in 1484 participants from the population-based Cardiovascular Risk in Young Finns Study. METHODS: Five variants of the CRP gene were used to investigate whether SEP differences in CRP levels are determined at conception. SEP and serum CRP were assessed in childhood (age 3-9), adolescence (age 12-18) and in adulthood (age 24-39). SEP was measured using parental education and occupational status in childhood and adolescence, and participants' own education and occupational status in adulthood. Participants with CRP > 10 mg/l were excluded. RESULTS: All CRP gene variants were associated with circulating CRP concentrations in childhood, but there were no differences in the distribution of these variants by SEP. No strong evidence was found of associations between parental SEP and CRP. A graded association between higher SEP and lower CRP was observed in adulthood for education (P = 0.0005) but not for occupational status. Trajectories that led to high educational achievement both in the participants and their parents were associated with lower (P

Role of skeletal muscle-fibre type in regulation of glucose metabolism in middle-aged subjects with impaired glucose tolerance during a long-term exercise and dietary intervention.

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.

Distribution and determinants of serum high-sensitive C-reactive protein in a population of young adults: The Cardiovascular Risk in Young Finns Study.

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).

Smoking history and serum cotinine and thiocyanate concentrations as determinants of rheumatoid factor in non-rheumatoid subjects.

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.

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. 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.

Consumption of black currants, lingonberries and bilberries increases serum quercetin concentrations.

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.

Effects of gender, apolipoprotein E phenotype and cholesterol-lowering by plant stanol esters in children: the STRIP study. Special Turku Coronary Risk Factor Intervention Project.

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.

Population-based twin study of the effects of migration from Finland to Sweden on endothelial function and intima-media thickness.

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.

Visceral fat and psychosocial stress in identical twins discordant for obesity.

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.

Hyperhomocystinemia: a risk factor or a consequence of coronary heart disease?

BACKGROUND: Mild hyperhomocystinemia has been suggested as an indicator of an increased risk of cardiovascular disease. OBJECTIVE: To examine whether serum homocysteine concentration is a predictor of coronary heart disease (CHD) events. METHODS: A case-control study, nested in a population-based cohort study was used. During a follow-up of 13 years, 166 major coronary events (death from CHD or nonfatal myocardial infarction) occurred in men with evidence of heart disease at baseline and 272 events in men without a history of heart disease. Two controls per case were selected by individual matching. RESULTS: Among men with known heart disease at baseline, the relative risk (95% confidence interval) of CHD events adjusted for age, smoking, hypertension, diabetes mellitus, serum cholesterol level, body mass index, and alcohol consumption was 2.23 (95% confidence interval, 1.03-4.85) in the highest serum homocysteine quintile compared with the lowest quintile. Among the men free of heart disease at baseline, the corresponding relative risk was 0.90 (95% confidence interval, 0.51-1.60). CONCLUSIONS: This prospective study does not support the hypothesis that a high concentration of serum homocysteine is a risk factor for coronary events in a population free of heart disease. However, it does suggest that mild hyperhomocystinemia predicts secondary coronary events in men with heart disease, possibly as a consequence of atherosclerotic changes.

Homocysteine and major coronary events: a prospective population study amongst women.

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.