Antti Aro

Antioxidants in adipose tissue and risk of myocardial infarction: the EURAMIC study

Laboratory and epidemiological studies suggest that the antioxidants, vitamin E and beta-carotene, protect against coronary heart disease. In a European multicentre case-control study alpha-tocopherol and beta-carotene concentrations were measured in adipose-tissue samples collected in 1991-92 from 683 people with acute myocardial infarction and 727 controls. Mean adipose-tissue beta-carotene concentration was 0.35 microgram/g in cases and 0.42 in controls, with age-adjusted and centre-adjusted mean difference 0.07 microgram/g (95% confidence interval [CI] 0.04-0.10). Mean alpha-tocopherol concentrations were 193 micrograms/g and 192 micrograms/g for cases and controls, respectively. The age-adjusted and centre-adjusted odds ratio for risk of myocardial infarction in the lowest quintile of beta-carotene as compared with the highest was 2.62 (95% CI 1.79-3.83). Additional control for body-mass index and smoking reduced the odds ratio to 1.78 (95% CI 1.17-2.71); other established risk factors did not substantially alter this ratio. The increased risk was mainly confined to current smokers: the multivariate odds ratio in the lowest beta-carotene quintile in smokers was 2.39 (95% CI 1.35-4.25), whereas it was 1.07 for people who had never smoked. A low alpha-tocopherol concentration was not associated with risk of myocardial infarction. Our results support the hypothesis that high beta-carotene concentrations within the normal range reduce the risk of a first myocardial infarction. The findings for alpha-tocopherol are compatible with previous observations of reduced risk among vitamin E supplement users only. The consumption of beta-carotene-rich foods such as carrots and green-leaf vegetables may reduce the risk of myocardial infarction.

Vitamin D Status and the Risk of Cardiovascular Disease Death

Accumulating evidence suggests that inadequate vitamin D levels may predispose people to chronic diseases. The authors aimed to investigate whether serum 25-hydroxyvitamin D (25(OH)D) level predicts mortality from cardiovascular disease (CVD). The study was based on the Mini-Finland Health Survey and included 6,219 men and women aged > or =30 years who were free from CVD at baseline (1978-1980). During follow-up through 2006, 640 coronary disease deaths and 293 cerebrovascular disease deaths were identified. Levels of 25(OH)D were determined from serum collected at baseline. Coxs proportional hazards model was used to assess the association between 25(OH)D and risk of CVD death. After adjustment for potential confounders, the hazard ratio for total CVD death was 0.76 (95% confidence interval (95% CI): 0.60, 0.95) for the highest quintile of 25(OH)D level versus the lowest. The association was evident for cerebrovascular death (hazard ratio = 0.48, 95% CI: 0.31, 0.75) but not coronary death (hazard ratio = 0.91, 95% CI: 0.70, 1.18). A low vitamin D level may be associated with higher risk of a fatal CVD event, particularly cerebrovascular death. These findings need to be replicated in other populations. To demonstrate a causal link between vitamin D and CVD, randomized controlled trials are required.

The Risk to Develop NIDDM Is Related to the Fatty Acid Composition of the Serum Cholesterol Esters

This investigation was undertaken to study whether the risk to develop non-insulin-dependent diabetes mellitus (NIDDM) among 50-year-old men during a 10-year follow-up period was related to the fatty acid composition of their serum cholesterol esters. There were highly significant differences in the initial health survey between the fatty acid composition in serum in subjects who remained normoglycemic (w = 1,753) and in those who later developed NIDDM (n = 75). The main differences were that the latter had higher proportions of saturated fatty acids and palmitoleic acid (16:ω-7), a low proportion of linoleic acid (18:2ω-6), and a relatively high content of γ-linolenic (18:3ω-6) and dihomo-γ-linolenic (20:3ω-6) acids in the serum cholesterol esters. The picture was similar also after adjusting for differences in body mass index. In a logistic model, a high proportion of dihomo-γ-linolenic acid remained a significant contributor to the development of diabetes, along with the height of the insulin index, the blood glucose concentration at 60 min, and the fasting insulin concentration. The increased risk to develop NIDDM related to the serum cholesterol ester fatty acid composition may be mediated by diet and/or genetic factors.

Adipose tissue isomeric trans fatty acids and risk of myocardial infarction in nine countries : the EURAMIC study

Dietary isomeric trans fatty acids-mainly produced by hydrogenation of oils-are suspected of increasing the risk of coronary heart disease. Dietary trans fatty acid intake is reflected in the fatty acid composition of adipose tissue. In an international multicentre study in eight European countries and Israel (EURAMIC), adipose tissue aspiration samples were obtained from 671 men with acute myocardial infarction (AMI), aged 70 years or less, and 717 men without a history of AMI (controls). The proportion of fatty acids, including isomeric trans monoenoic fatty acids with 18 carbon atoms (C18:1), was determined by gas chromatography. Although there were considerable differences between countries in mean (SD) proportion of adipose tissue C18:1 trans fatty acids, there was no overall difference between cases (1.61 [0.92]%) and the controls (1.57 [0.86]%). The risk of AMI did not differ significantly from 1.0 over quartiles of adipose C18:1 trans fatty acids: the multivariate odds ratio was 0.97 (95% CI 0.56-1.67) for the highest versus lowest quartile. After exclusion of subjects from Spanish centres because they had far lower proportions of adipose trans fatty acids than subjects from other countries, there was a tendency to increased risk of AMI in the upper quartiles of C18:1 trans; however, the trend was not statistically significant. Our results reflect considerable differences between countries in dietary intake of trans fatty acids but do not suggest a major overall effect of C18:1 trans fatty acids on risk of AMI. We cannot exclude the possibility that trans fatty acids have a significant impact on risk of AMI in populations with high intake.

Omega-3 Fatty Acids in Adipose Tissue and Risk of Myocardial Infarction The EURAMIC Study

Omega-3 fatty acids have potential antiatherogenic, antithrombotic, and antiarrhythmic properties, but their role in coronary heart disease remains controversial. To evaluate the association of omega-3 fatty acids in adipose tissue with the risk of myocardial infarction in men, a case-control study was conducted in eight European countries and Israel. Cases (n=639) included patients with a first myocardial infarction admitted to coronary care units within 24 hours from the onset of symptoms. Controls (n=700) were selected to represent the populations originating the cases. Adipose tissue levels of fatty acids were determined by capillary gas chromatography. The mean (+/-SD) proportion of alpha-linolenic acid was 0.77% (+/-0.19) of fatty acids in cases and 0.80% (+/-0.19) of fatty acids in controls (P=0.01). The relative risk for the highest quintile of alpha-linolenic acid compared with the lowest was 0.42 (95% confidence interval [CI] 0.22 to 0.81, P-trend=0.02). After adjusting for classical risk factors, the relative risk for the highest quintile was 0.68 (95% CI 0.31 to 1.49, P-trend=0.38). The mean proportion of docosahexaenoic acid was 0.24% (+/-0.13) of fatty acids in cases and 0.25% (+/-0.13) of fatty acids in controls (P=0. 14), with no evidence of association with risk of myocardial infarction. In this large case-control study we could not detect a protective effect of docosahexaenoic acid on the risk of myocardial infarction. The protective effect of alpha-linolenic acid was attenuated after adjusting for classical risk factors (mainly smoking), but it deserves further research.

Infant Feeding in Finnish Children <7 yr of Age With Newly Diagnosed IDDM

Objective We studied associations between the type of feeding in infancy and the incidence of insulin-dependent diabetes mellitus (IDDM). Research Design And Methods We studied 103 newly diagnosed diabetic children <7 yr of age and 103 age- and sex-matched population-based control children in a countrywide study. Results The risk of IDDM was decreased (P < 0.05) among children breast-fed for at least 7 mo (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.24–0.85) or exclusively breast-fed for at least 3 (OR 0.33, 95% CI 0.13–0.84) or 4 (OR 0.43, 95% CI 0.22–0.84) mo. Also, children who were ≥4 mo old at the time of introduction of supplementary milk feeding had a lower risk of diabetes (OR 0.48, 95% CI 0.26–0.91). Conclusions The protective effects of a long duration of breast-feeding and a late introduction of dairy products on the risk of IDDM remained significant after adjusting for the mothers education.

Dietary trans fatty acids increase conjugated linoleic acid levels in human serum

Conjugated linoleic acid (CLA), fatty acids with 18 carbon atoms and two conjugated cis/trans double bonds, have shown anticarcinogenic effects in experimental studies. We determined the proportion of CLA (the sum of cis-9, trans-11 and trans-9, cis-11 CLA) of total fatty acids in the diets and serum samples of healthy subjects who consumed for 5 weeks a diet high in saturated fatty acids mainly from dairy fat, followed by 5 weeks on a diet high (8.7% of energy, en%) in trans fatty acids from partially hydrogenated vegetable oil (40 subjects) or a similar diet high in stearic acid (9.3 en%, 40 subjects). All diets contained equal amounts of fat and cis-monounsaturated and cis-polyunsaturated fatty acids. The fatty acid compositions of the pooled diets and fasting serum samples drawn at the end of the diet periods were analyzed by gas chromatography, and CLA was identified by comparison with a standard of C18:2 conjugated dienes. The proportions of CLA in the dairy fat, trans fatty acid, and stearic acid diets were 0.37, 0.04, and 0.10% of total methylated fatty acids, respectively. The corresponding mean (SD) proportions in serum were 0.33 (0.07)% after the dairy fat diet, higher, 0.43 (0.12)%, P < 0.001, after the trans fatty acid diet, and lower, 0.17 (0.06)%, P < 0.001, after the stearic acid diet. The difference between dairy fat and stearic acid diets was explained by different dietary intakes but increased amounts of CLA not present in the diet were incorporated into serum lipids during the trans fatty acid diet. CLA in human tissues is partly derived from the diet but part of it may be formed by conversion from dietary trans fatty acids.

A Controlled Trial on the Effects of Patient Education in the Treatment of Insulin-dependent Diabetes

The effect of patient education on diabetic control in insulin-treated diabetic adults was studied in 77 subjects randomized into two groups: intensive patient education (group A) and control (group B). The subjects in group A received intensive patient instruction, both individually and in small groups, from a team of physicians, teaching nurses, and a dietitian. The patients in group B received a short instruction course consisting mainly of printed material. A highly significant improvement in diabetic control was observed in both groups immediately after the education programs, with gradual return to the original level during the following 3–6 mo. No difference was observed between the two groups in any of the measured parameters during the 18-mo investigation. Factors related to good control during the study included the length of school education, the quality of the control at the beginning of the study, and the high degree of self-confidence and lack of signs of anxiety in the psychological tests. The results demonstrate that the effects of educational programs are of limited value if they do not lead to permanent changes in attitudes and motivation, which are critical factors affecting long-term diabetic control.

Early Introduction of Dairy Products Associated with Increased Risk of IDDM in Finnish Children

Associations between infant-feeding patterns and risk of IDDM were investigated in a nationwide Finnish case-control study of 690 IDDM children <15 yr of age. Each child was matched by date of birth and sex to a randomly selected population-based control child. Univariate analysis revealed that the risk of IDDM was increased by ∼1.5 in children for whom breast-feeding was terminated at <2 mo of age, doubled in those who were exclusively breast-fed for <2 mo, and doubled in those who were introduced to dairy products at <2 mo of age. In further multivariate analyses of these factors, it was found that introduction of dairy products at an early age was the most important risk factor, and the observed univariate effects of duration of breast-feeding variables were explained by their correlation with this factor. This is the first observational study to show that early introduction of dairy products is independently associated with an increased risk of IDDM. Adjustment for mothers education and age, childs birth order, or birth weight did not affect the results.

Plasma concentrations of the flavonoids hesperetin, naringenin and quercetin in human subjects following their habitual diets, and diets high or low in fruit and vegetables.

Objectives: To determine the fasting plasma concentrations of quercetin, hesperetin and naringenin in human subjects consuming their habitual diets, and diets either high or low in fruit and vegetables. To investigate whether plasma concentrations of flavanones can serve as biomarkers of their intake.Design: This was a cross-over, strictly controlled dietary intervention consisting of a 2 week baseline period, and two 5 week dietary periods with a 3 week wash-out period in between. The low-vegetable diet contained few fruit and vegetables and no citrus fruit. The high-vegetable diet provided various fruits and vegetables daily including on average one glass of orange juice, one-half orange and one-half mandarin.Subjects: Thirty-seven healthy females.Results: The high-vegetable diet provided 132 mg of hesperetin and 29 mg of naringenin. The low-vegetable diet contained no flavanones. The mean plasma hesperetin concentration increased from 12.2 nmol/l after the low-vegetable diet to 325 nmol/l after the high-vegetable diet. The respective increase for naringenin was from <73.5 nmol/l for all subjects to a mean value of 112.9 nmol/l. The mean plasma quercetin concentration was 52 nmol/l after the baseline period, during which habitual diets were consumed, and it did not change significantly during the intervention. Interindividual variation in the plasma levels of hesperetin and naringenin was marked and, after the baseline and wash-out periods, and the low-vegetable diet, a majority of the samples had plasma flavanone levels below the limit of detection. After the high-vegetable diet, hesperetin and naringenin were detectable in 54 and 22% of all samples. Quercetin was detectable in nearly all samples after all study periods.Conclusion: Hesperetin, naringenin and quercetin are bioavailable from the diet, but the plasma concentrations of hesperetin and naringenin are poor biomarkers of intake.