Jorge Gómez-Aracena

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.

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.

DDT (dicophane) and postmenopausal breast cancer in Europe: case-control study.

Abstract Objective: To examine any possible links between exposure to DDE (1,1-dichloro-2,2-bis (p -chlorophenyl)ethylene), the persistent metabolite of the pesticide dicophane (DDT), and breast cancer. Design: Multicentre study of exposure to DDE by measurement of adipose tissue aspirated from the buttocks. Laboratory measurements were conducted in a single laboratory. Additional data on risk factors for breast cancer were obtained by standard questionnaires. Setting: Centres in Germany, the Netherlands, Northern Ireland, Switzerland, and Spain. Subjects: 265 postmenopausal women with breast cancer and 341 controls matched for age and centre. Main outcome measure: Adipose DDE concentrations. Results: Women with breast cancer had adipose DDE concentrations 9.2% lower than control women. No increased risk of breast cancer was found at higher concentrations. The odds ratio of breast cancer, adjusted for age and centre, for the highest versus the lowest fourth of DDE distribution was 0.73 (95% confidence interval 0.44 to 1.21) and decreased to 0.48 (0.25 to 0.95; P for trend=0.02) after adjustment for body mass index, age at first birth, and current alcohol drinking. Adjustment for other risk factors did not materially affect these estimates. Conclusions: The lower DDE concentrations observed among the women with breast cancer may be secondary to disease inception. This study does not support the hypothesis that DDE increases risk of breast cancer in postmenopausal women in Europe. Key messages Organochlorines such as polychlorinated biphenyls and DDT may increase the risk of breast cancer in women DDE concentrations among the women with cancer were lower than among the controls, and there was an inverse risk gradient with higher DDE concentrations which remained significant after adjustment for risk factors for breast cancer These results are clearly incompatible with an increased risk of breast cancer at increased concentrations of DDE, although associations with other organochlorines cannot be excluded

Flexible Flat Feet in Children: A Real Problem?

Objectives To estimate the prevalence of flexible flat feet in the provincial population of 4- to 13-year-old schoolchildren and the incidence of treatments considered unnecessary. Setting. Province of Málaga, Spain. Methods. We examined and graded by severity a sample of 1181 pupils taken from a total population of 198 858 primary schoolchildren (CI: 95%; margin of error: 5%). The sample group was separated into three 2-year age groups: 4 and 5 years, 8 and 9 years, and 12 and 13 years. The plantar footprint was classified according to Denis1 into three grades of flat feet: grade 1 in which support of the lateral edge of the foot is half that of the metatarsal support; grade 2 in which the support of the central zone and forefoot are equal; and grade 3 in which the support in the central zone of the foot is greater than the width of the metatarsal support. The statistical analysis for the evaluation of the differences between the groups was performed with Students t and χ2 tests as appropriate. Results. The prevalence of flat feet was 2.7%. Of the 1181 children sampled, 168 children (14.2%) were receiving orthopedic treatment, but only 2.7% had diagnostic criteria of flat feet. When we inspected the sample, we found that a number of children were being treated for flat feet with boots and arch supports. Most of them did not have a flat plantar footprint according to the criteria that we used for this work. Furthermore, in the group of children that we diagnosed as having flat feet, only 28.1% were being treated. We found no significant differences between the number of children receiving orthopedic treatments and the presence or absence of a flat plantar footprint. Children who were overweight in the 4- and 5-year-old group showed an increased prevalence for flat feet as diagnosed by us. Conclusion. The data suggest that an excessive number of orthopedic treatments had been prescribed in the province. When extrapolated to the 1997 population of schoolchildren within the age groups studied the figures suggested that ∼28 167 children in Málaga province probably would have been receiving orthopedic treatments with boots and insoles at the time of our study. Consequently, the total expenditure on orthopedic boots and insoles that year could be estimated as 676 008 000 pesetas (

Iron: Protector or Risk Factor for Cardiovascular Disease? Still Controversial

4 447 422 in US currency).

Association Between β-Carotene and Acute Myocardial Infarction Depends on Polyunsaturated Fatty Acid Status

Iron is the second most abundant metal in the Earth’s crust. Despite being present in trace amounts, it is an essential trace element for the human body, although it can also be toxic due to oxidative stress generation by the Fenton reaction, causing organic biomolecule oxidation. This process is the basis of numerous pathologies, including cardiovascular diseases (CVD). The relationship between iron and cardiovascular disease was proposed in 1981 by Jerome Sullivan. Since then, numerous epidemiological studies have been conducted to test this hypothesis. The aim of this review is to present the main findings of the chief epidemiological studies published during the last 32 years, since Sullivan formulated his iron hypothesis, suggesting that this element might act as a risk factor for cardiovascular disease. We have analyzed 55 studies, of which 27 supported the iron hypothesis, 20 found no evidence to support it and eight were contrary to the iron hypothesis. Our results suggest that there is not a high level of evidence which supports the hypothesis that the iron may be associated with CVD. Despite the large number of studies published to date, the role of iron in cardiovascular disease still generates a fair amount of debate, due to a marked disparity in results.

Myocardial infarction risk in relation to zinc concentration in toenails

Because antioxidants may play a role in the prevention of coronary heart disease by inhibiting the peroxidation of polyunsaturated fatty acids (PUFAs), the combined association of diet-derived antioxidants and PUFAs with acute myocardial infarction (MI) was investigated. This multicenter case-control study included 674 patients and 725 control subjects in eight European countries and Israel. Fatty acid composition and alpha-tocopherol and beta-carotene levels were determined in adipose tissue; selenium level was determined in toenails. For alpha-tocopherol no association with MI was observed at any PUFA level. The overall multivariate odds ratio (OR) for low (10th percentile) versus high (90th percentile) beta-carotene was 1.98 (95% confidence interval [CI], 1.39 to 2.82). The strength of this inverse association with MI was dependent on PUFA levels (in tertiles): for low PUFA, the OR for low versus high beta-carotene was 1.79 (95% CI, 0.98 to 3.25), for medium PUFA the OR was 1.76 (95% CI, 1.00 to 3.11), and for high PUFA 3.47 (95% CI, 1.93 to 6.24). For selenium increased risk was observed only at the lowest PUFA tertile (OR, 2.49; 95% CI, 1.22 to 5.09). This interaction between selenium and PUFAs was not significant and may at least partly be explained by a higher proportion of smokers at the low PUFA level. These findings support the hypothesis that beta-carotene plays a role in the protection of PUFAs against oxidation and subsequently in the protection against MI. No evidence was found that alpha-tocopherol or selenium may protect against MI at any level of PUFA intake.Abstract Because antioxidants may play a role in the prevention of coronary heart disease by inhibiting the peroxidation of polyunsaturated fatty acids (PUFAs), the combined association of diet-derived antioxidants and PUFAs with acute myocardial infarction (MI) was investigated. This multicenter case-control study included 674 patients and 725 control subjects in eight European countries and Israel. Fatty acid composition and α-tocopherol and β-carotene levels were determined in adipose tissue; selenium level was determined in toenails. For α-tocopherol no association with MI was observed at any PUFA level. The overall multivariate odds ratio (OR) for low (10th percentile) versus high (90th percentile) β-carotene was 1.98 (95% confidence interval [CI], 1.39 to 2.82). The strength of this inverse association with MI was dependent on PUFA levels (in tertiles): for low PUFA, the OR for low versus high β-carotene was 1.79 (95% CI, 0.98 to 3.25), for medium PUFA the OR was 1.76 (95% CI, 1.00 to 3.11), and for high PUFA 3.47 (95% CI, 1.93 to 6.24). For selenium increased risk was observed only at the lowest PUFA tertile (OR, 2.49; 95% CI, 1.22 to 5.09). This interaction between selenium and PUFAs was not significant and may at least partly be explained by a higher proportion of smokers at the low PUFA level. These findings support the hypothesis that β-carotene plays a role in the protection of PUFAs against oxidation and subsequently in the protection against MI. No evidence was found that α-tocopherol or selenium may protect against MI at any level of PUFA intake.

Vegetable consumption and carotenoids in plasma and adipose tissue in Malaga, Spain

Zn is an essential mineral. The role of Zn in atherosclerosis is not clear. Epidemiological studies, which have reported contradictory results, are limited by the use of serum Zn levels as a marker of intake. We assessed the association of toenail Zn, which integrates dietary Zn intake over 3 to 12 months, with the risk of a first myocardial infarction. Toenail Zn concentrations were determined by neutron activation analysis in the European multi-centre case-control study on antioxidants, myocardial infarction and breast cancer. This multi-centre case-control study included 684 cases and 724 controls from eight European countries and Israel. Toenail Zn levels of controls (adjusted for age and study centre) were positively associated with age, alpha-tocopherol and Se, but not with additional dietary variables or with classical risk factors for CHD. Average toenail Zn was 106.0 mg/kg in cases (95 % CI 103.1, 108.9) and 107.5 mg/kg in controls (95 % CI 104.5, 110.7). After controlling for cardiovascular risk factors and for centre, the adjusted odds ratios of myocardial infarction for quintiles 2-5 of toenail Zn with respect to the first quintile were 0.97 (95 % CI 0.59, 1.58), 1.15 (95 % CI 0.72, 1.85), 0.91 (95 % CI 0.56, 1.50), and 0.85 (95 % CI 0.52, 1.39). The P for trend was 0.45. In conclusion toenail Zn levels (reflecting long-term dietary intake) were not significantly associated with acute myocardial infarction.

Association between beta-carotene and acute myocardial infarction depends on polyunsaturated fatty acid status : the EURAMIC study

OBJECTIVE To study relationships between habitual dietary intake, adipose tissue concentrations of alpha-carotene, beta-carotene and lycopene, and plasma concentrations of alpha- and beta-carotene. DESIGN Cross-sectional study including assessment of food habits by a food frequency questionnaire and 48-hour recall and determination of carotenoid concentrations in adipose tissue and plasma. SUBJECTS 51 women (mean age of 62 years) from the control group of the European Community Multicentre Study on Antioxidants, Myocardial Infarction, and Breast Cancer (EURAMIC), Málaga, Spain. RESULTS In adipose tissue, beta-carotene was correlated with consumption of green pepper (r = 0.36; p < 0.05) and lycopene with total fruit/vegetable intake (r = 0.28; p < 0.05), green pepper (r = 0.31; p < 0.05), and carrot (r = 0.25; p < 0.10). In plasma, beta-carotene was correlated with total fruit/vegetable intake (r = 0.29; p < 0.10), lettuce (r = 0.34; p < 0.05), tomato (r = 0.26; p < 0.10), and lycopene with total fruit/vegetable intake (r = 0.27; p < 0.10). Age-, BMI- and waist circumference-adjusted regression coefficients for the regression of logn-transformed adipose and plasma concentrations on consumption of specific fruits and vegetables (per 100 g/day) were calculated. In adipose tissue, coefficients were: 1.50 (p < 0.05) for alpha-carotene/carrot; 1.90 (p < 0.10) and 0.51 (p < 0.10) for beta-carotene/green pepper and lettuce; 2.02 (p < 0.05), 1.25 (p < 0.05) and 0.18 (p < 0.05) for lycopene/green pepper, carrot and total fruit/vegetable intake. In plasma, coefficients were 1.14 (p < 0.05) and 0.21 (p < 0.05) for beta-carotene/lettuce and total fruit/vegetable intake. CONCLUSIONS Consumption of fruit and vegetables could be linked directly to carotenoid concentrations in adipose tissue and plasma. Although associations with individual food items are related to their carotenoid contents, the absorption and distribution of carotenoids needs more attention to improve their usefulness as biomarkers of exposure.