F.J. Kok

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.

AORTIC CALCIFICATION AS A PREDICTOR OF CARDIOVASCULAR MORTALITY

Since aortic calcification is seen on X-rays of the prelumbar region in many patients, its relation with cardiovascular disease (CVD) was investigated in a prospective study in The Netherlands. X-rays were taken of 1359 men and 1598 women, in 1975-78. In the subsequent 9 years, 50 men and 33 women died from CVD. The prevalence of aortic calcification was about 10% in middle-aged subjects and rose with age to a maximum of 45% in men and 75% in women. Aortic calcification was associated with a six-fold increased risk of CVD death in men aged 45 years, independent of major CVD risk factors. For each year of age over 45, risk associated with the presence of aortic calcification declined by 6%. Death rates in middle-aged women were too small for risk analysis. These results suggest that atherosclerosis in other than coronary or cerebral vessels may have predictive relevance for CVD death: its diagnosis indicates intervention on present CVD risk factors.

Increased risk of atherosclerosis in women after the menopause.

An increase in the incidence of cardiovascular disease has generally been observed in postmenopausal women, but there have been few studies of the association between menopausal state and atherosclerosis. In this study 294 premenopausal and 319 postmenopausal women aged 45 to 55 were examined radiographically for calcified deposits in the abdominal aorta, which have been shown to represent intimal atherosclerosis. Aortic atherosclerosis was present in eight (3%) of the premenopausal women and in 38 (12%) of the postmenopausal women. After adjustments for age and other indicators of cardiovascular risk women with a natural menopause had a 3.4 times greater risk of atherosclerosis than premenopausal women (95% confidence interval 1.2 to 9.7; p less than 0.05); women who had had a bilateral oophorectomy had a 5.5 times greater risk (1.9 to 15.8; p less than 0.005). No excess risk of atherosclerosis was observed among women who had had a hysterectomy without removal of both ovaries. These results suggest that when oestrogen production stops, either naturally or after surgery, the risk of atherosclerosis is increased.

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.

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

Physical exercise or micronutrient supplementation for the wellbeing of the frail elderly? A randomised controlled trial

Objective: To examine the effects of 17 weeks of physical exercise and micronutrient supplementation on the psychological wellbeing of 139 independently living, frail, elderly subjects (inactive, body mass index ≤25 or experiencing weight loss). Methods: Participants (mean (SD) age 78.5 (5.7)) were randomly assigned to: (a) comprehensive, moderate intensity, group exercise; (b) daily micronutrient enriched foods (25–100% recommended daily amount); (c) both; (d) neither. A social programme and identical regular foods were offered as attention control and placebo. Results: At baseline, moderate to low but significant correlations were found between general wellbeing scores and physical fitness (r = 0.28), functional performance (r = 0.37), and blood concentrations of pyridoxine (r = 0.20), folate (r = 0.25), and vitamin D (r = 0.23) (all p values ≤0.02), but not with physical activity levels and other blood vitamin concentrations. General wellbeing score and self rated health were not responsive to 17 weeks of exercise or nutritional intervention. Conclusion: Psychological wellbeing in frail elderly people was not responsive to 17 weeks of intervention with exercise and/or micronutrient enriched foods. The moderate but significant correlations between wellbeing and physical fitness and several blood vitamin concentrations at baseline suggest that changes in wellbeing may occur after long term interventions.

Aflatoxin and liver cancer in Sudan

This study investigated whether aflatoxin contamination of peanut products may contribute to the incidence of hepatocellular carcinoma (HCC) in Sudan. Thirty-seven peanut butter and peanut samples were collected from local markets. Aflatoxin concentrations were significantly higher in West Sudan [87.4 +/- 197.3 (SD) micrograms/kg], a high-risk area, than in Central Sudan (8.5 +/- 6.8 micrograms/kg), a low-risk area. In West Sudan, humid local storage conditions of peanut products were related to high aflatoxin concentrations. In a small case-control study of HCC patients (n = 24) and controls (n = 34), an odds ratio of 7.5 (95% confidence interval = 1.4-40.2) was observed for humid vs. dry local storage conditions. Development of an index of individual HCC exposure was less successful, probably because of year-to-year variability in aflatoxins in food. These preliminary findings justify further research into the role of aflatoxins and hepatitis in HCC incidence in Sudan.

Effects of snack consumption for 8 weeks on energy intake and body weight

Background:Consumption of snacks might contribute to the obesity epidemic. It is not clear how the moment of consumption and energy density of snacks can influence the compensatory response to consumption of snacks in the long term.Objective:To investigate the effects of snack consumption for 8 weeks on changes in body weight, emphasizing on moment of consumption and energy density.Design:In total, 16 men and 66 women (mean age 21.9 years (s.d. 0.3 year), mean body mass index 20.7 kg m−2 (s.d. 0.2 kg m−2)) were randomly assigned to one of four parallel groups in a 2 × 2 design: snacks consumed with or between meals and snacks having a low (<4 kJ g−1) or high (>12 kJ g−1) energy density. For 8 weeks, subjects consumed mandatory snacks that provided 25% of energy requirements on each day. Body weight, body composition, physical activity level (PAL) and energy intake were measured in week 1 and week 8.Results:There were no differences in changes in body weight between the four groups. Moment of consumption (P=0.7), energy density (P=0.8) and interaction (P=0.09) did not influence body weight. Similarly, there were no differences in changes in body composition, PAL and energy intake between the four groups.Conclusions:Body weight after 8 weeks of snack consumption was not affected by moment of consumption and energy density of snacks. This finding suggests that consuming snacks that are high or low in energy density does not necessarily contribute to weight gain. Healthy, nonobese young adults may be able to maintain a normal body weight through an accurate compensation for the consumption of snacks.

Effect of Fish Oil Supplementation on Quality of Life in a General Population of Older Dutch Subjects: A Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVES: To investigate the effect of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) supplementation on quality of life (QOL).

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

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.