R.A. Riemersma

Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene

The relation between risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene was examined in a population case-control study of 110 cases of angina, identified by the Chest Pain Questionnaire, and 394 controls selected from a sample of 6000 men aged 35-54. Plasma concentrations of vitamins C and E and carotene were significantly inversely related to the risk of angina. There was no significant relation with vitamin A. Smoking was a confounding factor. The inverse relation between angina and low plasma carotene disappeared and that with plasma vitamin C was substantially reduced after adjustment for smoking. Vitamin E remained independently and inversely related to the risk of angina after adjustment for age, smoking habit, blood pressure, lipids, and relative weight. The adjusted odds ratio for angina between the lowest and highest quintiles of vitamin E concentrations was 2.68 (95% confidence interval 1.07-6.70; p = 0.02). These findings suggest that some populations with a high incidence of coronary heart disease may benefit from eating diets rich in natural antioxidants, particularly vitamin E.

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.

LINOLEIC AND EICOSAPENTAENOIC ACIDS IN ADIPOSE TISSUE AND PLATELETS AND RISK OF CORONARY HEART DISEASE

The relation between the fatty-acid composition of adipose tissue and platelet membranes and the estimated relative risk of coronary heart disease (CHD) was examined in a case-control study of new angina pectoris (AP) and first acute myocardial infarction (AMI). There were progressive inverse relations between adipose linoleic acid and platelet-membrane eicosapentaenoic acid and the estimated relative risk of AP. These relations were statistically independent of each other and traditional CHD risk factors. For AMI there was a progressive inverse relation between adipose linoleic acid and the estimated relative risk, but it was confounded by smoking habit. Smokers consume less linoleic acid than non-smokers. Although eicosapentaenoic acid in platelet membranes was lower in AMI patients than in controls, this difference was not significant. The estimated proportionate increase in risk of AP, independent of other CHD risk factors, was 1.2 (1.1-1.3) for a 1% decrease in linoleic acid or a 0.1% decrease in eicosapentaenoic acid.

ADIPOSE TISSUE AND PLATELET FATTY ACIDS AND CORONARY HEART DISEASE IN SCOTTISH MEN

The relation between coronary heart disease (CHD) and fatty acid composition of adipose tissue and platelets was examined in a random sample of 448 middle-aged Scottish men. The linoleic acid (18:2n6) content in adipose tissue of 28 men with previously unidentified CHD was significantly lower than that in the rest of the group. Platelet linoleic and other fatty acids were not significantly different in men with new CHD. Fatty acid content of adipose tissue reflects long-term dietary intake, and a 7-day weighed dietary record in a random sub-sample of 164 men confirmed that intake of linoleic acid in 10 of the 28 new CHD cases was significantly lower than in the healthy men. In a multiple logistic analysis adipose tissue linoleic acid, age, high density lipoprotein cholesterol, and weight/height index each made an independent contribution to the explanation of new CHD. When all fatty acids were included in a second regression analysis, low concentrations of dihomo-gamma-linolenic (20:3n6) acid in adipose tissue showed a more significant relation with new CHD than did linoleic acid.

Trans isomers of oleic and linoleic acids in adipose tissue and sudden cardiac death

trans isomers of unsaturated fatty acids are formed by biological or industrial hydrogenation. A population case-control study of sudden cardiac death in mean was done to test the hypothesis that trans isomers of oleic acid and linoleic acid increase the risk of sudden cardiac death due to coronary artery disease. In adipose tissue obtained at necropsy from 66 cases of sudden cardiac death and taken from 286 healthy age and sex matched controls, the proportions of trans isomers of oleic and linoleic acid were measured by gas-liquid chromatography. In cases, the mean (SE) percentage of total trans fatty acids (C18:1 plus C18:2), expressed as a proportion of all fatty acids, was significantly lower (2.68 [0.08]%) than in healthy controls (2.86 [0.04]%; p < 0.05). trans C18:1 was 2.1 (0.7)% in cases compared with 2.27 (0.04)% (p < 0.05) in controls. The proportion of all trans isomers of linoleic acid was 0.58 (0.02)% in cases compared with 0.59 (0.01)% in controls (p = 0.98). The estimated relative risk for sudden cardiac death of trans C18:1 and C18:2 fatty acids combined did not differ significantly from 1.0 in relation to the distribution of these trans isomers by quintile in the control population. The relative risk (95% CI) of sudden cardiac death in the top quintile was 0.40 (0.15-1.02) for C18:1 and 1.08 (0.48-2.74) for C18:2 compared with the bottom quintiles of their respective control distributions. When these univariate relations for trans fatty acids were adjusted for coronary risk factors, smoking was the only factor that remained independently associated with risk of sudden cardiac death (2.27 [1.23-4.17]). Overall, there was no evidence of a relation between trans isomers of oleic and linoleic acids combined and sudden cardiac death. However, trans oleic acid was negatively associated with risk of sudden cardiac death, whereas no association with trans forms of linoleic acid was seen. This study does not support the hypothesis that trans isomers increase the risk of sudden cardiac death.

Serum cholesterol, triglycerides, and aggression in the general population

A higher than expected number of violent deaths and suicides in coronary prevention trials has provoked interest in the possibility that low serum cholesterol concentrations are associated in the general population with personality characteristics predisposing to aggressive and suicidal behaviour. We have investigated this possibility in the Edinburgh Artery Study. We measured serum lipid concentrations in blood samples taken from fasting subjects and assessed personality characteristics on the Bedford Foulds Personality Deviance Scales in a random sample of 1592 men and women aged 55-74 years, selected from age-sex registers of ten general practices in Edinburgh. Serum cholesterol concentration was not significantly associated with aggression in men, but it was associated in multivariate analysis (though not univariate analysis) with denigratory attitudes towards others among women. However, serum triglyceride concentration was related, especially in men, to hostile acts (r = 0.13, p < 0.001) and domineering attitude (r = 0.12, p < 0.001) independently of age, total and HDL cholesterol, cigarette smoking, and alcohol consumption. Subjects taking part in prevention trials have higher triglyceride concentrations than the general population and the relation between serum triglyceride concentration and aggression merits further investigation.

Sex differences in susceptibility to etiologic factors for peripheral atherosclerosis. Importance of plasma fibrinogen and blood viscosity.

Cardiovascular risk factors in men, such as cigarette smoking, hypercholesterolemia, and hypertension, also increase risk in women, but the relative susceptibility to risk factors between the sexes is not established. Our aim was to investigate a wide range of possible etiologic factors in a single population study and identify those that were more strongly related to peripheral atherosclerosis in men or women. We studied personal factors (age and social class), lifestyle factors (smoking, exercise, alcohol intake, and dietary nutrients), and intermediary factors (obesity, diabetes, serum lipids, coagulation, and rheological factors). In the Edinburgh Artery Study in 1988 we measured cardiovascular risk factors in a random population sample of 1592 men and women aged 55 to 74 years. The ankle-brachial pressure index (ABPI), which is inversely related to the degree of peripheral atherosclerosis, was assessed in each subject. Lifetime cigarette smoking was correlated with a lower ABPI equally in men and women (r = -.27, P < .001). Dietary nutrients and alcohol intake were not related differently between the sexes with ABPI. However, recall of strenuous and moderate leisure time exercise during the age range of 35 to 45 years was related more strongly to a higher ABPI in men than in women (P < .05). Plasma fibrinogen, plasma viscosity, and blood viscosity were the only intermediary factors that had stronger univariate correlations with lower ABPI in men than in women. On multivariate analysis, the sex differences persisted for plasma fibrinogen (P < .05) and blood viscosity (P < .001); high-density lipoprotein cholesterol was related to ABPI in men only (sex difference, P < .1).(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial infarction risk in relation to zinc concentration in toenails

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

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.