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CLINICAL RESEARCH STUDY

Total Antioxidant Capacity from Diet and Risk of Myocardial Infarction: A Prospective Cohort of Women
Susanne Rautiainen, MSc,a Emily B. Levitan, DrPh,b,c Nicola Orsini, PhD,a Agneta Åkesson, PhD,a Ralf Morgenstern, PhD,d Murray A. Mittleman, MD, DrPh,c Alicja Wolk, DrMedScia
Division of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; bDepartment of Epidemiology, University of Alabama at Birmingham; cCardiovascular Epidemiology Research Unit, Beth Israel Deaconess Medical Center, Boston, Mass; dDivision of Biochemical Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
a

ABSTRACT BACKGROUND: There are no previous studies investigating the effect of all dietary antioxidants in relation to myocardial infarction. The total antioxidant capacity of diet takes into account all antioxidants and synergistic effects between them. The aim of this study was to examine how total antioxidant capacity of diet and antioxidant-containing foods were associated with incident myocardial infarction among middleaged and elderly women. METHODS: In the population-based prospective Swedish Mammography Cohort of 49-83-year-old women, 32,561 were cardiovascular disease-free at baseline. Women completed a food-frequency questionnaire, and dietary total antioxidant capacity was calculated using oxygen radical absorbance capacity values. Information on myocardial infarction was identified from the Swedish Hospital Discharge and the Cause of Death registries. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazard models. RESULTS: During the follow-up (September 1997-December 2007), we identified 1114 incident cases of myocardial infarction (321,434 person-years). In multivariable-adjusted analysis, the HR for women comparing the highest quintile of dietary total antioxidant capacity to the lowest was 0.80 (95% CI, 0.67-0.97; P for trend 0.02). Servings of fruit and vegetables and whole grains were nonsignificantly inversely associated with myocardial infarction. CONCLUSIONS: These data suggest that dietary total antioxidant capacity, based on fruits, vegetables, coffee, and whole grains, is of importance in the prevention of myocardial infarction. © 2012 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2012) 125, 974-980 KEYWORDS: Antioxidants; Cohort; Myocardial infarction SEE RELATED EDITORIAL p. 947

Coronary heart disease is a major cause of death in women.1 High levels of reactive oxygen species and reactive nitrogen species have been implicated in the
Funding: The study was supported by the Swedish Research Council for Infrastructure and the Swedish Council for Working Life and Social Research. The funders have not played a role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript. Conflict of Interest: None. Authorship: All authors had access to the data and a role in writing the manuscript. Requests for reprints should be addressed to Susanne Rautiainen, MSc, Institute of Environmental Medicine, Karolinska Institutet, Box 210, Stockholm 171 77, Sweden. E-mail address: susanne.rautiainen@ki.se

initiation and progression of atherosclerosis,1-3 the underlying cause of coronary heart disease. Well-established coronary heart disease risk factors such as smoking4 and aging5 are associated with increased reactive oxygen species and reactive nitrogen species production, as are obesity,6 hypertension,7 and excessive alcohol consumption.8 Antioxidants are proposed to play a key role in mitigating the atherosclerotic process by scavenging reactive oxygen species and reactive nitrogen species.1 Accordingly, consumption of fruits and vegetables, major sources of antioxidants, have been inversely related to coronary heart disease.9 By contrast, the use of high-dose single-antioxidant supplements does not protect against

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The aim of the present in diet and the synergistic effects bedefined response categories. r was 0. the free-radical-remyocardial infarction. Because antioxidants in coffee and tea have tors. coffee.7 for individual naire served as the baseline in the present study. rangstudy was to examine how total tween them. coffee and tea).8. there were 31 items (including 17 to imply informed consent to participate in the study. vegetables. The from the population-based.Rautiainen et al Antioxidant Capacity and Myocardial Infarction 975 coronary heart disease and may even increase mortality.” Open-ended ● A diet high in total antioxidant capacantioxidant-containing foods were questions were used for foods and ity. 69)16 and diabetes (self-reported or recorded in the Swedish high-dose single-antioxidant supplements are not a good Hospital Discharge Registry) because these diagnoses may substitute for the very complex antioxidant network of lead to change in dietary habits. We excluded women having history of cancer (except nonand for dietary fiber. however. fruit and vegetable items. and use of some medicawas 0. no previous study has Other Exposures nary heart disease. The remaining cohort of thousands of compounds in foods.4 to 0. Because more information on potential risk factors for pacity of diet. fruit and vegetable items) with available ORAC values.5 (Wolk A. they consumed each present in foods and the synergis● Total antioxidant capacity measures in type of food or beverage during tic effects between these suba single value all antioxidants present the last year.984 women (70%). We also excluded women with cardiovascular Body mass index was calculated by dividing reported diseases (identified through the Swedish Hospital Discharge Registry.17 Briefly. a new questionnaire was sent in 1997 to all 56. for fruit and vegetanaire. code I11. melanoma skin cancer) and women reporting extreme total The total antioxidant capacity from diet was adjusted for energy intake ( 3 SD from the mean value for loge-transtotal energy intake using the residual method.030 absorption (6% for coffee and 4% for tea)21 when calculateligible cohort members. we calculated estimates of total antioxidant capacity from diet METHODS using a database of the most common foods in the United States analyzed with the oxygen radical absorbance capacity Ethics Statement (ORAC) assay.561 women was followed from September 1997 through tions far below those used in December 2007. There were 8 prestances. and resynergism between compounds. Self-reported weight .18-20 ORAC measures the antioxidant capacThe Regional Ethical Review Board at Karolinska Institutet ity of diet to reduce free radicals. for example. The expanded 1997 questionnaire ing total antioxidant capacity of diet. we took into account data. r ranged from 0. no study frequency Questionnairehas investigated the overall effect ● Dietary antioxidants are hypothesized based Total Antioxidant of the complex antioxidant netto protect against coronary heart disCapacity Estimates and work in diet in relation to coroease. unpublished data). showed myocardial infarction was collected in the 1997 questionreasonable good validity. weight (kg) by reported height (m2). based on fruits. this questionble consumption. history of diseases.22 formed energy).0. r was 0. Switzerland] born 1914-1948 were sent a questionnaire concerning diet. detail elsewhere. most randomized controlled trials. I50. was associated with (eg. I20-25. weight and height. in one all antioxidants present in the diet and food-frequency questionnaire on single value. and polyThe Swedish Mammography Cohort was established beunsaturated fatty acids) were calculated by multiplying the tween 1987 and 1990 among women residing in the Uppsala average frequency of consumption of each food by ORAC and Västmanland counties in central Sweden. as compared with food records. To expand exposure been shown to be poorly absorbed. which they were asked how often. and reproductive facportion sizes. present at concentra32. The correlation beincluded questions on diet and questions on all major lifetween total antioxidant capacity of diet and plasma ORAC style factors. equivalents (TE)/100 g) or nutrient content of age-specific educational level. Total antioxidant capacity of diet and nutrient intakes (satStudy Population urated fatty acids. All women ( mol Trolox [Hoffman-LaRoche. 10th Revision (ICD-10). taking into account the (Stockholm. ducing capacity of all antioxidants on average. calculation of total antioxidant caspective Swedish Mammography pacity estimates is described in Cohort. Food items contributing to total antioxidant cations. ing from “never/seldom” to “3 or antioxidant capacity of diet and more times per day. The total antiinvestigated the association between Women completed a 96-item oxidant capacity measures. In the 96-item food-freturn of the self-administrated questionnaire was considered quency questionnaire. and I6010-15 as shown by randomized controlled trials. Basel. prolower myocardial infarction incidence. for tea consumption. associated with incident myocarbeverages commonly consumed dial infarction among women and whole grains. Sweden) approved this investigation. International Statistical Classification of Disease.31. Thus. Assessment of FoodCLINICAL SIGNIFICANCE To our knowledge. completed by 38. 74% completed the questionnaire. bread. monounsaturated fatty acids.

24 Identification of Myocardial Infarction and Follow-up of the Cohort All women were followed from September 1997 (baseline) through December 2007. monounsaturated fatty acids. had higher consumption of fruit and vegetables (3-fold). and dietary supplement use (multivitamin use. Regarding dietary characteristics. past. Other contributors were whole grains (18%). which are considered nearly complete. hormone replacement therapy use (yes/no). women in the highest quintile of total antioxidant capacity of diet. Women with higher total antioxidant capacity of diet were more likely to be nonsmokers. 10-12. continuous). and results did not substantially change (HR for women in the top quintile was 0. 25-29. P-values . servings/day) to the model. educational level ( 10. no supplements use).434 personyears). housework. 30 kg/m2). we used the median value of each category to create a single continuous variable. and polyunsaturated fatty acids (all .5-24. Vol 125. women in the highest quintile of total antioxidant capacity of diet. Baseline characteristics of the women are presented in Table 1. 12 years). have 12 years of education.976 The American Journal of Medicine.7 years).23 Physical activity levels were estimated by multiplying the reported duration of 5 predefined activities (occupation. whichever came first. we identified 1114 cases of incident myocardial infarction (the average age of first myocardial infarction was 75. and multivitamin supplement use (non-supplement users/multivitamin users). compared with the lowest quintile. we evaluated whether the apparent inverse association with total antioxidant capacity of diet can be explained by consumption of fruit and vegetables by adding this variable (continuous. 18. A P-value for the linearity assumption between total antioxidant capacity and myocardial infarction was obtained by testing whether the quadratic term was equal to zero.05 were considered statistically significant. with 95% confidence intervals (CI)26 using the PHREG command in SAS (version 9.2. and to have hypercholesterolemia. walking or cycling. current [ 10. energy intake (calories/day. and height is highly correlated with measured values in Swedish women (r 0. and coffee consumption. Women were categorized into 4 categories of fruit and vegetable consumption. 95% CI. Inc. Cases of nonfatal and fatal myocardial infarction (I21) were ascertained through linkage via the national registration number to the Swedish Hospital Discharge Registry and the Cause of Death Registry. NC).81.02). Cary.9. P-values . respectively). we performed subgroup analyses by age ( 65 years/ 65 years). we further adjusted for fruit and vegetable consumption (gram/day. and polyunsaturated fatty acids (all continuous. whole grains (15%). Missing data on a covariate was treated as a separate category. gram/day). To assess trends across quintiles.02) lower risk of myocardial infarction. 0. 2007). When adjusting for intakes of saturated fatty acids. aspirin use (yes/ no).55. use of other supplements than multivitamin. hypercholesterolemia (yes/no). as compared with the lowest quintile. 3%33%. death. leisure-time exercise.. We also corrected the HR of myocardial infarction per 4000 mol/TE/day increment of ORAC (corresponding to approximately 1 standard deviation [SD] in the cohort) for bias due to dietary measurement error with the regression calibration method correcting for both random and systematic error. coffee (34%). In additional analyses. had a 20% (95% CI. SAS Institute. or the end of follow-up (December 31. as well as quintiles of total antioxidant capacity of diet. 10 cigarettes/day]). Cox proportional hazards models with age as the time-scale were used to estimate hazard ratios (HR).0. All P values shown are 2-sided.9 years of follow-up (321. including body mass index ( 18. The Pearson correlation coefficient between dietary total antioxidant capacity and fruit and vegetable consumption was 0.17 we used the validity coefficient between total antioxidant capacity from diet and plasma (r 0. The proportional hazards assumption was assessed by calculating During the average 9. family history of myocardial infarction (yes/no). body mass index ( 25/ 25). and inactive leisure time) by the intensity of these activities and expressed as multiples of the metabolic equivalent per day (kcal kg 1 h 1) of sitting quietly for 1 hour. and chocolate (38%). The registries for 1987 and 1995 were thoroughly validated and revealed high sensitivity (94%) and positive predictive value (86%) for myocardial infarction. smoking (never. coffee (14%).25 RESULTS Statistical Analysis All women were followed until the date of myocardial infarction. In sensitivity analyses. smoking (nonsmokers/current smokers). and we did not find evidence of violation of this assumption. hypertension (yes/no). October 2012 scaled Schoenfeld residuals. P for trend . as well as 27% lower intake of saturated fatty acids and 19% lower intake of monounsaturated fatty acids.6). and chocolate (4%).64-1.05 were considered statistically significant. alcohol consumption (gram/day.9.3). continuous) as well as intakes of saturated fatty acids. In the multivariable-adjusted model. continuous). The association between total antioxidant capacity of diet and incident myocardial infarction is presented in Table 2. To evaluate whether the effect of total antioxidant capacity from diet varied by risk factors for myocardial infarction. All HRs were adjusted for potential risk factors. whole grain consumption. monounsaturated fatty acids. All P values shown are 2-sided. No 10. The validity of the reported total physical activity against activity records in these women were satisfactory (r 0.5. physical activity (metabolic equivalent-hours in quartiles). The major contributors to dietary total antioxidant capacity were fruit and vegetables (44%).27 Based on a validation study of 108 women from the Swedish Mammography Cohort.9 and r 1. The likelihood ratio test was used to perform interaction tests.

87).8 3. To investigate whether the observed association could be due to reversed causality.16).0 1746 (499) 5. We found no significant evidence of departure from a constant change in the rate of myocardial infarction associated with every unit increase in total antioxidant capacity (P for nonlinearity .1 (1.1) 2.98).9 58. smoking.7 (7.58-0.99). 0.9 (3.1 57.94). mean (SD) 12 years of education.5 (5.3 4.5) 15.0 (8.779 61.0) (1.4 12.Rautiainen et al Table 1 Antioxidant Capacity and Myocardial Infarction 32.1 (1. 95% CI.4 24.76. 0. gram/day Monounsaturated fatty acids.2) 19. % Total energy.1) (0.6 5.8) 42.3) 17.1) (1.6 1.0) (1.4 62.71 (95% CI. women with body mass index 25 (HR 0.9 (2.5 1.3 (3.1 12. 0.0) (1.6 (4.2 26.88-1. ORAC oxygen radical capacity absorbance.1) 8. and current smokers (HR 0. 0.8 3.0) 8.5 1.81 (95% CI.78.0) (8. we examined whether the inverse association between dietary total antioxidant capacity and myocardial infarction varied by potential risk factors such as age.8 (1. servings/day Tea.0 28. gram/day (SD) Foods.6 43.502 61.2 4.9 (1.8) SD standard deviation.9 59.9 8.8) (1. as cardiovascular risk factors may be associated with changes in dietary habits.561)* 977 Age-standardized Background Characteristics of Women in the Swedish Mammography Cohort (n Quintiles of Total Antioxidant Capacity of Diet† Characteristics Median total antioxidant capacity of diet Non-dietary factors Age. servings/week Chocolate.00).0) (2.3 1738 (516) 5.4 (8.7) 42.7 25. mean (SD) Fruits and vegetables. gram/day).1 (3. % Supplement users.5 58.7 3. gram/day Q1 (n 8537 6512) Q2 (n 6512) Q3 (n 6512) Q4 (n 6512) Q5 (n 6513) 10. The association was similar for nonfatal myocardial infarction (HR 0.48-1. In subgroup analysis.0 (5. This sensitivity analysis did not indicate influence of reversed causality on the observed estimate. % Current and past users of hormone replacement therapy.8 (3.1 44.4) (2. An increment of 4000 ORAC units is equivalent to approximately 1-2 apples or 2 peppers. The association was somewhat stronger among women aged 65 years (HR 0.4 20.3 2.9) 31.0 5. The multivariable-adjusted HR of myocardial infarction for an increment of 4000 ORAC units/day (corresponding to approximately 1 SD in the study population) was 0. 0.8) 4.8 3. % Current smokers.5 41. However.5 4.0 3.8) 42.68-0.94).9 1749 (510) 5.95) and fatal myocardial infarction (HR 0.0 25. servings/day Whole grains. % Hypercholesterolemia.20). 95% CI.9) 8.9) 25.021 60.3 (12.8) 27. we observed a HR of 0.495 60.9 41.4 (9.0 (9.7 1770 (585) 5.8) 61. DISCUSSION In this large prospective population-based cohort study.1 25.1) 42.6 43.0) 19.1) 6. servings/week Nutrients.1 0.2 (5.8 (10. 0.4) 20.9 (7.7) (2.7) 43. 95% CI.25).6 (3.3 61.4 56.6) 21. comparing the highest quintile with the lowest.0 0.2 (2.3 60.5 (9.8) 21. saturated fatty acid intake.4 6.6 (4.7) 18.0 (1.5) (2.65-0. mean (SD) Total physical activity score.94 (95% CI. % Body mass index.2 (1.7 (3.8) (7.4 (4.1) 8.2) 14.58-0.8 (5. there were no statistically significant interactions observed between dietary total antioxidant capacity and the above risk factors (all P for interaction .6) (8. we excluded cases that occurred in the first 3 years of follow-up.4 3.59-0.1 7.1 61.7 21. 95% CI. and multivitamin supplement use. gram/day Polyunsaturated fatty acids.76.4) (8.0 (1. kcal/day (SD) Alcohol.0) (1.9 3.7) 4. *All variables except age are standardized to the age distribution of the cohort.2) 3. % Family history of myocardial infarction.0 6.1 1720 (490) 5. 0.9) (2.5) 7. the corrected HR (taking into account measurement error in the dietary total antioxidant capacity estimates) was 0.66. % Aspirin use.9 (3.0) 18. 95% CI.9) 20.7) (7.1 (1.1) (1.4 25.3 20.0) (2.79. we observed that higher total antioxidant capacity of diet was statistically significantly associated with lower risk of inci- .1) 29. Linear and quadratic relationships between total antioxidant capacity and myocardial infarction are presented in Figure.2 24. 0. women in the highest as compared with the lowest quintile had HR 0.0 (3.1) 12. continuous.4 13.3) (1. body mass index.0 (5.8 3. kcal kg 1 h 1) of sitting quietly for 1 hour.5) 18. † mol Trolox equivalents per day.8) 23.6) 17.‡ mean (SD) Hypertension.7) 18.1 (4.4 60.1 23.4 (6.6 (3.0 (4.7) 18.46-0.7) 23.7 7. mean (SD) Saturated fatty acids.74.4 3. as assessed with oxygen radical absorbance capacity assay.8 (8.7) 20. ‡Expressed as multiples of the metabolic equivalent per day (MET. servings/day Coffee.

33 Previous randomized controlled trials testing high doses of antioxidant supplements containing 1 to 3 compounds have failed to see any benefit on coronary heart disease.88 (0.75 (0. Moreover.03) 4.74-1.067 0. To our knowledge.75 (0.74-1. in a meta-analysis of high doses and very high doses of single supplements of vitamin A.08) 0.00 1. flavonoids also may inhibit the atherosclerotic process through other pathways.534 0.68-0.34 Notably. 100 g selenium.05) 0.502 203 64.87 (0.022 0. smoking.00 3 224 57.72-1.553 0.7 273 81. and intakes of total energy and alcohol.13) 2 408 113.00 2.62-0.85 (0.80 (0.00 1.72-1.79-1.225 1.87 (0. October 2012 Table 2 Antioxidant-containing Foods* and Total Antioxidant Capacity of Diet† in Relation to Risk of Myocardial Infarction among 32. 6 mg beta carotene.121 0.3-3.97) 0. servings/day No.561 Women Categories Fruit and vegetables.29.82 (0. servings/day No.81-1.779 231 64.73-1.63-0.97) .7 283 78.90 (0.48) 0.89 (0.06) 0.79-1.05 . and to have antiplatelet and anti-inflammatory effects.32 The pathogenesis of atherosclerosis involves oxidation of low-density lipoproteins caused by reactive oxygen species.05) 4 227 65. of cases Person-years Age-adjusted HR Multivariable HR‡ Coffee.88 (0.88) 0.769 0.01) 0.76 (0.95) 5 419 155.021 191 64.69-1.09 .10-15 One randomized controlled trial that studied the effect of a low-dose mixture of 5 antioxidant supplements (including 120 mg ascorbic acid. hypercholesterolemia. hypertension. Flavonoids have been shown to improve endothelial function.978 The American Journal of Medicine.75-1.269 1.99) P for Trend .495 201 64.3 298 83.13 (0.259 1. In particular. No 10.07) 4 179 56.00 1 8537 288 63.9 Whole grains (18% of total antioxidant capacity) also are suggested to lower coronary heart disease risk.90) 0.1 Antioxidants found in diet are thought to protect against coronary heart disease by scavenging reactive oxygen species.04) 2-4 455 133. and 20 mg zinc) did not observe any association with ischemic cardiovascular diseases.00 0 72 18.890 0.68-1.67-0. this is the first study investigating dietary total antioxidant capacity in relation to myocardial infarction.63-0.83 5 18. 30 mg vitamin E.00 1.28 Several foods that are major contributors to antioxidant intake in our study population have been linked to a decreased risk of coronary heart disease. which contributed 44% of the dietary total antioxidant capacity in our study. dent myocardial infarction in a dose-response manner. as shown by a meta-analysis of randomized controlled trials.366 0.89) 0.12) 2 10. high intake of fruit and vegetables. quintiles Median ORAC.385 0.93 (0.66-0. higher allcause mortality was reported.80 (0.74-1.91) 0.71-1.032 1.35 In contrast to supplements . of cases Person-years Age-adjusted HR Multivariable HR‡ Total antioxidant capacity of diet*. The single total antioxidant capacity estimate is assumed to give a better measure of all antioxidants than sum of individual antioxidants.95 (0.69-0. because it also reflects the synergism between the compounds. of cases Person-years Age-adjusted HR Multivariable HR‡ 2 244 44.69-0. we have previously observed in our study population that total antioxidant capacity of diet was inversely associated with incidence of total stroke. mol Trolox equivalents/day No.88 (0. Consumption of antioxidant-containing foods such as fruits and vegetables and whole grains were nonsignificantly inversely associated with the risk of myocardial infarction.68-1.73-1.26) 4 14.592 0.31 Chocolate consumption (4% of total antioxidant capacity) has been shown to have fa- vorable effects on cardiovascular risk biomarkers such as flow-mediated dilation and diastolic blood pressure.95 (0. Vol 125.257 1. *Foods contributing 10% of total antioxidant capacity of diet.995 0. physical activity.401 0. servings/day No.18 .12) 0.4-4.88 (0. hormone replacement therapy use.64-0.4 260 77. of cases Person-years Age-adjusted HR Multivariable HR‡ Whole grains.001 . body mass index.30 Coffee consumption (14% of total antioxidant capacity) has been inversely related to coronary heart disease in some but not in all studies.19) 0. education.15) 2. family history of myocardial infarction. ‡Adjusted for age.86-1. dietary supplement use. or vitamin E tested in several randomized controlled trials.76-1.1 In addition to antioxidant effects.81 (0.02 Hazard ratios (HR) with 95% confidence intervals were obtained from Cox proportional hazards models.00 1.13) 3 12.95) 0.74 (0.86 (0. to decrease blood pressure.96 (0. have been inversely related to coronary heart disease in many studies.008 .90 (0. † mol Trolox equivalents per day. aspirin use. -carotene.83 (0.95 (0.001 .14) 3.

we cannot rule out residual confounding by healthy lifestyle factors. 7. 6. Pharm Res. the results remained statistically significant. JAMA. aspirin use. J Nutr. Lee IM. education. and intakes of total energy and alcohol. coffee. 2000.90 Hazard Ratio 0. . 11. 1996. Hercberg S. after this adjustment the association between total antioxidant capacity of diet and myocardial infarction remained statistically significant. detailed data on diet and potential risk factors. 2. while the majority of the randomized controlled trials were performed among participants with established atherosclerosis who may not benefit from antioxidant supplementation. Touyz RM. our results can only be translated to food items and not to antioxidant supplements. including thousands of compounds. 9. smoking. Thomson MJ. Atherosclerosis and oxidant stress: the end of the road for antioxidant vitamin treatment? Cardiovasc Drugs Ther. however. Kaski JC. Lakatta EG. hypercholesterolemia. Puntmann V. absorption. 2008. Antioxidant content may vary with geographic location and growing conditions. Das SK. and metabolic consequences. The distribution of total antioxidant capacity is presented at the bottom of the figure as a histogram. Halliwell B. Vasudevan DM. Our study has several strengths. and whole grains. When adjusting for several potential confounders such as smoking. some potential limitations with our study. all of them in doses present in our usual diet. Measurement error in self-reported dietary intake may lead to misclassification of exposure. 2008. et al. J Am Coll Cardiol. Sesso HD. 2007. Murphy-Ullrich J. Mozaffarian D. 2006. adipocyte dysfunction. which does not include antioxidant capacity of endogenous antioxidants. et al. we observed a somewhat weak correlation between total antioxidant capacity from diet and plasma. The major contributors to dietary total antioxidant capacity were fruits. In our validation study. homeostatic control mechanisms of plasma antioxidants.13(5):649-662. and the extent of the metabolism of dietary antioxidants. Cell signaling by reactive nitrogen and oxygen species in atherosclerosis.70 0. 3. There are. Wang M. Barua RS. 2004. The perfect storm: obesity. hypertension. Clin Chem. et al. The observed association could be explained by consumption of fruit and vegetables. Patel RP. Solid curve represents point estimates of the linear trend. Inflammation and endothelial dysfunction during aging: role of NF-kappaB. Free Radic Biol Med. Moreover.105(4):1333-1341.54(6): 945-955. Ambrose JA. Cook NR.28(12):1780-1794. JAMA. our data suggest that a diet high in total antioxidant capacity is associated with lower risk of incident myocardial infarction. the misclassification is most likely to References 1. Because of the prospective design.43(10): 1731-1737. Ungvari Z. physical activity. the dietary total antioxidant capacity reflects all present antioxidants. family history of myocardial infarction.80 0. and the practically complete follow-up of the study cohort. including the prospective population-based design. Dauchet L. and the vascular system. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. an even stronger association was observed. we used American ORAC values. Alcohol-induced oxidative stress. 10. Intervention studies would be needed to definitively determine the health effects of total antioxidant capacity. We only estimated total antioxidant capacity of diet. Darley-Usmar V.44(3):248-252. Amouyel P.136(10):2588-2593. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women’s Health Study: a randomized controlled trial. Reactive oxygen species. and even takes into account their synergistic effects. µmol Trolox equivalents per day Figure Multivariable-adjusted hazard ratios for incident myocardial infarction according to dietary total antioxidant capacity. de Ferranti S. Csiszar A. The pathophysiology of cigarette smoking and cardiovascular disease: an update. 2005.294(1):56-65.Rautiainen et al Antioxidant Capacity and Myocardial Infarction 979 1. Fruit and vegetable consumption and risk of coronary heart disease: a meta-analysis of cohort studies. Gaziano JM. vascular oxidative stress. the observed inverse association could be due to a phenomenon in which women who eat an antioxidant-rich diet are more health conscious and have other healthy behaviors. based on the oxygen radical absorbance capacity assay ( mol Trolox equivalents). Life Sci. 2007. therefore. Blood radicals: reactive nitrogen species.00 0. thus. We did not have ORAC values for dietary supplements. of single antioxidants. this study included women who were healthy at study entry. vegetables. The total antioxidant capacity has not been measured for Swedish foods. Dotted line represents point estimates of the quadratic trend. Dashed lines represent 95% confidence intervals for the linear trend. 5.81(3):177-187. Christen WG. hormone replacement therapy use. and educational level. 4. be nondifferential and therefore lead to attenuation of the observed association. Dallongeville J. when we corrected for measurement error. 2008. however.21(3):195-210. Furthermore. 8. be generalized to men. dietary supplement use. such as endogenous antioxidants.300(18):2123-2133. Buring JE. body mass index. transition metal ions. and redox signaling in hypertension: what is the clinical significance? Hypertension. reactive oxygen species.17 which can be partly explained by the fact that plasma total antioxidant capacity values are influenced by many factors. however. Hazard ratios were adjusted for age. Moreover.60 5000 10000 15000 20000 25000 Total Antioxidant Capacity. In conclusion.36 The study was performed among women and cannot. Moellering D. 2004. J Appl Physiol. physical activity.

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