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American Journal of Epidemiology Advance Access originally published online on October 10, 2007
American Journal of Epidemiology 2008 167(1):42-50; doi:10.1093/aje/kwm267
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American Journal of Epidemiology © The Author 2007. Published by the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

ORIGINAL CONTRIBUTIONS

Longitudinal Association of Serum Carotenoids and Tocopherols with Hostility

The CARDIA Study

Tetsuya Ohira1,2, Atsushi Hozawa1,3, Carlos Iribarren4, Martha L. Daviglus5, Karen A. Matthews6, Myron D. Gross7 and David R. Jacobs, Jr.1,8

1 Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN
2 Department of Social and Environmental Medicine, Osaka University, Osaka, Japan
3 Department of Health Science, Shiga University of Medical Science, Shiga, Japan
4 Division of Research, Kaiser Permanente, Oakland, CA
5 Department of Preventive Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL
6 Departments of Psychiatry, Epidemiology, and Psychology, University of Pittsburgh, Pittsburgh, PA
7 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN
8 Department of Nutrition, University of Oslo, Oslo, Norway

Correspondence to Dr. David R. Jacobs, Jr., Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South 2nd Street, Suite 300, Minneapolis, MN 55454-1015 (e-mail: Jacobs{at}epi.umn.edu).

Received for publication February 6, 2007. Accepted for publication August 21, 2007.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Hostility is a personality trait associated with increased risk of coronary heart disease. No study has reported the association between hostility and antioxidants, which may be mediators for atherosclerosis. CARDIA (Coronary Artery Risk Development in Young Adults) Study participants were 3,579 men and women 18–30 years of age in 1985–1986. Serum carotenoids and tocopherols were measured at years 0 and 7, and hostility was measured at years 0 and 5. Analysis of covariance was used to test for covariate-adjusted differences in serum carotenoids and tocopherols across quartiles of hostility. After adjustment for age, gender, race, serum lipids, and baseline of the dependent variable, the mean carotenoid values at year 7 of the lowest and highest quartiles of hostility score at year 0 were 3.9 and 3.3 µg/liter for alpha-carotene (p < 0.001), 9.1 and 8.0 µg/liter for beta-cryptoxanthin (p < 0.001), and 50.6 and 46.8 µg/liter for the sum of four carotenoids (p < 0.001). Hostility scores at year 0 were unrelated to year 7 lycopene and tocopherols. In contrast, neither year 0 carotenoids nor tocopherols predicted the hostility score at year 5. High hostility predicted future low levels of some serum carotenoids, which may help to explain the association of hostility and cardiovascular risk observed in other epidemiologic studies.

antioxidants; carotenoids; health behavior; hostility; longitudinal studies

Abbreviations: CARDIA, Coronary Artery Risk Development in Young Adults; GGT, gamma-glutamyltransferase


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 
Although clinical trials have been inconclusive, several prospective studies have reported inverse associations between antioxidants such as carotenoids, tocopherols, and ascorbic acid and cardiovascular diseases. In the Nurses' Health Study, higher intakes of foods rich in carotenoids (alpha-carotene or beta-carotene) were associated with a reduction in risk of coronary heart disease among 73,286 women (1). Higher plasma levels of carotenoids (alpha-carotene, beta-carotene, and lycopene) were inversely related to risk of ischemic stroke in the Physicians' Health Study (2). Furthermore, recent pooled analysis showed a weak but significant inverse relation between dietary antioxidant vitamins (tocopherols and ascorbic acid) and incidence of coronary heart disease (3). Steinberg et al. (4) presented a coherent theory linking the oxidation of low density lipoprotein particles and their uptake by macrophages with the pathogenesis of atherosclerosis.

Hostility is also associated with cardiovascular disease, for example, increased risk of hypertension (5), lipid metabolic disorder (6), progression of carotid intimal-medial thickness (7), and coronary heart disease incidence (8). The causes and mechanisms of these associations are independent of standard risk factors for coronary heart disease. Therefore, it is plausible that oxidative damage to cells and tissues may be an explanation for the association of a high hostility level with incidence of cardiovascular diseases. No study, however, has been conducted to examine the relation between hostility and serum levels of antioxidants.

We hypothesize that hostility level is associated with changes in several serum antioxidants (carotenoids and tocopherols), even after accounting for confounding with health behaviors that are associated with both hostility and antioxidants. The hypothesis is supported by previous reports that showed positive relations between hostility and lifestyles such as alcohol consumption and current smoking (9, 10) and between serum antioxidants and lifestyles such as diet and smoking (11). Our underlying assumption is that a hostile state is accompanied by oxidative stress, which results in lower levels of serum antioxidants. Because a recent prospective study showed that concentrations of serum carotenoids were inversely associated with incidence of diabetes in nonsmokers but not in current smokers (12), we specifically considered whether the associations of carotenoid concentrations with hostility were modified by smoking.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 References
 
Study population
The Cardiovascular Risk Development in Young Adults (CARDIA) Study is a longitudinal investigation of coronary heart disease risk factors in 5,115 men and women aged 18–30 years at study inception. Details of the study design, recruitment, and procedures have been published elsewhere (13). Participants were recruited between 1985 and 1986 at four US clinical sites: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California. Participants were reexamined at 2, 5, 7, 10, and 15 years postbaseline, with reexamination rates among surviving cohort members of 91 percent, 86 percent, 81 percent, 79 percent, and 74 percent, respectively. The CARDIA Study sample was approximately balanced by age (45 percent aged 18–24 years, 55 percent aged 25–30 years), race (52 percent Black, 48 percent White), sex (46 percent men, 54 percent women), and education (40 percent having completed ≤12 years of education, 60 percent having completed >12 years). The Young Adult Longitudinal Trends in Antioxidants (YALTA) Study is an ancillary study to the CARDIA Study, the sole activity of which is to do biochemical assays on CARDIA Study samples. The study protocol was approved by the institutional review boards at each site, and informed written consent was obtained from each participant.

Measurements
Information on demographic characteristics (age, gender, and race) and education was collected via self-report on standardized questionnaires at each examination. Hostility levels were measured by the Cook-Medley 50-item scale, with possible scores ranging from 0 to 50 (low to high) (14). This questionnaire was self-administered at baseline and again during the year 5 examination. On the basis of the response, we computed global hostility scores that ranged from 1 to 46 in this sample.

During the examination, height and weight were measured. Body mass index was calculated as weight (kg)/height (m)2. Standard questionnaires were used to maintain consistency in the assessment of demographic and behavioral information across CARDIA Study examination visits. Information on alcohol consumption and cigarette smoking was determined by structured interview or by self-administered questionnaire. Alcohol intake (ml/day) was computed from the self-reported frequency of beer, wine, and liquor consumed per week. The interviewer-administered CARDIA Study diet history asked open-ended questions about dietary consumption in the past month within 100 food groups; this information was obtained at years 0 and 7, referencing 1,609 separate food items (15). Habitual physical activity was measured by use of the CARDIA Study Physical Activity History, a simplified version of the Minnesota Leisure Time Physical Activity Questionnaire (16). Participants were asked about the frequency of participation in 13 different activity categories (eight vigorous and five moderate) of recreational sports, exercise, leisure, and occupational activities over the previous 12 months. Because participants were not asked explicitly about duration of activity, physical activity scores are expressed in exercise units. A score of 100 exercise units is roughly equivalent to participation in a vigorous activity for 2 or 3 hours/week for 6 months of the year.

Participants were asked to fast at least 12 hours and to avoid smoking and heavy physical activity for at least 2 hours before each examination. Blood was drawn from participants, and aliquots were stored at –70°C until shipped on dry ice to a central laboratory. Plasma lipids from years 0 and 7 were measured at the University of Washington Northwest Lipid Research Clinic Laboratory (Seattle, Washington). Total cholesterol and triglycerides were measured by enzymatic methods. High density lipoprotein cholesterol was assayed after dextran sulfate-magnesium precipitation, and low density lipoprotein cholesterol was estimated from the Friedewald equation (the latter was not estimable in 11 participants who had triglyceride levels greater than 400 mg/dl). Gamma-glutamyltransferase (GGT) was measured with a SMAC II continuous-flow analyzer (Technicon Instruments Corp., Tarrytown, New York) by American BioScience Laboratories (now GlaxoSmithKline, Brentford, United Kingdom) at year 0 and by Linco Research, Inc. (St. Charles, Missouri), at year 10. Year 0 values were recalibrated to the year 10 scale after reanalysis of a subset of year 0 samples by Linco Research, Inc. The correlation between GGT measurements made in year 0 and remeasurements of the same samples at year 10 was 0.995 (17). Because in our data GGT appears to be an important oxidative stress marker (17), we analyzed it using year 0 and 10 data.

Serum obtained at CARDIA Study years 0 and 7 was used 8 years postbaseline to assay alpha- and gamma-tocopherol and the carotenoids alpha- and beta-carotene, lycopene, zeaxanthin plus lutein, and beta-cryptoxanthin (Molecular Epidemiology and Biomarker Research Laboratory, University of Minnesota, Minneapolis, Minnesota). Although blood contains a wide variety of antioxidant compounds, we focused on carotenoids and tocopherols because of their relatively high concentrations and close association with diet. The tocopherols and carotenoids were measured by a high-performance liquid chromatography-based assay. The assay was a modification of the method of Bieri et al. (18) with calibration as described by Craft et al. (19) and sample handling as described by Gross et al. (20). The intraclass correlation coefficients (ratio of between-person variance to between- plus within-person variance) were 0.93 for alpha-carotene, 0.98 for beta-carotene, 0.73 for lutein/zeaxanthin, 0.97 for beta-cryptoxanthin, and 0.73 for lycopene (21).

Statistical analysis
We excluded participants with missing hostility data (n = 199) at baseline and participants missing either year 0 or year 7 serum carotenoids or tocopherols (n = 1,337); most of the latter did not attend the year 7 examination. The remaining 3,579 participants were included in the analyses. There were no differences in baseline body mass index, serum lipids, and antioxidants, except for gamma-tocopherol, between the participants who did and did not complete the follow-up examination. In addition, there were no differences in hostility scores at baseline and year 5 between the two groups, although the mean body mass index at year 7 was higher among the participants who did not complete the follow-up examination than among the participants who did.

Cross-sectional associations were studied between year 0 serum antioxidants and year 0 hostility. Longitudinal associations were then studied between year 7 serum antioxidants as dependent variables and year 0 hostility as an independent variable, as well as between year 5 hostility as a dependent variable and year 0 serum antioxidants as independent variables. The latter were included to determine antecedent and consequent relations between the variables of interest, as it is possible that the associations were bidirectional. Analysis of covariance was used to examine the association of the quartiles of hostility with cardiovascular risk factors, adjusted for age (years), gender, race, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides (mg/dl), as well as the baseline of the dependent variable in longitudinal analysis. Blood lipids were included in the minimally adjusted model following recommendations for lipid standardization of fat-soluble antioxidant concentrations (22). Further covariates in the fully adjusted model included alcohol consumption (ml/day), smoking status (never, former, current smokers), body mass index (kg/m2), educational level, and physical activity. p values for tests of linear trends were calculated by use of the median value of hostility or antioxidant variable quartiles. We repeated the analyses after stratifying by smoking status (never/former, current smokers), alcohol consumption (never/former, current drinkers), and supplement use (nonuser/user of alpha-tocopherol, beta-carotene, and vitamin A or C).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 References
 
Table 1 shows age-, gender-, and race-adjusted mean values or proportion of risk characteristics at baseline according to hostility scores. As previously shown, younger age, African-American race/ethnicity, male sex, and shorter duration of education were associated with higher hostility scores, as were higher body mass index, ethanol intake, total energy intake, and proportion of current smoking also (10, 11). Furthermore, the mean values of triglycerides, GGT, and meat intake were positively associated with hostility scores. Most carotenoids except lycopene were inversely associated with body mass index, smoking, ethanol intake, total energy intake, and meat intake and positively associated with physical activity, fish intake, vegetable intake, and fruit intake, whereas the associations of lycopene and tocopherols with lifestyle factors were inconsistent (table 2).


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  		TABLE 1. Age-, gender-, and race-adjusted cardiovascular risk characteristics at year 0 (1985–1986) according to hostility score at year 0, CARDIA* Study

 

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  		TABLE 2. Age-, gender-, race-, and serum lipid-adjusted correlation coefficients between lifestyle factors at year 0 (1985–1986) and serum carotenoids and tocopherols at year 0, CARDIA{dagger} Study

 
Age-, gender-, race-, and serum lipid-adjusted mean values of alpha- and beta-carotene, zeaxanthin/lutein, beta-cryptoxanthin, and their sum at year 0 were significantly inversely associated with hostility scores at year 0 (table 3), while year 0 lycopene and tocopherols were unrelated to hostility. The associations of carotenoids with hostility were attenuated after adjustment for covariates, but they remained statistically significant.


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  		TABLE 3. Adjusted mean values of carotenoids and tocopherols at year 0 (1985–1986) according to hostility score at year 0 (cross-sectional association), CARDIA* Study

 
The mean values of most carotenoids and tocopherols increased slightly from year 0 to year 7 (22): 2.7 and 3.7 µg/dl for alpha-carotene, 15.3 and 18.0 µg/dl for beta-carotene, 18.5 and 19.1 µg/dl for zeaxanthin/lutein, 8.4 and 8.4 µg/dl for beta-cryptoxanthin, 30.1 and 32.6 µg/dl for lycopene, 45.0 and 49.3 µg/dl for the sum of four carotenoids, 91.9 and 101.7 µg/dl for alpha-tocopherol, and 19.8 and 19.1 for gamma-tocopherol. There was a moderate to strong correlation between the values of years 0 and 7; the tracking correlation coefficients were 0.55 for alpha-carotene, 0.48 for beta-carotene, 0.62 for zeaxanthin/lutein, 0.51 for beta-cryptoxanthin, 0.47 for lycopene, 0.61 for the sum of four carotenoids, 0.55 for alpha-tocopherol, and 0.47 for gamma-tocopherol.

The mean value of hostility score decreased from year 0 (mean: 19.3) to year 5 (mean: 16.9), with tracking correlation between examinations = 0.65 (p < 0.0001). In age-, gender-, race-, serum lipid-, and baseline carotenoid- or tocopherol-adjusted longitudinal analyses (table 4), hostility scores at year 0 significantly inversely predicted alpha- and beta-carotene, zeaxanthin/lutein, beta-cryptoxanthin, and their sum at year 7. However, hostility scores were not associated with serum lycopene and tocopherols at year 7. In gender-race–specific analyses, the associations of hostility score with carotenoids were consistent in each gender-race group, except for the lack of associations of hostility with alpha-carotene in White men and the sum of four carotenoids in White women (data not shown).


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  		TABLE 4. Adjusted mean values of carotenoids and tocopherols at year 7 according to hostility score at year 0 (1985–1986) (longitudinal association), CARDIA* Study

 
Findings were attenuated by additional adjustment for body mass index, alcohol consumption, smoking, physical activity, and education, but statistical significance remained for alpha-carotene, beta-cryptoxanthin, and the sum of four carotenoids. Further adjustment for dietary factors (energy intake, meat intake, vegetable intake, fruit intake, and fish intake) and GGT did not alter these associations materially. The adjusted mean values within the lowest and highest quartiles of hostility score at year 0 were 3.8 and 3.5 µg/dl for alpha-carotene (ptrend = 0.04), 8.8 and 8.2 µg/dl for beta-cryptoxanthin (ptrend = 0.01), and 49.8 and 48.0 µg/dl for the sum of four carotenoids (ptrend = 0.07). Furthermore, in age-, gender-, race-, serum lipid-, and baseline carotenoid- or tocopherol-adjusted longitudinal analyses, the hostility score at year 5 significantly inversely predicted alpha- and beta-carotene, zeaxanthin/lutein, beta-cryptoxanthin, and their sum at year 7. The adjusted mean values within the lowest and highest quartiles of hostility score at year 5 were 3.9 and 3.4 µg/dl for alpha-carotene (ptrend = 0.001), 19.2 and 16.8 µg/dl for beta-carotene (ptrend = 0.003), 19.8 and 18.4 µg/dl for zeaxanthin/lutein (ptrend < 0.001), 9.2 and 7.8 µg/dl for beta-cryptoxanthin (ptrend < 0.001), and 51.9 and 46.7 µg/dl for the sum of four carotenoids (ptrend < 0.001). In contrast, after adjustment for baseline hostility score and covariates, neither carotenoids nor tocopherols at year 0 predicted the hostility score at year 5 (table 5). There were no significant associations between changes in hostility score from baseline to year 5 and changes in carotenoids from baseline to year 7 (data not shown). Hostility scores at year 0 did not predict serum GGT at year 10 (data not shown).


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  		TABLE 5. Adjusted mean values of hostility score at year 5 according to carotenoids and tocopherols at year 0 (1985–1986) (longitudinal association), CARDIA* Study

 
The associations of hostility score at year 0 with serum carotenoids and tocopherols at year 7 did not differ between current (n = 1,026) and never/former (n = 2,530) smokers (pinteraction > 0.15). Age-, gender-, race-, serum lipid-, and baseline value-adjusted mean values of the sum of four carotenoids for participants with the lowest and the highest quartiles of hostility were 39.8 versus 37.5 µg/dl in current smokers (ptrend = 0.046) and 54.5 versus 51.1 µg/dl in never/former smokers (ptrend = 0.03), respectively. In addition, we found no interaction with other potential effect modifiers: Values for pinteraction of the sum of four carotenoids were 0.36 for alcohol drinkers (n = 2,207) versus nondrinkers (n = 1,354), 0.27 for supplement users (n = 1,114) versus nonusers (n = 2,465), 0.39 for men versus women, and 0.74 for African Americans versus Whites. Age-, gender-, race-, serum lipid-, and baseline value-adjusted mean values of the sum of four carotenoids for participants with the lowest and the highest quartiles of hostility were 50.6 versus 46.4 µg/dl for alcohol drinkers (ptrend = 0.001) and 50.3 versus 47.5 µg/dl for nondrinkers (ptrend = 0.13), as well as 58.8 versus 54.9 µg/dl for supplement users (ptrend = 0.25) and 46.9 versus 43.3 µg/dl for nonusers (ptrend < 0.001), respectively.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
References
 
The main findings of the present longitudinal study were that Cook-Medley hostility scores at baseline were inversely associated with age, gender-, race-, serum lipid-, and baseline carotenoid- or tocopherol-adjusted values of serum alpha-carotene, beta-carotene, beta-cryptoxanthin, zeaxanthin/lutein, and the sum of four carotenoids at year 7, but not with lycopene, alpha-tocopherol, or gamma-tocopherol. Although the associations were attenuated after adjustment for lifestyle factors that are associated with an increased hostility score, associations with alpha-carotene, beta-cryptoxanthin, and the sum of four carotenoids remained statistically significant. An association of hostility with incidence of coronary heart disease is well established, but the mechanisms underlying this association remain unclear. Our findings are consistent with the hypothesis that hostility may be associated with incidence of coronary heart disease in part through an associated decrease in some serum carotenoids, likely as a reflection of oxidative stress.

Although several studies have reported the associations of hostility with cardiovascular risk factors such as hypertension (5), metabolic syndrome (23), fibrinogen (6), and platelet activity (24), no study to date has reported an association between hostility and serum carotenoids. Previous studies showed that psychological factors such as depression and job stress were inversely associated with serum carotenoids or other serum antioxidants (25, 26). Our results provide further evidence that inverse associations between hostility scores and serum carotenoids were observed in women and men, both cross-sectionally and longitudinally.

Potential pathways through which hostility might decrease serum carotenoids have not been fully elucidated. High-hostility individuals smoke more (10) and consume more alcohol (10) and animal fat (27) and less fish (28) than low-hostility individuals. Thus, health-related behaviors could be an important factor mediating the influence of hostility on serum carotenoids. As we expected, the significant associations of hostility with serum carotenoids 7 years later were reduced after adjustment for health-related behaviors, but they remained statistically significant. Further, in analyses stratified by smoking, alcohol consumption, and supplement use, the associations between hostility and serum carotenoids were observed in nonsmokers, nondrinkers, and nonusers of supplement. Therefore, health behaviors accounted for some but not all of the variance in the association between hostility and serum carotenoids in our data. On the other hand, we cannot fully rule out residual confounding.

Compared with low-hostility individuals, high-hostility individuals in prior studies tended to feel more psychological stress (29) and to have higher cardiovascular reactivity during mental stress (30). In a comparison of those under little psychological stress with those under psychological stress, a previous study (31) has found elevations of oxidative stress in those with psychological stress. Conceivably, high-hostile individuals might benefit from consumption of more antioxidant-rich foods to combat oxidative stress. Such a recommendation may not extend to antioxidant supplements, as supplementation with isolated compounds outside the food matrix has been shown in several clinical trials to have adverse effects (32). Moreover, high hostility could be associated with an elevation in inflammatory markers, such as fibrinogen and C-reactive protein (6, 33). Because inflammatory insults could lead to a reduction in serum carotenoids (34, 35), high hostility may decrease serum carotenoids via inflammatory changes in the body. In this study, the mean values of body mass index and serum GGT were positively associated with the hostility score at baseline. Because body mass index and serum GGT were inversely associated with serum carotenoids (17, 36) and positively associated with serum C-reactive protein (37, 38), these factors, in part, may affect the associations between hostility and serum carotenoids.

Lycopene, alpha-tocopherol, and gamma-tocopherol were not associated with hostility in the present study either cross-sectionally or longitudinally, although we have no clear explanation for these differences among serum antioxidant substances. Several health-related behaviors related to hostility were associated with serum alpha- and beta-carotene, beta-cryptoxanthin, and the sum of four carotenoids but not with lycopene and tocopherols, which might explain, in part, the different associations of hostility with the carotenoids and tocopherols. In this study, meat intake was significantly inversely associated with age-, gender-, race-, and serum lipid-adjusted serum alpha-carotene, beta-carotene, beta-cryptoxanthin, and the sum of four carotenoids but positively associated with gamma-tocopherol and lycopene. Further, alcohol intake was significantly inversely associated with age-, gender-, race-, and serum lipid-adjusted serum alpha-carotene, beta-carotene, beta-cryptoxanthin, and the sum of four carotenoids but positively associated with lycopene. Thus, the mean value of lycopene measured in this study may be a marker of other lifestyles, not of oxidative stress.

We caution that the differences in multivariate-adjusted mean values of year 7 carotenoids between the lowest quartile and the highest quartile of year 0 hostility scores were relatively small, even though significant. Therefore, it is not clear whether or not the differences are importantly related to the risk of coronary heart disease. However, the associations of hostility with the incidence of cardiovascular events are dose dependent (1), suggesting that the observed differences may be meaningful to public health. Another limitation of this study is that, since our study was of healthy young adults, we could not examine the association between hostility and the incidence of coronary heart disease. Therefore, it is not clear whether or not the hostility-associated decrease of serum carotenoids could predict future incidence of coronary heart disease. We analyzed the associations between baseline hostility scores and serum carotenoids at year 7 using a single assessment of covariates at baseline, which may lead to an underestimation of the effects of lifestyle factors, such as smoking and alcohol consumption as they change over time, on the associations. However, even when we reanalyzed the associations between baseline hostility scores and serum carotenoids at year 7 using the data of covariates at year 5 or year 7, the trends of the associations were essentially the same.

The strength of the present study was our study's inclusion of a relatively large number of both African Americans and Whites. Further, we repeated the assessments of hostility after 5 years and of serum carotenoids and tocopherols after 7 years, which allowed us to perform longitudinal analyses. Finally, our ability to test the associations of baseline hostility with subsequent serum carotenoids and of baseline carotenoids with subsequent hostility allows us to establish that the association was unidirectional in this sample.

In conclusion, the present study showed that the inverse associations of hostility with serum carotenoids, but not lycopene or tocopherols, also existed over a 7-year follow-up in the CARDIA Study, suggesting that low levels of some serum carotenoids, conceivably reflecting oxidative stress, may be on the causal pathway in the association of hostility and cardiovascular risk. Whether any adverse effect of hostility on cardiovascular outcomes is mediated through decreasing serum carotenoids warrants further investigation.


   ACKNOWLEDGMENTS
 
This study was supported in part by National Heart, Lung, and Blood Institute contracts N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095 (CARDIA Study), and 1RO1-HL53560 (YALTA Study). Dr. Tetsuya Ohira was also supported by the Research Fellowship Program of the Uehara Memorial Foundation (Tokyo, Japan).

Conflict of interest: none declared.


   References
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 References
 

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D. Janicki-Deverts, S. Cohen, K. A. Matthews, M. D. Gross, and D. R. Jacobs Jr
Socioeconomic Status, Antioxidant Micronutrients, and Correlates of Oxidative Damage: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Psychosom Med, June 1, 2009; 71(5): 541 - 548.
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