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3 Department of Veterans Affairs Medical Center, San Francisco, CA 94121; 4 Division of General Internal Medicine, University of California, San Francisco, CA 94143; 5 Emory University School of Medicine, Atlanta, GA 30322; and 6 Sanford School of Medicine, University of South Dakota, Sioux Falls, SD 50175
* To whom correspondence should be addressed. E-mail: beth.cohen{at}ucsf.edu.
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ABSTRACT |
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 TOP ABSTRACT IntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
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Introduction |
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TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
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Low levels of particular (n-3) fatty acids, polyunsaturated fats that cannot be produced endogenously and thus must be obtained from the diet, are associated with increased coronary heart disease (CHD) risk and mortality (4–9). Most of this evidence points to 2 (n-3) fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), as being particularly important (10,11). Although some studies have challenged the assertion that (n-3) fatty acids are cardioprotective (12,13), more recent analyses (14) and organizations such as the AHA continue to recommend their intake for CVD prevention (10). Individuals with low SES report lower dietary intake of (n-3) fatty acids (15), but some have suggested that reporting bias may be responsible for this association (16). Two prior studies have examined the association of SES with serum levels of (n-3) fatty acids (17,18). Yeh et al. (17) found that lower occupational grade was associated with low serum levels of (n-3) fatty acids in Nigerian civil servants, excluding EPA levels. In the only known study to have evaluated this association in patients with CHD, Erkkila et al. (18) found no association between SES (measured by education level) and most serum (n-3) fatty acids.
We assessed 4 different SES variables (household income, education level, occupation, and housing status) and measured RBC levels of DHA and EPA in a cross-sectional study of 987 adults with CHD. We hypothesized that lower SES would be associated with lower levels of (n-3) fatty acids after adjusting for medication use, demographic characteristics, and other clinical indicators.
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Materials and Methods |
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TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
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Between September 2000 and December 2002, a total of 1024 Bay Area residents with stable CHD enrolled. Participants completed a baseline study visit, which included a medical history, comprehensive health status questionnaire, physical examination, exercise treadmill test, and a fasting venous blood draw. Subjects for whom frozen blood samples were not available (n = 37) were excluded, resulting in a sample size of 987 for this analysis. The protocol was approved by the appropriate institutional review boards, including ethical approval from the Committee on Human Research at the University of California, San Francisco. All participants provided written, informed consent.
SES.
Self-reported data on 4 SES variables, including household income, education level, housing status, and occupation, were collected in a questionnaire at the baseline interview. Methods for measuring both household income and education level have been previously described (20). For the regression analysis, we divided participants into 3 income groupings: <$20,000, $20,000 to $50,000, and >$50,000. We divided all participants into 3 education categories: 
11 y of education, high school graduate (high school graduate, some college or vocational schooling), and 
college degree (college graduate, or graduate or professional degree).
Housing status responses included house, single room occupancy (SRO)/shelter, apartment/flat, and retirement community. For the regression analysis, "retirement community" was grouped with "apartment/flat." Occupation categories included labor, service, protective service, manufacturing/transportation, craftsmen/foreman, clerical/sales, manager/official/proprietor, professional/technical, and other. For the regression analysis, we excluded participants (n = 150) who reported "other" occupation and divided the remaining participants into 4 categories: skilled/unskilled labor (labor, craftsman/foreman, and manufacturing/transportation), services/sales (clerical/sales, service, and protective services), manager/official/proprietor, and professional/technical.
RBC DHA and EPA levels. DHA and EPA were measured in the membranes of RBC from fasting venous blood samples. Upon enrollment, study participants refrained from smoking for 5 h, did not take aspirin for 1 wk, and completed an overnight 12-h fast (except for prescribed medications taken with water). RBC levels of fatty acids are thought to represent dietary intake and may act as a marker of tissue incorporation in general (21). We analyzed RBC levels of DHA and EPA as both continuous variables and ordinal variables divided into tertiles.
The fatty acid composition of RBC membranes was assessed by capillary GC using a GC2010 (Shimadzu) equipped with a SP2560, 100-m column (Supelco) after generation of fatty acid methyl esters (FAME) by treatment with boron trifluoride-methanol (22). FAME were identified by comparison with a weighed standard mixture consisting of 22 fatty acids characteristic of RBC membranes (GLC-727, Nuchek Prep). RBC levels of EPA and DHA were presented as a percentage composition of total FAME. Two RBC control pools were included with each batch to monitor analytical performance. Acceptable runs were those in which both controls fell within 2.5 SD. The inter-assay CV for EPA+DHA as a percentage of total RBC fatty acids was 5–6%, whereas the intra-assay CV was 2–3%.
Other variables. Age, sex, marital status, ethnicity, medical history, and history of tobacco and alcohol use were collected by self-report on baseline questionnaires. To denote their ethnicity, participants selected from 5 options: Hispanic, Asian, White, Black, or Other. We measured height and weight and calculated BMI. Participants rated their physical activity during the previous month using a 6-point Likert scale. Those responding "not at all active" or "a little active" were classified as physically inactive. Participants were also instructed to bring their medication bottles to the study appointment and the research team personnel recorded all current medications, including the use of statins and aspirin. Creatinine clearance was measured from 24-h urine collections using a Synchron LX 20 (Beckman Coulter). Fasting serum total cholesterol, HDL-cholesterol, and triglyceride concentrations were measured by enzymatic assays (23) using a Synchron LX 20 (Beckman Coulter). Serum LDL-cholesterol was calculated using Friedewald's formula (24).
Statistical analysis. To describe the relevant differences in general characteristics of subjects by levels of income and education, we used ANOVA for continuous variables and chi-square tests for dichotomous variables. Values presented in the text are means ± SD. Unadjusted chi-square tests were used to calculate significance in Figure 1. All statistical tests were 2-sided and P < 0.05 was considered significant.
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Results |
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TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
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80%) were men. The age of the study participants was 67 ± 11 y. Compared with those in the higher levels of income or education, those with lower levels had lower (n-3) fatty acids (Table 1). Those with lower income or education were more likely to be Hispanic or black, to have a history of hypertension or diabetes mellitus, and to be physically inactive. Participants with lower income or education also had increased serum total cholesterol concentrations.
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Prior to adjustment for potential confounding factors, both combined levels of DHA and EPA and individual levels of DHA and EPA were significantly associated with all 4 measures of SES (Table 2). Following multivariable adjustment (for age, sex, ethnicity, smoking, marital status, regular alcohol use, BMI, physical activity, statin use, and creatinine clearance), household income (P < 0.001), education level (P < 0.001), and occupation (P 0.004) remained associated with individual and combined RBC levels of DHA and EPA (Table 3). Housing status was not independently associated with RBC levels of DHA (P = 0.78), EPA (P = 0.95), or their combination (P = 0.89) after adjustment for potential confounders.
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Discussion |
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TOPABSTRACTIntroductionMaterials and MethodsResultsDiscussionLITERATURE CITED |
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Prior studies examining the association between SES and (n-3) fatty acids have relied on self-reported dietary intake questionnaires to estimate (n-3) levels (15,16). Such questionnaires may not capture hidden dietary fats and are susceptible to reporting errors (16,27,28). Computer simulations or published correlation coefficients were often used to convert dietary data to fatty acid levels. One prior study reported an association between occupation and measured serum levels of fatty acids in Nigerian civil servants (17). Another study, the only one known to address this question in patients with established CHD who are at highest risk for cardiovascular events, reported no association between education and serum levels of EPA or DHA (18). However, >85% of surveyed CHD patients in this study had <12 y of education (in contrast to <15% in our study) and >60% had <9 y of education, potentially limiting the ability to capture the true benefits of higher education.
Because (n-3) fatty acids cannot be synthesized in the body de novo, they must be obtained through dietary sources. The best sources for DHA and EPA are oily, coldwater fish (such as salmon, sardines, mackerel, and albacore tuna) and fish oils (10), as well as nonhydrogenated vegetable oils. However, the quantity of (n-3) fatty acids present varies greatly, depending on fish size and species, season, geography, and preparation methods (29,30). Vegetable oils, especially canola or soybean, contain 7–10% 
-linolenic acid, a short-chain (n-3) fatty acid that can be converted to EPA and DHA in the body but with very limited efficiency (31). The extent to which the differences in RBC EPA and DHA levels in the present study were the result of differences in the intake of fish or fish oil supplements is not known, because these data were not collected. There is, however, a clear dose-response relationship between fish intake (21) or fish oil supplementation (32) and EPA and DHA levels. Because lower levels of (n-3) fatty acids are associated with increased CHD risk (6) and increased intake reduces this risk (14), it seems reasonable to hypothesize that increased fish oil intake could reduce risk for CHD in lower SES populations.
Previous epidemiological studies have found significant differences in the diets and nutrient intakes of different socioeconomic classes (18,33–37). Specifically, reduced fish consumption has been associated with lower education levels and less-skilled, lower-paying occupations (15,38). Several explanations have been suggested to explain such dietary disparities, including the increased cost of healthy foods (39) and decreased health knowledge in lower SES individuals (40). However, such explanations are not yet conclusive. It has also been suggested that poorer social support and limited availability of affordable healthy foods in socioeconomically disadvantaged neighborhoods negatively influence diet (41).
Our study results raise the possibility that (n-3) fatty acids may be an important mediating factor in the association between low SES and CVD. Although a Cochrane meta-analysis has challenged the view that (n-3) fatty acids reduce adverse cardiac outcomes (12,13), the review has been criticized due to the controversial inclusion of the DART-2 trial (42), the use of composite endpoints, the wide range of intakes included, and the questionable exclusion of many potential cohorts (43,44). Despite such challenges, major cardiac societies and national health agencies continue to endorse the intake of (n-3) fatty acid for CVD prevention and treatment. The AHA currently recommends all adults eat fish at least twice a week and that all patients with CAD take 1 g/d of DHA and EPA through dietary and/or supplemental sources (45). It is not clear what levels of RBC DHA+EPA would represent an increased risk for CVD, but prior studies may provide some guidance. In a nested case-control analysis among men followed for up to 17 y in the Physicians' Health Study, baseline levels of EPA+DHA were significantly lower in 94 men who had sudden cardiac death than in 184 controls matched for age and smoking status (median EPA+DHA 3.84% vs. 4.22%) (46). The median level of EPA+DHA in our participants with known CHD was 3.6%, which is even lower than the cases from the Physician's Health Study and consistent with the high risk of our study population.
Current dietary recommendations to increase (n-3) fatty acid intake, a modifiable risk factor, are especially relevant to our cohort of patients with diagnosed CHD. In comparison to the general public, CHD patients would likely have more encounters with the healthcare system and should be more knowledgeable about their health condition and the cardioprotective role of (n-3) fatty acids. Our results demonstrate that significant socioeconomic disparities in (n-3) fatty acid levels still exist in this high-risk population, suggesting even stronger disparities may be affecting the general population. Current cardiovascular prevention strategies need to more adequately address the socioeconomic barriers to (n-3) consumption, especially in patients with CHD. More effective methods should be devised to uniformly disseminate knowledge regarding the benefits of (n-3) fatty acids. The RBC (n-3) fatty acid level has been proposed as a new risk factor for CHD (47) and a growing body of literature has been exploring the value and cost-effectiveness of using supplements, fortified foods, or bioengineered plant foods to increase (n-3) consumption (48–50). These dietary alternatives may help address economic, geographic, social, and cultural barriers to consuming foods rich in (n-3) fatty acids.
Several limitations must be considered in interpreting our results. First, the lack of data on dietary intake or use of dietary supplements limited our ability to confirm that dietary intake was responsible for the low RBC DHA and EPA levels found in patients with low SES. However, given that (n-3) fatty acids must be obtained through dietary sources and cannot be synthesized de novo in humans, it follows that RBC (n-3) fatty acid levels should be an accurate reflection of dietary intake. Second, the cross-sectional nature of our study precludes any definitive conclusions of causality in the association between SES and RBC (n-3) fatty acids. In this study, reverse causality is unlikely given that it is less plausible that adult (n-3) fatty acid consumption could significantly affect SES. Third, the study participants were mostly urban men and are thus not completely reflective of the general population. Finally, we cannot eliminate the possibility of residual confounding by factors correlated with both SES and RBC (n-3) levels. Although many factors can affect SES, it is unlikely these same factors alter RBC (n-3) levels, which are primarily a function of diet.
In summary, we found that 3 indicators of low SES, household income, education level, and occupation, were strongly associated with low RBC levels of 2 (n-3) fatty acids, EPA and DHA, among patients with CHD. These observations provide evidence that (n-3) fatty acids may be an important mediating factor in the association between lower SES and CVD. Future prevention efforts to raise awareness about and increase the dietary intake of (n-3) fatty acids in patients with CHD may help reduce existing socioeconomic disparities.
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FOOTNOTES |
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2 Author disclosures: B. E. Cohen, S. K. Garg, S. Ali, W. S. Harris, and M. A. Whooley, no conflicts of interest.
7 These authors contributed equally to this article.
8 Abbreviations used: CAD, coronary artery disease; CHD, coronary heart disease; CVD, cardiovascular disease; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; FAME, fatty acid methyl esters; SES, socioeconomic status; SRO, single room occupancy.
Manuscript received 12 November 2007. Initial review completed 21 December 2007. Revision accepted 12 March 2008.
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