The present findings suggest that SES during early/middle adulthood may be an important correlate of change in circulating CRP over the course of the following thirteen years. Specifically, among the individuals studied here, more education and higher household income each were associated with a smaller 13-year increase in CRP independent of demographics, medical diagnoses, medication use, OC/HRT use (women), and baseline CRP. These findings replicate and extend those of the only known study to date to report a prospective association between SES and circulating CRP (Gimeno et al., 2007
). Importantly, our data show that the apparent protective effects of higher SES on future CRP levels are reliable across SES indicators. Our results also show that the prospective association between SES and CRP observed in Whitehall II (Gimeno et al., 2007
) extends to a North American sample that is substantially younger (mean age 32 years vs. 50 years at baseline) and more equally distributed in terms of sex (54% vs. 28% female) and race (42% vs. 11% non-white). That we detected a prospective association between SES and CRP in a relatively young sample is striking, as much of what is known about SES and inflammation has been derived from samples of middle-aged and older adults (Friedman and Herd, 2010
; Gimeno et al., 2007
; Kershaw et al., 2010
; Nazmi and Victoria, 2007
Our examination of sex and race differences suggested that, in general, the associations of higher education and household income with less CRP did not differ between men and women or between blacks and whites. We did, however, detect a marginal effect of race on the association of education with CRP, such that education was protective for whites but not blacks, especially black men (data not shown). This finding is consistent with a report from an earlier cross-sectional analysis of CARDIA data (Gruenewald et al., 2009
), wherein Year 20 education was inversely associated with Year 20 CRP among white men and both black and white women but not among black men.
In addition to determining whether education and household income are related to future circulating CRP levels, our second aim was to investigate the relative importance of four health-related behaviors in explaining that association. Of the behaviors we examined, smoking status explained the largest proportion of variance in CRP attributable to either education or income. However, FV intake and in the case of household income, self-reported physical activity accounted for sizable proportions of variance in CRP attributable to SES as well. That smoking and FV intake made the largest contributions to the association of SES with CRP is consistent with the longitudinal findings of (Gimeno et al., 2007
), wherein smoking and poor diet contributed more to the association of employment grade with CRP than either exercise or alcohol consumption. (Kershaw et al., 2010
), as well, found smoking to account for the largest proportion of the variance in CRP attributable to education and poverty, respectively. However, exercise appeared to play a larger role than diet.
One common pathway through which smoking, FV intake, and physical activity are thought to influence circulating CRP concentrations involves their respective influences on more upstream mediators of inflammation. Smoking, for example, has been shown to promote inflammation in the lung by inducing fibroblast production of cyclooxygenase-2 and prostaglandin E2
synthase, two important early mediators of the inflammatory response (Martey et al., 2004
Whereas the pro-
inflammatory effects of smoking are thought to result from direct cellular insult, the anti-
inflammatory effects of regular FV intake and physical activity are thought to influence inflammation via an effect on intervening processes. Given the contribution of excess adipose tissue in creating a pro-inflammatory state (Mohamed-Ali et al., 1998
), weight control likely is an important pathway through which physical activity and healthy eating exert their anti-inflammatory effects (Hamer, 2007
). We found support for this explanation by showing that central weight gain—operationalized by increasing waist circumference over the follow-up, reduced the variance in CRP attributable to each of these health behaviors by approximately 50%. Yet, despite this reduction in explained variance, FV intake and physical activity continued to predict CRP independent of Year 7 weight status (BMI and waist circumference) and central weight gain, thus suggesting that these two health behaviors also may influence inflammation via mechanisms other than reduced body weight. For example, antioxidant nutrients present in fruits and vegetables are thought to have an attenuating effect on inflammation by scavenging reactive oxygen species and suppressing the NF-κB signaling pathway (Rahman et al., 2006
). One mechanism that has been suggested to explain the apparent anti-inflammatory effects of physical activity involves toll-like receptors (TLRs), which play an important role in modulating systemic inflammation. Specifically, individuals who engage in regular moderate exercise have been found to show decreased monocyte cell-surface expression of TLR4 (Gleeson et al., 2006
Alcohol consumption was unrelated to CRP when examined in multivariable analyses. However, ours is not the first study to report a lack of a mediating effect of alcohol consumption in the association of SES with CRP (Gimeno et al., 2007
; Kershaw et al., 2010
). Although the anti-inflammatory benefits of moderate drinking is a reliable finding (Imof et al., 2004
; Volpato et al., 2004
), the threshold at which alcohol consumption becomes detrimental in regard to levels of circulating inflammatory markers has yet to be determined (O’Connor and Irwin, 2010
). Thus, the apparent lack of a role for alcohol consumption in explaining the association of SES with CRP may be due to inaccurate modeling of an elusive effect rather than there being no effect at all.
Though statistically significant, the effect sizes we report are small. One likely explanation for this is the relatively young age range over which CRP change was examined (i.e., from an average age of 32 years to an average age of 55). In an older sample with more variable CRP concentrations, larger effects might have been observed. Another potential explanation for the small size of our effects involves the nature of the study design. Complex assessments in large-scale epidemiologic studies with heterogeneous samples are subject to greater error relative to smaller, more tightly controlled studies. This increased risk for error is compensated for, in part, by large sample sizes which provide power to detect very small effects, such as those reported here. Still, though significant, these effects likely underestimate true associations. Accordingly, SES may in fact explain a greater—though not necessarily large in an absolute sense—proportion of variance in future CRP levels than observed here. That said, SES likely is only one of several factors that influence CRP in healthy individuals Chronic psychological stress, for example, has been associated with comparatively elevated CRP concentrations (Ranjit et al., 2007
), as have depression and hostility (Suarez, 2004
). Moreover, given that persons of lower SES report more stress and tend to be more depressed than their higher SES counterparts (Adler et al., 1994
), it is possible that that psychological factors—either directly or via health behaviors, may mediate the association of SES with CRP. Finally, even small differences in CRP concentrations that are comparable in size to the change in CRP associated with SES that we report here, have been found to predict clinical disease risk. For example, among adults aged 45 and over and free of cardiovascular disease, a difference in one log-transformed CRP unit was associated with a nearly 40% increased risk for experiencing a future cardiovascular event (Park et al., 2002
The present findings should be considered within the context of a few limitations. Because our analyses were prospective and included several important explanatory variables, we both eliminated the possibility of reverse causation and reduced the likelihood of a third-factor explanation. Still, it remains possible that some unknown factor may be influencing both SES and CRP change. Also, the mean baseline (Year 7) CRP concentration for those who did not provide data at Year 20 (n
= 743)—and thus were excluded from the present analyses—was greater than the Year 7 mean reported here (data not shown). This difference in CRP levels likely results in part from the tendency of low educated and less healthy (i.e., higher BMI; smokers) individuals to become lost to follow-up. As these individuals also are more likely to show increases in CRP over time, their loss may have resulted in an underestimation of associations examined here. Third, all of our measures of health behaviors were self-reported. Thus, we cannot control for possible over-reporting of healthy behaviors by higher SES individuals. Finally, although CRP has been linked prospectively with risk for diseases of presumably inflammatory origin, whether mild elevations in CRP are themselves the result of underlying low-grade inflammation has been subject to debate (Kushner et al., 2006
). Accordingly, we cannot infer from the present data alone that SES—via health behaviors, is influencing inflammatory processes, per se. Replication of the present findings using known pro-inflammatory agents that do not closely correlate with those of CRP, such as tumor necrosis factor-α and interleukin-1β, would provide additional support for the SES-inflammation hypothesis.
In sum, the findings reported here suggest that SES is reliably associated with future circulating CRP concentrations, and that this association is accounted for to some extent by differences in smoking, FV intake, and physical activity among those at higher and lower ends of the socioeconomic hierarchy. These findings expand the existing literature on SES and CRP not only by underscoring the prospective nature of the association of SES with CRP via health behaviors, but also by demonstrating that this association exists when SES is operationalized either at the level of the person (education) or the family (household income). That the effects we report are small suggests that SES is not a primary determinant of future CRP concentrations in midlife. That is not to say, however, that the contribution of SES to CRP is unimportant. For example, individuals in the highest quartiles of education and income appeared to be relatively protected in terms of increasing CRP over time. Further investigation of the potential buffering effects of high SES on factors typically related to elevations in CRP may provide further insights into identifying why some individuals but not others appear to be at increased risk for future disease.