This is the first study to examine whether changes in risk factors over time included in the Framingham risk score could account for the effects of a putative social risk factor for coronary heart disease. Specifically, we assessed the hypothesis that the association of SES with coronary heart disease adjusted for baseline measures of traditional CHD risk factors is explained by changes in those risk factors over time. We found that accounting for these changes explained little of the risk associated with SES.
No studies to our knowledge have examined the effect of changes in FRS on the risk associated with SES on CHD incidence. However, our findings are broadly consistent with other studies examining cardiovascular disease. Stringhini et al examined the impact of baseline health behaviors (rather than factors included in Framingham risk scoring) and their changes over time on the association of SES with cardiovascular mortality in British civil servants . They found that baseline health behaviors explained 29% of the effect of SES on subsequent cardiovascular mortality. Notably, however, subsequent health behavior changes over time accounted for only 16% of the SES effect on cardio-vascular mortality. Yan et al examined the effect of baseline systolic blood pressure, smoking, waist circumference, physical activity, and total cholesterol on coronary artery calcium (CAC), a marker of subclinical atherosclerosis. Consistent with our findings, baseline adjustment had an appreciable effect on the risk associated with SES, but adjustment for changes over 15 years had little effect .
Our findings reinforce the current United Kingdom recommendations of considering an individual's SES in assessing cardiovascular risk [22, 26]. Specifically, our findings show that changes in Framingham risk factors explain little of the social risk for CHD. Thus, ignoring SES in risk stratification and treatment goals may result in undertreatment of low SES persons who are at higher risk for cornary heart disease than their Framingham risk score suggests. SES does not appear to be simply a proxy for poor access and adherence (though those factors are likely also important).
Our study was not designed to address pathways beyond the risk factors included in the Framingham risk score that may explain the higher coronary heart disease incidence among low SES persons. Previous studies suggest that low SES during childhood predicts early coronary heart disease independent of traditional risk factors [5, 27]. A growing body of evidence suggests that exposure to social disadvantage and adversity in childhood may result in lasting adaptation to stress, potentially through epigenetic effects . In addition, cumulative effects of social disadvantage across the life course adversely impact cardiovascular health . Such chronic stress appears to exact a physiological toll, likely through multiple, complex pathways involving the hypothalmic-pituitary-adrenal axis, autonomic nervous and immune systems . Thus, SES health effects may represent a proxy measure for life-long "wear and tear." While these and other pathways may be important in explaining how SES exerts its toll on CHD (and directly addressing these pathways may be important), it remains true that clinical decision-making based on Framingham risk scoring alone will under-estimate CHD risk in low SES persons.
Limitations to our findings merit comment. We did not include other biological (such as coronary calcium or C-reactive protein) or behavioral (such as obesity or exercise) risk factors because none are included in Framingham risk scoring currently used in cholesterol risk stratification and treatment guidelines. A prior analysis showed few consistent relationships between a variety of inflamatory markers and social mobility .
Participants' reports of smoking, changes in smoking, and anti-hypertensive medication use were not verified. Error in assessment of these risk factors, particularly if associated with SES bias, could result in underestimation of the contribution of these factors. Conversely, repeated measurement of these risk factors and the use of continuous cholesterol and blood pressure measures compared with the single baseline measurement of the dichotomous SES risk factor likely results in a measurement bias favoring the traditional risk factors. We were not able to assess changes in SES during the study period. For example, recent involuntary unemployment is associated with increases in inflammation  and higher cardiovascular mortality in some [32–34], but not all  studies. Failing to account for these changes in SES would result in misclassification of SES and result in a conservative estimate of the net effect of SES on coronary heart disease.
Missing follow-up data is another potential limitation. While missing follow-up data was relatively uncommon (6% overall), it was more common among low SES persons than among high SES persons. The direction of potential bias is difficult to estimate, depending on whether those with missing data were less or more likely to have changed their level of risk, and whether that change, if any, occurred differntially by SES. However, given the relatively small overall impact of risk factor change on the SES hazard ratio, we consider it unlikely that the potential bias would change our conclusion that there is a robust independent effect of SES on CHD.
In summary, we found that accounting for changes in key traditional coronary heart disease risk factors and anti-hypertensive medication explained little of the independent effect of SES on coronary heart disease risk. Ignoring SES in coronary heart disease risk assessment under-estimates the risk in lower SES persons [1, 3], and may, in turn, through relative undertreatment contribute to widening SES disparities in coronary heart disease. These findings provide further support for inclusion of SES into coronary heart disease risk assessment; methods to do so have been presented elsewhere [22, 23].