Life course socioeconomic position is associated with inflammatory markers: The Framingham Offspring Study☆
Introduction
Socioeconomic disparities in coronary heart disease (CHD) exist in many developed countries, where people of lower childhood or adulthood socioeconomic position (SEP) typically have higher risk for incident CHD (Galobardes et al., 2006, Gonzalez et al., 1998). There is interest in investigating whether biological risk markers for CHD are related to life course SEP, as a way to evaluate if there is mechanistic evidence consistent with the inverse associations found between SEP and CHD in observational studies. Extensive progress has been made in recent decades on the involvement of inflammatory processes in atherosclerosis and subsequent risk for CHD, however little is known about associations between life course SEP and many inflammatory markers. Below we introduce major frameworks by which life course SEP is conceptualized, as well as evidence on roles of several inflammatory markers in specific atherosclerotic processes, leading to gaps in knowledge between life course SEP and inflammatory markers.
Galobardes et al. defined several phases for life course SEP including childhood SEP (e.g., parent’s education or parent’s occupation), young adulthood SEP (e.g., educational attainment), active professional life SEP (e.g., occupation or income), and retirement SEP (e.g., wealth or household conditions) (Galobardes, Shaw, Lawlor, Lynch, & Davey Smith, 2006). A number of frameworks to conceptualize life course SEP have been hypothesized (Fig. 1), including the “accumulation of risk” framework (which focuses on the total cumulative amount of exposure to SEP across the life course), the “social mobility” framework, which recognizes that people have evolving (e.g., increasing, decreasing or stable) SEP across their life span, and the “sensitive periods” framework which suggests that there are certain time periods in the life course when an exposure may have a stronger effect on disease risk than it would during other phases in life (Kuh and Ben-Shlomo, 2004, Kuh et al., 2003).
Novel risk markers for CHD include inflammatory markers. Substantial evidence suggests there is an important inflammatory component in the pathogenesis of atherosclerosis and the pathophysiology is becoming better understood (Libby, 2006). Several inflammatory markers are inversely associated with CHD, including interleukin-6 (IL-6) (Cesari et al., 2003), monocyte chemoattractant protein-1 (MCP-1) (de Lemos et al., 2003), tumor necrosis factor-α (TNF-α) (often measured as soluble tumor necrosis factor receptor II (TNFR2)) (Pai et al., 2004), C-reactive protein (CRP) (Danesh et al., 2004, Ridker et al., 2005), fibrinogen (Keavney et al., 2006), ICAM-1 (Malik et al., 2001), P-selectin (Armstrong, Morrow, & Sabatine, 2006) and lipoprotein-associated phospholipase A2 (Lp-PLA2) (Garza et al., 2007). Whether these inflammatory markers are causally related to CHD, rather than simply predictive of CHD, is still under investigation (Elliott et al., 2009, Keavney et al., 2006).
With regard to associations between life course SEP and inflammatory markers, most studies demonstrate inverse associations of life course SEP with CRP, IL-6, fibrinogen and white blood cell count (Brunner et al., 1996, Gimeno et al., 2007, Gimeno et al., 2008, Koster et al., 2006, Lawlor et al., 2005, Loucks et al., 2006, Nazmi and Victora, 2007, Pollitt et al., 2007, Pollitt et al., 2008, Tabassum et al., 2008), however little is known about associations between life course SEP and other inflammatory markers including TNFR2, MCP-1, ICAM-1, P-selectin and Lp-PLA2.
The objectives of this study were to determine whether three life course SEP frameworks (i.e., “accumulation of risk”, “social mobility”, and “sensitive periods” SEP frameworks) are associated with several markers representing diverse inflammatory pathways and processes, including CRP, IL-6, ICAM-1, P-selectin, TNFR2, Lp-PLA2 activity, MCP-1 and fibrinogen. Further objectives were to evaluate whether CHD risk markers (including smoking, body mass index, systolic blood pressure, total:HDL cholesterol ratio, fasting glucose, cholesterol-lowering medication use, anti-hypertensive medication use and depressive symptomatology) may be explanatory mechanisms for any observed associations between life course SEP and inflammatory markers. It should be emphasized, as discussed by Hallqvist et al. that it is likely not possible to critically test individual contributions of accumulation of risk vs. social mobility vs. sensitive periods due to mutual confounding between the three SEP frameworks (Hallqvist, Lynch, Bartley, Lang, & Blane, 2004). Consequently, we do not propose to statistically compare the contributions of each of these SEP frameworks to each other. As triangulation of methodological approaches enables a more thorough understanding of health determinants, we utilized the three life course SEP framework to offer three approaches to evaluate the potential association of life course SEP with inflammatory markers. Utilizing information from all three SEP frameworks will provide a more complete picture of life course SEP determinants of inflammatory markers than if findings were presented on only one of the life course SEP frameworks.
Section snippets
Study sample
The Framingham Heart Study is a community-based observational cohort that was initiated in 1948. The Framingham Offspring Study began in 1971 with recruitment of 5124 men and women who were offspring (or offspring’s spouses) of the Original Framingham Heart Study participants. The design and selection criteria of the Framingham Offspring Study have been described elsewhere (Kannel, Feinleib, McNamara, Garrison, & Castelli, 1979). All study participants received routine medical history and
Results
Fifty-four percent of participants were women, and the mean age was 61.2 (8.6 SD) years. Higher cumulative SEP levels were associated with more favorable cardiovascular risk factors including smoking, body mass index, systolic blood pressure, fasting glucose, cholesterol-lowering medications, anti-hypertensive medications, and depressive symptomatology in age- and sex-adjusted analyses (Table 1). There were no associations between cumulative SEP score and total:HDL cholesterol ratio. Those with
Discussion
This study provided evidence that cumulative life course SEP is inversely associated with many inflammatory markers including CRP, IL-6, ICAM-1, TNFR2, LP-PLA2 activity, MCP-1 and fibrinogen in age- and sex-adjusted analyses. Own education was associated with almost all studied inflammatory markers (CRP, IL-6, ICAM-1, TNFR2, P-selectin, MCP-1 and fibrinogen), while father’s education, father’s occupation and own occupation were associated with several but not all inflammatory markers in age-
Conclusion
This study provides evidence that cumulative SEP across the life course is inversely associated with several inflammatory markers including CRP, IL-6, ICAM-1, TNFR2, LP-PLA2 activity, MCP-1 and fibrinogen in age- and sex-adjusted analyses. Own education was associated with almost all studied inflammatory markers (CRP, IL-6, ICAM-1, TNFR2, P-selectin, MCP-1 and fibrinogen), while father’s education, father’s occupation and own occupation were associated with several but not all inflammatory
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2022, Neuroscience and Biobehavioral ReviewsCitation Excerpt :As shown in other longitudinal and large cross-sectional studies (Iob et al., 2020; Loucks et al., 2010; Nakamura et al., 2021), this effect appears to persist into late life. For instance, in the Framingham Heart Study, prospectively-assessed childhood socioeconomic position was associated with elevated inflammatory markers CRP, TNF-a, intercellular adhesion molecule-1 (ICAM-1), and lipoprotein phospholipase A2 (Lp-PLA2) measured in late life (sample mean age = 61.2) (Loucks et al., 2010). In older adults, elevated inflammation is also associated with poor physical and cognitive function as well as changes in brain regions implicated in cognition (e.g., greater regional cerebral blood flow decline in ACC and hippocampus) (Brinkley et al., 2009; Warren et al., 2018).
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The Framingham Heart Study is supported by National Institutes of Health/National Heart, Lung and Blood Institute contract N01-HC-25195. The research was supported by Canadian Institutes of Health operating grant MOP81239 (EBL), National Institutes of Health grants HL064753, HL076784, AG028321 (EJB), and a Canadian Institutes of Health New Investigator Award (EBL). We are grateful to the National Heart, Lung and Blood Institute for providing us with the limited access dataset, in conjunction with Framingham Heart Study investigators who provided other important variables for analyses.
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Authors contributed equally to the study.