Life-course origins of social inequalities in adult immune cell markers of inflammation in developing southern Chinese population: the Guangzhou Biobank Cohort Study

Background: Socioeconomic position (SEP) throughout life is associated with cardiovascular disease, though the mechanisms linking these two are unclear. It is also unclear whether there are critical periods in the life course when exposure to better socioeconomic conditions confers advantages or whether SEP exposures accumulate across the whole life course. Inflammation may be a mechanism linking socioeconomic position (SEP) with cardiovascular disease. In a large sample of older residents of Guangzhou, in southern China, we examined the association of life course SEP with inflammation. Methods: In baseline data on 9,981 adults (≥ 50 years old) from the Guangzhou Biobank Cohort Study (2006-08), we used multivariable linear regression and model fit to assess the associations of life course SEP at four stages (childhood, early adult, late adult and current) with white blood, granulocyte and lymphocyte cell counts. Results: A model including SEP at all four life stages best explained the association of life course SEP with white blood and granulocyte cell count for men and women, with early adult SEP (education) making the largest contribution. A critical period model best explained the association of life course SEP with lymphocyte count, with sex-specific associations. Early adult SEP was negatively associated with lymphocytes for women. Conclusions: Low SEP throughout life may negatively impact late adult immune-inflammatory status. However, some aspects of immune-inflammatory status may be sensitive to earlier exposures, with sex-specific associations. The findings were compatible with the hypothesis that in a developing population, upregulation of the gonadotropic axis with economic development may obscure the normally protective effects of social advantage for men. Background Socioeconomic position (SEP) throughout life is usually inversely associated with morbidity and mortality from cardiovascular disease, although the underlying biological pathway is not entirely clear [1,2]. Cardiovascular disease has been associated with higher levels of inflammatory molecules, perhaps as a consequence of exposure to pathogenic organisms [3], although it is unclear whether pathogen burden mediates SEP differences in cardiovascular risk [3,4]. Poor early life conditions are usually associated with higher levels of inflammatory markers [5-11] and poorer adult immune function [12,13]. These associations are less clear, however, amongst men from middle income countries [10]. Furthermore, little is known about the association of SEP across the life course with immune function. The duration or number of exposures across the life course may be most important (the accumulation hypothesis) [14]. Alternatively, the timing of exposure to poor socioeconomic conditions may be crucial as a number of sensitive periods or simply as a single * Correspondence: [email protected] School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, SAR, China Full list of author information is available at the end of the article West et al. BMC Public Health 2012, 12:269 http://www.biomedcentral.com/1471-2458/12/269 © 2012 West et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. critical period (the critical period hypothesis). It is also possible that either interor intra-generational social mobility plays a part. Developmental trade-offs between growth, maintenance, and reproduction may occur when there are competing demands for energy resources between biological systems [13,15,16], potentially at the expense of immune function in resource-poor environments. Alternatively, intergenerationally and environmentally driven up-regulation of the gonadotropic axis with economic development may obscure some of the normally protective effects of social advantage in the first few generations of men to experience better living conditions [17,18], thus generating epidemiologically stage specific associations between SEP and immune-related functions, such as pro-inflammatory states, among men [18,19]. Rapidly developing mega-cities of China may provide a sentinel for the changes in non-communicable diseases expected with economic development and inform effective interventions to reduce the disease burden. In a large sample of older residents from one of the most developed mega-cities in China, Guangzhou in southern China, we assessed the association of SEP at four life stages with proxies of inflammation (total white blood cell, granulocyte, and lymphocyte counts) and compared models representing the accumulation, sensitive periods and critical period hypotheses. Additionally, we hypothesise that 1) higher life course SEP is protective for adult inflammation, 2) the normal protective effect of social advantage is obscured in men experiencing rapid socioeconomic development. Methods Sources of data The Guangzhou Biobank Cohort Study is a collaboration between the Guangzhou No. 12 Hospital (Guangzhou, China) and the universities of Hong Kong (Hong Kong, China) and Birmingham (Birmingham, United Kingdom). The study has been described previously in detail [20]. Participants were drawn from the Guangzhou Health and Happiness Association for the Respectable Elders (GHHARE), a community social and welfare association unofficially aligned with the municipal government, where membership is open to anyone aged 50 years or older for a nominal monthly fee of 4 yuan (US $0.50). Approximately 7 percent of permanent Guangzhou residents aged 50 years or more are members of the GHHARE. Eleven percent of the members were included in this study, who were capable of consenting, were ambulatory, and were not receiving treatments which if discontinued might have resulted in immediate, lifethreatening risk, such as chemotherapy, radiotherapy or dialysis. Those with less serious chronic illnesses or with acute illnesses were not specifically excluded from the study though they may have been less likely to attend. Participants were recruited in three phases and this study includes participants recruited in phase 3 only (recruited between 2006 and 2008), because only phase 3 has detailed information on childhood socioeconomic position and inflammatory markers. Participants underwent a detailed half-day medical interview, as well as a physical examination with fasting blood being sampled. Quantitative haematological analysis was performed using a SYSMEX KX-21 haematology analyser. The Guangzhou Medical Ethics Committee of the Chinese Medical Association approved the study and all participants gave written, informed, consent prior to participation. Socioeconomic position across the life course We used indicators of SEP at four life stages: childhood, early adult, late adult and current SEP. Childhood SEP was measured by an index of notable parental possessions that were appropriate to China in the mid-20th century, based on sociologic accounts of life in southern China at that time [17]. The items selected were a watch, a sewing machine, and a bicycle. These items were categorized, as previously, as none or at least one [21]. As in other similar studies, we used education and longest-held occupation as proxies for early and late adult SEP [22]. Early adult SEP was assessed from the highest level of education (primary or less versus secondary or more). Occupation was categorised as manual (agricultural work, factory work, or sales and service) or non-manual (administrative/managerial, professional/technical, or military/police). Current SEP was assessed from household income per head. Household income was recorded in six categories (<5,000 Yuan, 5000-9,999 Yuan, 10,00019,999 Yuan, 20,000-29,999 Yuan, 30,000-49,999 Yuan and ≥50,000 Yuan). Household income per head was estimated using the mid-point of each income category and assuming that those in the highest category had an annual income of 75,000 Yuan. The median household income per head was used as the cut-off point between low and high SEP. Outcome measures The primary outcome was total white blood cell count used, as in other studies, as a marker of a pro-inflammatory state [5], and less well functioning immune system. As we do not have a detailed breakdown of different white blood cell types, such as macrophages, we also considered granulocyte and lymphocyte counts as outcomes because these immune cell sub-populations largely relate to innate and adaptive immunity respectively. They have previously been used as markers of inflammation [23,24]. Other measures of inflammation (e.g. C-reactive protein) were not available. West et al. BMC Public Health 2012, 12:269 http://www.biomedcentral.com/1471-2458/12/269 Page 2 of 12