BA11 - Physical activity, obesity, inflammation and CHD in a multi-ethnic cohort of women

Investigator Names and Contact Information

I-Minn Lee (ilee@rics.bwh.harvard.edu)

Introduction/Intent

Dr. Lee and colleagues seek to clarify the mechanisms underlying the reduced risk of CHD conferred by physical activity and lower body fat, beyond their effects on traditional risk factors. Using data from the WHI Observational Study, the team will examine associations between physical activity and inflammatory markers and whether these associations vary by a person’s weight. They will also look at joint associations between physical activity combined with weight/obesity status and risk of CHD. The role of inflammatory markers in mediating the associations of physical activity and weight with CHD risk will be studied and compared with the role of traditional risk factors such as blood pressure and cholesterol levels.

Coronary heart disease (CHD) continues to be a leading cause of death both in the US and worldwide. Two well-established risk factors are physical inactivity and adiposity; however, the biologic mechanisms underlying their adverse effects are incompletely understood. In addition to their effects on traditional cardiovascular risk factors, a further promising mechanism underpinning the associations of physical activity and adiposity with the risk of CHD is inflammation.

Few data are available regarding the associations among physical inactivity, adiposity, and inflammation. These data are limited in that they primarily come from cross-sectional studies, thus rendering the direction of the association unclear (i.e., does physical activity lead to lower levels of inflammation, or, do lower levels of inflammation reflect a healthier individual who is more likely to be physically active?). Additionally, few data are available specifically on White, Black, Hispanic, Asian, and American Indian women, and this represents an important gap in knowledge since the prevalence of physical inactivity and obesity are particularly high in some minority groups. It is also unclear whether physical activity can ameliorate the increased levels of inflammation associated with higher levels of adiposity.

The prevalence of obesity continues to climb in the US and the long-term maintenance of weight loss is poor. A further gap in knowledge is the joint association of physical inactivity and adiposity with CHD risk – while it is clear that each significantly predicts higher CHD risk, the available data are inconsistent regarding their joint effects, leading to the so-called “fit-or-fat” debate. Studies are equivocal as to the relative benefits or risks of being “fit and fat” versus “unfit and lean” in the context of CHD prevention. Again, these studies primarily have been in White populations, with few data in minority populations.

To address the gaps in knowledge summarized above, this study has the following specific aims:

1. To examine whether changes in physical activity between baseline and year 3 lead to changes in the inflammatory markers C-reactive protein (CRP), IL-6, TNF-α, IL-1β, leptin, adiponectin, and resistin.
   • a. To further examine cross-sectional (baseline) and longitudinal (baseline to year 3) associations between physical activity and inflammatory markers separately among White, Black, Hispanic, Asian, and American Indian women.
   • b. To further understand the inter-relations of physical activity and adiposity with inflammatory markers by examining associations between physical activity and inflammatory markers, as well as changes in both, separately among women who were normal weight, overweight, or obese at baseline. Parallel analyses will also examine, separately, women who lost, maintained, or gained weight between baseline and year 3.
2. To conduct a case-cohort study of physical activity and adiposity (measured using various anthropometric measures) in relation to CHD risk.
   • a. Of specific interest are the independent versus joint associations of physical activity and adiposity, as well as changes in both, with CHD risk.
   • b. Of specific interest is the role of inflammatory markers in mediating the associations of physical activity and adiposity, as well as changes in both, with CHD risk, compared with clinical cardiovascular risk factors such as blood pressure, lipid levels, and fasting glucose level.

Results/Findings

For a complete, up-to-date list of WHI papers related to this ancillary study, please use the searchable Papers section of this website.