Adiposity, inflammation, and risk for death in black and white men and women in the United States: the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

CONTEXT It has been proposed that adiposity is a protective response to excess caloric supply, but it is cardiometabolically harmful once adipocytes become inflamed. OBJECTIVE The objective of the study was to assess whether elevated C-reactive protein (CRP), a measure of systemic inflammation, can differentiate individuals at higher mortality risk due to excess adiposity. DESIGN, SETTING, AND PARTICIPANTS We conducted an observational study of 16,486 white and 11,168 black men and women in the Reasons for Geographic and Racial Differences in Stroke study, a U.S. national cohort. MAIN OUTCOME The main outcome was all-cause mortality. RESULTS The mean age of the cohort was 64 ± 9 yr. Over a 6-yr period, 927 whites and 669 blacks died. The absolute risk of death was highest among underweight whites and blacks (9.2 and 14%, respectively), not the obese (4.7% whites; 4.0% blacks) or severely obese (5.9% whites; and 4.6% blacks). Among those with elevated CRP (≥3 vs. <1 mg/liter), underweight [hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.03-4.21] and normal-weight (HR 2.62, 95% CI 1.87-3.67) whites were at significantly higher mortality risk but not severely obese whites (HR 1.55, 95% CI 0.77-2.96), resulting in a statistical interaction (P = 0.01). Similar results were also seen for blacks, although a higher mortality risk among severely obese blacks with CRP 3 or greater vs. less than 1 mg/liter was also demonstrated (HR 2.58, 95% CI 1.04-6.41). Among whites and black women, higher waist circumference was associated with an increased mortality risk, although this relationship was not modified by CRP levels (P = 0.47 for whites and P = 0.25 for blacks). CONCLUSION Among middle-aged and older adults, the addition of CRP was most informative among underweight and normal-weight individuals, not the obese. This negated our hypothesis that increased levels of CRP would differentiate individuals at higher mortality risk due to excess adiposity.