Abstract / Summary
Background: Racial disparities in incident heart failure (HF) are well documented, yet the extent to which systemic inflammatory burden-shaped by structural determinants of environmental exposure-accounts for these disparities remains unquantified in multi-ethnic prospective cohorts. Methods: Among 6785 participants in the Multi-Ethnic Study of Atherosclerosis (enrolled 2000-2002; 4 racial/ethnic groups) followed for approximately 16 years, we estimated associations of 4 prespecified baseline inflammatory and hemostatic biomarkers (interleukin-6 [IL-6], C-reactive protein [CRP], fibrinogen, and D-dimer; per 1-SD increment) with incident HF (485 events) using Cox proportional hazards models. A composite inflammatory burden index was derived by principal components analysis. Race x biomarker multiplicative interactions were tested with Holm correction. Sequential biomarker adjustment quantified the percentage of the Black-White log-hazard difference explained relative to a clinical-only model. Robustness to ambient air pollution (PM2.5, NO2) was assessed in a geocoded subcohort. Results: All 4 biomarkers were independently associated with incident HF (IL-6: hazard ratio [HR], 1.20 [95% CI, 1.08-1.34]; D-dimer: 1.18 [1.06-1.30]; CRP: 1.14 [1.02-1.27]; fibrinogen: 1.13 [1.02-1.24]). The composite index (first principal component, 53.7% of variance explained) yielded an HR of 1.25 (1.12-1.39) per 1-SD increase. No multiplicative race x biomarker interaction was detected (all Holm-corrected P=1.0), indicating that the per-SD inflammatory hazard was directionally consistent across groups. Sequential biomarker adjustment reduced the Black-White log-hazard difference by 57.5%, a pattern consistent with-but not sufficient to prove-attenuation by inflammatory pathways. Associations were robust to PM2.5/NO2 co-adjustment. Conclusions: Inflammatory and hemostatic burden partially explains the Black-White disparity in incident HF. The null multiplicative interaction pattern indicates that per-unit biological risk is equitable across groups, consistent with differential structural exposure-rather than differential susceptibility-as a primary driver of disparity. Key Words: heart failure; inflammation; health equity; structural determinants; MESA; biomarkers