Inflammatory Burden, Structural Exposure, and Racial Disparities in Incident Heart Failure: Evidence from the Multi-Ethnic Study of Atherosclerosis

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 × 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 (PM _2.5 , NO ₂ ) 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 × 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 PM _2.5 /NO ₂ 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.

Clinical Perspective

What Is New?

• Baseline interleukin-6, C-reactive protein, fibrinogen, and D-dimer were each independently associated with incident heart failure in the Multi-Ethnic Study of Atherosclerosis, and a principal-components composite of the 4 markers outperformed any single marker.

• The per-SD hazard associated with inflammatory and hemostatic burden was consistent across the 4 racial and ethnic groups, whereas baseline burden was systematically higher among Black and Hispanic participants.

• Sequential adjustment for the 4-marker panel reduced the Black–White log-hazard difference for incident heart failure by 57.5%.

What Are the Clinical Implications?

• Inflammatory and hemostatic biomarkers may help identify individuals at elevated risk of heart failure who could benefit from intensified preventive strategies, although the incremental gain in discrimination beyond clinical risk factors was modest.

• Because per-unit biological risk was shared across groups while exposure burden differed, efforts to reduce racial disparities in heart failure should target the structural determinants that produce elevated inflammatory burden rather than presume group-specific biological susceptibility.

• Formal causal mediation and additive-interaction analyses are needed before inflammatory burden can be regarded as an established mediator of heart failure disparities.