Introduction: Both coagulation and inflammation may contribute to the higher risk for coronary heart disease (CHD) associated with high lipoprotein(a) [Lp(a)]. The association of Lp(a) with CHD is stronger in individuals with high versus low high-sensitivity C-reactive protein (hsCRP), a marker of inflammation. It is unclear if coagulation Factor VIII also modifies the association of Lp(a) with CHD independently of hsCRP.Hypothesis: Lp(a) is associated with incident CHD in adults with high Factor VIII after adjustment for hsCRP but not among those with low Factor VIII.Methods: We analyzed data from 6,495 adults 45 to 84 years of age without a history of cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis (MESA). Lp(a) mass concentration, Factor VIII antigen, and hsCRP were measured using blood collected at baseline (2000-2002). Lp(a), Factor VIII and hsCRP were categorized as high or low (≥75th or <75th percentile of the distribution). Participants were followed for incident CHD through 2015 (median follow-up 14 years).Results: The mean age of participants was 62 years and 47% were male. After log-transformation, the Pearson’s correlation between Factor VIII and hsCRP was 0.15 (p-value <0.001). High Lp(a) was associated with an increased risk for incident CHD in participants with high Factor VIII and high hsCRP, separately, but not among those with low Factor VIII or low hsCRP (Table). The adjusted hazard ratio (95%CI) for CHD associated with high Lp(a) was 1.09 (0.77, 1.53) in participants with low Factor VIII and low hsCRP, 1.49 (0.84, 2.67) in those with low Factor VIII and high hsCRP, 1.54 (0.92, 2.59) in those with high Factor VIII and low hsCRP, and 3.84 (1.85, 7.97) in those with high Factor VIII and high hsCRP (p-value comparing hazard ratios 0.02).Conclusions: High Lp(a) is a risk factor for incident CHD in adults with high Factor VIII or hsCRP. The activation of either the inflammation or coagulation pathway may modify the association of Lp(a) with CHD.