High-Sensitivity C-Reactive Protein Modifies the Cardiovascular Risk of Lipoprotein(a)

Little is known about the relationship between lipoprotein (a) (Lp[a]) and high-sensitivity C-reactive protein (hsCRP) and their joint association with atherosclerotic cardiovascular disease (ASCVD). To assess whether Lp(a)-associated ASCVD risk is modified by hsCRP in the context of primary prevention. The current study included 4,679 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) Apolipoprotein ancillary dataset. Cox proportional hazards models and Kaplan-Meier curves were used to assess the association between Lp(a), hsCRP, and time to CVD events. During a mean follow up of 13.6 years, 684 CVD events occurred. A significant interaction was observed between Lp(a) and hsCRP (P=0.04). With hsCRP < 2 mg/L, no significant CVD riskwas observed at any level of Lp(a) from < 50 mg/dL to above 100 mg/dL. However, with hsCRP ≥ 2 mg/L, a significant CVD risk was observed with Lp(a) of 50 to 99.9 mg/dL (HR, 1.36; 95%CI, 1.02–1.81) and Lp(a) ≥ 100 mg/dL (HR, 2.09; 95%CI, 1.40–3.13). Isolated elevations of either Lp(a) or hsCRP were not associated with increased CVD risk. In contrast, the combination of elevated Lp(a) (≥ 50 mg/dL) and hsCRP (≥ 2 mg/L) was independently associated with significant CVD risk (HR, 1.62; 95%CI, 1.25–2.10) and all-cause mortality (HR, 1.39; 95%CI, 1.12–1.72). Lp(a)-associated ASCVD risk is observed only with concomitant elevation of hsCRP. Individuals with concomitant presence of elevated Lp(a) and systemic inflammation have greater ASCVD risk and all-cause mortality, thus may merit closer surveillance and more aggressive ASCVD risk management.