Inflammation
Lp(a)-related cardiovascular risk only appears when hs-CRP is also elevated, a MESA analysis of 4,679 participants (J Am Coll Cardiol 2021)
Original title: High-Sensitivity C-Reactive Protein Modifies the Cardiovascular Risk of Lipoprotein(a): Multi-Ethnic Study of Atherosclerosis
In 4,679 participants from the MESA Apolipoprotein ancillary study followed a mean 13.6 years (684 cardiovascular events), a significant interaction was found between Lp(a) and high-sensitivity C-reactive protein (hsCRP) (P=0.04). With hsCRP below 2 mg/L, no significant cardiovascular risk was observed at any Lp(a) level from below 50 to above 100 mg/dL. However, with hsCRP >=2 mg/L, Lp(a) of 50-99.9 mg/dL and >=100 mg/dL were both associated with significantly higher cardiovascular risk (HR 1.36, 95% CI 1.02-1.81; and HR 2.09, 95% CI 1.40-3.13, respectively). Isolated elevation of either marker alone was not associated with increased risk, but the combination of elevated Lp(a) (>=50 mg/dL) and hsCRP (>=2 mg/L) independently predicted both cardiovascular events (HR 1.62, 95% CI 1.25-2.10) and all-cause mortality (HR 1.39, 95% CI 1.12-1.72). The findings show Lp(a)-associated cardiovascular risk manifests specifically in the presence of concomitant systemic inflammation.
Original abstract
Background: 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).
Objectives: The purpose of this study was to assess whether Lp(a)-associated ASCVD risk is modified by hsCRP in the context of primary prevention.
Methods: The current study included 4,679 participants from the MESA (Multi-Ethnic Study of Atherosclerosis) Apolipoprotein ancillary data set. Cox proportional hazards models and Kaplan-Meier curves were used to assess the association among Lp(a), hsCRP, and time to cardiovascular disease (CVD) events.
Results: 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 risk was observed at any level of Lp(a) from <50 mg/dL to >100 mg/dL. However, with hsCRP ≥2 mg/L, a significant CVD risk was observed with Lp(a) of 50-99.9 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).
Conclusions: 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, and thus may merit closer surveillance and more aggressive ASCVD risk management.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.