Background: Elevated lipoprotein(a) [Lp(a)] levels have been shown to be an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), but it is unclear if they are a determinant of residual cardiovascular risk in the setting of low LDL-C.
Objectives: This study examined the relationship of Lp(a) levels to cardiovascular outcomes in statin-treated ASCVD patients stratified by median levels of LDL-C (78 mg/dL) in the ACCELERATE trial.
Methods: Relationships of baseline Lp(a) levels to major adverse CV events (MACE: CV death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) were examined in 12,092 ASCVD statin-treated patients treated with evacetrapib or placebo, and followed for a median of 26 months. Univariate and adjusted (age, sex, race, risk factors) hazard ratios for endpoint events were determined for each quartile of Lp(a), with the first 3 quartiles combined serving as the referent group.
Results: While overall Lp(a) levels were associated with MACE risk in univariate and multivariate models, Lp(a) levels predicted MACE only in patients with baseline LDL-C below the median level [Figure]. In multivariate analysis, the event rates were significantly higher in the 4th quartile (≥107.4 nmol/L) compared to the first 3 Lp(a) quartiles combined, both in all patients (14.8% vs. 12.1%; HR=1.21, p=0.002) and in those with LDL-C below the median (15.1% vs. 11.2%; HR=1.34, p=0.001). Lowering Lp(a) with evacetrapib by an average of 27% had no impact on MACE rates.
Conclusions: In a contemporary ASCVD population, 25% of patients demonstrated Lp(a) levels ≥107.4 nmol/L (about ≥50 mg/dL). Lp(a) above the current desirable level predicted MACE risk in statin-treated ASCVD patients with lower LDL-C levels, suggesting that Lp(a) may be an additional therapeutic target in patients with optimal LDL-C levels.