Lipoprotein(a) and residual cardiovascular risks in Japanese patients with coronary artery disease who achieve guideline-recommended low-density lipoprotein cholesterol goals

Current guidance recommends better LDL-C control in patients with elevated Lp(a) as Lp(a) lowering therapies are unavailable. Whether risks attributable to Lp(a) are mitigated in patients with CAD who achieved LDL-C <55 mg/dL remains unknown.

Multicentre retrospective observational study analysed 1581 Japanese patients with CAD [Lp(a)-JAPAN: jRCT1050260016]. Risk of MACE (cardiac-caused death + nonfatal MI + coronary revascularization in non-culprit segments) was compared according to Lp(a) levels (<30, ≥30, and <50 mg/dL and ≥50 mg/dL) and amongst LDL-C strata (<55 mg/dL vs ≥55 mg/dL) 8 weeks after PCI.

During the 5.1-year observation amongst patients with LDL-C ≥55mg/dL (n=1069), MACE occurred in 21.3% with risk of MACE increasing with Lp(a) levels (3.9, 7.9, and 11.0 events per 100 person-years for <30, ≥30, and <50 mg/dL and ≥50 mg/dL, log-rank p<0.001). Amongst those with LDL-C <55mg/dL (n=512), the proportion with MACE was lower overall (4.3%, p<0.001). However, elevated Lp(a) levels still identified those at higher risk of MACE (1.4, 4.7, and 7.5 events per 100 person-years in Lp(a) <30, ≥30, and <50 mg/dL and ≥50 mg/dL, p<0.001). Standardized 5-year MACE rate was over twice and five times higher in patients with Lp(a) ≥30 and <50 mg/dL (17.0%: adjusted HR = 3.80, 95% CI = 1.78–8.11, p<0.001) and ≥50 mg/dL (33.4%: adjusted HR = 6.90, 95% CI = 3.53–13.46, p<0.001) compared to Lp(a) <30 mg/dL (5.0%), respectively. The ROC analyses identified Lp(a) ≥28.2 mg/dL as the threshold for MACE (AUC = 0.68, p<0.001).

Whilst lower achieved LDL-C attenuates in part the risk from Lp(a), elevated Lp(a) levels still associate with worse cardiovascular outcomes. The Lp(a) threshold amongst Japanese patients with CAD at risk of recurrent events appears lower than in Caucasian populations which merits further evaluation.