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

BACKGROUND AND AIMS: Current guidance recommends better low-density lipoprotein cholesterol (LDL-C) control in patients with elevated lipoprotein(a) [Lp(a)] as Lp(a) lowering therapies are unavailable. Whether risks attributable to Lp(a) are mitigated in patients with coronary artery disease (CAD) who achieve LDL-C <55 mg/dL remains unknown. METHODS: Multicentre retrospective observational study analysing 1581 Japanese patients with CAD [Lp(a)-JAPAN: jRCT1050260016]. Risk of major adverse cardiovascular events (MACE) (cardiac death + non-fatal myocardial infarction + coronary revascularization in non-culprit segments) was compared according to Lp(a) levels (<30, ≥30 and <50, and ≥50 mg/dL) and among LDL-C strata (<55 mg/dL vs ≥55 mg/dL) 8 weeks after percutaneous coronary intervention. RESULTS: During the 5.1-year observation among patients with LDL-C ≥55 mg/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 mg/dL, ≥30 and <50 mg/dL, and ≥50 mg/dL, respectively; log-rank p<0.001). Among those with LDL-C <55 mg/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 mg/dL, ≥30 and <50 mg/dL, and ≥50mg/dL, respectively; 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 hazard ratio [HR] 3.80, 95% confidence interval [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%). The receiver-operating characteristic analyses identified Lp(a) ≥28.2 mg/dL as the threshold for MACE (area under the curve 0.68, p<0.001). CONCLUSIONS: 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 among Japanese patients with CAD at risk of recurrent events appears lower than in Caucasian populations, which merits further evaluation.