Lipoprotein(a) and residual cardiovascular risk in statin-treated patients

AIMS: This study assessed the risk associated with moderately elevated lipoprotein(a) (Lpa) levels below current thresholds in a statin-treated population and explored possible differences in the effect of Lp(a) between individuals with and without established atherosclerotic cardiovascular disease (ASCVD). METHODS: The analysis included 17,376 patients aged ≥45 years with established ASCVD or type 2 diabetes from the UK Biobank. The primary endpoint was major adverse cardiovascular events (MACE), defined as non-fatal myocardial infarction (MI), non-fatal stroke, or cardiovascular (CV) mortality. CV outcomes were compared between lower and upper Lp(a)-tertiles (46.8 nmol/L) using adjusted Poisson regression models. Generalized additive Cox models were used to examine the continuous dose-response relationship between Lp(a) and MACE risk, stratified by baseline ASCVD status. RESULTS: Compared with the lower Lp(a)-tertile, the upper Lp(a)-tertile was associated with a 20% higher risk of MACE (p46.8 nmol/L) below current guideline thresholds are associated with significantly increased risk of CV events, with a substantially stronger effect observed in those without established ASCVD. These findings suggest that current Lp(a) thresholds may underestimate residual CV risk in statin-treated individuals, particularly those without established ASCVD with high CV risk.