Lp(a) above 46.8 nmol/L, below current guideline thresholds, still raises MACE risk 20% in statin-treated patients, UK Biobank cohort of 17,376 (Eur J Prev Cardiol 2026)

Aims: This study assessed the risk associated with moderately elevated lipoprotein(a) (Lp[a]) 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 (<12.5 vs. >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 (p<0.01), 27% higher risk of hospitalization for MI (p<0.05), 34% higher rate of coronary revascularization (p<0.001), and a 30% increased CV mortality (p<0.05). Stratified dose-response models showed a more pronounced effect of Lp(a) on MACE risk in individuals without established ASCVD.

Conclusion: In a statin-treated population at high CV risk, moderately elevated Lp(a) levels (>46.8 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.