Lp(a), platelet count, aspirin and cardiovascular outcome: a prospective cohort analysis

Elevated lipoprotein(a) [Lp(a)] and increased platelet count independently predict major adverse cardiovascular events (MACE), yet their interplay and joint value in cardiovascular risk stratification remain incompletely elucidated. We examined their separate and joint associations with incident MACE, with a secondary exploratory analysis of whether preventive benefit from aspirin differs across biomarker-defined subgroups.

We included 250,927 participants free of prior cardiovascular disease (CVD) from the UK Biobank (enrolled 2006-2010). Participants were categorized into four groups based on Lp(a) status (elevated: >125 nmol/L) and platelet count (increased: upper tertile, >273 × 10⁹/L). Multivariable Cox regression was applied to estimate hazard ratios (HRs) for MACE, adjusted for demographic, lifestyle, metabolic and medication-related covariates. Formal tests for additive and multiplicative interactions were performed. Over a median follow-up of 13.4 years, both elevated Lp(a) (HR 1.250; 95% CI 1.118-1.325) and increased platelet count (HR 1.056; 95% CI 1.005-1.110) were independently associated with higher MACE risk. Participants with concurrent elevation of both biomarkers carried the highest MACE risk (HR 1.391; 95% CI 1.256-1.541). Neither additive nor multiplicative interaction reached statistical significance, indicating that the joint effect reflects additive risk accumulation rather than biological synergy. In exploratory subgroup analyses, aspirin use was associated with lower MACE risk only in the double-high subgroup, but not in those with isolated elevated Lp(a).

Concomitant elevation of Lp(a) and platelet count identifies a subgroup of individuals at substantially higher risk for MACE. The observed potential benefit of aspirin in the double-high subgroup is exploratory and warrants further prospective investigation.