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AIMS: Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for coronary artery disease (CAD). Data on long-term outcomes following invasive coronary angiography (ICA) in those with elevated Lp(a) are limited. This study examined the association of Lp(a) levels with clinical outcomes after index ICA, accounting for baseline atherosclerotic plaque burden.METHODS AND RESULTS: Data were from participants with Lp(a) measurement who underwent index ICA between 2000 and 2023. Lp(a) levels were categorized as normal (<75 nmol/L), intermediate (75- < 125 nmol/L), high (125- < 175 nmol/L), and very high (≥175 nmol/L). Angiographic characteristics (severity, burden), CAD presentation (stable, acute), and subsequent clinical outcomes [acute myocardial infarction (AMI), revascularization, in-stent restenosis (ISR), and all-cause mortality] were assessed. Among 5118 participants, 973 (19.0%) had very high Lp(a). Compared with normal Lp(a), very high Lp(a) was associated with severe obstructive CAD {adjusted odds ratio (aOR), 1.51 [95% confidence interval (CI), 1.17-1.96]}, left main disease [aOR, 1.67 (95% CI, 1.22-2.29)], and a 14.04-point higher Gensini score (95% CI, 9.57-18.52). During a median (interquartile range) follow-up of 16.87 (6.38-18.99) years, participants with very high vs. normal Lp(a) had higher risk of AMI [adjusted hazard ratio (aHR), 1.20 (95% CI, 1.05-1.37)], revascularization [aHR, 1.32 (95% CI, 1.13-1.56)], ISR [aHR, 1.28 (95% CI, 1.04-1.56)], and mortality [aHR, 1.19 (95% CI, 1.05-1.34)]. Among 798 individuals undergoing coronary artery bypass grafting surgery after index ICA, those with very high vs. other Lp(a) were more likely to require subsequent percutaneous coronary intervention [aHR, 2.20 (95% CI, 1.06-4.58)].CONCLUSION: Elevated Lp(a) levels are associated with increased burden of coronary atherosclerosis and significant residual risk for adverse outcomes following ICA, highlighting a need for targeted risk-reduction strategies.