Abstract Body (Do not enter title and authors here): Background: Lipoprotein(a) [Lp(a)] is a potent risk factor for coronary artery disease (CAD) with novel Lp(a)-lowering therapeutics under investigation. Data regarding implications of elevated Lp(a) among patients undergoing coronary angiography are limited. We aimed to assess (i) the association between Lp(a) levels and angiographic characteristics of CAD and (ii) whether Lp(a) levels predict adverse angiographic and clinical outcomes after index coronary angiogram.

Methods: Patients who underwent coronary angiography and Lp(a) measurement between 2000-2023 were classified into four Lp(a) risk groups: normal (<75 nmol/L), intermediate (75-124 nmol/L), high (125-174 nmol/L), and very high (≥175 nmol/L). Angiographic characteristics (severity, burden, Gensini score—a continuous measure of angiographic CAD burden) and future outcomes starting 3 months after index angiogram (repeat angiogram, revascularization, in-stent restenosis [ISR], heart failure [HF], and all-cause mortality) were analyzed by Lp(a) risk category using Cox proportional hazard models adjusted for age, sex, and race.

Results: Among 5,118 patients (26.5% female; median [IQR] age 64 [55-74]; 84.9% White), 3,138 (61.3%) had normal Lp(a) levels, 543 (10.6%) intermediate, 464 (9.1%) high, and 973 (19%) very high. Compared to normal Lp(a) levels, very high Lp(a) was associated with obstructive CAD (adjusted odds ratio [AOR], 1.50; 95%CI, 1.16-1.94), multi-vessel disease (AOR,1.79; 95%CI, 1.39-2.30), left-main disease (AOR, 1.80; 95%CI, 1.33-2.45), and a 13.9-point increase in the Gensini score (P<.001). Over a mean follow-up of 11.01±7.58 years, patients with very high Lp(a) were significantly more likely to undergo a repeat angiogram (adjusted hazard ratio [AHR], 1.22; 95%CI, 1.09-1.36), revascularization (AHR, 1.40; 95%CI, 1.19-1.64), and ISR (AHR, 1.34; 95%CI, 1.10-1.63). However, no increased risk of HF was observed (P>.05). The risk of mortality was 17% higher in the very high Lp(a) group (95%CI, 1.04-1.32). These trends persisted even after adjusting for baseline CAD burden (Figure).

Conclusion: Very high Lp(a) levels are associated with increased burden and severity of CAD and are strongly predictive of future angiographic and clinical outcomes.