BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] emerging as a significant risk factor for coronary artery disease (CAD). However, the role and the impact of Lp(a) in the early formation and progression of complex CAD remains unclear. This study aimed to investigate the impact of Lp(a) levels on the age of first acute coronary events and CAD severity in acute coronary syndrome (ACS) patients. METHODS AND RESULTS: The RELACS study, a single-center prospective observational study that included 774 consecutive ACS patients. Lp(a) levels were measured and stratified into tertiles. Primary endpoint was the correlation between Lp(a) levels and the age of first acute coronary event. Secondary endpoint was correlation between Lp(a) levels and CAD complexity (SYNTAX I and Gensini scores). The mean (SD) age was 63.2 (12.6) years and 603 (78 %) were males. The clinical presentations included 40.1 % of patients with STEMI, 46.9 % with NSTEMI, and 13 % with unstable angina. Median baseline Lp(a) level was 21.85 mg/dL. Higher Lp(a) levels were linked to a younger age of the first coronary event (B coefficient -0.83, p = 0.002). Positive correlations were found between Lp(a) levels and Gensini (r = 0.16, p = 0.011) and SYNTAX scores (r = 0.14, p = 0.004). Each tertile increase in Lp(a) corresponded to an 8.01-point increase in Gensini score (p = 0.019) and a 2.92-point increase in SYNTAX score (p <
0.002). CONCLUSIONS: Elevated Lp(a) levels are associated with earlier onset and greater complexity of CAD in ACS patients. These findings suggest Lp(a) is a critical risk factor for early atherogenesis and may require aggressive lipid-lowering strategies in primary prevention settings.