BACKGROUND: Lipoprotein(a) [Lp(a)] levels and diabetic status have been recognized as risk factors for atherosclerosis. However, no studies on atherosclerosis have integrated these two indicators. This study aimed to evaluate the relationship between Lp(a) levels, diabetic status, and their combined effects on subclinical atherosclerosis. METHODS: This cross-sectional study included patients presenting with a first episode of chest pain at the First Affiliated Hospital of Chongqing Medical University from June 2018 to February 2022. All participants underwent coronary computed tomography angiography (CCTA) and carotid ultrasound to evaluate subclinical atherosclerosis. Logistic regression analysis was used to examine the associations of Lp(a) levels and diabetic status-both individually and in combination-with coronary artery calcium (CAC) and carotid arteriopathy. RESULTS: Among 912 patients, 473 (51.9%) had CAC and 637 (69.8%) had carotid arteriopathy. After adjusting the confounding variables, elevated Lp(a) levels associated with CAC [odds ratio (OR) 1.51, 95% confidence interval (CI): 1.02-2.24, P=0.040] and carotid arteriopathy (OR 1.77, 95% CI: 1.10-2.86, P=0.02) were statistically significant. After combining diabetic status, almost all Lp(a) levels were significantly associated with CAC and CAC score categories (CAC scores: 0.1-99.9, 100-399.9, ≥400) in the diabetes mellitus (DM) group. In this group, the highest risk for CAC and the most severe CAC score categories were observed in patients with Lp(a) levels of >300 mg/L. Among patients with DM, in the lower Lp(a) level group, the prevalence and severity of CAC were more pronounced than those in the medium Lp(a) level group. Additionally, in patients with DM only, elevated Lp(a) levels were associated with carotid arteriopathy (OR 3.38, 95% CI: 1.24-9.20; P=0.02), increased carotid intima-media thickness (cIMT; OR 3.67, 95% CI: 1.10-12.30; P=0.04), and stable/vulnerable carotid plaque (OR 3.39, 95% CI: 1.09-10.55; P=0.04; OR 3.21, 95% CI: 1.07-9.65; P=0.04). However, there were no significant differences between prediabetes and CAC or carotid arteriopathy. CONCLUSIONS: In patients with chest pain and DM without cardiovascular disease (CVD), Lp(a) level was significantly associated with subclinical atherosclerosis and had a synergistic effect with DM. Notably, lower Lp(a) levels in patients with DM may lead to an additional subclinical atherosclerosis risk, whereas prediabetes does not show the same association. Therefore, these findings highlight the importance of formulating early preventive strategies for subclinical atherosclerosis based on Lp(a) levels and diabetic status.