Background: Elevated lipoprotein(a) [Lp(a)] levels are associated with the presence and extent of coronary atherosclerosis on coronary computed tomography angiography (CCTA). In previous analyses by our group, high Lp(a) (≥125 nmol/L) correlated with coronary stenosis independent of age and LDL-cholesterol. However, no clear linear relationship between Lp(a) and plaque burden was found, unlike clinical data showing a linear link with cardiovascular events. As coronary plaque is the key mediator between Lp(a) and outcomes, this study evaluated different Lp(a) thresholds in relation to plaque extent and composition on CCTA.
Methods: Patients undergoing clinically indicated CCTA with a third-generation dual-source scanner for suspected coronary artery disease were included. All had available lipoprotein(a) [Lp(a)] measurements and were examined at a German outpatient center between July 2017 and June 2020. Quantitative plaque analysis of all coronary arteries was performed using validated semi-automated software. Total plaque burden was quantified and analyzed across Lp(a) thresholds (first and third quartiles, and fixed cut-offs of 100, 125, 150, 175, and 200 nmol/L).
Results: Complete data were available for 1,946 patients (mean age 63.3±11.1 years; 62.6% male). CCTA excluded coronary atherosclerosis in 629 patients (32.3%), identified non-obstructive CAD in 981 (50.4%), and obstructive CAD in 336 (17.3%). Lp(a) thresholds for the first and third quartiles were 7 nmol/L and 72 nmol/L, respectively. Across fixed cut-offs, 411 patients (21.1%) had Lp(a) ≥100 nmol/L, 336 (17.3%) ≥125 nmol/L, 263 (13.5%) ≥150 nmol/L, 203 (10.4%) ≥175 nmol/L, and 146 (7.5%) ≥200 nmol/L. At Lp(a) levels ≥175 nmol/L, patients exhibited significantly greater total plaque volumes compared with those below this threshold (67.4 [IQR 9.3–204.9] mm³ vs. 44.1 [IQR 0.0–165.0] mm³; P=0.011), affecting all plaque components: calcified (38.0 [IQR 3.9–118.0] vs. 25.1 [IQR 0.0–101.9] mm³; P=0.035), non-calcified (11.6 [IQR 0.1–57.6] vs. 7.0 [IQR 0.0–43.2] mm³; P=0.010), and lipid-rich plaques (0.1 [IQR 0.0–1.7] vs. 0.0 [IQR 0.0–1.0] mm³; P=0.034). With increasing Lp(a), the distribution shifted from “no atherosclerosis” toward “obstructive CAD,” significant at ≥175 nmol/L (P=0.003) and ≥200 nmol/L (P=0.017). The maximum mean stenosis was similar across quartiles but significantly higher at Lp(a) ≥100 nmol/L (P=0.029) and above. Coronary area stenoses > 80% (considered a high-risk plaque feature) were significantly less frequent in the lowest Lp(a) quartile compared with higher quartiles (2.9% vs. 6.2%; P=0.007).
Conclusions: Elevated Lp(a) levels were linked to a greater extent and higher-risk phenotype of coronary atherosclerosis on CCTA. Among the evaluated thresholds, ≥175 nmol/L emerged as the most relevant cut-off, identifying patients with higher plaque volumes, more obstructive CAD, and increased prevalence of high-risk features such as severe stenosis and positive remodelling. This threshold may mark a critical point beyond which plaque burden and vulnerability rise substantially, defining a target group for early coronary assessment and risk stratification by CCTA.
