High Lipoprotein(a) levels and coronary plaque burden: 175 nmol/L as a potential target for early CT-based risk assessment

Background Elevated lipoprotein(a) [Lp(a)] levels are associated with both the presence and extent of coronary plaque burden on coronary computed tomography angiography (CCTA). In contrast to clinical outcome data demonstrating a linear association between Lp(a) and cardiovascular events, no clear linear relationship was observed between Lp(a) and overall plaque burden in prior CCTA-analyses. Purpose Given that coronary plaque burden represents the key pathophysiological link between elevated Lp(a) and adverse cardiovascular outcomes, the present study aimed to evaluate different Lp(a) thresholds in relation to total plaque burden and plaque composition as assessed by CCTA. Methods Consecutive patients undergoing clinically indicated CCTA for suspected coronary artery disease (CAD) on a third-generation dual-source CT scanner (SOMATOM Force, Siemens Healthineers) at a German outpatient center between April 2018 and June 2020 were included. Lp(a) concentrations were determined using a fully automated particle-enhanced turbidimetric immunoassay on the cobas c 303 system (Roche Diagnostics). Quantitative plaque analysis was performed using validated semi-automated software. Results Including 1,946 patients (63.3 ± 11.1 years; 62.6% male), CCTA identified non-obstructive CAD in 981 (50.4%), and obstructive CAD in 336 patients (17.3%). 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 had significantly higher total plaque volumes compared with those below this threshold (67.4 vs. 44.1 mm³; P = 0.011). This increase was consistent across all plaque components, including calcified, non-calcified, and lipid-rich plaques (all P < 0.05). With rising Lp(a) levels, plaque distribution shifted from “no plaque burden” toward “obstructive CAD,” reaching statistical significance at ≥175 nmol/L (P = 0.003) and ≥200 nmol/L (P = 0.017). While mean maximum stenosis did not differ across quartiles, it was significantly higher at Lp(a) ≥100 nmol/L and above (P = 0.029). Severe coronary stenoses (>80%), considered a high-risk plaque feature, were less frequent in the lowest Lp(a) quartile compared with higher quartiles (2.9% vs. 6.2%; P = 0.007). Positive remodeling was more common at Lp(a) ≥175 nmol/L (P = 0.029), with a trend toward more low-attenuation plaques at these levels (P = 0.058). Conclusions Elevated Lp(a) levels were linked to a greater extent and higher-risk phenotype of coronary plaque burden. 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. This threshold may mark a critical point beyond which plaque burden and vulnerability rise substantially, defining a target group for early coronary assessment by CCTA.