Association of Lipoprotein (a) With Coronary-Computed Tomography Angiography–Assessed High-Risk Coronary Disease Attributes and Cardiovascular Outcomes

Background: Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular events. This study evaluated the relationship between Lp(a) and high-risk attributes by coronary computed tomography angiography as well as their prognostic value. Methods: Lp(a) and coronary computed tomography angiography from 377 consecutive patients at Zhongshan Hospital (Shanghai, China) were evaluated. High-risk attributes were defined as high-risk morphological attributes (low attenuation plaque, positive remodeling, napkin-ring sign, spotty calcification, minimum lumen area <4 mm2, or plaque burden [ratio between cross-sectional plaque area at the site of maximum stenosis and cross-sectional vessel area] ≥70%); inflammatory attribute represented by fat attenuation index; high-risk physiological attributes [lesion-specific ischemia defined by fractional flow reserve by coronary computed tomography angiography ≤0.8, physiologic diffuseness defined by fractional flow reserve by coronary computed tomography angiography pullback pressure gradient]. Total plaque volume in mm3 was also quantified. Quintiles or binary classification of Lp(a) levels were used to evaluate its relationships with plaque features and clinical outcomes with ANOVA, Cox models, and log-rank tests, as appropriate. The major adverse cardiovascular event included cardiovascular death, nonfatal myocardial infarction, and target vessel revascularization. Results: Lp(a) was significantly associated with total plaque volume (P=0.004), fat attenuation index (P=0.031), and fractional flow reserve by coronary computed tomography angiography pullback pressure gradient (P=0.038). Patients with a high Lp(a) level had a higher total plaque volume (393.3 mm3 versus 293.9 mm3, P<0.001), lower pullback pressure gradient (0.62 versus 0.69, P=0.023), higher fat attenuation index (−70.5HU versus −73.9HU, P=0.004), and higher incidence of major adverse cardiovascular event (14.5% versus 6.3%, adjusted hazard ratio: 2.52, 95% CI: 1.12–5.63, P=0.025). In a 4-group classification according to Lp(a) and high-risk attributes, patients with high Lp(a) and ≥3 high-risk attributes had the highest risk of major adverse cardiovascular event (25.9%; overall P<0.001). Causal mediation analysis revealed that around 40% of the prognostic effect of Lp(a) was mediated by high-risk attributes. Conclusions: Lp(a) level is associated with coronary computed tomography angiography high-risk characteristics, including morphologic, physiologic, and inflammatory attributes as well as major adverse cardiovascular event. This effect is partly mediated by inflammation and vulnerable plaque. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05323227