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 mm 2 , 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 mm 3 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 mm 3 versus 293.9 mm 3 , 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