Lipoprotein(A) is Associated with Long-Term Plaque Progression on Serial Coronary CT Angiography

Background and Aims: Lipoprotein(a) (Lp[a]) is causally associated with atherosclerotic cardiovascular disease (ASCVD), however, data on the relationship between Lp(a) and coronary plaque burden are conflicting. This study investigated the effect of Lp(a) on long-term plaque progression in patients suspected of coronary artery disease (CAD). Methods: Per-protocol, patients from a coronary CT angiography (CCTA) cohort (Diemen et al., 2021) were invited for repeat CCTA imaging, regardless of symptoms. A total of 299 patients underwent follow-up CCTA imaging with a median scan interval of 10.2 [IQR 8.7-11.2] years. Patients who underwent coronary artery bypass grafting were excluded. Scans were analyzed using artificial intelligence-guided quantitative CCTA (AI-QCT; Cleerly Inc.). Quantitative plaque volumes (total and non-calcified and calcified plaque subsets) were adjusted for vessel volume (percent atheroma volume; PAV). The association between Lp(a), baseline and follow-up PAV as well as PAV change was evaluated in a multivariate linear regression model adjusted for clinical risk factors. Results: In total, 272 patients were included, mean age was 57±7 years, 42% were women. At baseline, median PAV was 2.52% [IQR 0.69-8.05], which increased to 6.14% [IQR 1.18-12.88] at follow-up. An interquartile range (IQR; 103 nmol/l) higher plasma Lp(a) concentration was associated with an 1.17% higher baseline PAV, resulted in a 0.65% higher increase in PAV during follow-up, and led to an 1.83% higher PAV at follow-up imaging (Figure). Similar associations were found for calcified and non-calcified plaque volumes. Conclusions: Patients with high Lp(a) levels have an up to 50% increased coronary plaque burden and markedly increased coronary artery progression throughout 10-year follow-up.