Lipoprotein(a) Association with Plaque Progression and Cardiac Events on Serial CT Angiography

Background This study investigated the effect of lipoprotein(a) (Lp[a]) on long-term plaque progression, high-risk plaque (HRP) and pericoronary adipose tissue attenuation (PCATa) in patients suspected of coronary artery disease. 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 and vessels revascularized by percutaneous coronary intervention were excluded. Scans were analyzed using atherosclerosis-imaging quantitative CCTA (AI-QCT; Cleerly Inc.). The associations between high (Tertile 3; >67 nmol/l) and low Lp(a) (Tertile 1 and 2; ≤67 nmol/l), baseline and follow-up plaque burden and characteristics were evaluated using multivariable regression adjusted for clinical risk factors, statin use and scanner settings. Results: In total, 274 patients were included, mean age was 57±7 years, 42% were women. Patients with high Lp(a) levels had higher volumes of percent atheroma volume (PAV) at baseline and follow-up and higher rate of plaque progression (Figure 1A). The difference in PAV caused by high Lp(a) versus low Lp(a) patients was similar to the effect of a 12-year age difference. At baseline, patients in the highest tertile of Lp(a) levels had a higher prevalence of both HRP (OR 2.24; p=0.009) and above-median right coronary artery PCATa (OR 1.76; p=0.049). Finally, patients with high Lp(a) levels had a twofold higher incidence of major adverse cardiovascular events (MACE; Figure 1B; p=0.044). Conclusion: Patients with high Lp(a) levels had increased coronary plaque burden, increased prevalence of high-risk plaque and pericoronary inflammation as well as increased plaque progression leading to an increased incidence of MACE throughout 10-year follow-up.