Raised lipoprotein(a) associates with rapidly progressive coronary atherosclerosis after acute coronary syndrome

Background Lipoprotein(a), or Lp(a), is a genetically mediated lipid particle independently associated with the development of premature coronary artery disease and ischaemic events. Prior studies have shown that elevated levels promote inflammation and increase plaque volume and vulnerability over long-term follow-up. Here, we examined the short-term impact of Lp(a) on residual atheroma in survivors of acute coronary syndrome (ACS). Methods This multicentre, prospective study recruited individuals with an ACS who had undergone invasive coronary angiography and then had their residual atheroma imaged by serial photon-counting coronary computed tomography angiography (PC-CCTA) within 30 days, and 12 months later. Paired scans were analysed by semi-automated software to quantify plaque burden, volume and composition at a per-patient level. Lp(a) was analysed at 12 months using an immunoturbidimetric assay, with a threshold of 125 nmol/L used to define elevated levels. Results 82 participants were included (median age: 61.9 years; female: 22%; STEMI: 50%, NSTEMI: 41%, unstable angina: 9%). Participants received usual clinician-directed care during follow-up, with 96% on statins and median LDL-C reducing from 2.9 mmol/L (112 mg/dL) to 1.4 mmol/L (54 mg/dL). 18% had elevated Lp(a). There were no significant differences between low and high Lp(a) groups for other risk factors, medication use or level of risk factor control over the study duration. Although they also had comparable baseline measurements for plaque volume, burden and composition, high Lp(a) was associated with greater progression of total plaque (TP) volume (34.5 vs 5.0 mm3, P=0.020) and burden (5.9 vs 0.1%, P=0.005), and noncalcified plaque (NCP) volume (28.9 vs -3.8 mm3, P=0.030) and burden (4.9 vs -1.2%, P=0.007) over 12 months. In contrast, changes in calcified plaque (CP) and low-density noncalcified plaque (LD-NCP) were similar between the two groups. Using a threshold of 2% change for total plaque burden to define meaningful plaque progression, 73% of patients with high Lp(a) met progressor status, compared to 34% in those without raised Lp(a) (P=0.01). Conclusion Raised Lp(a) levels >125 nmol/L are present in almost 20% of people presenting with an ACS and associate with at least five-fold greater progression of total and noncalcified plaque over the first year of usual clinician-directed treatment.