Lp(a) rarely coexists without coronary atherosclerosis

Background Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein with proatherogenic, proinflammatory, and prothrombotic properties. Elevated Lp(a) levels are genetically determined and have been established as an independent causal risk factor for atherosclerotic cardiovascular disease. Beyond its role in plaque initiation, Lp(a) has been implicated in the progression and calcification of atherosclerotic lesions through different mechanisms. In the setting of acute coronary syndromes (ACS), Lp(a) may play a dual pathophysiologic role, contributing not only to atherosclerotic plaque burden but also to plaque instability and thrombosis. Purpose To assess the prevalence and pattern of coronary artery disease (CAD) on Coronary computed tomography angiography (CCTA) among ACS patients with elevated Lp(a). Methods We analyzed a subgroup of 74 patients with elevated Lp(a) from a prospective cohort of 1001 individuals with an ACS undergoing CCTA. Patients over 18 years of age with a diagnosis of ACS without ST elevation who did not meet high-risk criteria (hemodynamic instability, dynamic changes in the ST segment or T wave, ventricular arrhythmia, GRACE score >140, refractory angina, heart failure or cardiorespiratory arrest) were included. Data collection was carried out between May 11, 2022 and February 20, 2026. Results 74 patients were included, with a mean age of 59 years, of which 40% were women and 60% men. Among the admission diagnoses, 20% were NSTEMI and 80% were unstable angina according to the 4th universal definition of acute myocardial infarction (AMI). The median high-sensitivity cardiac troponin T value was 8 nanograms per litre (interquartile range, 5 to 15) for the first troponin sample, and 8 nanograms per litre (interquartile range, 7 to 20) for the second one. CCTA was not performed in 3 patients due to a CAC score >400 AU. Among patients who underwent CCTA, 5% had no coronary plaques and 39% had non-obstructive coronary artery disease (<50% stenosis), while 50% had obstructive disease and 6% had nondiagnostic studies. High-risk plaque features were identified in 20%. All 4 patients with normal coronary arteries were women (mean age 56 years). Conclusion In patients with an ACS undergoing CCTA, elevated Lp(a) identifies a population with a markedly low likelihood of normal coronary arteries and a high burden of both obstructive and non-obstructive CAD (95%), supporting its role as a potent pro-atherogenic driver of anatomical coronary disease. The observation that all normal studies occurred in women suggests potential sex-specific differences in the anatomical expression of Lp(a)-associated risk, warranting further investigation. Possible mechanisms may include hormonal influences, differences in plaque composition, microvascular predominance, or delayed phenotypic conversion to obstructive epicardial disease.