Relation of Lp(a) with plaque characteristics and clinical events: ATHEROREMO and IBIS_3 cohorts

Background & aims Although lipoprotein(a) [Lp(a)] is an established independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in primary prevention settings, it remains unclear whether Lp(a) contributes to an increased risk of adverse cardiovascular events in patients with established ASCVD. Objective Ascertain the prognostic value of Lp(a) in patients with established ASCVD and determine its associations with coronary plaque characteristics as assessed by intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS). Methods The current analysis combines the ATHEROREMO and IBIS-3 observational studies, which together enrolled 798 patients undergoing coronary angiography for stable angina pectoris or acute coronary syndrome. IVUS pullback and NIRS (in 273 patients) were performed to assess coronary plaque characteristics in a non-stenotic study segment. Linear and Cox regression models were applied to relate Lp(a) with coronary plaque characteristics and long-term (up to 10 year) clinical outcomes. Lp(a) was analysed both as a continuous and categorical variable, using 75 nmol/L as threshold. Results Mean (standard deviation) age of the patients was 61.6 (10.8) years; 75% were male; 32% had Lp(a) >75 nmol/L. Patients with Lp(a) >75 nmol/L had a significantly higher prevalence of hypercholesterolemia and prior percutaneous coronary intervention. These patients demonstrated higher IVUS-derived plaque burden (40.1% vs. 38.3%, p=0.024), though no associations were found with other plaque characteristics, e.g. minimum lumen area, thin-cap fibroatheroroma, and NIRS-derived lipid core burden index. No association was found between Lp(a) and long-term major adverse cardiac events (hazard ratio [HR] 1.12, 95% confidence interval [CI] 0.80–1.57, p = 0.51) and all-cause mortality (HR 0.69, 95% CI 0.46–1.02, p = 0.070). Conclusions Among patients with established ASCVD, Lp(a) was associated with plaque burden, supporting evidence that relates Lp(a) to atherosclerotic processes. However, Lp(a) was not associated with long-term cardiac adverse events or mortality in these patients.