Characterization of lipidic coronary atheroma under control of low-density lipoprotein <1.8 mmol/l and lipoprotein (a) <50 mg/dl in patients with coronary artery disease

Abstract

Abstract Background Lp(a) has been considered as a potential therapeutic target associated with atherosclerosis. In particular, Lp(a) ≧50 mg/dL has been shown to predict an elevated cardiovascular risk even under lowering LDL-C level, indicating that lowering of both LDL-C and Lp(a) may be more beneficial to halt atherogenesis. However, atherosclerotic features with favorable control of these lipid targets have not been fully characterized yet. The REASSURE-NIRS registry (NCT04864171) is an on-going multi-center registry which enrolls CAD patients receiving near-infrared spectroscopy (NIRS)/IVUS-guided PCI in Japan. Given that NIRS enables to quantitatively evaluate lipidic plaque materials, this registry provides an opportunity to investigate lipidic plaque features in association with LDL-C and Lp(a) levels. Objectives The aim of this study was to elucidate NIRS-derived characteristics of coronary atheroma in patients with CAD who exhibited both LDL-C<1.8 mmol/L and Lp(a) <50 mg/dL. Methods From the REASSURE-NIRS registry (n=1013), we investigated 549 culprit lesions in 498 patients with measurement of both LDL-C and Lp(a) levels at the index of PCI. Maximum 4-mm lipid core burden index (max LCBI4mm) at culprit lesions were measured with NIRS imaging prior to PCI. Study subjects were stratified into 4 groups according to LDL-C and Lp(a) levels: LDL-C<1.8mmol/L and Lp(a)<50mg/dL, LDL-C≧1.8mmol/ and Lp(a)<50mg/dL, LDL-C<1.8mmol/L and Lp(a)≧50mg/dL, LDL-C≧1.8mmol/L and Lp(a)≧50mg/dL. Clinical characteristics and max LCBI4mm were compared in 4 groups. Results In the current study, 30.6% of patients was ACS. Under the use of lipid-lowering therapies (statin: 68.4% and high-intensity statin: 26.0%), 33.1% of study population exhibited both LDL-C<1.8mmol/L and Lp(a)<50mg/dL. Patients with LDL-C<1.8mmol/L and Lp(a)<50mg/dL were more likely to be male (p=0.002) and smoker (p=0.002) and have a history of previous MI (p<0.001). As expected, statin was more frequently used in those with both LDL-C<1.8mmol/L and Lp(a)<50mg/dL (p<0.001). On NIRS imaging analysis, patients with low LDL-C<1.8mmol/L and Lp(a)<50mg/dL were associated with significantly lower max LCBI4mm (Figure). Of note, even in patients with LDL-C<1.8mmol/L, max LCBI4mm was lower in those achieving Lp(a) <50 mg/dL compared to those with Lp(a) ≧50 mg/dL (p=0.001). Multivariate analysis adjusting for ACS, LDL-C levels and statin use, Lp(a) levels revealed emerged as independent predictor of maxLCBI4mm (β=1.0, 95%CI: 0.06 to 2.04, p=0.04). Conclusion Patients with LDL-C<1.8mmol/L and Lp(a)<50mg/dL more likely exhibited a smaller amount of lipidic plaque materials on NIRS imaging. Our findings support that lowering both LDL-C and Lp(a) may be more beneficial to modulate lipidic plaque component, which ultimately results in the further reduction of ASCVD risks.Comparison of clinical characteristics