Lipidic Plaque Features of Polyvascular Disease in Response to Low-Density Lipoprotein Cholesterol <55 mg/dL: Implication of Circulating Lipoprotein(a) Levels.

BACKGROUND: Patients with polyvascular disease (PolyVD) or atherosclerosis in the coronaries and at least 1 additional arterial bed are at increased risk of subsequent clinical cardiovascular events. While lowering low-density lipoprotein cholesterol (LDL-C) is recommended in the secondary prevention settings, whether PolyVD favorably responds to LDL-C control remains unknown. METHODS: The current study analyzed in 422 patients (422 target lesions) with coronary artery disease by using near-infrared spectroscopy imaging before percutaneous coronary intervention in the REASSURE-NIRS (Revelation of Pathophysiological Phenotypes of Vulnerable Lipid-Rich Plaque on Near-Infrared Spectroscopy; NCT04864171) multicenter registry. PolyVD was defined as concomitance of coronary artery disease and cerebrovascular disease or lower extremity arterial disease. RESULTS: Maximum 4-mm lipid-core burden index, as a near-infrared spectroscopy-derived marker of plaque instability, and lipoprotein(a) [Lp(a)] were compared across LDL-C levels (<55, 55-69, and ≥70mg/dL) in patients with (n=189) and without PolyVD (n=233). The proportion of LDL-C <55 mg/dL was 15.3 and 9.4% in patients with and without PolyVD, respectively. In patients without PolyVD, LDL-C <55 mg/dL was associated with lower maximum 4-mm lipid-core burden index (P=0.045). Furthermore, a lower frequency of Lp(a) ≥50 mg/dL was observed in patients without PolyVD who achieved LDL-C <55 mg/dL (P=0.042). Only 4.5% of them presented with Lp(a) ≥50 mg/dL. However, achieved LDL-C <55 mg/dL was not associated with lower maximum 4-mm lipid-core burden index in patients with PolyVD (P=0.085). Moreover, Lp(a) remained comparable regardless of LDL-C levels (P=0.902). Of note, 20.7% of patients with PolyVD with LDL-C <55 mg/dL exhibited Lp(a) ≥50 mg/dL. CONCLUSIONS: Coronary atheroma in patients with PolyVD was resistant to lowering LDL-C <55 mg/dL. Given that >20% of those with LDL-C <55 mg/dL exhibited Lp(a) ≥50 mg/dL, Lp(a) may be a potential therapeutic target to delipidate coronary atheroma.