Sex-specific association between low-density lipoprotein cholesterol and layered plaque formation

Sex-specific mechanisms in atherosclerosis have been suggested, with low-density lipoprotein cholesterol (LDL-C) playing a less prominent role in predicting cardiovascular risk in women than in men.

The aim of this study was to assess sex-specific differences in the association between LDL-C levels and plaque morphology.

In this multicenter observational study, 325 patients with coronary artery disease underwent optical coherence tomography (OCT) before percutaneous coronary intervention. The plaque morphology at target lesions was assessed using OCT.

Among the participants, 263 were men, and 62 were women. Patients were stratified into the following LDL-C tertiles: low (<72 mg/dL), moderate (72-97 mg/dL), and high (≥98 mg/dL). In men, higher LDL-C levels correlated with an increased prevalence of lipid-rich plaques, macrophage infiltration, cholesterol crystals, and multilayered plaque. The LDL-C levels were also associated with a maximal layer arc (low vs moderate vs high LDL-C levels: 0 vs 131 vs 169) and a greater maximal lipid arc (low vs moderate vs high LDL-C levels: 160 vs 214 vs 252). In contrast, no corresponding associations were observed in women.

LDL-C levels were associated with plaque vulnerability in men, particularly lipid accumulation and layered plaque formation, but not in women, underscoring sex-specific differences in lipid-driven coronary pathology.