Lipid-rich necrotic core of the carotid plaque and the risk of major adverse cardiovascular and cerebrovascular events: a meta-analysis and systematic review

Background Carotid atherosclerosis drives major adverse cardiovascular and cerebrovascular events (MACCEs), but the role of lipid-rich necrotic core (LRNC) remains controversial. We aimed to clarify this via systematic review and meta-analysis. Methods PubMed, Embase, Web of Science, and Cochrane were searched for studies reporting LRNC prevalence or size and MACCEs from inception to March 1, 2026. Study quality was assessed using the Agency for Healthcare Research and Quality (AHRQ) and Newcastle-Ottawa Scale (NOS) tools. Results Our meta-analysis included 18 studies, involving 5,682 patients and 6,257 carotid plaques. Our results showed that in individuals with lipid-core-containing carotid plaques, the cumulative incidence of MACCEs over a mean follow-up of ∼32.2 months (range 3.1–61.2 months) was approximately 7.6% (95% CI 0.059–0.098). When a stroke occurred, the probability of it occurring on the same side as a lipid-core-containing plaque was approximately 58.0% (95% CI 0.427–0.720). Moreover, the presence of a lipid core in carotid plaques was a risk factor for MACCEs, increasing their incidence (HR: 1.570, 95% CI 1.006–2.450; OR: 2.042, 95% CI 1.474–2.828). Compared with patients without MACCEs, those with MACCEs had larger mean LRNC volumes (in mm 3 ) (MD: 8.284 mm 3 , 95% CI 1.353–15.215), larger maximum LRNC volumes (in mm 2 ) (MD: 8.68 mm 2 , 95% CI 4.095–13.265), and a higher proportion of LRNC in the plaque (in %) (MD: 0.471%, 95% CI 0.073–0.868). Additionally, patients with MACCEs had a higher proportion of lipid core volume in the plaque (in %) (MD: 2.283%, 95% CI 0.354–4.211). Conclusions Despite limited studies, LRNC presence and size are MACCE risk factors, suggesting therapeutic targeting prevents MACCEs.