Aging and Sex Modify the Risk of Carotid Plaque Thrombosis Related to Dyslipidemic Profile

Abstract

Background: Dyslipidemia plays a critical role in carotid plaque instability and related cerebrovascular events. Reduction of low-density lipoprotein cholesterol (LDL-C) levels decreases ischemic stroke risk; however, a residual cardiovascular risk persists. Starting from this evidence, this study evaluated the impact of dyslipidemia on carotid plaque instability while also considering age and sex.

Methods: In this observational study, a total of 354 carotid plaques from symptomatic and asymptomatic patients undergoing endarterectomy were analyzed histologically. Dyslipidemic profiles, including high LDL-C, remnant cholesterol, triglycerides, and low high-density lipoprotein cholesterol, were assessed alongside other risk factors. Logistic regression identified independent predictors of unstable plaques, and subgroup analyses evaluated the influence of age (<70, ≥70 years) and sex.

Results: Unstable plaques were observed in 45.2% of cases. High LDL-C emerged as the strongest independent risk factor for plaque instability. The combination of high LDL-C with elevated remnant cholesterol or triglycerides significantly increased the risk of plaque destabilization. Age and sex influenced the risk associated with dyslipidemic profiles, with women who had elevated LDL-C combined with high-remnant cholesterol or triglycerides showing a substantially higher risk of carotid plaque instability compared with men. Furthermore, individuals <70 years of age exhibited a greater risk of plaque instability compared with older patients, highlighting the critical role of these nonmodifiable factors.

Conclusions: The data reported here highlight the importance of a personalized medicine approach to lipid management, addressing not only LDL-C but also remnant cholesterol and triglycerides. Tailored interventions targeting specific dyslipidemic profiles could more effectively reduce the risk of carotid plaque rupture and cerebrovascular events, particularly in women and patients aged <70 years.

Keywords: atherosclerosis; cholesterol; dyslipidemia; ischemic stroke; triglycerides.

Figure 1.

Histological aspects of atherosclerotic carotid plaques. A, A fibrocalcific carotid plaque with foci of bone metaplasia. B, A stable fibroatheromatic plaque characterized by a thick fibrous cap. C, A thrombotic ruptured plaque. D, A plaque with erosion associated with an acute thrombus. Scale bar represents 800 µm.

Figure 2.

Multivariate analysis. Graph presents the odds ratios (ORs) of plaque instability with 95% CIs for examined variables including high low-density lipoprotein cholesterol (LDL-C) alone and in combination with remnant cholesterol (RC) and triglycerides (TG). Each point represents the estimated OR for the corresponding condition, with the horizontal bars illustrating the range of the 95% CI. The red dashed line at OR=1 serves as the reference point, indicating no effect or association. HDL-C indicates high-density lipoprotein cholesterol.