Introduction: The lion’s share of atherosclerosis risk is not explained by traditional risk factors alone as more than half of coronary artery disease (CAD) patients do not have more than one risk factor. The presence of high-risk features in coronary atherosclerotic plaques, such as large lipid-rich necrotic core (LRNC), may indicate increased risk of rupture and events. Despite the systemic nature of atherosclerosis, it remains unclear whether high-risk features in distant arteries, such as the carotid artery, are significantly associated with CAD risk. We hypothesized that the carotid LRNC volume is independently associated with CAD risk.
Methods: Bilateral carotid magnetic resonance imaging was performed in 3 cohorts of middle-aged men, free of symptomatic carotid disease, exhibiting graded CAD risk: 1) without symptomatic CAD or risk factors (NRF); 2) without symptomatic CAD, but with cardiovascular risk factors (CVRF); and 3) with symptomatic CAD.
Results: The NRF (n=113, 30.7 ± 8.4 years), CVRF (n=226, 44.5 ± 11.4 years) and CAD (n=152, 60.8 ± 8.9 years) cohorts presented graded CAD risk, illustrated by incrementally progressive 10-year Framingham risk score (FRS) (respectively, 2.3 ± 2.5 vs. 10.7 ± 9.5 vs. 31.2 ± 17.3%, p<0.001). The prevalence of carotid artery LRNC increased from NRF to CVRF to CAD cohorts (35.7 vs. 49.6 vs. 69.7%, p<0.001). The LRNC volume also progressed from NRF to CVRF to CAD cohorts (1.9 ± 3.6 vs. 3.6 ± 5.9 vs. 5.8 ± 7.2 mm3/4 mm, p<0.001) and was strongly correlated to maximum wall thickness (NRF: r=0.74; CVRF: r=0.69; CAD: r=0.61; p<0.001 for all). The carotid atherosclerosis score, estimated from the maximum %LRNC and wall thickness, increased from NRF to CVRF to CAD cohorts (p<0.001) and was associated to the presence of CAD, even after adjusting for the FRS (odds ratio [OR]: 3.53, p<0.001). Finally, the presence of CAD was associated with the carotid artery LRNC volume (OR: 1.07, p<0.001), even after adjusting for FRS and maximum wall thickness (OR: 1.06, p=0.035).
Conclusion: For the first time, we demonstrated that the carotid artery LRNC volume increases with CAD risk in middle-aged men. Screening for carotid artery LRNC may improve risk stratification beyond traditional risk scores and atherosclerosis burden measurement alone.