High sdLDL Cholesterol can be Used to Reclassify Individuals with Low Cardiovascular Risk for Early Intervention: Findings from the Chinese Multi-Provincial Cohort Study

Aim: A high-risk strategy has been implemented for lipid-lowering therapy in the primary prevention of cardiovascular disease. However, atherosclerosis and cardiovascular events are common among individuals with low cardiovascular risk. This study aimed to determine whether the small dense low-density lipoprotein cholesterol (sdLDLC) level can predict carotid atherosclerosis progression and identify high-risk individuals. Methods: Baseline sdLDLC and low-density lipoprotein cholesterol (LDLC) were measured in 808 particip ants from the Chinese Multi-provincial Cohort Study, aged 45–74 years. Adjusted relative risk was calculated using a modified Poisson regression model to assess the relationship between sdLDLC and 5-year atherosclerosis progression, as indicated by the progression, incidence, and multi-territorial extent of carotid plaque. Results: The 5-year atherosclerosis progression increased significantly with increased sdLDLC. Baseline sdLDLC was significantly associated with the short-term risk of plaque progression after multivariable adjustment, even in participants with low LDLC or a 10-year estimated cardiovascular risk. sdLDLC predicted plaque progression (relative risk 2.05; 95% confidence interval 1.43–2.93) in participants with LDLC < 130 mg/dL. Furthermore, participants with the highest sdLDLC but intermediate or low cardiovascular risk (accounting for 16% of the cohort) had double the risk of plaque progression, which was comparable to those with the same sdLDLC and high cardiovascular risk, relative to those with the lowest sdLDLC levels and low cardiovascular risk. Conclusions: sdLDLC is independently associated with the progression of carotid atherosclerosis, which may provide a basis for clinicians to reclassify individuals believed to be at low cardiovascular risk into the high-risk category, and those with high sdLDLC may benefit from more aggressive cholesterol-lowering treatment.