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

Abstract

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 participants 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.

Keywords: Carotid atherosclerosis; Community-based cohort study; High-risk strategy; Risk reclassification; Small dense low-density lipoprotein cholesterol.

Supplementary Fig. 1.

Distribution of Small Dense Low-density Lipoprotein Cholesterol LDL, low-density lipoprotein. Data are shown as number for the distribution of small dense LDL cholesterol among total study participants.

Supplementary Fig. 2.

Distribution of Small Dense LDL Cholesterol in Participants Stratified According to LDL Cholesterol Level LDL, low-density lipoprotein. Data are shown as number for the distribution of small dense LDL cholesterol among the subgroup of LDL cholesterol level ≥ 160 mg/dL (A), 130–159 mg/dL (B), 100–129 mg/dL (C), and < 100 mg/dL (D).

Supplementary Fig. 3.

Progression of Carotid Atherosclerosis in Participants Stratified According to Small Dense LDL Cholesterol or LDL Cholesterol LDL, low-density lipoprotein. Data are shown as progression and incidence of carotid plaque in participants stratified according to small dense LDL cholesterol (A and B), or LDL cholesterol (C and D), respectively.

Fig. 1.

Plaque Progression Stratified According to Small Dense LDL Cholesterol Quartile in Participants with LDL Cholesterol Levels ≥ 160 mg/dL or < 100 mg/dL LDLC, low-density lipoprotein cholesterol; sdLDLC, small dense low-density lipoprotein cholesterol. Data are shown as the percentage (number of participants with plaque progression/total number of participants in the subgroup) demonstrating plaque progression among participants with LDLC levels ≥ 160 mg/dL or < 100 mg/dL.

Supplementary Fig. 4.

Relative Risk (95% Confidence Interval) of Plaque Progression Associated with the Highest Quartile of Small Dense LDL Cholesterol Compared with the Lowest Quartile in Subgroups of Known Cardiovascular Risk Factors CI, confidence interval; LDL, low-density lipoprotein; LDLC, low-density lipoprotein cholesterol; RR, relative risk; sdLDL, small dense low-density lipoprotein. Relative risk was calculated using a modified Poisson regression model after adjustment for known cardiovascular disease risk factors, lipid-lowering treatment, large buoyant LDL cholesterol. ^†P value for interaction analysis.

Fig. 2.

Relative Risk of Plaque Progression According to Subgroup of Small Dense LDL Cholesterol Quartile and Differing Cardiovascular Risk RR, relative risk; sdLDLC, small dense low-density lipoprotein cholesterol. Cardiovascular risk was calculated according to the 2016 Chinese guidelines for the management of dyslipidemia in adults. Relative risk was calculated using a modified Poisson regression model after adjustment for lipid-lowering treatment and large buoyant LDL cholesterol. *p < 0.050; **p < 0.010; ***p < 0.001.

Supplementary Fig. 5.

Relative Risk of Plaque Incidence According to Subgroup of Small Dense LDL Cholesterol Quartile and Differing Cardiovascular Risk LDL, low-density lipoprotein; RR, relative risk; sdLDLC, small dense low-density lipoprotein cholesterol. Cardiovascular risk was calculated according to the 2016 Chinese guideline for the management of dyslipidemia in adults. Relative risk was calculated using a modified Poisson regression model after adjustment for lipid-lowering treatment, and large buoyant LDL cholesterol in participants who had no plaque at baseline (n = 649). *P < 0.050; **P < 0.010; ***P < 0.001.