Background Carotid intima-media thickening is an important indicator of early atherosclerotic changes in arteries. Early identification and active intervention can effectively reverse the condition.
Objective To explore the association between the longitudinal trajectories of non-high-density lipoprotein cholesterol (nHDL-C) and carotid intima-media thickening in adults, and to predict the risk of carotid intima-media thickening in a health checkup population.
Methods This ambidirectional cohort study enrolled individuals who participated in health examinations at Peking University Third Hospital between 2013 and 2023. Baseline data and physical examination indicators were collected, and CIMT was measured. Participants with normal baseline CIMT were followed up until the occurrence of carotid intima-media thickening or loss to follow-up. Separate dynamic trajectories of nHDL-C with age were constructed for male and female subjects. All nHDL-C records before the occurrence of the outcome were included. A joint latent class model (JLCM) was used to identify heterogeneous nHDL-C change trajectories and predict the risk differences of CIMT among different trajectories. The optimal number of latent classes was determined using the Akaike information criterion (AIC) , Bayesian information criterion (BIC) , sample-adjusted Bayesian information criterion (SABIC) , entropy>0.5, and conditional independence assumption (Score Test P>0.05) . Cox models were constructed using baseline nHDL-C values and nHDL-C change trajectories, respectively. The area under the receiver operating characteristic (ROC) curve (AUC) and concordance index (C-index) of each model were compared, and the goodness of fit of the models was tested and evaluated.
Results A total of 5 741 subjects with normal baseline lipid levels were included, with 2 487 males and 3 254 females. Among male participants, 393 developed carotid intima-media thickening. There were statistically significant differences in follow-up time, age, BMI, systolic blood pressure (SBP) , diastolic blood pressure (DBP) , total cholesterol (TC) , triglycerides (TG) , low-density lipoprotein cholesterol (LDL-C) , nHDL-C, and the proportion of hypertension between those with and without CIMT (P<0.05) . Among female participants, 330 developed carotid intima-media thickening. There were statistically significant differences in follow-up time, age, BMI, SBP, DBP, TC, TG, LDL-C, nHDL-C, and the proportion of hypertension between the two groups (P<0.05) . In the male population, the three-class model had the highest entropy, the smallest BIC and SABIC, and met the conditional independence assumption (Score Test P=0.207 9) , so the three-class model was selected as the best-fitting model. In the female population, the four-class model had little change in entropy, BIC, and SABIC compared with the three-class model and met the conditional independence assumption (Score Test P=0.267 8) , so the four-class model was selected as the best-fitting model. Among the three latent classes of nHDL-C in the male check-up population, Class 1 showed a trajectory curve that first slowly increased and then remained stable at a low level, named the "low-level stable group" , accounting for 83.80%; Class 2 showed a rapid increase, named the "rapidly increasing group" , accounting for 1.09%; Class 3 showed a slow increase, named the "slowly increasing group" , accounting for 15.12%. The rapidly increasing group had the highest risk, followed by the slowly increasing group, and the low-level stable group had the lowest risk. Compared with the low-level stable group, the hazard ratios (HR) of the slowly increasing group and the rapidly increasing group in males were 10.51 (95%CI=7.90-13.98) and 23.25 (95%CI=10.40-51.98) , respectively. Among the four latent classes of nHDL-C in the female check-up population, Class 1 showed a stable low level, named the "low-level stable group" , accounting for 93.09%; Class 2 showed a U-shaped trajectory, named the "low-level stable-increasing group" , accounting for 1.26%; Class 3 had stable lipid levels at a moderate level without significant fluctuations, named the "moderate-level stable group" , accounting for 4.58%; Class 4 showed a rapid increase in lipid levels, named the "rapidly increasing group" , accounting for 1.08%. The rapidly increasing group had the highest risk. Before the age of 40, the risks of the low-level stable group, low-level stable-increasing group, and moderate-level stable group were similar. After the age of 40, the CIMT thickening risk of the moderate-level stable group increased rapidly, and after the age of 50, the risk of the low-level stable-increasing group increased rapidly. Compared with the low-level stable group, the HR of the low-level stable-increasing group, moderate-level stable group, and rapidly increasing group in females were 3.69 (95%CI=2.27-5.99) , 15.48 (95%CI=10.56-22.70) , and 13.93 (95%CI=5.44-35.69) , respectively. The results of model goodness-of-fit tests and evaluations showed that in both male and female populations, compared with the baseline model, the Class model and the Class+nHDL-C model had significantly increased AUC and C-index values at multiple time points.
Conclusion In the health check-up population, both males and females have different trajectories of nHDL-C levels, and different trajectory categories significantly affect the risk of CIMT. Compared with a single baseline nHDL-C value, trajectory classification can more accurately predict the risk of CIMT thickening. Continuous lipid monitoring is of great significance for individual health management. The risk assessment method combined with trajectory analysis helps to identify high-risk individuals early and provides a basis for individual risk stratification and active intervention.
