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BACKGROUND: Elevated low-density lipoprotein (LDL) cholesterol levels represent a significant modifiable risk factor for atherosclerotic cardiovascular disease. However, a residual risk persists, possibly attributed to other atherogenic lipoproteins such as non-high-density lipoprotein (non-HDL) and remnant cholesterol. Nevertheless, few studies have explored the independent associations between these lipid biomarkers and early atherosclerotic disease.

OBJECTIVE: To evaluate the relative contributions of LDL, non-HDL, and remnant cholesterol to subclinical atherosclerosis, assessed by carotid ultrasonography.

METHOD: In this cross-sectional study, we included 1929 previously healthy individuals from the pragmatic VIPVIZA trial who had available lipid levels and carotid ultrasonography results to assess subclinical disease. Non-HDL, LDL, and remnant cholesterol were calculated from a standard lipid profile. Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT) and the presence of carotid plaques.

RESULTS: We found that all lipid variables (LDL, non-HDL, and remnant cholesterol) were associated with subclinical atherosclerosis in univariable models (P < .01 across all models for cIMT and P < .001, P < .001, P = .003 respectively for carotid plaques). In multivariable-adjusted models, increasing LDL and non-HDL cholesterol levels were still significantly associated with increased odds of having carotid plaques (P < .001 for both) and increased cIMT (P < .001 for both). However, no independent association between remnant cholesterol and subclinical atherosclerosis was observed in the model adjusted for LDL cholesterol levels (P = .073 for cIMT and = .818 for plaque).

CONCLUSION: Increasing LDL and non-HDL cholesterol levels, but not remnant cholesterol, seem to contribute to carotid subclinical atherosclerosis.