Available online 21 August 2025

LDL and non-HDL were independently associated with subclinical atherosclerosis.

Remnant cholesterol showed no association after LDL adjustment.

Findings highlight LDL and non-HDL relevance in subclinical atherosclerosis.

The role of remnant cholesterol remains to be clarified

The results are based on 1,929 healthy VIPVIZA study participants

Elevated 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-HDL and remnant cholesterol. Nevertheless, few studies have explored the independent associations between these lipid biomarkers and early atherosclerotic disease.

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

In this cross-sectional study, we included 1,929 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.

We found that all lipid variables (LDL, non-HDL, and remnant cholesterol) were associated with subclinical atherosclerosis in univariable models (p < 0.01 across all models for cIMT and p < 0.001, p <0.001, p = 0.003 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 < 0.001 for both) and increased cIMT (p <0.001 for both). However, no independent association between remnant cholesterol and subclinical atherosclerosis was observed in the model adjusted for LDL cholesterol levels (p = 0.073 for cIMT and p = 0.818 for plaque).

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

LDL cholesterol

Non-HDL cholesterol

Remnant cholesterol

Atherosclerosis

Carotid Ultrasonography

Dyslipidaemia

Carotid intima-media thickness

Carotid plaques

© 2025 Published by Elsevier Inc. on behalf of National Lipid Association.