Residual Risk From Remnant Cholesterol and Inflammation Despite Lipid‐Lowering Therapy and Association With Incident Peripheral Artery Disease in Type 2 Diabetes
- 1Southern Medical University
- 2South China University of Technology
Abstract
BACKGROUND: Despite guideline-recommended lipid-lowering therapy, patients with type 2 diabetes retain a significant residual risk for peripheral artery disease (PAD). The contributions of remnant cholesterol (RC) and systemic inflammation in this treated population, particularly beyond achieved low-density lipoprotein cholesterol, remain incompletely understood. METHODS: This prospective cohort study included 18 741 participants with type 2 diabetes from the UK Biobank who were free of PAD and were on lipid-lowering therapy at baseline. Plasma RC and hsCRP (high-sensitivity C-reactive protein) levels were measured at baseline. Incident PAD was ascertained over a median follow-up of 13.6 years. Multivariable Cox models were used to estimate hazard ratios after adjustment for demographic, clinical, metabolic, and treatment-related covariates, including low-density lipoprotein cholesterol and baseline coronary artery disease. RESULTS: During follow-up, incident PAD occurred in 1223 participants (6.5%). Elevated RC and hsCRP levels were each independently linked to an increased risk of PAD. Participants with concurrent elevations in both RC and hsCRP exhibited the highest risk of incident PAD. These associations remained robust across multiple sensitivity analyses, including exclusion of participants with baseline coronary artery disease, removal of events within the initial 2-year follow-up, elimination of individuals with hsCRP >10 mg/L, competing-risk analyses accounting for death, and further adjustment for detailed lipid-lowering therapy categories. CONCLUSIONS: Among patients with type 2 diabetes receiving lipid-lowering therapy for primary prevention of PAD, elevated RC and systemic inflammation are independently and jointly associated with future PAD risk. These findings highlight substantial residual risk beyond managed low-density lipoprotein cholesterol and support the need for further strategies targeting both remnant lipoproteins and inflammation in this high-risk population.
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BibTeX
@article{liao2026residual,
title = {{Residual Risk From Remnant Cholesterol and Inflammation Despite Lipid‐Lowering Therapy and Association With Incident Peripheral Artery Disease in Type 2 Diabetes}},
author = {Ruoxi Liao and Zhiwen Xiao and Chixiong Huang and Lin Chen and Ying Liu and Xiaomin Wei and Mingjue Li and Mengjia Shen and Zhiqi Hu and Jianping Bin},
journal = {Journal of the American Heart Association},
year = {2026},
month = oct,
doi = {10.1161/jaha.126.049813},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.126.049813},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Residual Risk From Remnant Cholesterol and Inflammation Despite Lipid‐Lowering Therapy and Association With Incident Peripheral Artery Disease in Type 2 Diabetes
AU - Ruoxi Liao
AU - Zhiwen Xiao
AU - Chixiong Huang
AU - Lin Chen
AU - Ying Liu
AU - Xiaomin Wei
AU - Mingjue Li
AU - Mengjia Shen
AU - Zhiqi Hu
AU - Jianping Bin
PY - 2026
DA - 2026/10/23
JO - Journal of the American Heart Association
DO - 10.1161/jaha.126.049813
UR - https://www.ahajournals.org/doi/10.1161/JAHA.126.049813
AB - BACKGROUND: Despite guideline-recommended lipid-lowering therapy, patients with type 2 diabetes retain a significant residual risk for peripheral artery disease (PAD). The contributions of remnant cholesterol (RC) and systemic inflammation in this treated population, particularly beyond achieved low-density lipoprotein cholesterol, remain incompletely understood. METHODS: This prospective cohort study included 18 741 participants with type 2 diabetes from the UK Biobank who were free of PAD and were on lipid-lowering therapy at baseline. Plasma RC and hsCRP (high-sensitivity C-reactive protein) levels were measured at baseline. Incident PAD was ascertained over a median follow-up of 13.6 years. Multivariable Cox models were used to estimate hazard ratios after adjustment for demographic, clinical, metabolic, and treatment-related covariates, including low-density lipoprotein cholesterol and baseline coronary artery disease. RESULTS: During follow-up, incident PAD occurred in 1223 participants (6.5%). Elevated RC and hsCRP levels were each independently linked to an increased risk of PAD. Participants with concurrent elevations in both RC and hsCRP exhibited the highest risk of incident PAD. These associations remained robust across multiple sensitivity analyses, including exclusion of participants with baseline coronary artery disease, removal of events within the initial 2-year follow-up, elimination of individuals with hsCRP >10 mg/L, competing-risk analyses accounting for death, and further adjustment for detailed lipid-lowering therapy categories. CONCLUSIONS: Among patients with type 2 diabetes receiving lipid-lowering therapy for primary prevention of PAD, elevated RC and systemic inflammation are independently and jointly associated with future PAD risk. These findings highlight substantial residual risk beyond managed low-density lipoprotein cholesterol and support the need for further strategies targeting both remnant lipoproteins and inflammation in this high-risk population.
SN - 2047-9980
ER -