Joint associations of LDL-C and HDL-C with in-hospital major bleeding in Chinese patients with acute coronary syndrome undergoing PCI: findings from the CCC-ACS project

Low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) have each been associated with bleeding risk; however, their joint association with bleeding outcomes remains insufficiently characterized. We included patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) and were enrolled in the Improving Care for Cardiovascular Disease in China-ACS project between 2014 and 2019. This study was registered at ClinicalTrials.gov (NCT02306616) on November 29, 2014. Restricted cubic spline analysis assessed dose–response relationships, and multivariable fractional polynomial interaction analysis evaluated lipoprotein interdependence. Heatmaps visualized risk patterns across LDL-C/HDL-C combinations. Among 42,378 patients, 615 in-hospital major bleeding events were recorded. Restricted cubic spline analysis revealed a J-shaped association between HDL-C and bleeding risk, with HDL-C levels below 28 mg/dL associated with a 38% increased bleeding risk (adjusted odds ratio 1.38, 95% CI 1.07–1.79). In the multivariable fractional polynomial interaction analysis, the higher estimated bleeding risk associated with LDL-C < 70 mg/dL was most evident at HDL-C levels below approximately 45 mg/dL ( P for interaction = 0.012), whereas the reverse interaction analysis for HDL-C < 28 mg/dL across continuous LDL-C levels was not statistically significant ( P for interaction = 0.608). Heatmap visualization showed higher estimated bleeding risks when both LDL-C and HDL-C were in lower ranges. In this nationwide ACS registry, HDL-C showed a J-shaped association with in-hospital major bleeding, and LDL-C and HDL-C were jointly associated with in-hospital major bleeding among patients undergoing PCI. Higher estimated risk was observed when both lipoproteins were in lower ranges, consistent with a conditional joint risk pattern.

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Journal
European journal of medical research
Published
2026-08-27
DOI
https://doi.org/10.1186/s40001-026-05077-2
Primary Topic
Antiplatelet Therapy and Cardiovascular Diseases
Type
article
Field-Weighted Citation Impact
0.00

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article

Joint associations of LDL-C and HDL-C with in-hospital major bleeding in Chinese patients with acute coronary syndrome undergoing PCI: findings from the CCC-ACS project

Jifu Li, Jinglan Diao, Hailong Lin, Chunlin Lai et al.
European journal of medical research
Antiplatelet Therapy and Cardiovascular Diseases
article

Joint associations of LDL-C and HDL-C with in-hospital major bleeding in Chinese patients with acute coronary syndrome undergoing PCI: findings from the CCC-ACS project

Jifu Li, Jinglan Diao, Hailong Lin, Chunlin Lai, Honghua Deng, Changqian Wang, Jinru Wei, Congliang Zhang, Guoxiong Chen, Haiyun Lin, Jiong Tang, Dongsheng Chai, Jing Xu, Biao Xu, Fakuan Tang, Guixia Zhang, Jiabin Xi, Guangshu Han, Honhju Wang, Jianhao Li, Guoqin Xin, Jiawang Ding, Chuntong Wang, Huimin Chu, Chunyang Wu, Bing Fu, Dawen Xu, Jianhong Tao, Chuanyu Gao, Chuanliang Liang, L. Liu, Hui Dong, Bosong Yang, Hualing Liu, Daoquan Peng, Genshan Ma, Xin Zhou, Jinxing Yi, Fanju Meng, Guoduo Chen, Changyong Liu, Guosheng Fu, JiaoMei Yang, Gengsheng Sang, Haiping Guo, Dongmei Zhu, Jiayi Tong, Hangkuan Liu, Бин Ли, Guoqing Li, Hong Liu, Wenjun Zhu, Aihua Li, Bao Li, Huifang Zhang, Jianwen Liu, Jie Jiang, Jun Xiao, Fang Zhao, Jianfeng Ye, Huifeng Wang, Tianqi Yang, Jie Yang, Guo Li, Fengwei Li, Caidong Luo, Jinchuan Yan, Guizhou Tao, Fudong Gan, the CCC-ACS Investigators, Fangfang Huang, B Sun, Shuting Liu, Jingbo Yang, Qing Yang, Bo Yu, Geru Aa, Jinzi Su, Jingfeng Wang, Dongyan Li, Hong Zhang, Jiyan Chen, Hong Jiang, Cui Bin, Bin Wang, Hong Luan, Lan Huang, Jie Chen, Hui Liu, Chunyan Zhang, Linjie Li, Bin Liu, Pengfei Sun, Di Wu, Chuanyi Huang, Jian Yang, Jingshan Zhao, Gang Xu, Hongwei Li, Jing Hu
article en

Abstract

Low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) have each been associated with bleeding risk; however, their joint association with bleeding outcomes remains insufficiently characterized. We included patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) and were enrolled in the Improving Care for Cardiovascular Disease in China-ACS project between 2014 and 2019. This study was registered at ClinicalTrials.gov (NCT02306616) on November 29, 2014. Restricted cubic spline analysis assessed dose–response relationships, and multivariable fractional polynomial interaction analysis evaluated lipoprotein interdependence. Heatmaps visualized risk patterns across LDL-C/HDL-C combinations. Among 42,378 patients, 615 in-hospital major bleeding events were recorded. Restricted cubic spline analysis revealed a J-shaped association between HDL-C and bleeding risk, with HDL-C levels below 28 mg/dL associated with a 38% increased bleeding risk (adjusted odds ratio 1.38, 95% CI 1.07–1.79). In the multivariable fractional polynomial interaction analysis, the higher estimated bleeding risk associated with LDL-C < 70 mg/dL was most evident at HDL-C levels below approximately 45 mg/dL ( P for interaction = 0.012), whereas the reverse interaction analysis for HDL-C < 28 mg/dL across continuous LDL-C levels was not statistically significant ( P for interaction = 0.608). Heatmap visualization showed higher estimated bleeding risks when both LDL-C and HDL-C were in lower ranges. In this nationwide ACS registry, HDL-C showed a J-shaped association with in-hospital major bleeding, and LDL-C and HDL-C were jointly associated with in-hospital major bleeding among patients undergoing PCI. Higher estimated risk was observed when both lipoproteins were in lower ranges, consistent with a conditional joint risk pattern.

European journal of medical research
Tianjin Medical University General Hospital (CN)
National Natural Science Foundation of China, Tianjin Science and Technology Committee
Good health and well-being
Openalex Percentile: Top 10%
Antiplatelet Therapy and Cardiovascular Diseases
DOIOpen Access PDFOpenAlex
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