Associations between plasma caspase-1 levels and cardiovascular disease, with the mediating role of metabolic syndrome

Yajuan Zhang; Yumei Huang; Shaobo Hu; Gang Liu; Tianshu Zeng; An Pan; Yunfei Liao

doi:10.1016/j.atherosclerosis.2024.119090

Associations between plasma caspase-1 levels and cardiovascular disease, with the mediating role of metabolic syndrome

Atherosclerosis. 2024 Dec 11:401:119090. doi: 10.1016/j.atherosclerosis.2024.119090. Online ahead of print.

Authors

Yajuan Zhang¹, Yumei Huang¹, Shaobo Hu², Gang Liu³, Tianshu Zeng¹, An Pan⁴, Yunfei Liao⁵

Affiliations

¹ Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China.
² Department of Liver Transplant Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Epidemiology and Biostatistics, Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.
⁵ Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Provincial Clinical Research Center for Diabetes and Metabolic Disorders, Wuhan, China. Electronic address: yunfeiliao2012@163.com.

PMID: 39708635
DOI: 10.1016/j.atherosclerosis.2024.119090

Abstract

Aims: This study aimed to explore the association between plasma caspase-1 levels and cardiovascular disease (CVD), as well as the potential mediating role of metabolic syndrome (Mets) in the association.

Methods: This study analyzed the UK Biobank Precision Proteomics Project (UKB-PPP), which detected plasma caspase-1 levels in participants. CVD was defined by ICD-9/ICD-10 codes. The Cox proportional hazards regression model was used to explore the hazard ratio (HR) of plasma caspase-1 levels with CVD. Mediation analysis was conducted to investigate the mediating effect of Mets and its components on this relationship.

Results: This study included a total of 41,499 participants. Among them, 4869 (11.7 %) participants were documented to have developed CVD during a median follow-up of 13.6 years. In the fully adjusted model, compared with individuals in the lowest tertile of plasma caspase-1 levels, the highest tertile was significantly associated with an increased risk of CVD (HR = 1.11, 95 % CI, 1.04-1.19). Per one-unit Normalized Protein eXpression (NPX) increment in plasma caspase-1 concentrations was associated with a 6 % higher risk of CVD (p＜0.001). The mediating effect of Mets was the largest, at 17.5 %, with its components hypertension, central obesity, hypertriglyceridemia, hyperglycemia and dyslipidemia mediated the effects by 13.52 %, 9.72 %, 7.35 %, 4.63 % and 2.74 %, respectively.

Conclusions: Higher plasma caspase-1 levels were associated with a higher risk of CVD. This association may be partially mediated by Mets and its components, suggesting that caspase-1 may increase the risk of CVD by increasing the occurrence of Mets.

Keywords: Cardiovascular disease; Caspase-1; Metabolic syndrome.