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

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.