Impact of inclisiran on the cardiometabolic–inflammatory index: a real-world observational study
Q Zhang, S Eryani, X Chen, M Li, S Qiu, H Liang, X Zhang, Y Chen, W Zhai, W Nai, J XiuAbstract
Background
Substantial residual cardiovascular risk persists despite effective LDL-C reduction and is increasingly recognized as being driven by metabolic dysfunction and systemic inflammation. The C-reactive protein-triglyceride-glucose index, also known as cardiometabolic inflammation index(CTI) , it has emerged as an innovative composite marker for evaluating metabolic-inflammatory dysregulation, integrating markers of insulin resistance and systemic inflammation, However, real-world data describing CTI dynamics after inclisiran therapy remain scarce.
Purpose
To evaluate the effect of inclisiran on CTI and to identify clinical factors associated with CTI response in routine clinical practice.
Methods
We performed a retrospective, single-center observational study including adult patients treated with inclisiran in routine care. Among 80 individuals who received inclisiran, 45 had complete paired laboratory data enabling CTI calculation at baseline and follow-up. CTI was defined as TyG index + 0.412 × ln(CRP). Paired analyses were conducted to assess changes in CTI and its metabolic components. Multivariable linear regression identified independent predictors of post-treatment CTI and ΔCTI.
Results
Mean CTI decreased from 5.32 ± 0.70 at baseline to 4.88 ± 0.53 at follow-up (absolute change −0.44; 95% CI −0.63 to −0.24; −8.24%; P < 0.001). LDL-C was reduced by 29.5%, total cholesterol by 22.6%, and triglycerides by 29.0% (all P < 0.01). Overall, 71% of patients demonstrated improvement in CTI. Although reductions in CRP and fasting glucose did not reach statistical significance at the population level, contribution analysis indicated that individual changes in CRP were the principal driver of CTI improvement. Baseline CTI and HDL-C independently predicted post-treatment CTI, whereas higher baseline CTI and treatment frequency pattern were associated with greater CTI reduction. No clinically relevant hepatic, renal, or muscle-related safety signals were observed.
Conclusion
In real-world clinical practice, inclisiran was associated with significant improvement in integrated cardiometabolic–inflammatory burden as reflected by CTI. These findings highlight the potential relevance of targeting combined metabolic and inflammatory pathways beyond LDL-C reduction and support further prospective investigation in larger populations.