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Serum Cystatin C and 90-Day Neurological Functional Prognosis in Acute Ischemic Stroke: Insights from a Prospective
Yongxing Deng1,2, Qing Zhu1,2, Jianan Wu3
1Department of Neurology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People's Republic of China.
Insights
Elevated cystatin C levels are linked to poor outcomes and higher mortality in acute ischemic stroke (AIS) patients. Mendelian randomization suggests cystatin C may causally increase ischemic stroke risk, highlighting its prognostic and predictive potential.
Area of Science:
- Neurology
- Biomarkers
- Stroke Research
Background:
- The prognostic value of cystatin C in acute ischemic stroke (AIS) requires further elucidation.
- Understanding the causal relationship between cystatin C and stroke outcomes is crucial for clinical management.
Purpose of the Study:
- To investigate the association between serum cystatin C levels and 90-day neurological functional prognosis in AIS patients.
- To assess the potential causal effect of cystatin C on ischemic stroke risk using Mendelian randomization (MR).
Main Methods:
- Prospective cohort study of 786 AIS patients, measuring cystatin C within 48 hours of admission.
- Logistic and Cox regression analyses for functional outcome and mortality; mediation analysis for inflammatory markers.
- Two-sample MR analysis to infer causality between cystatin C and ischemic stroke risk.
Main Results:
- Elevated cystatin C independently predicted adverse 90-day functional outcome (aOR=2.13) and increased mortality (aHR=1.97).
- Systemic inflammation markers mediated 16.1%-20.2% of cystatin C's effect on prognosis.
- MR analysis indicated genetically predicted higher cystatin C is associated with increased ischemic stroke risk (OR=1.10).
Conclusions:
- Cystatin C is significantly associated with worse outcomes and higher mortality in AIS, partly mediated by inflammation.
- MR findings suggest a potential causal role for cystatin C in ischemic stroke pathogenesis.
- Cystatin C may serve as a valuable biomarker for predicting AIS prognosis and ischemic stroke risk.
Introduction:
The relationship between cystatin C levels and 90-day neurological functional prognosis in acute ischemic stroke (AIS) is not fully understood. This study investigated this association prospectively and employed Mendelian randomization (MR) analysis to assess potential causality.
Methods:
A prospective cohort study enrolled 786 patients with AIS admitted to a tertiary Stroke Center between 2021 and 2023. Serum cystatin C levels were measured within 48 hours of admission. Associations with adverse 90-day neurological functional outcome (modified Rankin Scale score > 2) were assessed using univariate and multivariable logistic regression. Cox regression models evaluated all-cause mortality during long-term follow-up. Mediation analysis examined the role of inflammatory mediators (Monocyte-to-Lymphocyte Ratio [MLR], Neutrophil-to-Lymphocyte Ratio [NLR], Systemic Inflammatory Response Index [SIRI], Systemic Immune-Inflammation Index [SII]) in the cohort. Causality was further evaluated using a two-sample MR approach with genetic instruments to infer the effect of cystatin C on ischemic stroke risk.
Results:
Elevated cystatin C levels were independently associated with higher odds of adverse 90-day functional outcome (adjusted odds ratio [OR] = 2.13, 95% CI: 1.34-3.38, p=0.001) and increased mortality risk (adjusted hazard ratio [HR] = 1.97, 95% CI: 1.09-3.54, p=0.024). Mediation analysis identified systemic inflammation markers as significant mediators, accounting for 16.1% to 20.2% of the total effect of cystatin C on adverse prognosis. MR analysis provided evidence supporting a causal relationship, indicating that genetically predicted higher cystatin C levels were associated with an increased risk of ischemic stroke (OR = 1.10, 95% CI: 1.02-1.18, p=0.011).
Conclusion:
Elevated cystatin C levels demonstrated a significant association with worse 90-day functional outcome and higher mortality in these patients, partially mediated through systemic inflammation. MR findings suggested a potential causal role of cystatin C in ischemic stroke pathogenesis. Cystatin C may represent a valuable integrated biomarker for both prognosticating outcomes in AIS and predicting ischemic stroke risk.
