Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
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2021-08-11
Published articles
Journal：Frontiers in Neurology
Publication type: Article
IF(IF): 4.003
PMID: 34456843 Link To Pubmed Full text Download
Background And Purpose
Previous studies have suggested that elevated serum cystatin C levels are associated with increased risk of ischemic stroke and predict cardiovascular events and death after ischemic stroke onset,it is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation.In addition,epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD.The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to outcomes in the acute ischemic stroke independent of renal function.
Method
Methods: We measured serum CysC levels in 10,256 AlS patients from Third China National Stroke Registry(CNSR-ll). The primary outcome was a combination of all-cause mortality and major disability(modified Rankin scale score,3-6). Secondary outcomes included stroke recurrence and combined vascular events at 1 year. Outcomes were analyzed using logistic regression and Cox proportional hazards models, respectively.
Conclusion
Conclusions: CysC showed a U-shaped correlation with 1-year stroke clinicaloutcome, suggesting that serum CysC may not only be a simple candidate marker of renal function.
Main results
Results: The median CysC of included patients was 0.95 mg/l(interquartile range,0.83-1.10mg/).A U-shaped association was observed between CysC and primary outcome(all-cause mortality or major disability)[ quartile(Q)1 vs.Q2: adjusted odds ratio (aOR)1.29,95% Cl 1.06-1.58,p=0.012;Q3 Vs.Q2: aOR 1.12,95% CI0.93-1.35,p=0.242;Q4Vs.Q2: aOR 1.35,95% CI 1.10-1.65,p=0.004].A similar trend also existed in "preserved renal function"patients. Adding CysC to a model containing conventional risk factors improved the model performance with integrated discrimination improvement(D) of 0.13%(o=0.016) and net reclassification index(NRI) of 13.10%(o<0.001)for primary outcome. No significant association was observed for stroke recurrence or combined vascular event rate in different CysC quartiles.