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Serum cystatin C and stroke risk: a national cohort and Mendelian randomization study
Yitian Qi1, Xinyun Shang1, Tianjiao Han1
1China-Japan Union Hospital of Jilin University, Jilin University, Changchun, Jilin, China.
Insights
Higher serum cystatin C levels are linked to increased stroke risk in older adults. This association is confirmed by both measured levels and genetic predictions, suggesting cystatin C as a potential stroke risk biomarker.
Area of Science:
- Gerontology
- Epidemiology
- Biomarkers
Background:
- The relationship between cystatin C and stroke risk in older populations requires further clarification.
- Investigating both measured and genetically predicted cystatin C levels is crucial for understanding this association.
Purpose of the Study:
- To evaluate the association between serum cystatin C levels and stroke incidence in adults aged 45 and above.
- To determine if genetically predicted cystatin C levels influence stroke risk.
Main Methods:
- Retrospective cohort study using the China Health and Retirement Longitudinal Study (CHARLS) dataset.
- Multivariate logistic regression analysis for measured cystatin C.
- Two-sample Mendelian randomization framework for genetically predicted cystatin C.
Main Results:
- Higher quartiles of serum cystatin C were associated with increased stroke incidence (OR, 1.380; 95% CI, 1.046-1.825).
- Genetically predicted cystatin C levels showed a positive association with total stroke risk (OR, 1.114; 95% CI, 1.041-1.192).
Conclusions:
- Elevated serum cystatin C is a significant risk factor for stroke in older adults.
- Mendelian randomization analysis supports a causal link between genetically predicted cystatin C and stroke risk.
Purpose:
The debate over the causal and longitudinal association between cystatin C and stroke in older adults persists. Our aim was to assess the link between cystatin C levels, both measured and genetically predicted, and stroke risk.
Methods:
This study employed a retrospective cohort design using samples of the China Health and Retirement Longitudinal Study (CHARLS), which is a nationally representative cohort recruiting individuals aged 45 years or above. A multivariate logistic model and the two-sample Mendelian randomization framework were used to investigate the longitudinal and genetically predicted effect of serum cystatin C on stroke.
Results:
The study population had a mean age of 59.6 (SD ±9.5), with 2,996 (46.1%) women. After adjusting for confounding factors, compared to those in the first quartile of cystatin C, those in the last quartile had the greatest risk of stroke incidence [odds ratio (OR), 1.380; 95% confidence interval (CI), 1.046-1.825]. The Mendelian randomization analysis showed that a genetically predicted cystatin C level was positively associated with total stroke (OR by inverse variance-weighted method, 1.114; 95% CI, 1.041-1.192).
Conclusions:
This national cohort study suggests that higher serum cystatin C is associated with an increased risk of total stroke, which is further supported by Mendelian randomization.
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