Serum cystatin C and stroke risk: a national cohort and Mendelian randomization study

Front Endocrinol (Lausanne). 2024 Apr 12:15:1355948. doi: 10.3389/fendo.2024.1355948. eCollection 2024.

Abstract

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.

Keywords: EGFR; Mendelian randomization; cohort study; cystatin C; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • China / epidemiology
  • Cohort Studies
  • Cystatin C* / blood
  • Cystatin C* / genetics
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Mendelian Randomization Analysis*
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Stroke* / blood
  • Stroke* / epidemiology
  • Stroke* / genetics

Substances

  • Cystatin C
  • Biomarkers

Grants and funding

The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.