Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China (D.Y., J.J., A.J., Y.Y., X.M., J.L., H.L., Yongjun Wang, Y.P., Yilong Wang).
China National Clinical Research Center for Neurological Diseases, Beijing (D.Y., J.J., A.J., Y.Y., X.M., J.L., H.L., Yongjun Wang, Y.P., Yilong Wang).
Stroke. 2022 Oct;53(10):3123-3132. doi: 10.1161/STROKEAHA.122.039277. Epub 2022 Jul 12.
The aim of this study was to investigate the relationship between serum cystatin C levels and the presence and severity of cerebral small vessel disease (CSVD).
Community-dwelling residents in the Lishui city in China from the cross-sectional survey of the PRECISE (Poly-Vascular Evaluation for Cognitive Impairment and Vascular Events) cohort study were included in present study from 2017 to 2019. Total CSVD burden and modified total CSVD burden score, as well as the markers of CSVD on magnetic resonance imaging, including white matter hyperintensity, lacunes, cerebral microbleeds, and perivascular spaces, were assessed at baseline survey. Participants were divided into 4 groups according to the quartiles of cystatin C. The association of serum cystatin C with total CSVD burden and imaging markers was analyzed using ordinal or binary logistic regression models. Furthermore, 2-sample Mendelian randomization analysis was performed to investigate the genetically predicted effect of cystatin C on CSVD.
A total of 3061 participants were included in this study. The mean age of the participants was 61.2±6.7 years, and 1637 (53.5%) were women. Higher level of cystatin C was associated with an increased total CSVD burden and modified total CSVD burden (Q4 versus Q1: common odds ratio [OR], 1.30 [95% CI, 1.03-1.64] and 1.32 [95% CI, 1.01-1.73]) after adjustment for covariates. Further, compared with the first quartile of cystatin C, subjects in the last quartile had higher risk of lacunes (OR, 1.99 [95% CI, 1.05-3.76]), modified white matter hyperintensity burden (common OR, 1.42 [95% CI, 1.07-1.90]), and moderate-to-severe perivascular spaces (OR, 2.15 [95% CI, 1.29-3.59]) but not cerebral microbleeds. The Mendelian randomization analysis showed that a genetically predicted higher cystatin C level was associated with increased risk of lacunar stroke (OR, 1.16 [95% CI, 1.06-1.27]).
In this community-based study, we found a possible association between cystatin C and CSVD, especially for lacunes, that was independent of estimated glomerular filtration rate.
本研究旨在探讨血清胱抑素 C 水平与脑小血管疾病（CSVD）的发生和严重程度之间的关系。
本研究纳入了 2017 年至 2019 年来自中国丽水市 PRECISE（多血管评估认知障碍和血管事件）队列研究的横断面调查的社区居民。在基线调查时评估了总 CSVD 负担和改良总 CSVD 负担评分，以及磁共振成像上的 CSVD 标志物，包括脑白质高信号、腔隙、脑微出血和血管周围间隙。参与者根据胱抑素 C 的四分位数分为 4 组。采用有序或二元逻辑回归模型分析血清胱抑素 C 与总 CSVD 负担和影像学标志物之间的关系。此外，进行了双样本 Mendelian 随机化分析，以研究胱抑素 C 对 CSVD 的遗传预测作用。
本研究共纳入 3061 名参与者。参与者的平均年龄为 61.2±6.7 岁，1637 名（53.5%）为女性。调整协变量后，较高的胱抑素 C 水平与总 CSVD 负担和改良总 CSVD 负担增加相关（Q4 与 Q1：常见比值比 [OR]，1.30 [95%CI，1.03-1.64] 和 1.32 [95%CI，1.01-1.73]）。此外，与胱抑素 C 第一四分位数相比，第四四分位数的受试者腔隙性脑梗死（OR，1.99 [95%CI，1.05-3.76]）、改良脑白质高信号负担（常见 OR，1.42 [95%CI，1.07-1.90]）和中重度血管周围间隙（OR，2.15 [95%CI，1.29-3.59]）的风险更高，但脑微出血除外。Mendelian 随机化分析表明，遗传预测的胱抑素 C 水平升高与腔隙性卒中风险增加相关（OR，1.16 [95%CI，1.06-1.27]）。
在这项基于社区的研究中，我们发现胱抑素 C 与 CSVD 之间可能存在关联，尤其是与腔隙性脑梗死相关，且这种关联独立于估计的肾小球滤过率。
