■先前的流行病学研究表明,全髋关节和膝关节置换术后患者发生神经血管疾病的风险增加。然而,关于置换后卒中风险增加的确切结论仍然难以捉摸.因此,我们进行了一项双样本孟德尔随机研究,以调查全髋和膝关节置换术与卒中之间的因果关系.
■我们利用了公开的全基因组关联研究(GWAS)的汇总数据。有关全髋关节置换的数据(THR,N=319,037)和全膝关节置换(TKR,N=252,041)来自骨关节炎遗传学(GO)联盟。卒中相关数据来自国际卒中遗传学协会,包含任何笔划(AS),任何缺血性卒中(AIS),大血管缺血性卒中(LV-IS),心脏栓塞性缺血性卒中(CE-IS),和小血管缺血性卒中(SV-IS)。我们的主要因果推断方法是逆方差加权(IVW)方法,辅以加权中位数和MR-Egger回归作为次要推断方法。我们利用MR-PRESSO全局测试进行异常检测,Cochran的Q统计量来评估异质性,并使用MR-PRESSO和MR-Egger回归的p值评估了我们发现的多重性和稳定性,和留一法,分别。
■我们确定了THR与AS(IVWp=0.0001,OR=1.08,95%CI=1.04-1.12)和AIS(IVWp=0.0016,OR=1.07,95%CI=1.03-1.12)之间的显着遗传关联。在TKR和AS之间也观察到显着关联(IVWp=0.0002,OR=1.08,95%CI=1.04-1.12),以及AIS(IVWp=0.0005,OR=1.15,95%CI=1.06-1.24)。
■我们的研究结果在基因上支持全髋关节和膝关节置换后中风的风险增加。然而,需要进一步的研究来阐明置换后卒中发作的具体机制.
UNASSIGNED: Previous epidemiological studies have indicated an increased risk of neurovascular diseases in patients following total hip and knee replacements. However, definitive conclusions regarding the increased risk of stroke post-replacement remain elusive. Therefore, we conducted a two-sample Mendelian randomization study to investigate the causal relationship between total hip and knee replacements and stroke.
UNASSIGNED: We utilized summary data from publicly available genome-wide association studies (GWAS). Data concerning total hip replacements (THR, N = 319,037) and total knee replacements (TKR, N = 252,041) were sourced from the Genetics of Osteoarthritis (GO) Consortium. Stroke-related data were obtained from the International Stroke Genetics Consortium, encompassing any stroke (AS), any ischemic stroke (AIS), large vessel ischemic stroke (LV-IS), cardioembolic ischemic stroke (CE-IS), and small vessel ischemic stroke (SV-IS). Our primary causal inference method was the inverse variance weighted (IVW) approach, supplemented by weighted median and MR-Egger regression as secondary inference methods. We utilized the MR-PRESSO global test for outlier detection, Cochran\'s Q statistic to assess heterogeneity, and assessed the multiplicity and stability of our findings using p-values from MR-PRESSO and MR-Egger regressions, and the leave-one-out method, respectively.
UNASSIGNED: We identified significant genetic associations between THR and both AS (IVW p = 0.0001, OR = 1.08, 95% CI = 1.04-1.12) and AIS (IVW p = 0.0016, OR = 1.07, 95% CI = 1.03-1.12). Significant associations were also observed between TKR and AS (IVW p = 0.0002, OR = 1.08, 95% CI = 1.04-1.12), as well as AIS (IVW p = 0.0005, OR = 1.15, 95% CI = 1.06-1.24).
UNASSIGNED: Our findings genetically support an increased risk of stroke following total hip and knee replacements. However, further studies are necessary to elucidate the specific mechanisms underlying stroke episodes post-replacement.