Observational studies have indicated that high blood pressure (BP) may be a risk factor to frailty. However, the causal association between BP and frailty remains not well determined. The purpose of this bi-directional two-sample Mendelian randomization (MR) study was to investigate the causal relationship between BP and frailty. Independent single nucleotide polymorphisms (SNPs) strongly (P < 5E-08) associated with systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) were selected as instrumental variables. Two different published genome-wide association studies (GWAS) on BP from the CHARGE (n = 810,865) and ICBP (n = 757,601) consortia were included. Summary-level data on frailty index (FI) were obtained from the latest GWAS based on UK Biobank and Swedish TwinGene cohorts (n = 175,226). Inverse variance weighted (IVW) approach with other sensitivity analyses were used to calculate the causal estimate. Using the CHARGE dataset, genetic predisposition to increased SBP (β = 0.135, 95% CI = 0.093 to 0.176, P = 1.73E-10), DBP (β = 0.145, 95% CI = 0.104 to 0.186, P = 3.14E-12), and PP (β = 0.114, 95% CI = 0.070 to 0.157, p = 2.87E-07) contributed to a higher FI, which was validated in the ICBP dataset. There was no significant causal effect of FI on SBP, DBP, and PP. Similar results were obtained from different MR methods, indicating good stability. There was potential heterogeneity detected by Cochran’s Q test, but no horizontal pleiotropy was observed in MR-Egger intercept test (P > 0.05). These findings evinced that higher BP and PP were causally associated with an increased risk of frailty, suggesting that controlling hypertension could reduce the risk of frailty.

观察性研究表明，高血压（BP）可能是导致虚弱的危险因素。然而，血压与虚弱之间的因果关系尚未明确。这项双向双样本孟德尔随机化 (MR) 研究的目的是调查血压与虚弱之间的因果关系。选择与收缩压 ( SBP  )、舒张压 (DBP) 和脉压 (PP)密切相关的独立单核苷酸多态性 (SNP ) 作为工具变量。 其中包括来自 CHARGE ( n  = 810,865) 和 ICBP ( n = 757,601) 联盟的两项不同的已发表的关于 BP 的全基因组关联研究 (GWAS)。衰弱指数 (FI) 的概要级数据来自基于英国生物银行和瑞典 TwinGene 队列的最新 GWAS（n  = 175,226）。使用逆方差加权（IVW）方法和其他敏感性分析来计算因果估计。使用 CHARGE 数据集，遗传倾向增加 SBP（β  = 0.135，95% CI = 0.093 至 0.176，P  = 1.73E-10）、DBP（β  = 0.145，95% CI = 0.104 至 0.186，P  = 3.14E- 12）和 PP（β  = 0.114，95% CI = 0.070 至 0.157，p  = 2.87E-07）导致较高的 FI，这在 ICBP 数据集中得到了验证。FI 对 SBP、DBP 和 PP 没有显着的因果影响。不同的MR方法得到了相似的结果，表明稳定性良好。Cochran's Q 检验检测到存在潜在的异质性，但 MR-Egger 截距检验未观察到水平多效性（P  > 0.05）。这些发现表明，较高的血压和PP与虚弱风险增加存在因果关系，这表明控制高血压可以降低虚弱风险。