Turner Michael, Kuri-Morales Pablo, Alegre-Díaz Jesús, Baca Paulina, Garcilazo-Ávila Jose Adrián, González-Carballo Carlos, Ramirez-Reyes Raul, Rivas Fernando, Aguilar-Ramírez Diego, Bragg Fiona, Gnatiuc Friedrichs Louisa, Herrington William G, Hill Michael, Trichia Eirini, Vergara-Lope Alejandra, Wade Rachel, Zhu Doreen, Collins Rory, Peto Richard, Berumen Jaime, Staplin Natalie, Torres Jason, Haynes Richard, Emberson Jonathan R, Tapia-Conyer Roberto
Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health (NDPH), University of Oxford, United Kingdom (M.T., D.A.-R., F.B., L.G.F., W.G.H., M.H., E.T., A.V.-L., R.W., D.Z., R.C., R.P., N.S., J.T., R.H., J.R.E.).
Instituto Tecnológico y de Estudios Superiores de Monterrey, Mexico (P.K.-M.).
Hypertension. 2025 Nov;82(11):1896-1905. doi: 10.1161/HYPERTENSIONAHA.125.25348. Epub 2025 Sep 17.
Observational studies relating blood pressure in middle age to mortality may underestimate lifelong effects. Mendelian randomization can reduce the impact of confounding and reverse causality and may better estimate lifelong effects of blood pressure on mortality.
Mendelian randomization analyses used 125 895 Mexico City Prospective Study participants aged 35 to 74 years at recruitment with valid genetic and other data. Cox regression, adjusted for confounders and regression dilution bias, related blood pressure to mortality in 133 027 participants aged 35 to 74 years without prior chronic disease (other than diabetes) at recruitment.
In the genetic analyses (40 560 [32%] men; mean age 50 years, mean body mass index 29 kg/m) there were 13 153 deaths before age 75 years (3478 cardiovascular, 2053 kidney, and 7622 other). Each 10 mm Hg higher genetically predicted lifelong systolic blood pressure was associated with 73% higher cardiovascular mortality at ages 35 to 74 years (rate ratio, 1.73 [95% CI, 1.44-2.06]), 42% higher kidney death (1.42 [95% CI, 1.15-1.75]), but no clear increase in death from other causes. These lifelong rate ratios were higher than those estimated by observational analyses relating blood pressure in middle age to risk. Mendelian randomization analyses of lifelong diastolic blood pressure confirmed strong associations with cardiovascular but not kidney death. Mortality rate ratios were similar for men and women and in those with versus without diabetes, and broadly similar at different ages and at different proportions of Indigenous American ancestry. Sensitivity analyses gave consistent results.
In this Mexican population, genetically informed lifelong differences in blood pressure were strongly related to death from cardiovascular and kidney disease.
将中年血压与死亡率相关联的观察性研究可能低估了终生影响。孟德尔随机化可以减少混杂因素和反向因果关系的影响，并且可能更好地估计血压对死亡率的终生影响。
孟德尔随机化分析使用了125895名墨西哥城前瞻性研究参与者，这些参与者在招募时年龄为35至74岁，拥有有效的基因数据和其他数据。在133027名招募时无既往慢性病（糖尿病除外）、年龄为35至74岁的参与者中，采用经混杂因素和回归稀释偏倚调整的Cox回归分析血压与死亡率的关系。
在基因分析中（40560名[32%]男性；平均年龄50岁，平均体重指数29kg/m²），有13153人在75岁之前死亡（3478例心血管疾病死亡、2053例肾脏疾病死亡和7622例其他原因死亡）。基因预测的终生收缩压每升高10mmHg，在35至74岁时心血管死亡率高73%（率比，1.73[95%CI，1.44 - 2.06]），肾脏疾病死亡高42%（1.42[95%CI，1.15 - 1.75]），但其他原因导致的死亡没有明显增加。这些终生率比高于将中年血压与风险相关联的观察性分析所估计的率比。终生舒张压的孟德尔随机化分析证实与心血管疾病死亡有很强的关联，但与肾脏疾病死亡无关。男性和女性以及有糖尿病和无糖尿病者的死亡率比相似，在不同年龄和不同美洲原住民血统比例的人群中大致相似。敏感性分析得出了一致的结果。
在这个墨西哥人群中，基于基因信息的血压终生差异与心血管疾病和肾脏疾病死亡密切相关。
