Department of Medicine, Division of Cardiology (M.A., W.S.P., J.W.M.), Johns Hopkins University, Baltimore, MD.
Department of Biomedical Engineering (M.A., A.B.), Johns Hopkins University, Baltimore, MD.
Circulation. 2021 Mar 2;143(9):895-906. doi: 10.1161/CIRCULATIONAHA.120.049819. Epub 2020 Nov 30.
Recent clinical guidelines support intensive blood pressure treatment targets. However, observational data suggest that excessive diastolic blood pressure (DBP) lowering might increase the risk of myocardial infarction (MI), reflecting a J- or U-shaped relationship.
We analyzed 47 407 participants from 5 cohorts (median age, 60 years). First, to corroborate previous observational analyses, we used traditional statistical methods to test the shape of association between DBP and cardiovascular disease (CVD). Second, we created polygenic risk scores of DBP and systolic blood pressure and generated linear Mendelian randomization (MR) estimates for the effect of DBP on CVD. Third, using novel nonlinear MR approaches, we evaluated for nonlinearity in the genetic relationship between DBP and CVD events. Comprehensive MR interrogation of DBP required us to also model systolic blood pressure, given that the 2 are strongly correlated.
Traditional observational analysis of our cohorts suggested a J-shaped association between DBP and MI. By contrast, linear MR analyses demonstrated an adverse effect of increasing DBP increments on CVD outcomes, including MI (MI hazard ratio, 1.07 per unit mm Hg increase in DBP; <0.001). Furthermore, nonlinear MR analyses found no evidence for a J-shaped relationship; instead confirming that MI risk decreases consistently per unit decrease in DBP, even among individuals with low values of baseline DBP.
In this analysis of the genetic effect of DBP, we found no evidence for a nonlinear J- or U-shaped relationship between DBP and adverse CVD outcomes; including MI.
最近的临床指南支持强化血压治疗目标。然而,观察性数据表明,过度降低舒张压(DBP)可能会增加心肌梗死(MI)的风险,反映出 J 形或 U 形关系。
我们分析了来自 5 个队列的 47407 名参与者(中位数年龄 60 岁)。首先,为了证实先前的观察性分析,我们使用传统的统计方法来检验 DBP 与心血管疾病(CVD)之间的关联形状。其次,我们创建了 DBP 和收缩压的多基因风险评分,并生成了 DBP 对 CVD 影响的线性孟德尔随机化(MR)估计。第三,使用新的非线性 MR 方法,我们评估了 DBP 与 CVD 事件之间的遗传关系中的非线性。对 DBP 的综合 MR 研究要求我们还对收缩压进行建模,因为这两者是强相关的。
我们的队列的传统观察性分析表明 DBP 与 MI 之间存在 J 形关联。相比之下,线性 MR 分析表明,DBP 增加对 CVD 结局的不良影响,包括 MI(MI 危险比,DBP 每单位增加 1mmHg 增加 1.07;<0.001)。此外,非线性 MR 分析没有发现 J 形关系的证据;相反,它证实了 MI 风险会随着 DBP 的每单位降低而持续降低,即使在基线 DBP 值较低的个体中也是如此。
在对 DBP 的遗传效应进行分析时,我们没有发现 DBP 与不良 CVD 结局(包括 MI)之间存在非线性 J 形或 U 形关系的证据。