Linear and Nonlinear Mendelian Randomization Analyses of the Association Between Diastolic Blood Pressure and Cardiovascular Events: The J-Curve Revisited.
Linear and Nonlinear Mendelian Randomization Analyses of the Association Between Diastolic Blood Pressure and Cardiovascular Events: The J-Curve Revisited.
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DOI：
10.1161/circulationaha.120.049819
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发表时间：
2021-03-02
期刊：
影响因子：
37.8
通讯作者：
McEvoy JW
中科院分区：
文献类型：
--
作者：
Arvanitis M;Qi G;Bhatt DL;Post WS;Chatterjee N;Battle A;McEvoy JW
最近的临床指南支持强化血压(BP)治疗目标。然而，观察数据表明，舒张压(DBP)的过度降低可能会增加心肌梗死(MI)的风险；反映出一种J型或U型关系。我们分析了来自5个队列(平均年龄60岁)的47,407名参与者。首先，为了证实先前的观察分析，我们使用传统的统计方法来检验DBP和CVD之间的联系形式。其次，我们创建了DBP和SBP的多基因风险评分(PR)，并生成了DBP对心血管疾病影响的线性孟德尔随机化(MR)估计。第三，使用新的非线性磁共振方法，我们评估了DBP和CVD之间的遗传关系的非线性。对舒张压进行全面的磁共振检查需要我们也模拟SBP，因为两者有很强的相关性。对我们队列的传统观察分析表明，DBP和MI之间存在J型关联。相比之下，线性MR分析显示，增加舒张压增量对心血管疾病结果有不利影响，包括心肌梗死(MI危险比=舒张压每单位毫米汞增加1.07，p<；0.001)。此外，非线性MR分析没有发现J形关系的证据，相反，证实了即使在基线DBP值较低的个体中，DBP每单位下降，MI风险也会持续下降。在这项对DBP遗传效应的分析中，我们没有发现证据表明DBP和包括心肌梗死在内的不良心血管结局之间存在非线性的J型或U型关系。
Recent clinical guidelines support intensive blood pressure (BP) treatment targets. However, observational data suggest that excessive diastolic BP (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 prior observational analyses, we used traditional statistical methods to test the shape of association between DBP and CVD. Second, we created polygenic risk scores (PRS) of DBP and SBP and generated linear Mendelian randomization (MR) estimates for the effect of DBP on CVD. Third, using novel non-linear MR approaches, we evaluated for non-linearity in the genetic relationship between DBP and CVD. Comprehensive MR interrogation of DBP required us to also model SBP, given the two 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 mmHg increase in DBP, p<0.001). Furthermore, non-linear 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 non-linear J- or U-shaped relationship between DBP and adverse CVD outcomes; including MI.