Department of Epidemiology and Biostatistics School of Public Health Imperial College London London United Kingdom.
Institute for Stroke and Dementia Research University Hospital of Ludwig-Maximilians-University Munich Germany.
J Am Heart Assoc. 2020 Jul 21;9(14):e016773. doi: 10.1161/JAHA.120.016773. Epub 2020 Jul 4.
Background Elevated blood pressure is a major cause of cardiovascular morbidity and mortality. However, it is not known whether midlife blood pressure affects later life cardiovascular risk independent of later life blood pressure. Methods and Results Using genetic association estimates from the UK Biobank and CARDIoGRAMplusC4D consortium, univariable mendelian randomization was performed to investigate the total effect of genetically predicted mean arterial pressure (MAP) at age ≤55 years on coronary artery disease (CAD) risk, and multivariable mendelian randomization was performed to investigate the effect of genetically predicted MAP on CAD risk after adjusting for genetically predicted MAP at age >55 years. In both univariable and multivariable mendelian randomization analyses, there was consistent evidence of higher genetically predicted MAP at age ≤55 years increasing CAD risk. This association persisted after adjusting for genetically predicted MAP at age >55 years, when considering nonoverlapping populations for the derivation of MAP and CAD risk genetic association estimates, when investigating only incident CAD events after age >55 years, and when restricting the analysis to variants with most heterogeneity in their associations with MAP ≤55 and >55 years. For a 10-mm Hg increase in genetically predicted MAP at age ≤55 years, the odds ratio of later life CAD was 1.43 (95% CI, 1.16-1.77; =0.001) after adjusting for genetically predicted MAP at age >55 years. Conclusions These mendelian randomization findings support a cumulative lifetime effect of elevated blood pressure on increasing CAD risk. Clinical and public health efforts toward cardiovascular disease reduction should optimize blood pressure control throughout life.
背景 高血压是心血管发病率和死亡率的主要原因。然而，目前尚不清楚中年时期的血压是否会独立于晚年时期的血压影响晚年时期的心血管风险。
方法和结果 使用英国生物库和 CARDIOGRAMplusC4D 联盟的遗传关联估计，进行单变量孟德尔随机化分析，以研究≤55 岁时遗传预测平均动脉压（MAP）对冠心病（CAD）风险的总影响，并进行多变量孟德尔随机化分析，以研究遗传预测 MAP 对>55 岁时遗传预测 MAP 调整后的 CAD 风险的影响。在单变量和多变量孟德尔随机化分析中，均有一致的证据表明，≤55 岁时遗传预测的 MAP 升高会增加 CAD 风险。这种关联在考虑到 MAP 和 CAD 风险遗传关联估计的推导人群不重叠、仅在>55 岁后研究 CAD 事件、以及仅将分析限制在与 MAP≤55 和>55 年关联具有最大异质性的变体时，仍持续存在。对于遗传预测 MAP 在≤55 岁时增加 10mmHg，在调整>55 岁时遗传预测 MAP 后，晚年 CAD 的比值比为 1.43（95%CI，1.16-1.77；=0.001）。
结论 这些孟德尔随机化研究结果支持高血压对增加 CAD 风险的终身累积影响。为减少心血管疾病，临床和公共卫生工作应优化整个生命周期的血压控制。
