From the Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Germany (M.K.G., R.M., M.D.).
Department of Biostatistics and Epidemiology, School of Public Health, Imperial College London, United Kingdom (D.G.).
Hypertension. 2020 Sep;76(3):953-961. doi: 10.1161/HYPERTENSIONAHA.120.15136. Epub 2020 Jul 6.
Hypertension is the leading risk factor for stroke. Yet, it remains unknown whether blood pressure pulsatility (pulse pressure [PP]) causally affects stroke risk independently of the steady pressure component (mean arterial pressure [MAP]). It is further unknown how the effects of MAP and PP on stroke risk vary with age and stroke cause. Using data from UK Biobank (N=408 228; 38-71 years), we selected genetic variants as instruments for MAP and PP at age ≤55 and >55 years and across age deciles. We applied multivariable Mendelian randomization analyses to explore associations with ischemic stroke, intracerebral hemorrhage, and their subtypes. Higher genetically predicted MAP was associated with higher risk of ischemic stroke and intracerebral hemorrhage across the examined age spectrum. Independent of MAP, higher genetically predicted PP only at age >55 years was further associated with higher risk of ischemic stroke (odds ratio per-SD-increment, 1.23 [95% CI, 1.13-1.34]). Among subtypes, the effect of genetically predicted MAP on large artery stroke was attenuated, whereas the effect of genetically predicted PP was augmented with increasing age. Genetically predicted MAP, but not PP, was associated with small vessel stroke and deep intracerebral hemorrhage homogeneously across age deciles. Neither genetically predicted MAP nor PP were associated with lobar intracerebral hemorrhage. Beyond an effect of high MAP at any age on ischemic and hemorrhagic stroke, our results support an independent causal effect of high PP at older ages on large artery stroke. This finding warrants further investigation for the development of stroke preventive strategies targeting pulsatility in later life.
高血压是中风的主要危险因素。然而，目前尚不清楚血压脉动（脉压[PP]）是否独立于稳定压力成分（平均动脉压[MAP]）对中风风险产生因果影响。此外，尚不清楚 MAP 和 PP 对中风风险的影响如何随年龄和中风原因而变化。我们使用英国生物银行（N=408228；38-71 岁）的数据，选择遗传变异作为 MAP 和 PP 在≤55 岁和>55 岁及各年龄十分位数的工具。我们应用多变量孟德尔随机化分析来探讨与缺血性中风、脑出血及其亚型的关联。在检查的年龄范围内，遗传预测的 MAP 越高，与缺血性中风和脑出血的风险越高相关。独立于 MAP 之外，遗传预测的仅在>55 岁时的 PP 进一步与缺血性中风的高风险相关（每-SD 增量的优势比，1.23[95%CI，1.13-1.34]）。在亚型中，遗传预测的 MAP 对大动脉性中风的影响减弱，而遗传预测的 PP 随着年龄的增加而增加。遗传预测的 MAP，但不是 PP，与小血管性中风和深部脑出血在各年龄十分位数上均相关。遗传预测的 MAP 或 PP 均与脑叶性脑出血无关。除了任何年龄的高 MAP 对缺血性和出血性中风的影响之外，我们的结果还支持在老年时高 PP 的独立因果作用对大动脉性中风的影响。这一发现值得进一步研究，以制定针对生命后期脉动的中风预防策略。
