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妊娠血压与血管生成标志物:妊娠高血压的致病因素及其对子代心血管风险的影响。

Blood Pressure and Angiogenic Markers in Pregnancy: Contributors to Pregnancy-Induced Hypertension and Offspring Cardiovascular Risk.

机构信息

From the experimental and Clinical Research Center, a joint cooperation between Max-Delbrück-Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Germany (A. Birukov, F.H., M.G., K.K., N.H., D.N.M., R.D.).

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Germany (A. Birukov, F.H., M.G., K.K., N.H., D.N.M., R.D.).

出版信息

Hypertension. 2020 Sep;76(3):901-909. doi: 10.1161/HYPERTENSIONAHA.119.13966. Epub 2020 Jun 8.

Abstract

Pregnancy-induced hypertension is a severe pregnancy complication, increasing risk of long-term cardiovascular disease in mothers and offspring. We hypothesized that maternal blood pressure in pregnancy associated with offspring blood pressure; that the associations were sex-specific; and that maternal circulating placental angiogenic markers (PlGF [placental growth factor] and sFlt-1 [soluble fms-like tyrosine kinase-1]) mediated this relationship. We analyzed data from 2434 women and 2217 children from the Odense Child Cohort, a prospective Danish cohort study. Offspring blood pressure trajectory from 4 months to 5 years was highly associated to maternal first, second, and third trimester blood pressure, and mean blood pressure in pregnancy, independent of maternal and offspring covariates. There were offspring sex-specific associations: Girls from mothers in the highest quartile of first and third trimester blood pressure had significantly higher systolic blood pressure at 5 years than the rest of the cohort (mean difference±SEM: 1.81±0.59 and 2.11±0.59 mm Hg, respectively, all <0.01); whereas boys had significantly higher diastolic blood pressure at 5 years (mean difference±SEM: 1.11±0.45 and 1.03±0.45, respectively, all <0.05). Concentrations of PlGF at gestational week 28 correlated inversely to maternal gestational blood pressure trajectory, independent of the diagnosis of pregnancy-induced hypertension, adjusted β coefficients (95% CI) for predicting systolic blood pressure (SBP): -3.18 (-4.66 to -1.70) mm Hg, for predicting diastolic blood pressure (DBP): -2.48 (-3.57 to -1.40) mm Hg. In conclusion, maternal gestational blood pressure predicted offspring blood pressure trajectory until 5 years in a sex-differential manner. Furthermore, subtle alterations in blood pressure in early pregnancy preceded hypertension or preeclampsia, and PlGF was a mediator of cardiovascular health in pregnancy.

摘要

妊娠高血压是一种严重的妊娠并发症,会增加母亲和后代患长期心血管疾病的风险。我们假设孕妇怀孕期间的血压与后代的血压有关;这种关联具有性别特异性;并且母体循环胎盘血管生成标志物(PlGF [胎盘生长因子]和 sFlt-1 [可溶性 fms 样酪氨酸激酶-1])介导了这种关系。我们分析了来自丹麦前瞻性奥登塞儿童队列的 2434 名女性和 2217 名儿童的数据。从 4 个月到 5 岁的后代血压轨迹与母亲的第一、第二和第三孕期血压以及怀孕期间的平均血压高度相关,而与母亲和后代的协变量无关。存在与后代性别特异性相关的关联:母亲处于第一和第三孕期血压最高四分位数的女孩在 5 岁时的收缩压明显高于队列中的其他女孩(平均差异±SEM:分别为 1.81±0.59 和 2.11±0.59 mmHg,均 <0.01);而男孩在 5 岁时的舒张压明显升高(平均差异±SEM:分别为 1.11±0.45 和 1.03±0.45,均 <0.05)。妊娠 28 周时 PlGF 的浓度与孕妇的妊娠血压轨迹呈负相关,与妊娠高血压的诊断无关,预测收缩压(SBP)的调整β系数(95%CI):-3.18(-4.66 至-1.70)mmHg,预测舒张压(DBP):-2.48(-3.57 至-1.40)mmHg。总之,母亲怀孕期间的血压以性别差异的方式预测了 5 岁以下的后代血压轨迹。此外,早期妊娠时血压的细微变化先于高血压或子痫前期发生,PlGF 是怀孕期间心血管健康的一个中介。

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