Anwer Tooba, Cantonwine David E, Seely Ellen W, Gray Kathryn, McElrath Thomas F
Division of Maternal Fetal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
medRxiv. 2025 Jul 23:2025.07.22.25330603. doi: 10.1101/2025.07.22.25330603.
We investigated the independent and comparative association of a history of hypertensive disease of pregnancy and elevated serum soluble fms-like tyrosine kinase 1 to placental growth factor (sFlt-1/PlGF) ratio during the second half of pregnancy with the development of HTN up to 15 years after delivery.
N=1,238 singleton pregnancies were part of a prospective birth cohort study that enrolled patients from 2006-2008. Serum sFlt-1/PlGF was collected at a median of 26.0 and 35.1 weeks gestation. Adjusted Cox proportional hazard models estimated hazard ratios and 95%CI for the time to diagnosis for Stage 1 and Stage 2 HTN within 15 years PP in association with diagnoses of HDP and interquartile range of sFlt-1/PlGF. We adjusted for confounders.
Of the n=993 women, n=260 (29.18%) were diagnosed with stage 1 and n=169 (17.0%) with Stage 2 HTN within 15 years of delivering. A history of PE or a history of gestational hypertension were both significantly associated with developing HTN later in life with adjusted hazard ratios of 2.17 (95% CI, 1.44-3.28) and 3.50 (95% CI, 2.21-5.54). There was no significant association between the hazard of developing HTN and the sFlt/PlGF ratio. However, mean PlGF levels during pregnancy in those who remained normotensive in the follow-up were higher at 546.7 pg/mL (SD= 369.5) compared to 513.7 pg/mL (SD=389.9) in the group with stage 1 and stage 2 HTN combined and 471.7 pg/mL (SD=471.7) in the stage 2 only group (p=0.008 and p=0.001).
In patients followed for up to 15 years after delivery, a clinical history of hypertensive disease of pregnancy was significantly associated with the hazard of developing HTN later in life, while elevated sFlt-1/PlGF biomarker levels were not. However, mean PlGF levels in the latter half of pregnancy were significantly lower in those who developed HTN later in life.
我们研究了妊娠高血压疾病史以及妊娠后半期血清可溶性fms样酪氨酸激酶1与胎盘生长因子（sFlt-1/PlGF）比值升高与产后15年内高血压发生之间的独立关联及比较关联。
N = 1238例单胎妊娠参与了一项前瞻性出生队列研究，该研究于2006年至2008年招募患者。在妊娠26.0周和35.1周的中位数时间采集血清sFlt-1/PlGF。调整后的Cox比例风险模型估计了产后15年内1期和2期高血压诊断时间的风险比和95%置信区间，这些与妊娠期高血压疾病诊断以及sFlt-1/PlGF的四分位间距有关。我们对混杂因素进行了调整。
在n = 993名女性中，n = 260名（29.18%）在分娩后15年内被诊断为1期高血压，n = 169名（17.0%）被诊断为2期高血压。既往有子痫前期病史或妊娠期高血压病史均与日后发生高血压显著相关，调整后的风险比分别为2.17（95%置信区间，1.44 - 3.28）和3.50（95%置信区间，2.21 - 5.54）。发生高血压的风险与sFlt/PlGF比值之间无显著关联。然而，随访期间血压正常者孕期的平均PlGF水平较高，为546.7 pg/mL（标准差 = 369.5），而1期和2期高血压合并组为513.7 pg/mL（标准差 = 389.9），仅2期高血压组为471.7 pg/mL（标准差 = 471.7）（p = 0.008和p = 0.001）。
在产后随访长达15年的患者中，妊娠高血压疾病的临床病史与日后发生高血压的风险显著相关，而sFlt-1/PlGF生物标志物水平升高则不然。然而，日后发生高血压者妊娠后半期的平均PlGF水平显著较低。
