Pregnancy as a Window to the Future: Outcomes of Antihypertensive Therapy and Superimposed Preeclampsia in Pregnant Women with Mild Chronic Hypertension (CHAP Maternal Follow-up Study)

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PROJECT SUMMARY/ABSTRACT The large randomized multicenter Chronic Hypertension and Pregnancy (CHAP) trial (2015-2021) was designed to evaluate the short-term benefits and safety of pharmacologic treatment of pregnant women with mild chronic hypertension (CHTN). This proposed CHAP Maternal Follow-Up project (2021-2026) is a follow-up study of the well-characterized women in CHAP to address the critical knowledge gaps regarding whether future long-term cardiovascular disease (CVD) and other outcomes are associated with 1) antihypertensive therapy use early in pregnancy and 2) the development of superimposed preeclampsia (SI PRE). CHTN is the most common major medical disorder seen in pregnancy, is most often mild (i.e. BP <160/110 mmHg), and associated with adverse outcomes, including preeclampsia, death, preterm birth and small for gestational age (SGA) infants (birth weight <10th percentile). Whereas antihypertensive therapy is a priority for the general population, the American College of Obstetricians and Gynecologists (ACOG), recommends withholding antihypertensive therapy during pregnancy unless CHTN is severe (BP≥160/110 mm Hg) due to uncertain benefits and concern that therapy may increase the risk of SGA infants. An international controversy regarding optimal treatment during pregnancy will be informed by these data on long-term outcomes. Whereas preeclampsia in women without CHTN increases their future risk of CHTN and CVD, the long-term effects of SI PRE and antihypertensive therapy in women with preexisting CHTN are uncertain. During this proposed 5- year project, our consortium of up to 60 sites, will follow-up the CHAP participants every 6 months (in-person or remotely, review medical records and administer questionnaires) to obtain interval history, serial BPs and outcome data, and collect bio-specimens. We anticipate 1804 (75%) of the 2404 in CHAP will be studied to address the following Specific Aims: Specific Aim 1: Test the hypothesis that antihypertensive therapy for mild CHTN during pregnancy to achieve a BP goal <140/90 compared with no treatment reduces the frequency of maternal CVD outcomes 5 to 10 years postpartum, including the primary composite of severe CHTN (a marker of future CVD), heart failure, stroke, myocardial infarction/angina, renal failure, venous thromboembolism (VTE) or death. Specific Aim 2: Test the hypothesis that the development of SI PRE in pregnant women with mild CHTN increases the risk of maternal CVD outcomes 5 to 10 years postpartum, including the primary composite of severe CHTN, heart failure, stroke, myocardial infarction/angina, renal failure, VTE and death. Specific Aim 3 (Exploratory): Test whether available components of the ACC/AHA ASCVD risk score (age, race-ethnicity, diabetes mellitus, smoking status, baseline BP, pre-pregnancy treatment) and pregnancy data (treatment and SI PRE) in women with mild CHTN predict maternal CVD outcomes 5-10 years postpartum. We will also collect and store maternal blood and urine for future biomarker and biological studies.