Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy

Authors, Journal, Affiliations, Type, DOI

• Vesna D. Garovic (Chair), Ralf Dechend, Thomas Easterling, S. Ananth Karumanchi, Suzanne McMurtry Baird, Laura A. Magee, Sarosh Rana, Jane V. Vermunt, Phyllis August (Vice Chair)
• On behalf of the AHA Council on Hypertension; Council on the Kidney in Cardiovascular Disease; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; Council on Peripheral Vascular Disease; and Stroke Council
• Hypertension. 2022;79:e21–e41
• AHA Scientific Statement
• DOI: 10.1161/HYP.0000000000000208

Overview

HDP (chronic hypertension, gestational hypertension, preeclampsia/eclampsia, superimposed preeclampsia) affect 7.5% of pregnancies but 15.3% of women across their reproductive lives, and are the second leading cause of global maternal mortality. This statement focuses on three major areas: (1) the striking long-term CVD sequelae of HDP — surviving women face HF HR 2.7, stroke HR 1.9, coronary disease HR 2.1, vascular dementia aHR 2.4, and ESKD RR 6.6 after preeclampsia; (2) the BP treatment threshold controversy — US (ACOG) uses ≥160/110 mmHg while most international guidelines use ≥140/90 mmHg, with CHIPS trial data supporting tighter control; and (3) the molecular heterogeneity of preeclampsia (placental vs maternal phenotypes driven by sFlt-1/VEGF imbalance and failed spiral artery remodeling). The statement calls for lower treatment thresholds, personalized antihypertensive therapy, and urgent attention to racial disparities in maternal mortality.

Keywords

AHA Scientific Statements, cardiovascular diseases, diagnosis, hypertension, pregnancy, therapeutics

Key Takeaways

Epidemiology

• HDP affect 7.5% per pregnancy; per-woman incidence 15.3% — better reflects population at future CVD risk sources/ht-pregnancy-aha-2022 (rating: high)
• HDP are the 2nd leading cause of global maternal mortality (behind hemorrhage); CVD accounts for up to 50% of all maternal deaths
• Pregnancy-related stroke hospitalizations increased >60% from 1994 to 2011; HDP-associated stroke rates doubled vs non-HDP
• Incidence increasing due to advanced maternal age at first pregnancy and rising prevalence of obesity and cardiometabolic risk factors

Immediate Complications (Table 1 — selected key estimates)

Maternal:

• Preeclampsia: mortality aOR 2.6; MI aOR 3.0; stroke aOR 5.7; peripartum cardiomyopathy aOR 3.3
• Preeclampsia on chronic HT: stroke aOR 7.8
• Eclampsia: stroke aOR 65.9
• Chronic HT: MI aOR 3.4; peripartum cardiomyopathy aOR 3.8

Fetal/neonatal:

• SGA: HDP RR 1.6; preeclampsia OR 1.5
• Stillbirth: HDP RR 1.4; preeclampsia aOR 1.3
• Preterm birth <37w: preeclampsia aOR 3.1; superimposed preeclampsia aOR 4.7
• Placental abruption: preeclampsia aOR 2.3

Long-Term Sequelae (Table 2 — selected key estimates)

• Hypertension: preeclampsia OR 11.6 (10.6–12.7); aHR 4.5 (4.3–4.6); develops 10 years earlier than in normotensive pregnancies
• Type 2 diabetes: HDP HR 1.8; preeclampsia aHR 1.8
• Heart failure: HDP HR 2.7; preeclampsia aHR 2.1; RR 4.2 (2.1–8.4)
• Coronary heart disease: HDP aHR 1.9; preeclampsia aHR 2.1; RR 2.5
• Atrial fibrillation: HDP HR 1.4; preeclampsia aHR 1.7
• All stroke: HDP aHR 1.8; preeclampsia aHR 1.9
• Vascular dementia: gestational HT aHR 3.0; preeclampsia aHR 2.4
• CKD: preeclampsia RR 2.3; gestational HT RR 1.5
• ESKD: preeclampsia RR 6.6 (2.7–14.8); gestational HT RR 3.6
• VTE: HDP OR 1.5; preeclampsia aHR 1.6
• Approximately two-thirds of HDP-associated CVD risk is mediated by established risk factors; remainder is likely HDP-specific pathogenesis
• Associations with future CVD/CKD/dementia persist after adjustment for traditional CVD risk factors — HDP is an independent CVD risk factor

Offspring Long-Term Outcomes

• CVD (severe preeclampsia): aHR 2.3 by childhood
• Stroke (preeclampsia): HR 1.9
• Higher BMI (mean difference 0.36 kg/m²) and higher BP in offspring of preeclamptic mothers

Pathophysiology

• Normal pregnancy: SVR ↓, plasma volume ↑, CO ↑; BP drops 1–2 mmHg in 2nd trimester; renal blood flow and GFR increase 50%
• Preeclampsia core mechanism: failure of uterine spiral artery remodeling → ↓utero-placental perfusion → ischemia-reperfusion injury, oxidative stress
• Angiogenic imbalance: ↑sFlt-1 (antiangiogenic, placental origin) → neutralizes VEGF and PlGF → endotheliosis, hypertension, proteinuria, glomerulopathy
• Podocyturia: urinary loss of podocytes contributes to proteinuria; documented before clinical diagnosis
• Placental preeclampsia (early, <34 wks): pronounced sFlt-1 elevation, fetal growth restriction, marked placental ischemia
• Maternal preeclampsia (late): maternal vascular dysfunction predominates (preexisting HT, DM, obesity), fewer fetal complications, pregnancy acts as "physiological stress test unmasking preexisting endothelial dysfunction"
• Both phenotypes coexist with varying contributions; strict discrimination is oversimplistic
• Cardiometabolic changes in normal pregnancy (↑insulin resistance, ↑TG, ↑cholesterol) are more pronounced in preeclamptic women
• Hypercoagulability of normal pregnancy is exaggerated in preeclampsia (↑thrombin, fibrinogen, ↓protein S)
• Senescence-associated secretory phenotype may impair angiogenesis and contribute to placental dysfunction

Prevention

• Low-dose aspirin (81–150 mg/day, start 12–16 weeks): reduces preeclampsia and related adverse outcomes by 10–20% in high-risk women; ACOG recommends when ≥1 high-risk or ≥2 moderate risk factors present
• Exercise: may reduce gestational HT by ~30% and preeclampsia by ~40% (meta-analysis)
• Dietary interventions: meta-analysis of 44 RCTs — reduce gestational weight gain and improve pregnancy outcomes
• Pravastatin: promising experimental evidence; fetal safety concerns remain
• Metformin: may prevent preeclampsia by reducing sFlt-1/soluble endoglin; clinical trial evidence emerging

Risk Factors for Preeclampsia (Table 3)

High-risk (aspirin indicated if ≥1 present):

• Prior preeclampsia RR 8.4; chronic stage 2 HT RR 5.1; pregestational DM RR 3.7; multifetal pregnancy RR 2.9; APS RR 2.8; SLE RR 2.5; CKD OR 10.4

Moderate-risk (aspirin if ≥2 present):

• Age >35 RR 1.2; prepregnancy BMI >30 aOR 3.7; family history RR 2.9; Black race aHR 1.6; low SES aOR 4.91; nulliparity RR 2.1

Other risk factors: white coat HT, gestational DM, insulin resistance, ART/oocyte donation, new paternity, migraine

BP Measurement in Pregnancy

• Office BP standard; oscillometric automated devices validated in pregnant women
• White coat HT prevalence 4–30% in pregnancy; associated with higher preeclampsia risk vs normotension (RR 2.4) but lower than sustained HT
• Definition of hypertension requires 2 readings ≥4 hours apart
• Self-measured BP useful for chronic/gestational HT monitoring
• Secondary HT: consider if age <35, severe/resistant, no family history, hypokalemia, elevated creatinine, or albuminuria early in pregnancy

BP Treatment Controversy

• US ACOG threshold: treat ≥160/110 mmHg (acute/severe); goal 120–160/80–105 mmHg for chronic HT
• International consensus (WHO, NICE, ISSHP, ESC): treat ≥140/90 mmHg; target ≤135/85 mmHg
• CHIPS trial: tight control (achieved 133/85 mmHg) vs less tight → halved severe HT; trend to less preterm birth; less thrombocytopenia/elevated liver enzymes; no significant fetal harm
• CHAP trial (near completion at time of writing): chronic HT — BP <140/90 vs no treatment until ≥160/105 mmHg
• AHA position: supports lower BP thresholds; endorses personalized/informed decision-making; women at highest risk (Black race, preexisting heart/kidney disease, obesity) should receive special attention
• Lower BP during pregnancy (vs ≥140/90) independently associated with lower preeclampsia and preterm delivery rates (retrospective studies)
• Using ACC/AHA lower threshold (≥130/80 mmHg) for HDP may better identify women at risk for preeclampsia and adverse fetal outcomes

Pharmacotherapy

Non-severe hypertension (first-line):

• Labetalol, methyldopa, long-acting nifedipine — no clear superiority of one over another (Cochrane review)
• Atenolol: associated with fetal growth restriction — avoid; other β-blockers (metoprolol, oxprenolol) acceptable when labetalol unavailable

Severe acute hypertension:

• Parenteral labetalol, parenteral hydralazine, or oral nifedipine — comparable safety/efficacy per Cochrane review

Contraindicated (COR 3:Harm):

• ACEi, ARBs, direct renin inhibitors (block fetal renal development)
• Nitroprusside (fetal cyanide accumulation)
• Spironolactone/MRA (antiandrogenic fetal effects)

Diuretics: generally avoided in pregnancy (historical plasma volume concerns); safe in salt-sensitive chronic HT or CKD at lower doses; furosemide RCT showed 60% reduction in persistent postpartum HT (adjusted RR 0.40) — effective and safe postpartum

NSAIDs: no significant BP increase up to 2–4 days postpartum (vs acetaminophen); evidence low quality; caution with extended use in older women with chronic HT/CKD

Postpartum Hypertension

• ~60% of all maternal deaths occur within the first year postpartum
• Prevalence: up to 8% in women without antepartum HT; up to 50% with prior preeclampsia at 6–12 weeks postpartum
• Complications: stroke, seizures, peripartum cardiomyopathy, insulin resistance, weight gain
• sFlt-1/PlGF ratio rate of rise is independent predictor of persistent postpartum hypertension
• Preeclampsia-associated endothelial dysfunction and altered cerebrovascular autoregulation persist postpartum
• Remote hypertension monitoring programs have potential to improve early recognition

Racial Disparities

• Maternal mortality ratio (2016): White 13; American Indian/Alaska Native 30; Black American 41 per 100,000 live births
• HDP disproportionately affects Black, American Indian, and Alaska Native women — predominantly due to higher CVD risk factor prevalence, but biological factors (genetic variants) may also contribute to preeclampsia risk in Black women
• Preeclampsia-related severe morbidity and mortality higher for Black women
• Hispanic women: pregnancy outcomes tend to be better than Black or White women of similar risk (Hispanic paradox)
• Implicit racial bias within the US health care system worsens management of severe maternal morbidity in Black and AIAN women
• Studies must include sufficient Black participants to address disparities and inform clinical practice

Postpartum Screening

• All major guidelines recommend CVD risk factor follow-up after HDP; recommendations largely vague and imprecise
• Early postpartum visit within 7–10 days (ACOG) or referral to primary care/cardiologist
• Lifestyle interventions (obesity, HT, dyslipidemia) are good clinical practice
• RCTs testing statins, aspirin, or RAASi post-HDP needed

Limitations of the Document

• CHAP trial results not yet available at time of writing (published 2022 post-statement); statement's BP controversy section is partially superseded by CHAP results
• Most antihypertensive safety data from small trials; only 5 of 47 studies considered high quality in systematic review of in utero antihypertensive exposure
• Long-term neurodevelopmental outcomes of offspring from antihypertensive-exposed pregnancies inadequately studied
• Causality between HDP and subsequent CVD cannot be fully established from observational data
• Sparse data from disaggregated racial/ethnic subgroups; genetic basis of disparities understudied
• Fetal safety of pravastatin/metformin remains unproven despite promising mechanistic data

Key Concepts Mentioned

• concepts/Hypertensive-Disorders-of-Pregnancy — central entity of this source; 4 types, epidemiology, immediate/long-term complications
• concepts/Preeclampsia — detailed pathophysiology, sFlt-1/VEGF, phenotypes, aspirin prevention
• concepts/Adverse-Pregnancy-Outcomes — HDP as the major APO driving long-term CVD
• concepts/Prepregnancy-Cardiovascular-Health — preconception health as upstream modifiable risk

Key Entities Mentioned

• entities/Maternal-Health-Disparities — maternal mortality ratios; HDP racial burden; implicit bias
• entities/Hypertension — BP thresholds, treatment targets, pharmacotherapy in pregnancy

Wiki Pages Updated

• wiki/sources/ht-pregnancy-aha-2022.md (created)
• wiki/concepts/Hypertensive-Disorders-of-Pregnancy.md (created)
• wiki/concepts/Preeclampsia.md (created)
• wiki/concepts/Adverse-Pregnancy-Outcomes.md (updated: long-term CVD risk quantified)
• wiki/entities/Maternal-Health-Disparities.md (updated: maternal mortality ratios, HDP race data)
• wiki/entities/Hypertension.md (updated: pregnancy section expanded)
• wiki/wikiindex.md (updated)
• wiki/sourceindex.md (updated)
• wiki/log.md (updated)