Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association

Abstract

Hypertensive disorders of pregnancy (HDP) remain one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Affected women are also at increased risk for cardiovascular disease later in life, independently of traditional cardiovascular disease risks. Despite the immediate and long-term cardiovascular disease risks, recommendations for diagnosis and treatment of HDP in the United States have changed little, if at all, over past decades, unlike hypertension guidelines for the general population. The reasons for this approach include the question of benefit from normalization of blood pressure treatment for pregnant women, coupled with theoretical concerns for fetal well-being from a reduction in utero-placental perfusion and in utero exposure to antihypertensive medication. This report is based on a review of current literature and includes normal physiological changes in pregnancy that may affect clinical presentation of HDP; HDP epidemiology and the immediate and long-term sequelae of HDP; the pathophysiology of preeclampsia, an HDP commonly associated with proteinuria and increasingly recognized as a heterogeneous disease with different clinical phenotypes and likely distinct pathological mechanisms; a critical overview of current national and international HDP guidelines; emerging evidence that reducing blood pressure treatment goals in pregnancy may reduce maternal severe hypertension without increasing the risk of pregnancy loss, high-level neonatal care, or overall maternal complications; and the increasingly recognized morbidity associated with postpartum hypertension/preeclampsia. Finally, we discuss the future of research in the field and the pressing need to study socioeconomic and biological factors that may contribute to racial and ethnic maternal health care disparities.

Keywords: AHA Scientific Statements; cardiovascular diseases; diagnosis; hypertension; pregnancy; therapeutics.

Figure 1:. Pathogenesis of hypertensive disorders of pregnancy

Pre-existing maternal co-morbidities, non-modifiable patient characteristics, reproductive history, genetic and immune factors increase the risk of developing a HDP (hypertensive disorder of pregnancy). The molecular and pathophysiological mechanisms of preeclampsia are largely unknown, but the etiology is likely a combination of, and interaction between, factors from both maternal and placental pathways. Variable contributions of the underlying maternal and placental pathophysiological pathways result in the heterogeneous phenotypes of HDP. The associated widespread endovascular damage and dysfunction may be long-lasting with a possible intergenerational effect. TPR, total peripheral resistance; CO, cardiac output; GFR, glomerular filtration rate; ROS, reactive oxygen species; uNK, uterine natural killer cell; sFlt1, soluble fms-like tyrosine kinase 1; sENG, soluble endoglin; VEGF, vascular endothelial growth factor; PlGF, placental growth factor; IL-10, Interleukin 10; Th-1, Type 1 T helper cell; AT1-AA, angiotensin II receptor 1 autoantibodies; ET-1,endothelin-1; TNF-α, tumor necrosis factor alpha; SASP, senescence-associated secretory phenotype; RAS, renin angiotensin system; Ang I, Angiotensin I; Ang II, Angiotensin II; ACE, Angiotensin converting enzyme; ATR1, Angiotensin II type 1 receptor; DIC, disseminated intravascular coagulation; VTE, venous thromboembolism; PRES, posterior reversible encephalopathy syndrome; MI, myocardial infarction; PCM, peripartum cardiomyopathy; SCAD, spontaneous coronary artery dissection; CAD, coronary artery disease; HF, heart failure; AKI, acute kidney injury; CKD, chronic kidney disease; ESKD end stage kidney disease; SGA, small for gestational age; FGR, fetal growth restriction. Podocyturia: the urinary loss of podocytes (glomerular epithelial cells) in preeclamptic women contributes to the development of proteinuria and has been documented both before and at the time of preeclampsia diagnosis. Senescence: an irreversible cell-cycle arrest mechanism that leads to systematic metabolic and functional decline and which may play a role in impaired angiogenesis in preeclampsia.