Preeclampsia: Pathophysiology and Clinical Presentations

Ives CW, Sinkey R, Rajapreyar I, Tita AT, Oparil S.
Preeclampsia—Pathophysiology and Clinical Presentations: JACC State-of-the-Art Review. J Am Coll Cardiol 2020;76:1690-1702.

The following are key points to remember from this JACC state-of-the-art review on preeclampsia—pathophysiology and clinical presentations:

  1. Preeclampsia is a hypertensive disorder of pregnancy that occurs in 2-8% of pregnancies and causes substantial morbidity and mortality.
  2. Preeclampsia is defined as new-onset hypertension and new-onset end-organ damage after 20 weeks’ gestation. Proteinuria is no longer required for the diagnosis.
  3. The complex pathophysiology of preeclampsia begins with abnormal placental development, endothelial dysfunction, and immunologic aberrations, possibly related to genetic susceptibility. Clinical features of preeclampsia include hypertension, proteinuria, renal dysfunction, neurological abnormalities, eclampsia, cardiac dysfunction, pulmonary edema, hepatic dysfunction, hematologic dysfunction, and fetal growth restriction.
  4. Hypertension is necessary for the diagnosis of preeclampsia, defined as systolic blood pressure (SBP) ≥140 mm Hg or diastolic BP (DBP) ≥90 mm Hg on two occasions ≥4 hours apart after 20 weeks’ gestation in a woman with previously normal BP; or SBP ≥160 mm Hg or DBP ≥110 mm Hg on one occasion.
  5. Proteinuria: The imbalance between proangiogenic and antiangiogenic factors likely causes podocyte injury leading to increased risk of hypertension and chronic kidney disease. Proteinuria can take up to 2 years to resolve after preeclampsia.
  6. Renal dysfunction in preeclampsia is defined as serum creatinine >1.1 mg/dl or a doubling of baseline creatinine. Inflammatory cytokines lead to endothelial dysfunction and thrombotic microangiopathy of the kidneys, and decreased intravascular volumes in preeclampsia increases sodium and free-water retention.
  7. Neurologic dysfunction includes headaches, visual disturbances, seizure, posterior reversible encephalopathy syndrome, and hemorrhagic stroke. The classic preeclampsia headache is progressive, bilateral, pulsating/throbbing, associated with visual changes, worse with higher BP, worsened by physical activity, and not relieved by over-the-counter medications.
  8. Eclampsia is defined as new-onset tonic-clonic, focal or multifocal seizures in the setting of pregnancy-related hypertension. Magnesium reduces the risk of eclampsia by 59%.
  9. Cardiac dysfunction: Impaired placentation in preeclampsia causes increased vascular resistance and higher afterload, resulting in mild-to-moderate left ventricular diastolic dysfunction with concentric left ventricular hypertrophy. Preeclampsia is also a risk factor for peripartum cardiomyopathy (defined as left ventricular systolic function <45%).
  10. Pulmonary edema is rare in preeclampsia and is related to: 1) increased vascular permeability, 2) cardiac dysfunction, 3) corticosteroids/tocolytics, and 4) iatrogenic volume overload.
  11. Hepatic dysfunction is defined as transaminases ≥2x the upper limit of normal (AST typically < ALT) with right upper quadrant or epigastric tenderness.
  12. Hematologic disturbances in preeclampsia include thrombocytopenia (due to increased platelet activation, aggregation, and consumption) and disseminated intravascular coagulopathy (due to consumption coagulopathy, hepatic injury and decreased clotting factors, and/or inflammatory response).
  13. Fetal growth restriction (defined as an estimated fetal weight <10th percentile for gestational age) occurs commonly in pregnancies complicated by preeclampsia. Several mechanisms of uterine and placental dysfunction contribute to intrauterine growth restriction.
  14. Low-dose aspirin is recommended for prevention of preeclampsia in high-risk women. Possible benefits of exercise, pravastatin, and metformin are being investigated. The definitive treatment for preeclampsia is delivery.
  15. Further research to understand the link between preeclampsia and subsequent short- and long-term cardiovascular disease is needed.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Vascular Medicine, Acute Heart Failure, Hypertension

Keywords: Aspirin, Cardiomyopathies, Eclampsia, Fetal Growth Retardation, Headache, Hypertension, Hypertension, Pregnancy-Induced, Hypertrophy, Left Ventricular, Pre-Eclampsia, Kidney Diseases, Pregnancy, Primary Prevention, Proteinuria, Pulmonary Edema, Renal Insufficiency, Seizures, Stroke, Thrombocytopenia, Vascular Diseases

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