Prevention and treatment of pregnancy-associated hypertension: what have we learned in the last 10 years?
High blood pressure (BP) complicates approximately 10% of all pregnancies. Hypertension in pregnancy falls into four categories: (1) preeclampsia-eclampsia, (2) chronic hypertension of whatever cause, (3) preeclampsia-eclampsia superimposed to chronic hypertension or renal disease, and (4) transient or late hypertension (gestational hypertension). Preeclampsia, the association of hypertension, proteinuria, and edema, accounts for more than 50% of all the hypertensive disorders of pregnancy and is a major cause of fetal and maternal morbidity and mortality. Unfortunately, distinguishing between preeclampsia and other causes of hypertension on clinical grounds can be difficult because of the lack of specific tests for differential diagnosis. Increased vascular resistance has been claimed as the primary cause of preeclampsia; however, a variable hemodynamic profile with relatively high cardiac outputs, normal filling pressures, and inappropriately high systemic vascular resistances is now reported by most investigators. Imbalance between vasodilator and vasoconstrictor eicosanoids may account for platelet activation and increased responsiveness to pressor peptides. Altered prostacyclin (PGI2) to thromboxane A2 (TxA2) ratio in maternal uteroplacental vascular bed may favor local platelet activation and vasoconstriction contributing to placental insufficiency and fetal distress. Alternatively, recent evidence seems to suggest that fetal umbilical placental circulation may be the site of the primary vascular injury. Whether low-dose aspirin prevents preeclampsia because it inhibits the excessive maternal TxA2 or whether the partial inhibition of fetal TxA2 is also of therapeutic value remains to be established. Treatment of severe hypertension in pregnancy is probably important to prevent cardiac failure or cerebrovascular accidents in the mother. The need for pharmacological therapy of mild to moderate hypertension is still debated, since no formal studies are available to clarify whether pharmacological treatment in such instances effectively reduces maternal or fetal risk. For the treatment of preeclampsia, hydralazine and nifedipine may be used when delivery is not applicable. Labetalol and diazoxide are effective for hypertensive emergencies. Life-threatening hypertension that does not respond to more conventional therapy is an indication for the use of sodium nitroprusside. For chronic hypertension, alpha-methyldopa remains the treatment of choice; if ineffective, hydralazine or beta-blockers are suitable. Effectiveness and safety of other molecules remain elusive.
Remuzzi
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G
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Ruggenenti
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P
D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure; D002908:Chronic Disease; D003937:Diagnosis, Differential; D004461:Eclampsia / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D011225:Pre-Eclampsia / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology; D011453:Prostaglandins / Q000096:biosynthesis; D012084:Renin-Angiotensin System
D000959:Antihypertensive Agents; D011453:Prostaglandins