George Mangos

Guidelines for the management of hypertensive disorders of pregnancy 2008

This is the Executive Summary of updated guidelines developed by the Society of Obstetric Medicine of Australia and New Zealand for the management of hypertensive diseases of pregnancy. They address a number of challenging areas including the definition of severe hypertension, the use of automated blood pressure monitors, the definition of non‐proteinuric pre‐eclampsia and measuring proteinuria. Controversial management issues are addressed such as the treatment of severe hypertension and other significant manifestations of pre‐eclampsia, the role of expectant management in pre‐eclampsia remote from term, thromboprophylaxis, appropriate fluid therapy, the role of prophylactic magnesium sulfate and anaesthetic issues for women with pre‐eclampsia. The guidelines stress the need for experienced team management for women with pre‐eclampsia and mandatory hospital protocols for treatment of hypertension and eclampsia. New areas addressed in the guidelines include recommended protocols for maternal and fetal investigation of women with hypertension, preconception management for women at risk of pre‐eclampsia, auditing outcomes in women with hypertensive diseases of pregnancy and long‐term screening for women with previous pre‐eclampsia.

Cushing, Cortisol, and Cardiovascular Disease

Cushings syndrome of glucocorticoid excess is named after the eminent Boston neurosurgeon Harvey W. Cushing (1869-1939). The recognition that glucocorticoid excess produces hypertension led to examination of the role of cortisol in essential hypertension, but it is only over the last decade that evidence has emerged to support the concept. Despite the widespread assumption that cortisol raises blood pressure as a consequence of renal sodium retention, there are few data consistent with the notion. Although it has a plethora of actions on brain, heart and blood vessels, kidney, and body fluid compartments, precisely how cortisol elevates blood pressure is unclear. Candidate mechanisms currently being examined include inhibition of the vasodilator nitric oxide system and increases in vasoconstrictor erythropoietin concentration.

CORTISOL AND HYPERTENSION

1. In humans, the hypertensive effects of adrenocorticotropic hormone (ACTH) infusion are reproduced by intravenous or oral Cortisol. Oral Cortisol increases blood pressure in a dose‐dependent fashion. At a dose of 80–200 mg/day, the peak increases in systolic pressure are of the order of 15mmHg. Increases in blood pressure are apparent within 24 h.

Cortisol inhibits cholinergic vasodilatation in the human forearm

Exogenous cortisol raises blood pressure (BP) in humans and there is accumulating evidence of abnormalities of glucocorticoid activity in essential hypertension. In this study we tested the hypothesis that exogenous cortisol attenuates the cholinergic dilator response in the forearm circulation. Fourteen healthy normotensive men were studied. Using bilateral forearm venous plethysmography, we examined forearm blood flow responses to intra-arterial acetylcholine (ACh) and sodium nitroprusside (SNP) pre- and post-NG-monomethyl-L-arginine (LNMMA) after 2 or 5 days of oral cortisol or placebo in a randomized, double-blind crossover study. Exogenous cortisol increased supine systolic (P < .05) and standing systolic (P < .05) BP and produced expected metabolic changes and suppressed serum cortisol concentration (P < .001). Baseline forearm blood flow did not differ between placebo and cortisol treatments at 2 or 5 days. Cholinergic vasodilatation was impaired after cortisol administration, reaching statistical significance at 5 days (P < .05). Cortisol did not affect responses to SNP. NG-monomethyl-L-arginine inhibited cholinergic vasodilatation in placebo-treated groups but had no additional effect in the presence of cortisol. These results support our hypothesis and suggest that the mechanism of impaired cholinergic dilatation in glucocorticoid-treated subjects involves abnormalities of the endothelial nitric oxide system.

The nitric oxide system in glucocorticoid-induced hypertension

The blood pressure-raising effects of adrenocortical steroids with predominantly glucocorticoid activity, both naturally occurring and synthetic, are well known. Recent evidence suggests that the nitric oxide system plays a key role in the hypertension produced by glucocorticoids. Glucocorticoid actions at various sites in the nitric oxide synthase (NOS) pathway may result in elevated blood pressure. These include: alterations in l-arginine availability or transport; NOS2 and NOS3 downregulation; reduced cofactor bioavailability; NOS uncoupling; a concomitant elevation in reactive oxygen species and removal of nitric oxide (NO) from the vascular environment; alterations in whole body antioxidant status; and erythropoietin induced resistance to NO.

The natural history of white coat hypertension during pregnancy.

Objective  White coat hypertension (WCH) is a common phenomenon with a long term prognosis intermediate between those with true hypertension and true normotension. The natural history of this phenomenon throughout pregnancy remains unknown. We assessed the likelihood of women with an initial diagnosis of WCH developing pre‐eclampsia (PE) as their pregnancy progressed.

Markers of cardiovascular disease risk after hypertension in pregnancy.

Objectives: Women with a history of preeclampsia or gestational hypertension have an increased risk of cardiovascular disease. Underlying cardiovascular risk factors, persistent endothelial dysfunction or sympathetic overactivity may contribute to this risk. We studied markers of cardiovascular disease risk in nonpregnant women with a history of hypertension in pregnancy. Methods: Women with a history of preeclampsia (n = 39), gestational hypertension (n = 27) and normal pregnancies (n = 35) were studied 2–12 years after delivery. Laboratory measures included plasma fasting lipids, glucose, insulin, creatinine and urinary albumin-to-creatinine ratio. Blood pressure was measured by 24-h ambulatory blood pressure monitoring, endothelial function by flow-mediated dilatation and sympathetic activity by both head-up tilt test and cold pressor test, including the response of the circulating renin–angiotensin system to tilt testing. Results: Compared with women who had previous normal pregnancies, women with a history of preeclampsia or gestational hypertension have higher ambulatory blood pressure, BMI and relative insulin resistance. Glomerular filtration rate, albumin-to-creatinine ratio, endothelial function and sympathetic activity was similar among the three groups. Conclusion: Women with a history of preeclampsia or gestational hypertension have features of the metabolic syndrome which are presumably present already before pregnancy, predisposing them to hypertensive disorders of pregnancy and later cardiovascular risk. In this study, we found no evidence for early renal damage, endothelial dysfunction or sympathetic overactivity in the postpartum state.

Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: a retrospective cohort study

Please cite this paper as: Hawkins T, Roberts J, Mangos G, Davis G, Roberts L, Brown M. Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: a retrospective cohort study. BJOG 2012 2012;119:484–492.

Can spot urine protein/creatinine ratio replace 24 h urine protein in usual clinical nephrology?

Background:  This prospective study was designed to assess whether a single urine specimen, collected at the time of clinical assessment, could be used to estimate 24 h urinary protein excretion.

Non-proteinuric pre-eclampsia: a novel risk indicator in women with gestational hypertension.

Objective To determine whether outcomes differed for women with pre-eclampsia according to the presence of proteinuria and whether non-proteinuric pre-eclampsia is similar to gestational hypertension. Design From 1987 to 2005, at three hospitals in Sydney, Australia, women referred to the obstetric medicine team were recruited. Outcomes for three groups were compared: proteinuric pre-eclampsia, non-proteinuric pre-eclampsia and gestational hypertension. Results Women with proteinuric pre-eclampsia were more likely to have severe hypertension (39 versus 30%, P = 0.003), deliver preterm infants (39 versus 30%, P = 0.007) and had a higher perinatal mortality rate (25.2 versus 5.7 per 1000, P = 0.02) than those with non-proteinuric pre-eclampsia, who were more likely to have thrombocytopenia and liver disease. Women with non-proteinuric pre-eclampsia were more likely to have multiple pregnancies (3.9 versus 9.9%, P < 0.001), experience severe hypertension (8.9 versus 29.7%, P < 0.001), and deliver preterm infants (11.3 versus 30.2%, P < 0.001) who were small for gestational age (12.7 versus 20.9%, P < 0.001) than those with gestational hypertension. Conclusion This study highlights differences between non-proteinuric pre-eclampsia and gestational hypertension. The subclassification of ‘non-proteinuric pre-eclampsia’ should be added to existing classification systems to alert clinicians to potential risks.