Vellore J. Karthikeyan

Are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers safe in pregnancy: a report of ninety-one pregnancies

Background Both angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor antagonists (ARBs) have been reported to be associated with an excess of congenital abnormalities in infants born to women who took these drugs in pregnancy. Methods To investigate this possible association further, we have examined the outcome in 91 pregnancies in which the mother took either an ACE-I (n = 71) or an ARB (n = 20) in early pregnancy. We also examined the United Kingdom adverse drug reaction reporting system to assess the total number of reported associations of ACE-I or ARB use in pregnancy and congenital anomalies reported. Results Eight (8.8%) of the pregnancies led to an infant with a developmental anomaly, but all save one of these (craniosynostosis with tower skull) anomalies were considered to be relatively minor. The adverse drug reaction reporting system revealed a total of 43 reported defects in women taking an ACE-I and 12 in women taking an ARB. Conclusion We have not found any convincing excess of congenital anomalies in women taking angiotensin-blocking drugs in early pregnancy. However, this does not exclude the possibility that ACE-I or ARB use in pregnancy might lead to adverse obstetrical outcomes. Until this matter is settled, we support recommendations that these drugs should not be used in pregnancy or in women who are likely to become pregnant.

Matrix metalloproteinases and their tissue inhibitors in hypertension-related pregnancy complications

Matrix metalloproteinases (MMPs) are a family of endopeptidases that degrade the components of the extracellular matrix (ECM) such as collagen, and thus contribute to the remodelling and the physiological homeostasis of the ECM and its blood supply. The activities of these enzymes are regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs), and it has been suggested that a balance between MMPs and TIMPs plays an important role in vascular remodelling, angiogenesis and vasodilatation in a number of physiological situations. It follows that, regarding a relationship between MMPs and TIMPs, an imbalance between these molecules may lead to pathology in a wide range of conditions, including hypertension, cancer and pulmonary disease, and in the pathophysiology of reproduction. Indeed, regarding the latter, abnormalities in the maternal peripheral vasculature have been proposed as being (partly) responsible for the effects of hypertension on pregnancy and the development of complications including pre-eclampsia and eclampsia. However, the associations between MMPs, TIMPs and disease may be simply of association, not of pathology. This brief review explores current literature on the role of abnormalities of the ECM in general, focusing on the pathogenesis of hypertension and its complications during pregnancy as a model of disordered angiogenesis and remodelling.

Hypertension in Pregnancy: Pathophysiology & Management Strategies

Hypertension is the most common medical condition encountered in and complicating pregnancy, with significant implications on maternal and perinatal morbidity and mortality. It is also one of the areas of clinical practice that has been studied extensively, yet less well understood. The hypertensive disorders of pregnancy are a spectrum of conditions that are classified into 4 categories based upon recommendations of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. This article provides an overview of the pathophysiology and current pharmacologic management of hypertension in pregnancy.

Atrial fibrillation in primary aldosteronism

Introduction. Primary aldosteronism (PA) is caused by autonomous hypersecretion of aldosterone from the adrenal cortex, classically from an adenoma, resulting in sodium and water retention, hypokalaemia and raised blood pressure. The sodium and water retention causes suppression of renin release. The possible cardiac sequelae of aldosterone excess are encountered primarily in patients with secondary hyperaldosteronism due to heart failure, where plasma renin, angiotensin and aldosterone levels are all raised. However, there is also evidence that primary aldosterone excess, in the presence of low renin levels, may also be cardiotoxic. Patients. In this report, we describe five patients with PA, who developed atrial fibrillation (AF) in the absence of structural cardiac lesions and in one case despite good control of blood pressure and electrolytes. Conclusion. In patients with hypertension and AF, who have no evidence of coronary disease or any other underlying cause of AF with preserved systolic function, a diagnosis of PA should be considered.

Angiogenin and Hemoxygenase in Pregnancy: Influence of Hypertension.

The pathophysiology of hypertension and preeclampsia involves angiogenesis and endothelial damage/dysfunction, as shown by abnormal growth factors (vascular endothelial growth factor [VEGF], and its receptor sFlt-1) and von Willebrand factor (vWf) in the plasma. Angiogenin and hemoxygenase are abnormal in hypertension and angiogenesis but data on pregnancy are scant. We hypothesized altered angiogenin and hemoxygenase in 38 hypertensive pregnant women (HTPW) compared to 38 normotensive pregnant women (NTPW) and 50 nonpregnant controls (NonPCs). Plasma markers were measured by enzyme-linked immunosorbent assay (ELISA). Hypertensive pregnant women had lower VEGF than NonPCs (P < .01), vWf was raised in both pregnant groups (P < .01), but sFlt-1 was no different. Both angiogenin and hemoxygenase were lower in NTPW compared to NonPCs (both p<0.02). In both pregnancy groups, angiogenin correlated with vWf (r > .33, P < .05), but in NonPCs this was not significant (r = .13, P = .367). These changes may reflect differences in endothelial cell physiology and pathology in the hypertension in pregnancy.

Angiogenin and apoptosis in hypertension in pregnancy

Hypertension is a common medical condition that complicates pregnancy, and has significant adverse effects on pregnancy outcomes, including maternal and perinatal morbidity and mortality. In seeking the aetiology of pregnancy-related hypertension there has been a shift in focus from the foeto-placental axis to the maternal vasculature, and two possibly related pathophysiological mechanisms have been introduced - angiogenesis and apoptosis. Both processes have been extensively studied as possible pathophysiological mechanisms underlying a variety of diseases, including cardiovascular diseases such as hypertension, myocardial infarction, as well as conditions such as malignancy states, and there is a slowly developing body of knowledge justifying hypothesis of roles in pregnancy. This review presents the data regarding this position and explores the role of angiogenesis and apoptosis in the pathogenesis of hypertension in pregnancy and their effects on pregnancy outcomes.

Blood pressure control and prevention of stroke

Hypertension is an important risk factor for stroke. The latter results in disability and premature death and represents a major public health problem. Various studies have established a strong relationship between increasing blood pressure and stroke risk, as well as clear evidence of a reduction in the incidence of strokes in response to even relatively small decreases in blood pressures. In this review, the pharmacological treatment of hypertension and the benefit on stroke prevention is outlined.