Dreaded maternal and fetal complications are more likely to occur in pregnant women with preexisting hypertension. Alterations in calcium metabolism, the renin angiotensin system, and intracellular free calcium concentration have been identified in this high risk population. The overall objective of this project is to determine: a) the clinical benefits, if any, and b) mechanistic (hormonal and cellular) consequences of oral calcium supplementation in pregnant women with chronic hypertension. We hypothesize that oral calcium supplementation, as compared to placebo, will: a) lower blood pressure, b) reduce the need for antihypertensive drugs, and c) reduce the incidence of preeclampsia/eclampsia in pregnant women with chronic hypertension. We propose further that the beneficial effects of calcium supplementation on blood pressure and the incidence of superimposed preeclampsia are due to correction of the hormonal and cellular basis for vasoconstriction. We hypothesize that oral calcium will lower parathyroid hormone (PTH), reduce intracellular free calcium, and decrease vascular endothelin production. These alterations will result in vasodilation and compensatory stimulation of the renin-angiotensin system. Our hypotheses will be tested with a prospective, randomized double-blind comparison of 2 gm supplemental elemental calcium with placebo in 150 pregnant women with chronic hypertension (study population). Therapy will be initiated at 13 - 15 weeks of gestation. The goals of this trial are: 1) To determine the effect of oral calcium supplementation on: a) the level of blood pressure (determined by standard auscultatory technique as well as by a novel, electronic, precise and objective blood pressure technique, K2 analysis), b) the need for antihypertensive drugs, and c) forearm and peripheral vascular resistance (by venous plethysmography and K1 analysis); 2) To determine the effect of oral calcium supplementation on the incidence of maternal complications, including preeclampsia and eclampsia; and 3) To determine the effect of oral calcium supplementation on: a) plasma levels of 1,25 dihydroxyvitamin D3, ionized calcium, PTH, plasma renin activity, angiotensin II, endothelin, nitrate/nitrite and the urinary metabolite of prostacyclin, 6 keto PGF1alpha and b) intracellular (lymphocytes and platelets) free calcium concentration. These parameters will be determined prior to randomization, and longitudinally (every two months) throughout pregnancy as well as post-partum.
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| Hojo, M; Suthanthiran, M; Helseth, G et al. (1999) Lymphocyte intracellular free calcium concentration is increased in preeclampsia. Am J Obstet Gynecol 180:1209-14 |
| Hojo, M; August, P (1995) Calcium metabolism in normal and hypertensive pregnancy. Semin Nephrol 15:504-11 |
