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Preeclampsia and Future Cardiovascular Disease: Potential Role of Altered Angiogenesis and Insulin Resistance

Renal Unit (M.W., M.S., R.T.) and the Department of Obstetrics and Gynecology (J.L.E., R.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; Endocrinology, Diabetes, and Hypertension Division (E.W.S.), Brigham and Women’s Hospital, Boston, Massachusetts 02115; Renal Division (C.L., V.P.S., S.A.K.), Beth Israel-Deaconess Medical Center, Boston, Massachusetts 02215; Magee-Womens Research Institute and Department of Obstetrics and Gynecology and Reproductive Sciences (C.A.H., R.B.N., A.R., A.D., A.S.M.S., J.M.R.), University of Pittsburgh, Pittsburgh, Pennsylvania 15213; and Department of Epidemiology (R.B.N., J.M.R.), University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania 15261

Address all correspondence and requests for reprints to: Ravi Thadhani, M.D., M.P.H., Bulfinch 127, 55 Fruit Street, Massachusetts General Hospital, Boston, Massachusetts 02114. E-mail: rthadhani{at}partners.org.

Altered angiogenesis and insulin resistance are associated with preeclampsia and cardiovascular disease (CVD), and women with preeclampsia appear to be at increased risk of future CVD. We hypothesized that these factors are detectable in asymptomatic postpartum women with a history of preeclampsia and may represent pathophysiological mechanisms bridging preeclampsia and future CVD. We measured fasting insulin, glucose, vascular endothelial growth factor, and its circulating inhibitor, soluble fms-like tyrosine kinase (sFlt-1) in 29 normotensive women with a history of preeclampsia and 32 women with prior normotensive pregnancies at 18.0 ± 9.7 months postpartum. The homeostasis model of insulin resistance (HOMA_IR) [(insulin [microunits per milliliter] x glucose [millimoles per liter])/22.5] was calculated. Compared with women with normal pregnancies, women with prior preeclampsia had significantly increased levels of sFlt-1 (41.6 ± 6.7 vs. 30.4 ± 10.2; P < 0.01) and median HOMA_IR (2.8 vs. 1.9; P = 0.04). Membership in the upper quartile of either sFlt-1 or HOMA_IR was associated with prior preeclampsia (odds ratio 5.7; 95% confidence interval 1.7, 20.0; P < 0.01), and all five women in the upper quartiles of both sFlt-1 and HOMA_IR had a history of preeclampsia. Women with a history of preeclampsia demonstrate altered expression of angiogenesis-related proteins and increased HOMA_IR more than 1 yr postpartum. These factors may contribute to their risk of future CVD.

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