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

• DOI: 10.1210/jc.2004-0548
• Publication Date: 2004-12-03T23:47:38Z
• Authors: Myles Wolf; Carl A. Hubel; Chun Lam; Marybeth Sampson; Jeffrey L. Ecker; Roberta B. Ness; Augustine Rajakumar; Ashi Daftary; Alia S. M. Shakir; Ellen W. Seely; James M. Roberts; Vikas P. Sukhatme; S. Ananth Karumanchi; Ravi Thadhani
• Keywords: Adult; Blood Glucose; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Neovascularization, Pathologic; Fasting; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Pre-Eclampsia; Solubility; Cardiovascular Diseases; Pregnancy; Case-Control Studies; Humans; Insulin; Female; Insulin Resistance

Abstract 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 (HOMAIR) [(insulin [microunits per milliliter] × 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 HOMAIR (2.8 vs. 1.9; P = 0.04). Membership in the upper quartile of either sFlt-1 or HOMAIR 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 HOMAIR had a history of preeclampsia. Women with a history of preeclampsia demonstrate altered expression of angiogenesis-related proteins and increased HOMAIR more than 1 yr postpartum. These factors may contribute to their risk of future CVD.