Preeclampsia and Future Cardiovascular Disease: Potential Role of Altered Angiogenesis and 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 (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.

Risk factors for cardiovascular disease ten years after preeclampsia

“…Other authors have correlated preeclampsia with more frequent cardiovascular disease. 11,16,18,20,22 Significantly higher diastolic pressure presented in the group of women with preeclampsia/eclampsia, compared with the control group, was also described by Wilson et al 23 and Forest et al 24 The BMI and abdominal circumference measurements were significantly higher among women in our study who had had preeclampsia/eclampsia, and this was thought to indicate centripetal distribution of fat, since the waist/hip ratio did not differ. Abdominal fat distribution is also an early risk factor for cardiovascular disease, hypertension 25 and insulin resistance 26 in this group of patients.…”

Preclinical safety evaluation of subretinal AAV2.sFlt-1 in non-human primates

“…In spite of the regular increase in sFlt-1 protein levels, the female vasculature appears to be unaffected, suggesting that systemic sFlt-1 protein levels up to B500 pg ml --1 are safe in females. Furthermore, sFlt-1 levels significantly increase in both men and women with essential hypertension (33 vs 24 ng ml --1 ), in women with prior pre-eclampsia 53 and after thrombolytic therapy for acute myocardial infarction (5.6 vs 26.5 ng ml --1 in males and females, respectively). 54 In this study, sFlt-1 protein levels were within the ranges observed in healthy humans, reaching 380 pg ml --1 in the eye and 80 --180 pg ml --1 in plasma.…”

Prediction of pregnancy-induced hypertension by a shift of blood pressure class according to the JSH 2009 guidelines

“…1,4,5 Furthermore, the long-term prognosis of women with a history of PIH includes increased risks of cerebrovascular disease, ischemic heart disease and renal disease. [6][7][8][9][10][11][12] These data indicate that the early identification, and subsequent monitoring and management of PIH are critical for maternal and fetal well-being.…”