Preeclampsia is a hypertensive disorder of pregnancy characterized by new-onset hypertension with evidence of organ injury, affecting 2% to 8% of all pregnancies worldwide. 1 The majority of women with preeclampsia present clinically near term with favorable maternal and infant outcomes; however, a subset of women develop severe disease characterized by the need for preterm delivery typically before 34 weeks of gestation because of end-organ injury, severe hypertension, or intrauterine growth restriction.2 Women with severe preeclampsia demonstrate significant cardiovascular impairment during pregnancy and the immediate postpartum period and a higher risk of cardiovascular disease later in life.3-7 Given the significant shortand long-term maternal cardiovascular effects of preeclampsia, elucidating its pathogenesis has been of much interest in recent years. However, as yet, there is no agreement concerning the most effective pharmacological therapy for the prevention of preeclampsia in screen-positive women beyond aspirin, with clinical symptoms typically only resolving on delivery. Low molecular weight heparin (LMWH) has been evaluated for the prevention of various placenta-mediated pregnancy complications, including severe preeclampsia and recurrent miscarriage. Multiple trials and systematic reviews have concluded that LMWH reduces the incidence of recurrent severe preeclampsia in high-risk women, as well as perinatal mortality, preterm birth, and infant birth weight <10th percentile for gestational age, whereas other studies have found no treatment effect.9,10 Because the majority of previous trials have consisted of clinical end points, the mechanism of action of LMWH for the possible prevention of severe preeclampsia is currently unknown. Evidence suggests that observed beneficial effects do not result from heparin's anticoagulant actions within the placenta.11,12 An alternative hypothesis is that LMWH exerts vascular actions in the maternal compartment that reverse the systemic vascular dysfunction characteristic of preeclampsia. Previous trials in patients with coronary artery disease have determined that LMWH demonstrates beneficial endothelial effects, possibly through increased bioavailability of NO. 13,14The objective of the current study was to investigate the endothelial effects of LMWH in pregnant women at high risk of preeclampsia. We first compared baseline cardiovascular Abstract-Low molecular weight heparin (LMWH) has been investigated for the prevention of severe preeclampsia, although the mechanisms of action are unknown. The objective of this study was to investigate the cardiovascular effects of LMWH in pregnant women at high risk of preeclampsia. Pregnant women at high risk of preeclampsia (n=25) and low-risk pregnant controls (n=20) at 22 to 26 weeks' gestation underwent baseline cardiovascular assessments. Highrisk women were then randomized to LMWH or saline placebo (30 mg IV bolus and 1 mg/kg subcutaneous dose). Cardiovascular function was assessed 1 and 3 hours post randomization. T...