H ypertensive disorders of pregnancy (HDP) affect 5% to 10% of pregnant women, 1 are the most common medical complication of pregnancy in developed countries, 2 and are a leading cause of maternal and fetal death worldwide. 3 HDP include preeclampsia, gestational hypertension, chronic hypertension, and superimposed preeclampsia. Preeclampsia targets the vascular endothelium causing widespread maternal vascular endothelial dysfunction. Antiangiogenic proteins have been implicated as being pathogenic in the development of the observed vascular endothelial dysfunction.
4Overexpression of soluble fms-like tyrosine kinase-1 (sFlt1), an endogenous vascular endothelial growth factor inhibitor, is associated with preeclampsia-like phenotypes in a rodent model and symptoms diminish with the addition of vascular endothelial growth factor or placental growth factor. [5][6][7] Multiple human clinical studies have established that levels of the sFlt1 and soluble endoglin (sEng) increase in the circulation of pregnant women with preeclampsia. 4,6,[8][9][10] sFlt1 and sEng levels are elevated weeks before the clinical onset of preeclampsia, and the degree of elevation correlates with adverse maternal and fetal outcomes. 8,[11][12][13][14][15][16] Few adverse outcomes occur in the absence of angiogenic factor abnormalities. 17,18 Although previous studies have detected changes in myocardial function in HDP, 19,20 a direct association between preeclampsia biomarkers, including sFlt1 and sEng, has not been described. In other abnormal cardiovascular states such as congestive heart failure, increased circulating levels of antiangiogenic proteins have been associated with development of endothelial vascular dysfunction, myocardial dysfunction, and adverse cardiovascular outcomes.
21Women with HDP have abnormalities in both systolic and diastolic cardiac function that seem before clinical symptoms.19,22 Despite preservation of left ventricular ejection fraction (LVEF), 23 longitudinal muscle fiber shortening is decreased, suggesting the presence of subclinical left ventricular systolic dysfunction. 20 This finding suggests a Abstract-Hypertensive disorders of pregnancy (HDP) are associated with subclinical changes in cardiac function. Although the mechanism underlying this finding is unknown, elevated levels of soluble antiangiogenic proteins such as soluble fms-like tyrosine kinase-1 (sFlt1) and soluble endoglin (sEng) are associated with myocardial dysfunction and may play a role. We hypothesized that these antiangiogenic proteins may contribute to the development of cardiac dysfunction in HDP. We prospectively studied 207 pregnant women with HDP and nonhypertensive controls and evaluated whether changes in global longitudinal strain (GLS) observed on echocardiography is specific for HDP and whether these changes correlate with HDP biomarkers, sFlt1 and sEng. A total of 62 (30%) patients were diagnosed with preeclampsia (group A), 105 (51%) did not have an HDP (group B), and 40 (19%) were diagnosed with chronic or gestational hype...