Abstract

Introduction: Preeclampsia (PEC) increases the long-term risk for heart failure with preserved ejection fraction (HFpEF). While the underlying pathogenesis is unknown, angiotensin II type 1 receptor autoantibodies (AT1-AA) have been implicated. AT1-AA bind agonistically to the AT1 receptor and may result in clinical manifestations of preeclampsia. We aimed to determine whether women with PEC have elevated AT1-AA levels compared to normotensive women (controls) during pregnancy and at 4 years postpartum, and whether AT1-AA levels correlate with abnormal echocardiographic parameters. Methods: We performed a prospective longitudinal cohort study comparing women with PEC (n=21) to controls (n=20). AT1-AA and echocardiographic measurements were obtained during pregnancy and 4 years postpartum. Linear regression analyses were performed to evaluate the association between AT1-AA levels and important echocardiographic parameters. Results: Mean AT1-AA level during pregnancy differed significantly between women with PEC versus healthy pregnant controls (10.21±3.20 vs 6.33±3.40 μg/ml, p<0.001). Women with PEC were more likely to be black and deliver at an earlier gestational age. Higher AT1-AA was associated with increased systolic/diastolic blood pressure, echocardiographic markers of biventricular systolic function (tricuspid annular systolic plane excursion and left ventricular (LV) ejection fraction), concentric LV hypertrophy and worsened diastolic function. AT1-AA remained persistently elevated at 4 years in women with PEC at baseline compared to controls (12.76±5.13 vs 4.47±1.49 μg/ml, p<0.001) (Figure 1). Conclusions: Women with PEC have elevated AT1-AA compared to controls, both during pregnancy and 4 years postpartum. Higher AT1-AA is associated with abnormal diastolic parameters, LV remodeling, and hyperdynamic biventricular function. These findings suggest that AT1-AA plays an important role in the risk of HFpEF in PEC.

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