Long-term cardiovascular assessment in women with preeclampsia

Background: Preeclampsia (PE) is one of the most common medical multi-organ, pregnancy-specific disorder. PE is associated with endothelial dysfunction, elevated blood pressure, and inflammation. In addition to vascular dysfunction, preeclampsia is associated with cardiac remodeling and left ventricular (LV) dysfunction. Whether these cardiovascular changes eventually resolve remains unclear.

Aims: This thesis is aimed to study the long-term effects of PE on the cardiovascular system in women with a history of PE-complicated pregnancy.

Material and Methods: Studies I and II examined 15 women with a history of PE (mean age 39±4 years) and 16 matched healthy women with an uncomplicated pregnancy (41±3 years) 10-12 years following the index pregnancy. Assessment of medical and family history, physical examination, anthropometric measurements, and biochemical markers were evaluated. In Study I forearm flow-mediated vasodilatation (FMD), pulse wave analyses (PWA), 24-h ambulatory blood pressure measurement (ABPM), plasma concentrations of glucose metabolism, lipid metabolism, inflammatory markers, and vascular function were assessed. In Study II echocardiography including Tissue Doppler Imaging and two-dimensional speckle-tracking echocardiography for myocardial strain imaging was used for evaluation of systolic and diastolic, left ventricular (LV), and right ventricular function (RV). LV global strain, atrial size, indices of ventricular-arterial coupling (VAC), and concentrations of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) were analyzed.

Results: In Study, I endothelial function assessed as hyperemia, hyperemia-induced FMD, and as responses to glyceryl trinitrate were similar in both groups (+10.7±5.4 % vs +9.0±4.7 %, and +29.1±9.7 % vs +25.1±8.8 %). ABPM showed slightly higher blood pressure (24-h 117±11/75±8 mm Hg vs 112±11/71±9 mm Hg) and reduced systolic and diastolic night/day ratios (0.81±0.06 vs 0.76±0.05, and 0.88±0.04 vs 0.84±0.04; both p=<0.05) in women with a history of PE. They also had an increased body mass index (26±6 vs 23±3 kg/m2; p=<0.05), reduced glucose tolerance (HOMA 10.9±10.8 vs 6.6±3.8 mmol/l x pmol /l, p=<0.05), increased ICAM (102±15vs120±29 μg/ l, p=<0.05), and higher TNF receptor (11.62± 0.24 vs1.91±0.47 μg/ l, p=<0.05) concentrations. In Study II there were no significant differences in LV or RV dimensions, systolic function, or global LV strain. Indices of diastolic LV function left and right atrial size, VAC variables, or NT-pro-BNP levels did not differ between the study groups. The offspring weight was inversely correlated to the maternal central BP (SBP r - 0.33, p=0.07, DBP r -0.37, p=0.04) and brachial BP (SBP r -0.34, p=0.062, DBP r - 0.40, p=0.029) and LV end-diastolic diameter. The relations for the birth weight centile were generally similar but weak. There was no association between the placenta weight and cardiac indices or VAC. I sub-group analyses according to the severity of PE; 6 women with early and severe PE had a greater night/day ratio for ambulatory SBP and DBP than 9 women with neither early nor severe PE. The subgroups of PE were similar concerning NT-pro-BNP, cardiac structure and function, and indices of VAC.

Conclusion: A long-term follow-up (10-12 years after index pregnancy) of women with a history of PE-complicated pregnancy showed normalized endothelial function despite higher blood pressure and impaired glucose tolerance in comparison to women without a previous PE. Extensive echocardiographic examinations could not demonstrate significant alterations in systolic or diastolic LV function or VAC. We suggest that pre-existing risk factors may be more important for future cardiovascular complications than myocardial and vascular damage occurring during pregnancy in women with PE. This highlights the importance of early treatment of risk factors, integrating adequate preventive strategies, and long- term surveillance with close monitoring.

List of scientific papers

I. Östlund E, Al-Nashi M, Hamad RR, Larsson A, Eriksson M, Bremme K, Kahan T. Normalized endothelial function but sustained cardiovascular risk profile eleven years following a pregnancy complicated by preeclampsia. Hypertens Res. 2013;36(12):1081-7.
https://doi.org/10.1038/hr.2013.81

II. Al-Nashi M, Eriksson MJ, Östlund E,Bremme K, Kahan T. Cardiac structure and function and ventricular-arterial interaction 11 years following a pregnancy complicated with preeclampsia. J Am Soc Hypertens. 2016;10(4):297-306.
https://doi.org/10.1016/j.jash.2016.01.012