Preeclampsia as a Form of Type 5 Cardiorenal Syndrome: An Underrecognized Entity in Women’s Cardiovascular Health

Abstract

Background: Preeclampsia is a multisystem vascular disorder of pregnancy that remains a leading cause of maternal and fetal morbidity and mortality. Preeclampsia remains an underrecognized risk factor for future cardiovascular and kidney disease in women and represents the confluence of preexisting vascular risk factors with superimposed endothelial injury from placental mediated anti-angiogenic factors. Summary: This review highlights the close relationship between preeclampsia and future cardiovascular and kidney disease. It describes the pathophysiology and current understanding of biomarkers that form the molecular signature for long-term endothelial dysfunction in preeclamptic women. Finally, it describes strategies for early identification and management of women with preeclampsia with elevated risk for cardiovascular and kidney disease. Key Messages: Future rigorous studies on cardiovascular risk modification in this phenotype of disease are essential to reduce the burden of cardiovascular and kidney disease, in women with preeclampsia.

A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia

“…As a consequence, follow-up after a PE episode is not established. [1][2][3][4][13][14][15][16][17][18][19][20][21][22][23][31][32][33][34][35][36][37][38][39][40][41] There are several reasons why the results of the analyses of these long-term health effects are not fully clear: the pathogenesis of PE is only partially understood; the recent trend Delivery before the 34th wk of gestation, blood pressure >140/90 mm Hg, and proteinuria >300 mg/24 h. f Diastolic blood pressure $90 mm Hg with proteinuria ($0.3 g/24 h) diagnosed between the 20th and 32nd wk of gestation. g Diastolic pressure >90 mm Hg on 2 occasions at least 4 h apart or a single reading of >110 mm Hg; from the 20th wk of gestation onward in a previously normotensive woman plus at least 1 episode of proteinuria of 0.3 g/24 h. Increased BP after the 20th wk of gestation (>140/90 mm Hg) and proteinuria (>0.3 g in a 24-h urine specimen or $1þ on a urinary dipstick reading).…”

“…The relationship between CKD and PE is likewise complex and non-univocal: on the one hand, PE may be a cause or a marker of future CKD; on the other hand, there is an increased occurrence of PE in patients with CKD and many predisposing factors, including diabetes, obesity, metabolic syndrome, and hypertension, are shared by PE and CKD. [34][35][36][37][38][39][40][41][42]69 Available evidence allows us to conclude that there is an increased risk of kidney diseases after PE, but does not permit us to quantify that risk, something which must be done if follow-up strategies are to be defined. What distinguishes our review from the meta-analysis carried out by McDonald et al is not only the inclusion of recent studies but also the focus on studies that include only medium-to long-term follow-up (at least 4 years, instead of at least 6 weeks postpartum).…”

“…[1][2][3][4][21][22][23][24][25][26][27][28][29][30] PE is no longer considered as a transitory disease and has been associated with a vast array of cardiovascular and renal diseases, of which the pregnancy-related affection may be a herald, a cause, or a consequence. [31][32][33][34][35][36] Most of the studies and virtually all the systematic reviews show that patients who had PE in $1 pregnancy are at an increased risk of developing cardiovascular and metabolic diseases. [31][32][33][34][35][36][37][38][39][40][41] However, the entity of the risk, the timing of the development of clinical problems, and the control strategies that can be used are not clear, and large prospective cohort studies are still lacking.…”

“…[31][32][33][34][35][36] Most of the studies and virtually all the systematic reviews show that patients who had PE in $1 pregnancy are at an increased risk of developing cardiovascular and metabolic diseases. [31][32][33][34][35][36][37][38][39][40][41] However, the entity of the risk, the timing of the development of clinical problems, and the control strategies that can be used are not clear, and large prospective cohort studies are still lacking.…”

Hypertensive disorders of pregnancy and the risk of chronic kidney disease: A Swedish registry-based cohort study

“…However, there is increasing evidence that some women experience sustained renal dysfunction, and large cohort studies have reported an increased risk of end-stage kidney disease (ESKD) [ 7 – 10 ]. Biological mechanisms are uncertain; this may be due to lasting vascular endothelial dysfunction related to elevated levels of anti-angiogenic proteins—such as soluble fms-like tyrosine kinase-1—or it may be due to direct glomerular damage related to underexpression of nuclear factor erythroid 2–related factor 2 (NRF-2) [ 11 – 13 ]. Other changes in the renin-angiotensin-aldosterone system, metabolic system, and factors causing endothelial dysfunction may also be involved.…”