Prognostic Impact of Placental Growth Factor on Mortality and Cardiovascular Events in Dialysis Patients

Abstract

Background: Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, has recently emerged as a predictor of survival and cardiovascular risk. Along with others, we have shown an independent association between PlGF and cardiovascular events in CKD patients, but not much is known about patients receiving dialysis. Methods: We studied 205 dialysis patients undergoing cardiac catheterization at the Nara Medical University between April 1, 2004, and December 31, 2012. Serum levels of PlGF and VEGF were measured with ELISA in all the patients. Results: During a median follow-up of 20 months, 121 participants died from any cause or experienced a cardiovascular event. In the fully adjusted analysis, having an above-median PlGF or VEGF level was associated with a hazards ratio for adverse outcomes of 2.55 (1.72-3.83) and 1.39 (0.95-2.04), respectively. Using a multimarker strategy in a model with age, serum albumin, history of coronary artery disease, brain natriuretic peptide and PlGF, patients with 2, 3 and 4 positive markers had a 3.82-, 5.77- and 6.59-fold higher risk of mortality or a cardiovascular event, respectively, compared to those with no positive markers. The model with PlGF had a significantly higher c-statistic, integrated discrimination improvement index and category-free net reclassification improvement index than the model without PlGF. Conclusion: PlGF is independently associated with mortality and cardiovascular events, but the association between VEGF and adverse events was attenuated with covariate adjustment. The addition of PlGF to models with established clinical predictors provides additional useful prognostic information in patients receiving dialysis.

Evidence for a protective role of placental growth factor in cardiovascular disease

“…The pro-atherogenic potential of PlGF has been attributed to the ability to activate endothelial adhesion molecule expression and monocyte recruitment to the arterial wall (14). The concept of a pro-atherogenic role of PlGF has also been supported by epidemiological studies demonstrating associations between elevated plasma PlGF and risk of cardiovascular events (19,20,22,23). Moreover, the expression of PlGF in human atherosclerotic plaques correlates with plaque content of inflammatory markers such as hsCRP and CD40 ligand (31).…”

“…Benschop and co-workers (18) recently reported that women with low PlGF at midpregnancy developed signs of increased vascular aging 6 to 9 years later including increased arterial stiffness and left ventricular mass, supporting the notion that PlGF is required for maintaining normal cardiovascular function. In contrast, others have found that high PlGF is associated with increased risk of cardiovascular mortality (19)(20)(21)(22)(23). Together, these studies have provided indirect support for a role of PlGF in CVD, but it has been unclear whether the observations of an association between elevated PlGF and cardiovascular risk reflect activation of a protective response by a stressed vasculature or whether PlGF is pro-atherogenic.…”

Placental Growth Factor as a Novel Marker in Uremia-Related Cardiovascular Disease

“…Placental growth factor (PlGF) is a circulating protein that belongs to the family of vascular endothelial growth factors (VEGFs) that is emerging as another promising biomarker. The article by Matsui et al published in this issue of AJN evaluates the prognostic value of PlGF in predicting mortality and cardiovascular events in ESRD patients on dialysis [3]. They conducted an observational study involving 205 dialysis patients who received a cardiac catheterization; 162 (79% of patients) were on hemodialysis and 43 (21% of patients) were on peritoneal dialysis.…”