An Elevated Ratio of Placental Growth Factor to Soluble Fms-like Tyrosine Kinase-1 Predicts Adverse Outcomes in Patients with Stable Coronary Artery Disease

Matsumoto, Takaki; Uemura, Shiro; Takeda, Yukiji; Matsui, Masaru; Okada, Sadanori; Nishida, Taku; Soeda, Tsunenari; Okayama, Satoshi; Somekawa, Satoshi; Ishigami, Kousei; Onoue, Kenji; Kawata, Hiroyuki; Kawakami, Rika; Horii, Manabu; Saito, Yoshihiko

doi:10.2169/internalmedicine.52.9073

Cited by 20 publications

(19 citation statements)

References 31 publications

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“…An association between PlGF and NYHA classes was previously documented [26]. A previous report also showed that sFlt-1 was independently associated with HF severity and natriuretic peptides [13]. Furthermore, the combined assessment of sFlt-1 and BNP in the present study yielded higher predictive accuracy with adverse outcomes [13].…”

Section: Discussionsupporting

confidence: 73%

“…Beside preeclampsia, PlGF was demonstrated to contribute to the development of coronary atherosclerosis, by enhancing intramural angiogenesis and promoting inflammatory monocytes and macrophages migration into the arterial wall [12]. It was also recently reported that circulating levels of sFlt-1 and PlGF are elevated in patients with advanced coronary atherosclerosis and HF [13,14]. A paracrine role of sFlt-1 and PlGF as regulators of cardiac adaptation and hypertrophy was also suggested [8,9].…”

Section: Introductionmentioning

confidence: 97%

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Sflt-1 in heart failure: relation with disease severity and biomarkers

Gruson

Hermans

Ferracin

et al. 2016

Scandinavian Journal of Clinical and Laboratory Investigation

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Soluble fms-like tyrosine kinase-1 (sFlt-1) is an endogenous inhibitor of endothelial growth factors, such as placental growth factor (PlGF), which modulates cardiovascular (CV) remodeling. We determine sFlt-1 levels in patients with heart failure (HF) and its relationship to adverse cardiovascular (CV) events and biomarkers of cardiovascular risk. Levels of sFlt-1 and PlGF levels were also determined in healthy volunteers and patients with type 2 diabetes mellitus (T2DM). SFlt-1 and PlGF were clearly increased in HF patients in comparison to T2DM patients or healthy subjects (p < 0.01). Concentration of sFlt-1 was related to HF severity (p < 0.001) and was correlated to NT-proBNP (ρ = 0.37, p < 0.01), soluble ST2 (ρ = 0.52, p < 0.01), Galectin-3 (ρ = 0.38, p < 0.01), aldosterone (ρ = 0.25, p = 0.01) and PTH(1-84) (ρ = 0.38, p < 0.01). Furthermore, sFlt-1 levels were associated to long-term CV risk. These results suggest a potential role of sFlt-1 in HF and its potential role as biomarker of CV risk.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 97%

Sflt-1 in heart failure: relation with disease severity and biomarkers

Gruson

Hermans

Ferracin

et al. 2016

Scandinavian Journal of Clinical and Laboratory Investigation

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“…9.4 (9.0-9.7) 9.3 (9.0-9.6) 9.3 (8.9-9.5) 9.3 (9.0-9.7) 0.01 Recently, a growing body of clinical evidence suggests that PlGF alone or in combination with other biomarkers is a powerful predictor of survival or cardiovascular events in patients with stable and unstable coronary artery disease [17][18][19][20]24 ; however, some studies have not demonstrated that PlGF is independently associated with survival in patients with chronic heart failure or suspected acute myocardial infarction. 22,23 More recently, a single-center study showed that elevated PlGF level is an independent predictor of increased mortality but not cardiovascular events in patients with…”

Section: Discussionmentioning

confidence: 99%

Placental Growth Factor as a Predictor of Cardiovascular Events in Patients with CKD from the NARA-CKD Study

Matsui¹,

Uemura²,

Takeda³

et al. 2015

Journal of the American Society of Nephrology

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Placental growth factor (PlGF) contributes to atherogenesis through vascular inflammation and plaque destabilization. High levels of PlGF may be associated with mortality and cardiovascular disease, but the relationship between PlGF level and adverse outcomes in patients with CKD is unclear. We conducted a prospective cohort study of 1351 consecutive participants with CKD enrolled in the Novel Assessment of Risk management for Atherosclerotic diseases in CKD (NARA-CKD) study between April 1, 2004, and December 31, 2011. During a median follow-up of 3 years, 199 participants died and 383 had cardiovascular events, defined as atherosclerotic disease or heart failure requiring hospitalization. In adjusted analyses, mortality and cardiovascular risk increased in each successive quartile of serum PlGF level; hazard ratios (HRs) (95% confidence intervals [95% CIs]) for mortality and cardiovascular risk, respectively, were 1.59 (0.83 to 3.16) and 1.55 (0.92 to 2.66) for the second quartile, 2.97 (1.67 to 5.59) and 3.39 (2.20 to 5.41) for the third quartile, and 3.87 (2.24 to 7.08) and 8.42 (5.54 to 13.3) for the fourth quartile. The composite end point of mortality and cardiovascular events occurred during the study period in 76.4% of patients in both the highest PlGF quartile ($19.6 pg/ml) and the lowest eGFR tertile (,30 ml/min per 1.73 m 2 ). The association between PlGF and mortality or cardiovascular events was not attenuated when participants were stratified by age, sex, traditional risk factors, and eGFR. These data suggest elevated PlGF is an independent risk factor for all-cause mortality and cardiovascular events in patients with CKD.

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“…It binds PlGF and VEGF and acts as a decoy receptor, inhibiting the effects of both PlGF and VEGF. PlGF and sFlt-1 have emerged as practical clinical predictors of mortality and cardiovascular disease in patients with chronic heart failure, ischemic heart disease, diabetes, and CKD [5,12,18,19,20,21]. In addition, as shown by Guo et al [10], sFlt-1 is independently associated with all-cause mortality in HD patients; however, the association between PlGF and adverse outcomes has not yet been investigated in PD patients.…”

Section: Discussionmentioning

confidence: 99%

Angiogenic Factors and Risks of Technique Failure and Cardiovascular Events in Patients Receiving Peritoneal Dialysis

et al. 2016

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Background: Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family that acts as a pleiotropic cytokine capable of stimulating angiogenesis and accelerating atherogenesis. Soluble fms-like tyrosine kinase-1 (sFlt-1) antagonizes PlGF action. Higher levels of PlGF and sFlt-1 have been associated with cardiovascular events in patients with chronic kidney disease, yet little is known about their relationship with adverse outcomes in patients on peritoneal dialysis (PD). The aim of this study was to investigate the association of PlGF and sFlt-1 with technique survival and cardiovascular events. Methods: We measured serum levels of PlGF and plasma levels of sFlt-1 in 40 PD patients at Nara Medical University. Results: PlGF and sFlt-1 levels were significantly correlated with the dialysate-to-plasma ratio of creatinine (r = 0.342, p = 0.04 and r = 0.554, p < 0.001) although PlGF and sFlt-1 levels were not correlated with total creatinine clearance and total Kt/V. Additionally, both PlGF and sFlt-1 levels were significantly higher in patients with high transport membranes compared to those without (p = 0.039 and p < 0.001, respectively). Patients with PlGF levels above the median had lower technique survival and higher incidence of cardiovascular events than patients with levels below the median, with hazard ratios of 11.9 and 7.7, respectively, in univariate Cox regression analysis. However, sFlt-1 levels were not associated with technique survival or cardiovascular events (p = 0.11 and p = 0.10, respectively). Conclusion: Elevated PlGF and sFlt-1 are significantly associated with high transport membrane status. PlGF may be a useful predictor of technique survival and cardiovascular events in PD patients.

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An Elevated Ratio of Placental Growth Factor to Soluble Fms-like Tyrosine Kinase-1 Predicts Adverse Outcomes in Patients with Stable Coronary Artery Disease

Cited by 20 publications

References 31 publications

Sflt-1 in heart failure: relation with disease severity and biomarkers

Sflt-1 in heart failure: relation with disease severity and biomarkers

Placental Growth Factor as a Predictor of Cardiovascular Events in Patients with CKD from the NARA-CKD Study

Angiogenic Factors and Risks of Technique Failure and Cardiovascular Events in Patients Receiving Peritoneal Dialysis

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