Association of vascular endothelial factors with cardiovascular outcome and mortality in chronic kidney disease patients: A 4-year cohort study

Rambod, Mehdi; Heine, Gunnar H.; Seiler, Sarah; Dominic, Elizabeth A.; Rogačev, Kyrill S.; Dwivedi, R. S.; Ramezani, Ali; Wing, Maria R.; Amdur, Richard L.; Fliser, Danilo; Raj, Dominic S.

doi:10.1016/j.atherosclerosis.2014.07.026

Cited by 13 publications

(16 citation statements)

References 36 publications

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“…A role of vascular endothelial growth factor, which can trigger sFlt-1, in angiotensin II-induced vascular inflammation and remodeling, was also suggested [21]. Despite a lack of significant correlation with aldosterone in T2DM patients, we observed a significant relation between sFlt-1 and Gal-3, a known mediator of the fibrotic effect of aldosterone [22]. These data are consistent with the fact that mineralocorticoid activation in vascular smooth muscle cells (SMCs) activates factors that promote leukocyte chemotaxis via monocytic VEGFR1 [6,23,24].…”

Section: Discussioncontrasting

confidence: 36%

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: Discussioncontrasting

confidence: 36%

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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“…25 Therefore, the relationship between circulating PlGF and outcomes remains unclear. However, in our setting of CKD, we found for the first time, to our knowledge, an increased risk of both mortality and cardiovascular events with increasing PlGF levels, with patients in the highest quartile having a 3.87-and 8.42-fold increased risk compared with those in the lowest quartile, respectively.…”

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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“…Elevations in PlGF have been attracting attention due to clinical utility. Recently, a growing amount of clinical evidence has demonstrated that PlGF is a useful predictor of mortality or major cardiovascular events not only in patients with cardiac disorders, but also in patients with diabetes or CKD [11,12,15,19,20,21]. Likewise, VEGF is significantly associated with left ventricular systolic function and cardiovascular diseases in prevalent dialysis patients [22,23]; however, a strong relationship between VEGF and adverse outcomes was not observed in this study.…”

Section: Discussionmentioning

confidence: 99%

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

Matsui

Samejima²,

Takeda³

et al. 2015

Am J Nephrol

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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.

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Association of vascular endothelial factors with cardiovascular outcome and mortality in chronic kidney disease patients: A 4-year cohort study

Cited by 13 publications

References 36 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

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

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