Usefulness of Soluble Fms-like Tyrosine Kinase-1 as a Biomarker of Acute Severe Heart Failure in Patients With Acute Myocardial Infarction

Onoue, Kenji; Uemura, Shiro; Takeda, Yukiji; Somekawa, Satoshi; Iwama, Hajime; Nishida, Taku; Morikawa, Yoshinobu; Nakagawa, Hitoshi; Tsutsumi, Takeshi; Sung, Ji Hee; Takemoto, Y.; Soeda, Tsunenari; Okayama, Satoshi; Ishigami, Kousei; Kawata, Hiroyuki; Horii, Manabu; Nakajima, Takahito; Saito, Yoshihiko

doi:10.1016/j.amjcard.2009.07.016

Cited by 48 publications

(39 citation statements)

References 21 publications

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“…17 These angiogenesis inhibitors are released under inflammatory state. 18,19 These circulating proteins have been shown to have pathogenetic roles in hypertension in preeclampsia, 20 in human chronic kidney disease, 21 coronary artery disease 22 and in animal models of hypertension. 23,24 However, none of the studies have examined the relationship between endothelial dysfunction and hypertension in relationship to hypoxia exposure in OSA patients.…”

Section: Introductionmentioning

confidence: 99%

Endothelial dysfunction and hypertension in obstructive sleep apnea – Is it due to intermittent hypoxia?

Jafari

Mohsenin

2013

Journal of Cardiovascular Disease Research

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a b s t r a c tBackground: Obstructive sleep apnea (OSA) is a prevalent disorder causing hypertension. Endothelial dysfunction appears to underlie development of hypertension. It is not known whether hypoxia during sleep is necessarily the prerequisite process for endothelial dysfunction and hypertension in OSA. We therefore examined the relationship between endothelial-dependent vasodilatory capacity, hypoxia and circulating angiogenesis inhibitors in OSA. Methods and results:We studies 95 subjects with and without OSA and hypertension. Endothelialdependent vasodilation was assessed using brachial artery flow-mediated vasodilation method (FMD). Plasma angiogenesis inhibitors, endoglin (sEng) and fms-like tyrosine kinase-1 (sFlt-1), were measured using ELISA. The apneaehypopnea indexes were 41 AE 5 and 48 AE 4 events/hr in normotensive OSA (N-OSA) and hypertensive OSA (H-OSA), respectively, indicating severe OSA. The sleep time spent with SaO 2 < 90% (T < 90%) were 34 AE 8 and 40 AE 9 min, respectively. FMD was markedly impaired in H-OSA (8.0% AE 0.5) compared to N-OSA (13.5% AE 0.5, P < 0.0001), H-non-OSA (10.5% AE 0.8, P < 0.01), and N-non-OSA (16.1% AE 1.0, P < 0.0001). There was no correlation between T < 90% and FMD. Both OSA groups had elevated levels of sFlt-1 (62.4 AE 5.9 and 63.9 AE 4.7 pg/ml) compared to N-non-OSA (32.1 AE 6.5, P ¼ 0.0008 and P ¼ 0.0004, respectively) and H-non-OSA (41.2 AE 7.0, P < 0.05 and P ¼ 0.03, respectively). In contrast, sEng was only elevated in H-OSA (4.20 AE 0.17 ng/ml) compared with N-OSA (3.64 AE 0.14, P ¼ 0.01) and N-non-OSA (3.48 AE 0.20, P ¼ 0.01). There was a modest but statistically significant inverse correlation between sEng and FMD in only H-OSA group (r ¼ À0.38, P < 0.05). Conclusion: These data show that patients with OSA and hypertension have marked impairment of FMD, independent of hypoxia exposure, which is associated with increased sEng.Copyright Ó 2013, SciBioIMed.Org, Published by Reed Elsevier India Pvt. Ltd. All rights reserved. Key MessagesObstructive sleep apnea is a highly prevalent disorder with associated high morbidity and mortality. Obstructive sleep apnea is now considered as one of the causes of systemic hypertension. No all patients with obstructive sleep apnea develop hypertension. There appears to be divergent responses to apnea-associated hypoxia. In this article a group of patients with severe obstructive sleep apnea and hypoxia exposure during sleep had normal blood pressure and relatively preserved endothelial-dependent vasodilatory capacity. A comparable group of patients with similar apnea severity and hypoxia exposure had marked impairment in endothelial-dependent vasodilatory capacity and hypertension. This group had significantly elevated circulating levels of soluble endoglin, an angiogenesis inhibitor, with known effect on endothelial function and development of hypertension. It is conceivable that inflammatory state of obstructive sleep apnea provokes release of angiogenesis inhibitors causing downstream perturbation of endothelial...

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Section: Introductionmentioning

confidence: 99%

Endothelial dysfunction and hypertension in obstructive sleep apnea – Is it due to intermittent hypoxia?

Jafari

Mohsenin

2013

Journal of Cardiovascular Disease Research

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“…11) In patients with chest pain and acute coronary syndrome, higher PlGF levels have been observed in those with MI and are associated with an increased risk of short-and long-term adverse outcomes. [12][13][14] There are conflicting results regarding circulating sFlt-1 levels in patients with CAD, with some studies noting higher levels during acute MI compared with control pa-tients, 15) and others showing lower plasma sFlt-1 levels in patients during the acute phase of MI compared with control subjects. 16,17) Although PlGF and sFlt-1 might be important biomarkers of chronic heart failure, neither factor has been fully studied in patients with heart failure.…”

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Soluble Fms-like Tyrosine Kinase 1 Is a Novel Predictor of Brain Natriuretic Peptide Elevation

et al. 2013

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SummarySoluble fms-like tyrosine kinase 1 (sFlt-1) is an endogenous inhibitor of vascular endothelial growth factor, which is involved in cardiovascular remodeling and atherosclerosis development. To examine the predictive role of sFlt-1 levels in patients with asymptomatic heart failure, we measured circulating sFlt-1 in patients with or without coronary artery disease (CAD). We analyzed 88 Japanese patients with CAD or patients at high risk for atherosclerosis and who were undergoing total risk management for cardiovascular disease prevention. Circulating sFlt-1 levels correlated with the increase in plasma brain natriuretic peptide levels (ΔBNP) from baseline to the observed levels 5 years later in CAD patients, patients with previous myocardial infarction, and men. ΔBNP levels correlated with sFlt-1 levels in the high-sFlt-1 patients with CAD (r = 0.511, P < 0.01). In all patients, end-systolic volume index (ΔESVI) increased in correlation with a decrease in left ventricular ejection fraction (ΔEF) in the long-term observation, independent of their history of myocardial infarction (ΔESVI = 2.5 mL/m 2 increase/year). Baseline level of sFlt-1 was independent of ΔESVI or ΔEF. The present 5-year observational study demonstrated that high sFlt-1 levels predicted moderate increases in BNP levels in CAD patients. Moreover, ΔBNP was correlated with ΔESVI/year in CAD patients with high-sFlt-1 levels. These data suggest that high sFlt-1 levels may be an effective biomarker to predict the progression of heart failure in patients with CAD. (Int Heart J 2013; 54: 133-139)

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“…However, previous studies have shown that chronic excess of the VEGF expression also contributes to proatherosclerotic processes by inducing intramural microvessel growth (6)(7)(8). It was recently demonstrated that a proangiogenic factor, placental growth factor (PlGF), also plays an important role in the development of coronary atherosclerosis (9)(10)(11)(12). PlGF is a member of the VEGF cytokine family that has been shown to accelerate atherosclerosis by enhancing intramural angiogenesis and stimulating migration of inflammatory monocytes and macrophages into the arterial wall by activating VEGF receptor-1 (fms-like tyrosine kinase 1 ) (4,13,14).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2013

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Objective To investigate the predictive values of placental growth factor (PlGF) and its endogenous antagonist, soluble fms-like tyrosine kinase-1 (sFlt-1), for the long-term prognosis of patients with stable coronary artery disease (CAD). Both PlGF and sFlt-1 play important roles in the pathological mechanisms of atherosclerosis. We recently demonstrated that the plasma levels of these molecules are correlated with the severity of coronary atherosclerosis. Methods We enrolled 464 patients with stable CAD who consecutively underwent coronary angiography. Baseline blood samples were collected from the femoral artery immediately before coronary angiography (after the administration of 20 units of heparin), and the plasma levels of PlGF and sFlt-1 were measured. A Cox proportional hazard regression analysis was performed to evaluate the relationship between these parameters and the occurrence of all-cause death (ACD) and total cardiovascular events (TCVE) during a median follow-up of 3.3 years. Results A total of 31 ACDs and 51 TCVEs occurred. Patients with higher PlGF/sFlt-1 ratios (>4.22×10-2 ) had a significantly higher risk of both ACD and TCVE than patients with lower ratios (<4.22×10-2 ) (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.43 to 7.72, p=0.005, and HR: 2.23, 95% CI: 1.23 to 4.03, p=0.008, respectively). A multivariate analysis showed the PlGF/sFlt-1 ratio to be an independent predictor for ACD, but not TCVE. Conclusion The baseline PlGF/sFlt-1 ratio is an independent predictor of long-term adverse outcomes in patients with stable CAD.

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Usefulness of Soluble Fms-like Tyrosine Kinase-1 as a Biomarker of Acute Severe Heart Failure in Patients With Acute Myocardial Infarction

Cited by 48 publications

References 21 publications

Endothelial dysfunction and hypertension in obstructive sleep apnea – Is it due to intermittent hypoxia?

Endothelial dysfunction and hypertension in obstructive sleep apnea – Is it due to intermittent hypoxia?

Soluble Fms-like Tyrosine Kinase 1 Is a Novel Predictor of Brain Natriuretic Peptide Elevation

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

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