Osteoprotegerin and osteoprotegerin/TRAIL ratio are associated with cardiovascular dysfunction and mortality among patients with renal failure

Kuźniewski, Marek; Fedak, Danuta; Dumnicka, Paulina; Stępień, Ewa; Kuśnierz-Cabała, Beata; Cwynar, Marcin; Sułowicz, Władysław

doi:10.1016/j.advms.2016.03.003

Cited by 25 publications

(25 citation statements)

References 38 publications

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“…When reviewing the full text of the remaining 283 articles, we excluded a further 264 additional articles, leaving 19 prospective studies17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 eligible for inclusion in the meta‐analysis. Patients were recruited on the basis of having diabetes mellitus in 2 studies, kidney disease in 7 studies, preexisting heart disease in 5 studies, and recent acute coronary syndromes in 5 studies.…”

Section: Resultsmentioning

confidence: 99%

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

Tschiderer

Klingenschmid

Nagrani

et al. 2018

JAHA

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BackgroundOsteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease (CVD) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear.Methods and ResultsThree independent reviewers systematically searched PubMed, EMBASE, and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow‐up of 4.2 years, 4066 CVD events were recorded. In a random‐effects meta‐analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12–1.50; P<0.001; I2=68.3%). There was evidence for presence of publication bias (P value from Egger's test=0.013). Correction for publication bias using the trim‐and‐fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03–1.42; P<0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow‐up.ConclusionsIn populations at high CVD risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future CVD events. The magnitude of association appears weaker than in the general population.

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Section: Resultsmentioning

confidence: 99%

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

Tschiderer

Klingenschmid

Nagrani

et al. 2018

JAHA

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“…Similarly, an inverse association between TRAIL levels and mortality risk was observed in patients with advanced heart failure and CKD [32]. In particular, Kuznieeski and colleagues reported that CKD patient exhibited high OPG levels and OPG/TRAIL ratio and that OPG levels were associated with a higher risk of CVD and mortality among patients with renal failure [211]. The same Authors observed that OPG levels and OPG/TRAIL ratio predicted long-term mortality (all-cause and CVD mortality) and that they correlated with aortic pulse wave velocity and with N-terminal pro b-type natriuretic peptide, that are two independent predictors of CVD morbidity and mortality, supporting the role of OPG and OPG/TRAIL ratio as biomarkers of CV dysfunction and predictor of mortality in late stage of CKD.…”

Section: Role Of Trail Opg and Tweak In Cardiovascular Disease Of Cmentioning

confidence: 94%

TRAIL, OPG, and TWEAK in kidney disease: biomarkers or therapeutic targets?

et al. 2019

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Ligands and receptors of the tumor necrosis factor (TNF) superfamily regulate immune responses and homeostatic functions with potential diagnostic and therapeutic implications. Kidney disease represents a global public health problem, whose prevalence is rising worldwide, due to the aging of the population and the increasing prevalence of diabetes, hypertension, obesity, and immune disorders. In addition, chronic kidney disease is an independent risk factor for the development of cardiovascular disease, which further increases kidney-related morbidity and mortality. Recently, it has been shown that some TNF superfamily members are actively implicated in renal pathophysiology. These members include TNF-related apoptosis-inducing ligand (TRAIL), its decoy receptor osteoprotegerin (OPG), and TNF-like weaker inducer of apoptosis (TWEAK). All of them have shown the ability to activate crucial pathways involved in kidney disease development and progression (e.g. canonical and non-canonical pathways of the transcription factor nuclear factor-kappa B), as well as the ability to regulate cell proliferation, differentiation, apoptosis, necrosis, inflammation, angiogenesis, and fibrosis with double-edged effects depending on the type and stage of kidney injury. Here we will review the actions of TRAIL, OPG, and TWEAK on diabetic and non-diabetic kidney disease, in order to provide insights into their full clinical potential as biomarkers and/or therapeutic options against kidney disease.

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“…Even though adrenomedullin exerts protective biological mechanisms, elevated plasma levels are associated with worse prognosis 175,178,179 . Biomarkers of the TNF protein superfamily (TNF-R1, TNF-R2 and TRAIL-2) are involved in extrinsic cellular apoptosis and inflammation, which plays an important role in the atherosclerotic disease development [180][181][182] . TRAIL-2 is also associated with cardiovascular outcomes in the general population and in patients with carotid plaques 183 184 in addition to associations of RD in elderly patients 165 .…”

Section: Proteomics To Predict Adverse Outcomes In MImentioning

confidence: 99%

SWEDEHEART-1-year data show no benefit of newer generation drug-eluting stents over bare-metal stents in patients with severe kidney dysfunction following percutaneous coronary intervention

Edfors

James

Szummer

et al. 2020

Coronary Artery Disease

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Bakgrund Ungefär en tredjedel av alla patienter med akut hjärtinfarkt har njursvikt, vilket innebär en markant ökad risk för såväl komplikationer som nya hjärthändelser. Syftet med detta avhandlingsarbete var att undersöka vilken betydelse olika grader av njursvikt har för överlevnad och kliniska utfall, att utvärdera utfallen efter olika medicinska-och interventionella behandlingar och hur de skiljer sig åt hos patienter med njursvikt samt att utifrån blodprovsanalyser studera olika biomarkörers koppling till njursvikt och kardiovaskulära händelser. Metoder och resultat Studie I: Data från det svenska hjärtsjukvårdsregistret SWEDEHEART användes för att undersöka hur olika grader av njursvikt påverkar risken för död och kliniska utfall efter en kranskärlsröntgen p.g.a. stabil kranskärlssjukdom. Resultaten påvisade att trots justering för flertalet kliniska bakgrundsfaktorer, samsjuklighet, grad av ischemi och olika revaskulariseringmetoder, hade patienter med njursvikt en signifikant ökad risk för död, återinsjuknande i akut hjärtinfarkt och hjärtsvikt. Studie II: Registerstudie där alla patienter med hjärtinfarkt som registrerats i SWEDEHEART och som erhållit blodförtunnande behandling med antingen clopidogrel eller ticagrelor studerades. Samkörning av flera register utfördes. Jämfört med clopidogrel, var behandling med ticagrelor förknippat med lägre risk för död, återinläggning med hjärtinfarkt och stroke, dock på bekostnad av en ökad blödningsrisk, hos både njurfriska och patienter med måttlig njursvikt. Bland patienter med uttalad njursvikt observerades inte någon säker nytta, men däremot ökade risker för blödning. Studie III: Alla patienter i SWEDEHEART som genomgått kranskärlsröntgen och erhållit en kranskärlsstent (läkemedelsbärande stent (n-DES) eller stent av metall (BMS)) inkluderades i denna studie, där risken för förnyad förträngning (restenos) och akut ocklusion (stenttrombos) i stenten studerades utifrån njurfunktion. I jämförelse med BMS, innebar stentinläggning med n-DES en lägre 1-årsrisk för både restenos och stenttrombos hos patienter med lätt eller måttlig njursvikt, medan ingen skillnad noterades hos patienter med uttalad njursvikt. Studie IV: SWEDEHEART användes för både provinsamling och prospektiv långtidsuppföljning hos 1,098 patienter som vårdats med akut hjärtinfarkt. Blodprover sparades i SWEDEHEARTbiobank och 175 olika biomarkörers uttryck analyserades hypotesfritt angående kopplingar till njursvikt och kliniska utfall, som registrerades i befolknings-och patientregistret. Resultaten påvisade att flertalet av de sex stycken biomarkörer som var starkast relaterade till njursvikt också var starkt relaterade till risken för att drabbas av död, hjärtinfarkt och hjärtsvikt. Slutsats Njursvikt är en stark och oberoende riskmarkör för överdödlighet och kardiovaskulära utfall hos patienter med kranskärlssjukdom. Andra okända faktorer än de vi kunnat justera för (riskfaktorer, samsjuklighet, CAD, behandlingar) har betydelse för den försämrade prognos hos patienter med kranskärlssjukdom och nj...

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Osteoprotegerin and osteoprotegerin/TRAIL ratio are associated with cardiovascular dysfunction and mortality among patients with renal failure

Cited by 25 publications

References 38 publications

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

Osteoprotegerin and Cardiovascular Events in High‐Risk Populations: Meta‐Analysis of 19 Prospective Studies Involving 27 450 Participants

TRAIL, OPG, and TWEAK in kidney disease: biomarkers or therapeutic targets?

SWEDEHEART-1-year data show no benefit of newer generation drug-eluting stents over bare-metal stents in patients with severe kidney dysfunction following percutaneous coronary intervention

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