Evidence map›Paper›PMID 22315282›Full record

Trial reportCirculation2012

Systemic and vascular oxidation limits the efficacy of oral tetrahydrobiopterin treatment in patients with coronary artery disease.

Colin Cunnington, Tim Van Assche, Cheerag Shirodaria, Ilias Kylintireas, Alistair C Lindsay, Justin M Lee, Charalambos Antoniades, Marios Margaritis, Regent Lee, Ruha Cerrato and 8 more

Open access · bronzeAbstract readComparative StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Circulation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed, 1 pooled it
11.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

78 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. A single dose of dietary nitrate supplementation protects against endothelial ischemia-reperfusion injury in early postmenopausal women.Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · 2022
    Trial
  4. No effect of acute tetrahydrobiopterin (BHJournal of applied physiology (Bethesda, Md. : 1985) · 2022
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18 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 1 institution in 1 country.

Colin CunningtonDepartment of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Tim Van Assche
Cheerag Shirodaria
Ilias Kylintireas
Alistair C Lindsay
Justin M Lee
Charalambos Antoniades
Marios Margaritis
Regent Lee
Ruha Cerrato
Mark J Crabtree
Jane M Francis
Rana Sayeed
Chandi Ratnatunga
Ravi Pillai
Robin P Choudhury
Stefan Neubauer
Keith M Channon
John Radcliffe Hospital · GB

Funding

British Heart Foundation PG/08/119/26263British Heart Foundation RG/07/003/23133British Heart Foundation RG/12/5/29576Department of Health IS-BRC-0211-10025Wellcome Trust 088291Wellcome Trust 090532
6 · The paper itself

Abstract

backgroundThe endothelial nitric oxide synthase cofactor tetrahydrobiopterin (BH4) plays a pivotal role in maintaining endothelial function in experimental vascular disease models and in humans. Augmentation of endogenous BH4 levels by oral BH4 treatment has been proposed as a potential therapeutic strategy in vascular disease states. We sought to determine the mechanisms relating exogenous BH4 to human vascular function and to determine oral BH4 pharmacokinetics in both plasma and vascular tissue in patients with coronary artery disease. METHODS AND

resultsForty-nine patients with coronary artery disease were randomized to receive low-dose (400 mg/d) or high-dose (700 mg/d) BH4 or placebo for 2 to 6 weeks before coronary artery bypass surgery. Vascular function was quantified by magnetic resonance imaging before and after treatment, along with plasma BH4 levels. Vascular superoxide, endothelial function, and BH4 levels were determined in segments of saphenous vein and internal mammary artery. Oral BH4 treatment significantly augmented BH4 levels in plasma and in saphenous vein (but not internal mammary artery) but also increased levels of the oxidation product dihydrobiopterin (BH2), which lacks endothelial nitric oxide synthase cofactor activity. There was no effect of BH4 treatment on vascular function or superoxide production. Supplementation of human vessels and blood with BH4 ex vivo revealed rapid oxidation of BH4 to BH2 with predominant BH2 uptake by vascular tissue.

conclusionsOral BH4 treatment augments total biopterin levels in patients with established coronary artery disease but has no net effect on vascular redox state or endothelial function owing to systemic and vascular oxidation of BH4. Alternative strategies are required to target BH4-dependent endothelial function in established vascular disease states.

Indexed as

Administration, OralAgedBiopterinsCoronary Artery DiseaseDouble-Blind MethodEndothelium, VascularFemaleHumansMaleOxidation-ReductionTreatment OutcomeBiopterinssapropterin

Identifiers

PMID22315282
PMCPMC5238935
OpenAlexW1987686985

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.