Biomarkers and Risk Scores for Risk Stratification of Unstable Angina
Can a Multi-marker Strategy Improve Risk Stratification and Expedite Discharge in Unstable Angina? A Comparison With High Sensitive Troponin T
調査の概要
状態
条件
詳細な説明
Chest pain accounts for up to 1% of visits to GPs in England, about 700000 visits (5%) to emergency departments and up to 25% of emergency admissions to hospitals. Recent epidemiological studies indicate a substantial and increasing rate of admissions with chest pain even as admissions with acute myocardial infarction are falling. From 1986 to 2000 the rate of admissions for chest pain in Scottish hospitals more than doubled. Further work by the same group indicates that admission to hospital with angina, excluding those coded for acute coronary syndrome or acute myocardial infarction, is associated with a 30 day mortality of 1.5%. Other studies have identified a sizable event rate in patients who have been 'troponin negative'. This increasing phenomenon places great strain on the NHS and indeed any health provider. Any form of testing that adds significant incremental value to established tests and that can effectively rule out myocardial ischaemia and moreover demonstrate good medium and long-term outcome could potentially benefit both patients and the NHS delivery of healthcare.
Brain Natriuretic Peptide Biochemical markers of left ventricular wall stress or ischaemia could enhance the diagnostic accuracy of exercise tolerance tests. These have been used successfully for the detection of left ventricular dysfunction, heart failure and in the risk stratification of acute coronary syndromes.
Biomarkers of acute stress
Growth Differentiation Factor -15 Transforming growth Factor constitute a superfamily of cytokines that exert prominent actions in adult haemostasis and adaptation by regulating cell survival, proliferation and differentiation. GDF-15 is a distant member of the TGF-B superfamily. In animal models it is induced in response to ischaemia-reperfusion injury, pressure overload and heart failure possibly via pro-inflammatory cytokine and oxidative stress dependent signalling pathways. There is both evidence of an adverse outcome in patients with an elevated GDF-15 level in highly selected trials with NSTEMI as well as the non-selected chest pain population. This latter analysis was a post-hoc one and there are no prospective studies in an unselected chest pain population evaluating GDF-15.
Heart Type Fatty Acid Binding Protein (HFABP)- Direct evidence of myocardial ischaemia HFAP is a low molecular weight protein that is involved in the intracellular uptake and buffering of free fatty acids in the myocardium. It has been shown to be a sensitive and early marker of myocardial infarction providing direct evidence of myocardial ischaemia as well as myocyte necrosis unlike HSCRP and BNP. This is intuitive given its small molecular size and consequently its propensity to be leaked from the porous membranes of ischaemic myocardial cells. In the study by Kilcullen et al even Tn negative patients were well stratified by HFABP.
The role of inflammation and specifically HS-CRP Inflammatory processes play an integral part in the process of atherogenesis and atherothrombosis. There is clear evidence of their involvement in the processes that lead to the development of intermediate and mature atheromatous plaques. Inflammatory cells and mediators are also clearly implicated in the final breach between the thin fibrous cap and circulating platelets and coagulation proteins. Several mediators have been investigated. These include HS-CRP, serum amyloid A, myeloperoxidase and interleukin-6. They are detectable in a large proportion of patients with ACS including those with no evidence of myocyte necrosis. It is not clear if these markers directly contribute to the pathology of plaque destabilisation and ischaemia or whether they are largely a 'byproduct' of the inflammation engendered by ischaemia and plaque rupture. CRP promotes uptake of LDL cholesterol by monocytes, induces the production of tissue factor, activates complement within arterial plaque as well as stimulating the expression of adhesion molecules. In this regard at least it maybe postulated that CRP is a direct participant in atherothrombosis. It has also been demonstrated that the measurement of Hs-CRP can grant additional prognostic information to patients with negative serial cardiac troponins. However both of these studies were post-hoc sub-studies of randomised controlled trials. Posthoc analyses of the PROSPER study however indicated that measurement oinf HS-CRP added only a small incremental prognostic value to patients at risk of vascular events. Recent results of the Jupiter study gives rise for hope that inflammation as determined by CRP can improve outcome if used a therapeutic decision tool for rosuvastatin treatment in patients who do not fulfil criteria for primary treatment of hyperlipidaemia. This does suggest the potential value of therapeutic decision making with HS-CRP albeit in a different setting.
Rationale for study In consecutive series of patients admitted with troponin negative chest pain the investigators aim to evaluate the independent prognostic value of resting NT-pro BNP, basal HFABP, GDF-15 and HS-CRP. The relationship of these markers to long term hard endpoints will be investigated . The investigators aim to specifically assess whether alone or in combination these can aid in the risk stratification of acute chest pain admissions that do not have evidence for myocyte necrosis. A range of parameters such as the presence of anaemia, ECG changes and pain characteristics will be included in a model to assess the tested parameters relative effect and relationship with clinical outcome. The aim is to define the independent, cumulative incremental benefit of resting NT-pro BNP, resting HFABP, GDF-15 and HS-CRP and to determine whether either alone or in combination this information may help improve risk stratification and ultimately therapeutic decision making in patients with troponin negative chest pain.
研究の種類
入学 (実際)
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
- Admission with chest pain which could be due to underlying ischaemic heart disease
- HSTroponin T < 15ng/L in patients with possible ischaemic sounding chest pain admitted to hospital at least 6 hours since onset of chest pain or in those with pain <3hours since admission with no STEMI, a baseline HStroponin T <15ng/l (time 0 on admission) and HSTroponin T <15ng/l at 3 hours and <20% increase compared to baseline (time 0)
- Ability to give informed consent for extraction of blood for biochemical screening
説明
Inclusion Criteria:
- Patients presenting within 12 hours of chest pain thought to be cardiac in origin but with no ST segment elevation on ECG
- 5th generation troponin T <15ng/l
- Consent for inclusion in study and consent for follow-up over 3 years either by telephone or GP contact
Exclusion Criteria:
- Troponin positive patients, Tn T>=15ng/lµg/l
- Diagnosis of non-cardiac chest pain made at outset
- Known History of chronic heart failure or cardiomyopathy
研究計画
研究はどのように設計されていますか?
デザインの詳細
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Major Adverse Cardiac Event: death, myocardial infarction, revascularisation
時間枠:3 years
|
All cause death, myocardial infarction and revascularisation within 3 years of index presentation
|
3 years
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (予想される)
研究の完了 (予想される)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- AintreeNHS1
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
胸痛の臨床試験
-
Dexa Medica Group完了