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Co-morbidities and ACS: Do they have a role in risk stratification?
- Venkataswamy Narayana Mahesh (11 October 2006)
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Re: Co-morbidities and ACS: Do they have a role in risk stratification?
- Keith AA Fox (12 October 2006)
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Risk stratification-Are we practicing evidence based medicine?
- Satheesh B Nair, Surya P Rajeev,SHO in Diabetes and Endocrinology,Prince Charles Hospital,Merthyr Tydfil. (13 October 2006)
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Free fatty acid measurements will increase accurate prediction of the risk of death.
- Michael F Oliver (28 November 2006)
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Re: Free fatty acid measurements will increase accurate prediction of the risk of death.
- Keith A. A. Fox (29 November 2006)
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Venkataswamy Narayana Mahesh, SpR Gastroenterology University Hospital of North Durham, Durham, DH15TW
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Editor- Fox et al and the GRACE group have done this important and clinically relevant study, presenting us with a remarkably easy to apply tool for risk stratification at the point of diagnosis and aid appropriate identification of patients for more intensive treatment incluiding reperfusion therapy compared to the currently used TIMI scoring.(1) Given the patients in the GRACE registry spans the spectrum of acute coronary syndrome and is based on an unselected contemporary population, this predictive model do not have the limitations seen with large clinical trial databases. Of particular interest is the non-inclusion of co-morbidities like stroke, diabetes and atrial fibrillation in the risk prediction tool, since as shown in this study, they do attain statistical significance in both death and death/MI model(2). STROKE- Death model: x2 of 69.2, CI 1.8 (1.56 to 2.10), Death/MI model x2 of 36.5, CI 1.4 (1.26 to 1.58); DIABETES - Death model x2 of 61.2, CI 1.5 (1.36 to 1.67), Death/MI model: x2 of 29.4, CI 1.2 (1.15 to 1.35) and ATRIAL FIBRILLATION- Death model: x2 of 152.8,CI 2.3 (2.00 to 2.60), Death/MI model- x2 of 46.9, CI 1.5 (1.33 to 1.66). In the UKPDS study (3) a subgroup analysis suggested that reducing the HbA1C value by 1% was associated with an 18% percent reduction in MI and a 15% reduction in stroke. Another interesting difference from the TIMI risk score is the usage of aspirin in last 7 days not been tested, also prior coronary artery disease not attaining statistical significance (2)- Coronary artery disease: Death model x2 of 13.4, CI 0.8 (0.72 to 0.91)and Death/MI model x2 of 78.1, CI 0.7 (0.63 to 0.74). This study will definitely help in initial and further management decisions of patients presenting with acute coronary syndromes to A&E and MAU. Prospective data on its usage will further consolidate the relevance of this risk prediction tool. REFERENCES: 1. Antman, EM, Cohen, M, Bernink, PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA 2000; 284:835. 2. Keith A A Fox et al, for the GRACE Investigators. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE);BMJ, doi:10.1136/bmj.38985.646481.55 (published 10 October 2006) 3. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837. Competing interests: None declared |
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Keith AA Fox, Professor of Cardiology University of Edinburgh, EH16 4SB
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We thank Dr Mahesh for the comments on the GRACE risk tool including the observation that this large registry does not have the limitations seen with clinical trial databases, or tools derived from them. Indeed, independent groups have demonstrated superiority of the GRACE predictor compared with the TIMI or PURSUIT score (1). Dr Mahesh is incorrect in assuming that co-morbidities like stroke, diabetes and atrial fibrillation were not included. Indeed they are listed in the univariate predictors in table 1. However, these co- morbidities did not emerge as independent predictors of death or myocardial infarction. In the final risk tool it was essential to simplify the model for ease of use and hence we included only those elements that predicted 90% of total risk. We fully accept that diabetes, atrial fibrillation, hypertension and other factors will predict long term outcome, but that is beyond the scope of this risk tool which aims to guide treatment after presentation with ACS. (1). de Araujo Goncalves P, Ferreira J, Aguiar C, Seabra-Gomes R. TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value and interaction with revascularization in NSTE-ACS. Eur Heart J 2005;26:865- 72) Competing interests: None declared |
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Satheesh B Nair, Clinical Fellow in Cardiology Manchester Heart Centre,Oxford Road,M13 9WL, Surya P Rajeev,SHO in Diabetes and Endocrinology,Prince Charles Hospital,Merthyr Tydfil.
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Cardiovascular and cerebrovascular diseases are the most common causes of morbidity and mortality in Europe.Thanks to author Fox and the GRACE group for another clinical risk prediction tool for estimating the cumulative risk of death and myocardial infarction to facilitate management of Acute Coronary Syndrome patients(1)after the TIMI risk score(2).Inspite of these simple scores which can be easily calculated at patient presentation which does not require a computer and identifies at risk patients,the utilisation of these in clinical practice remains a question. An example of this is the ABCD score which can be used to identify individuals at high early risk of stroke after a Transient Ischemic Attack(3).As many as one in five people who have a `mini-stroke'or TIA will go on to have a stroke within a month according to the stroke association reports.This led to the development of a simple tool,the ABCD score as a way of identifying which people who have had a TIA are at highest risk of having a stroke.Carotid endarterectomy is effective in stroke prevention for patients with severe symptomatic carotid artery stenosis and the SPACE trial has shown that carotid artery stenting is another alternative(4).However,there is variation between hospitals and within the hospital in the way in which they manage patients with suspected TIA event and many patients leave the hospital without even having a carotid ultrasound scan. The incorporation of these simple,user friendly scores in the Integrated Care Pathways for the management of Acute Coronary Syndromes and TIA or stroke will definitely help in the identification of high risk individuals who require emergency investigation and treatment. References 1.Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome:prospective multinational observational study(GRACE),BMJ,doi:10.1136/bmj38985.646481.55(published 10 October 2006). 2.The TIMI Risk Score for Unstable Angina/Non-ST Elevation MI, JAMA- Vol284 No7,August16,2000,835-842. 3.A simple risk score(ABCD)to identify individuals at high early risk of stroke aftertransient ischemic attack, The Lancet-Vol366,Issue9479,02 July 2005, 29-36. 4.Thirty days results from the SPACE trial of Stent Protected Angioplasty versus Carotid Endarterectomy in symptomatic patients: a randomised non-inferiority trial The Lancet-Current Issue, Vol368, 07 October 2006,1248-1253. Competing interests: None declared |
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Michael F Oliver, Retired London E14 8DH
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Editor - Prediction of the risk of death and myocardial infarction after an acute coronary syndrome is important, as Fox et al emphasise from their analyses of the GRACE study [1]. Further refinement might be achieved by adding in plasma free fatty acid (FFA/NEFA) concentrations measured on admission. The Paris Prospective Study of 5250 men without coronary disease showed after 22 years of follow-up that an increase in plasma FFA at base-line examination was significantly related to subsequent sudden death [2]. This was independent of other risk factors. A recent detailed study has confirmed an independent relationship between raised FFA and subsequent death with a follow-up of 5.38 years in 3315 patients undergoing coronary angiography [3]. FFA levels also increased with the severity of subsequent heart failure. The authors recommend the prognostic use of FFA levels. The authors of the GRACE study would do well to recognise that increased adrenergic tone during the initial episode - manifest by activation of adipose lipolysis and increased plasma FFA - may recur in the same individuals. A surge of FFA may temporarily overwhelm normal metabolism in the acutely ischaemic myocardium, reduce myocardial energy efficiency, impair glucose utilisation and lead to arrhythmias [4] and heart failure [5]. The inclusion of plasma FFA concentrations in any predictive index should sharpen its prognostic power and also open the way to selective and specific intervention in order to combat their adverse metabolic effects [6]. It is encouraging that one new large trial is including FFA measurements. M F Oliver
1. Fox KAA, Dabbous OH, Goldber RJ, Pieper KS, Eagle KA et al. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ 2006;333:1091-4. 2. Jouven X, Charles M-A, Desnos M, Ducimetiere P. Circulating non-esterified fatty acid level as a predictive risk factor for sudden death in the population.Circulation 2001;104:756-61. 3. Pilz S, Scharnagl H, Tiran B, Seelhorst U, Wellnitz B et al. Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease.J Clin Endocrinol Metab 2006;91:2542-47. 4. Kurien VA, Oliver MF.A metabolic cause for arrhythmias during acute myocardial hypoxia. Lancet 1970;ii:813-5. 5. Opie LH. The metabolic vicious cycle in heart failure. Lancet 2004;364:1733-4. 6. Oliver MF. Sudden cardiac death: the lost fatty acid hypothesis. QJMed 2006;99:701-9. Competing interests: None declared |
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Keith A. A. Fox, Professor of Cardiology University and Royal Infirmary of Edinburgh
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The Authors thank Michael Oliver for the comments. The ongoing GRACE Programme will explore the extent to which various biomarkers and products of gene expression may further enhance the GRACE risk prediction model. More sensitive markers of myocyte injury are now available, than those available at the time of the original Paris Prospective Study (patients recruited between 1967 and 1972)(1). Before accepting the independence of FFA it is necessary to demonstrate the extent to which the elevations in FFA reflect myocyte injury during ACS. It may not be appropriate to extrapolate from patients with stable coronary disease and diagnostic angiography (2). Keith A A Fox 1. Jouven X, Charles M-A, Desnos M, Ducimetiere P. Circulating non- esterified fatty acid level as a predictive risk factor for sudden death in the population.Circulation 2001;104:756-61. 2. Pilz S, Scharnagl H, Tiran B, Seelhorst U, Wellnitz B et al. Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease.J Clin Endocrinol Metab 2006;91:2542-47. Competing interests: None declared |
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