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Table the primary event.
- Tom Oommen (12 March 2000)
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New Sheffield tables
- Paul N Durrington (11 April 2000)
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Importance of family history on risk
- John Younger (18 April 2000)
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Tom Oommen, Associate Professor in Pharmacology Fr. Muller's Medical College, Mangalore, India
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According to the prevailing theory of atherogenesis (1) the response- to-injury hypothesis, atherosclerosis is caused by a repetitive insult to the vascular endothelium, which eventually leads to an excessive inflammatory fibro-proliferative response to the endothelium and smooth muscle to the arterial wall. Injury may be induced by a variety of factors such as modified low-density lipoproteins, mechanical force, immunological factors or viruses. One of the earliest events observed following the endothelial insult is an increased monocyte adhesion to the endothelial surface, which is a critical component of atherogenesis. This is followed by recruitment of monocytes into the sub-endothelial space and ingestion of modified LDL by these cells, leading to the formation of foam cells. Accumulation of the modified LDL such as oxidized LDL and lyso-phosphatidylcholine (LysoPC) in turn stimulates endothelial cells to induce the expression of pro- inflammatory molecules such as ICAM-1 and VCAM-1 which further promote monocyte migration and development of atherosclerotic lesions. T- lymphocytes also migrate into the intima, and together with the foam cells they form fatty streaks. Subsequently, the vascular smooth muscle cells also infiltrate into the intima and proliferate, leading to the formation of atherosclerotic plaques. Miyasaka et al (2) observed that while monocyte attachment to the endothelial surface appears to be the initiator of a cascade of events that leads to the development of atherosclerosis, the molecular mechanism of such a process needs to be fully elucidated. It has also been suggested that the vascular endothelium directs the accumulation of leukocytes into the inflamed tissue by expressing appropriate receptors, namely selectins, which mediate the first step of leukocyte extravasation or rolling. Different types of adhesion molecules expressed by the activated endothelial cells are involved in mediating the inflammatory process. In particular, the E-, L- and P- selectins are thought to play a pivotal role in mediating the process, bringing leukocytes in close proximity to the endothelial lining of the inflamed vessel (3). In short, the Sheffield Risk Table may have a 97% sensitivity and 95% selectivity for screening of primary prevention of coronary and cardiovascular risk estimates (4). Bit it does not highlight the primary event in atherogenesis which is considered to be one of the foremost of risk factors that lead to coronary events. References: 1. Ross R. The pathogenesis of atherosclerosis, a perspective for the 1900s. Nature 1993; 362: 801-809 2. Miyasaka M et al. Involvement of selectins in atherogenesis: a primary or secondary event? Ann New Y Acad Sci. 1996; 811: 25-35 3. Yoshida M & Gibrone MA. Novel roles for E-selectin in endothelial-leukocyte adhesion. Ann New Y Acad Sci. 1996; 811: 493-97 4. Wallis E et al. Coronary and cardiovascular risk estimates and primary prevention. BMJ 2000; 320: 671-676 |
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Paul N Durrington, Professor of Medicine Manchester Royal Infirmary
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Dear Sir Wallis and her colleagues are to be congratulated on the new Sheffield tables [1] which by the inclusion of HDL cholesterol are considerably more accurate than the earlier version [2]. We continue, however, to disagree with their means of assessing the accuracy of risk prediction methods by applying them to the whole population when such methods are intended to identify high risk populations. Inevitably when a whole population approach is employed the majority of people will have a risk which is substantially below the threshold CHD risk for which the tables are designed (in this case 15% over the next 10 years). Accuracy should be tested in people who are closer to this threshold, because they represent the type of patient for whom the clinical decision about drug therapy is to be made in practice. We have therefore compared the accuracy of the new Sheffield tables and the Joint British Societies chart for CHD risk [3] and the New Zealand charts for cardiovascular risk [4] with the Framingham risk equation on which they are based [5] in a series of 386 patients referred to our Lipid Clinic by their physicians for advice about whether drug therapy was justified. The Joint British Societies charts identified correctly 88% of the patients to whom they could be applied, the new Sheffield table 81%, but the New Zealand charts only 63% [6]. Thus, in terms of accuracy the Sheffield tables performed similarly to the Joint British Societies charts. We were surprised by the inaccuracy of the New Zealand tables, which stems from their use of both systolic and diastolic blood pressure on the same axis when the curves for CHD risk generated by these two measurements of blood pressure relative to the total serum to HDL cholesterol ratio are not parallel [5]. This is not really overcome by the use of boxes rather than curves. We appreciate that many clinicians are reluctant to abandon diastolic blood pressure, but it is less accurately measured than systolic and does not predict risk as precisely. The new Sheffield tables were considered by the Joint British Societies for inclusion in their guidelines [3], but were not adopted because they do not allow practitioners to judge the level of risk between 15% and 30% and the Joint British Guidelines recommend that, as statins become cheaper and more resources are available, people at lower risk will progressively be targeted for cholesterol-lowering treatment. It would now appear that this decision was further justified by the findings of the study by Isles and colleagues that nurses and doctors found the New Sheffield tables more difficult to use than the charts adopted in the Joint British recommendations [7]. Rather than tables or charts, for those physicians with access to a computer, the programme produced by the Joint British Societies available from us, the British Heart Foundation or on the British Hypertension Society and Family Heart Association websites ( www.hyp.ac.uk/bhs or www.familyheart.org respectively) was considered preferable in the Joint British Guidelines. This provides both CHD and stroke risk for both systolic and diastolic blood pressure so that physicians can obtain a more comprehensive understanding of an individual's cardiovascular risk and plan antihypertensive or lipid- lowering drug therapy accordingly. Yours faithfully P.N. Durrington MD FRCPath FRCP
REFERENCES 1. Wallis, E.J., Ramsay, L.E., Haq, I.U., Ghahramani, P., Jackson, P.R., Rowland-Yeo, K., Yeo, W.W. Coronary and cardiovascular risk estimation for primary prevention: validation of a new Sheffield table in the 1995 Scottish health survey population. Brit. Med. J. 2000; 320: 671-6. 2. Durrington, P.N., Prais, H., Bhatnagar, D., France, M., Crowley, V., Khan, J., Morgan. J. Indications for cholesterol-lowering medication: comparison of risk-assessment methods. Lancet. 1999; 353: 278-281. 3. Wood, D., Durrington, P.N., Poulter, N., McInnes, G., Rees, A., Wray, R. Joint British Recommendations on prevention of coronary heart disease in clinical practice. Heart 1998; 80 Suppl 2: S1-S29. 4. Dyslipidaemia Advisory Group, on behalf of the Scientific Committee of the National Heart Foundation of New Zealand. 1996 National Heart Foundation Guidelines for the Assessment and Management of Dyslipidaemia. N.Z. Med. J. 1996; 109: 224-32. 5. Anderson, K.M., Odell, P.M., Wilson, P.W.F., Kannel, W.B. Cardiovascular disease risk profiles. Am. Heart J. 1990; 121: 293-8. 6. Durrington, P.N., Prais, H. Methods for the prediction of coronary heart disease risk. Heart 2000. In press. 7. Isles, C.G., Ritchie, L.D., Murchie, P., Norrie, J. Risk assessment in primary prevention of coronary heart disease: randomised comparison of three scoring methods. Brit. Med. J. 2000; 320: 690-1. |
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John Younger
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Editor - The New Sheffield Table1 and it's alternatives make little use of a cardinal risk factor that is easy to assess. A family history of coronary artery disease, especially when premature, is a powerful and independent indicator of an individual's risk. Failure to include this element will cause these tables to underestimate the 10 year risk of cardiovascular disease, and cannot be corrected for by simply adding 6 years to the patients age, as suggested in the Sheffield table. The increase in risk is variable depending on the exact details of the family history, the age, and the sex of the patient. The GISSI-EFRIM investigators2 showed that a family history of MI is an independent risk factor for MI, with the number of relatives and the age at which they were affected influencing the strength of the association. Compared with subjects without a family history, those with one or two affected first-degree relations had relative risks for MI of 2.0 and 3.0 respectively. The danger seems to be greater for women than for men, and is especially high if a sister is affected. In one study of MI patients under 60 years3, the cumulative risk to women of IHD before 65 years is almost twice as high if a sister, rather than a brother is affected (26% vs. 16%). Using more precise definitions of a positive family history allows for a more accurate assessment of coronary risk. An Australian survey4 found that compared with an affected parent, an affected sibling carries a relative risk of 2.5 for coronary artery disease, regardless of age. Hence any females defined by the Sheffield table to have a 10 year CHD risk of 15%, but who have an affected sister of similar age, may actually have a risk of >30%. Family history of coronary artery disease cannot be ignored and should feature prominently in all guidelines for primary prevention of cardiovascular disease. Dr. John Younger
1. Wallis EJ, Ramsay LF, Iftikhar UH, Ghahramani P, Jackson PR, Rowland-Yeo K, Yeo W. Coronary and cardiovascular risk estimation for primary prevention : validation of a New Sheffield table in the 1995 Scottish health survey population. BMJ 2000; 320: 671-676 (11 March) 2. Roncagliono MC, Santoro L, D'Avanzo B, et al. Role of family history with Myocardial Infarction. An Italian case-control study. GISSI- EFRIM Investigators. Circulation 1992; 85(6) : 2065-72 3. Pohjola-Sintonen S, Rissanen A, Liskola P, Luomanmaki K. Family history as a risk factor of coronary heart disease in patients under 60 years of age. Eur-Heart-J. 1998; 19(2): 235-239 4. Silberberg J, Wlodarczyk J, Fryer J, Robertson R, Hensley MJ. Risk associated with various definitions of family history of coronary artery disease. The Newcastle Family History Study II. Am-J-Epidemol. 1998; 147(12): 1133 |
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