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EDITORIALS: A Rosengren Cholesterol: how low is low enough? BMJ 1998; 317: 425-426 [Full text]

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Let's get real

James Moult   (18 August 1998)

Average cholesterol is not "normal"

Michael Pignone   (18 August 1998)

Screening the population

B C Rao   (18 August 1998)

Cholesterol : how low is low enough?

A R P Walker   (3 September 1998)

Doctors have been slow to get evidence on cholesterol lowering into practice

A S Wierzbicki   (16 September 1998)

Let's get real 18 August 1998
James Moult, locum Send response to journal: Re: Let's get real	The ideal world scenario is great, but what's happening on the wards? With my limited experience, depending on where one works, there's no consensus and so it's a "which consultant believes what response", leading to confusion as to whether to start a statin or not. I'd love as a junior house officer or an SHO to have, for example, a patient's cholesterol level automatically 'flag-up' a guideline that's being used ,if not country-wide then hospital-wide. So why don't we, on the strength of this apparently overwhelming current evidence, put into place a 'rule in, rule out' patient cholesterol-lowering strategy that makes at least the ward round "should we start a statin?" - question, an easy one. P.S. I'll help, if you want!
Average cholesterol is not "normal" 18 August 1998
Michael Pignone, Asst Prof Medicine UNC Chapel Hill Send response to journal: Re: Average cholesterol is not "normal"	I would like to call attention to a subtle but important semantic error in Rosengren's otherwise excellent editorial "Cholesterol: how low is enough?" Dr. Rosengren states that RCT's have demonstrated ability to reduce cardiovascular events in patients with "high and normal" cholesterol levels, and makes reference to the 4S and CARE studies. The CARE study, in fact, examined subjects with "average" cholesterol levels (as stated in the title) not "normal" values. What actually constitutes "normal" is difficult to assess in the context of the high prevalence of heart disease in industrialized society; however, CARE subjects had mean LDL values of 139 mg per dl. I am concerned that if the distinction between "average" and "normal" is forgotten, we may see increases in the inappropriate use of pharmacologic treatment of cholesterol, particularly in the primary prevention setting.
Screening the population 18 August 1998
B C Rao, GP 1056,HAL2NDSTAGE BANGALORE 560008 Send response to journal: Re: Screening the population	If one is going to achieve 20 to 30% reduction in the incidence of ischaemic heart disease would it be economical to screen the whole population? This would certainly not be feasible in a country like India. The next alternative is to identify and screen the high risk groups including the young siblings.As high mortality, earlier age of onset seem to be a feature here such screening may be worth it.But after that what? Given the current cost of statins few can afford the treatment and follow up. Still it is worth doing for the few who can manage it.
Cholesterol : how low is low enough? 3 September 1998
A R P Walker Send response to journal: Re: Cholesterol : how low is low enough?	EDITOR, - In his stimulating editorial, Professor A Rosengren (August 15, p.425)1 considers that reaching target levels may be better than relative reductions. He stated that 'in observational studies a prolonged difference in usual serum cholesterol value of 0.6mmol/l is associated with an almost 30% reduction in risk of coronary disease.' None would question the need for the reduction of serum cholesterol level in large proportions of adults in Western populations. However, the whole field of cholesterol level and its pathological significance is one of complexities. Firstly, known risk factors for coronary heart disease (CHD) of which serum cholesterol is one, explain only one half of the variance in the occurrence of the disease.2 Next, there are numerous contextual problems. For example, in the Sheffield risk table, in the high risk moiety cholesterol reduction may be called for at 5.5mmol/l; whereas for those at low risk, intervention may not be needed until 9.0mmol/l level.3 There is also the dichotomy of experience of CHD in Belfast and Toulouse. While mean cholesterol levels in the two cities are similar, 6.19 and 5.94 mmol/l, CHD mortality rate is 3-4 times higher in the former compared with the latter city.4 Perplexities are also common in developing populations, as in South Africa.5 In early studies on African men, mean cholesterol level of the middle aged was about 4.0 mmol/l. At that time, observations at necropsy revealed a very low level of atherosclerotic lesions of the aorta, and negligible deaths from the disease. Currently, in Soweto (3-4 million inhabitants), mean cholesterol level is about 5mmol/l. Yet CHD remains very uncommon, being responsible for less than 0.5% of total deaths. Like reports of its relative rarity have emanated from big cities in other countries in Africa. As a comparison, in the Seven Countries Study, it was reported that the same mean level of serum cholesterol, about 5.15mmol/l, prevails in Mediterranean countries, but where CHD is responsible for 4.7% of total deaths. An additional complicating factor is the wide range of cholesterol levels in a community. In African village schoolchildren, almost all of the same poor socio-economic state and accustomed to the same low atherogenic diet, cholesterol level was found to vary from 2.5 to 4.2 mmol/l. To re-iterate, while there is no intention of belittling the role of cholesterol level in CHD, it is important to recognize that a given level of the parameter has widely different connotations for ill, as affected by familiality, ethnicity, gender, and environmental factors. A.R.P. WALKER Head: Human Biochemistry Research Unit, Department of Tropical Diseases, School of Pathology of the University of the Witwatersrand, and the South African Institute for Medical Research, Johannesburg REFERENCES 1. Rosengren A. Cholesterol: how low is low enough? BMJ 1998; 317: 425-6. 2. Leeder S, Gliksman M. Prospects for preventing heart disease. Br Med J 1990; 301: 1004-5. 3. Haq IU, Jackson PR, Yeo WW, Ramsay LE. Sheffield risk and treatment table for cholesterol lowering for primary prevention of coronary heart disease. Lancet 1995; 346: 1467-71. 4. Evans AE, Ruidavets J-B, McCrum EE, et al. Autres pays, autres coeurs? Dietary patterns, risk factors and ischaemic heart disease in Belfast and Toulouse. Q J Med 1995; 88: 469-77. 5. Walker ARP, Sareli P. Coronary heart disease: outlook for Africa. J Roy Soc Med 1997; 90: 937-8.
Doctors have been slow to get evidence on cholesterol lowering into practice 16 September 1998
A S Wierzbicki Send response to journal: Re: Doctors have been slow to get evidence on cholesterol lowering into practice	Sir, The editorial by Rosengren 1 rightly states that treatment of patients with established coronary heart disease is mandatory. Prolonged statin therapy reduces events more than 30% as the 8 year results of the Scandinavian Simvastatin Survival Study (4S) show a 45% reduction 2. However the suggested target of LDL< 2.6 mmol/L differs from the advice of the Standing Medical Advisory Committee of <3.2 mmol/L post- infarction. There is little evidence, except for patients with coronary bypass grafts (< 2.6 mmol/L), for which target is correct. For many patients their first infarct is terminal. The Air Force- Texas Coronary Artery Prevention study (AF-TexCAPS) including both sexes has shown a 34% reduction in events starting at a risk of 1.2 % per year 3 and the West of Scotland Coronary Prevention Study (WOSCOPS) a 33% reduction in mortality at a risk of 1.5% per year in men. Yet, Ramsay 4 and others still suggest use of a 3% per year threshold rather than the internationally recognised 2% per year. The Sheffield tables are an attempt to ration statin therapy despite the evidence not because of it. Patients with familial hyperlipidaemias are common (1 in 250) and have a large excess mortality and morbidity at an early age when calculated risk does not approach 1% per year. The Sheffield tables fail to define patients with a familial hyperlipidaemia accurately as physical signs are often absent and the penetrance of coronary heart disease may be poor. In the case of a euthyroid patient with a total cholesterol of 10 mmol/L, after exclusion of renal disease, which incidentally has 4-fold increased risk of coronary disease, the chances of this being due to non- familial causes are < 1 in 104. We agree with Ramsay et al that GPs ought to decide. Yet it seems strange that opinion from lipid specialists on the utility of the Sheffield tables is not worthy of note by others involved in the production of guidelines. The tables cited by MacLeod and Armitage5 or the European Societies allow individual GPs to calculate an approximate risk and then decide in the light of international recommendations. In contrast a prescriptive approach is adopted in the Sheffield tables. Guidelines excepted, it is a depressing fact that most patients with coronary artery disease are still not on statin therapy 4 years after the publication of the 4S study and the vast majority of those treated are treated inadequately. Dr. A.S. Wierzbicki Professor T.M. Reynolds Senior Lecturer Dept of Chemical Pathology King's College Burton Hospital St.Thomas' Hospital Campus Belvedere Road London SE1 7EH Burton-on-Trent DE13 0RB References 1. Rosengren M. Cholesterol: how low is low enough? Brit Med J 1998; 317 : 425-6 2. Pedersen T. Seven year results of the Scandinavian Simvastatin Survival Study. Presented at Drugs and Lipid Metabolism Symposium, Florence, 1998. 3. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholestreol levels. Results of The Air Force-Texas Coronary artery prevention study. JAMA 1998; 279 : 1615-22 4. Ramsay LE, Wallis EJ, Haq IU, Williamson R, Yeo WW, Jackson PR. Use of statins: ..the Sheffield table is useful. Brit Med J 1998; 317 : 473-4 5. MacLeod AJ, Armitage M. Use of statins: ..but New Zealand tables are better. Brit Med J 1998; 317 : 474