MANAGEMENT of HYPERLIPIDAEMIA 361 Postgrad Med J: First Published As 10.1136/Pgmj.69.811.359 on 1 May 1993
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Postgrad Med J (1993) 69, 359- 369 i) The Fellowship of Postgraduate Medicine, 1993 Postgrad Med J: first published as 10.1136/pgmj.69.811.359 on 1 May 1993. Downloaded from Special Article Management ofhyperlipidaemia: guidelines ofthe British Hyperlipidaemia Association D.J. Betteridge, P.M. Dodson', P.N. Durrington2, E.A. Hughes3, M.F. Laker4, D.P. Nicholls5, J.A.E. Rees6, C.A. Seymour7, G.R. Thompson8, A.F. Winder9, P.H. Winocour'° and R. Wray" Department ofMedicine, University College London Medical School London; 'East Birmingham NHS Trust, Birmingham; 2Department ofMedicine, University ofManchester; 3Sandwell District General Hospital, West Bromwich; 4Department ofMedicine, University ofNewcastle upon Tyne; 'Royal Victoria Hospital, Belfast; 6University Hospital of Wales, Cardiff; 7St George's Hospital Medical School, London; 8MRC Lipoprotein Team, Hammersmith Hospital, London; 9Department ofChemical Pathology, Royal Free NHS Trust and School ofMedicine, London; '0Department ofMedicine, University ofNewcastle upon Tyne; and "'Department ofMedicine, Hastings andRother NHS Trust, UK Introduction There have been considerable advances in the Justification for attributing a causal role for understanding of plasma cholesterol and tri- LDL cholesterol in atherosclerosis has received glyceride metabolism and the lipoprotein particles considerable support from the outcome of both which transport these important lipids. Epidemi- primary and secondary CHD prevention trials ological evidence linking plasma cholesterol to employing lipid modifying therapy.6'7 Although copyright. coronary heart disease (CHD) risk has been streng- indirect evidence also points to the benefits of thened by the findings ofthe prospective part ofthe increasing plasma HDL concentrations and Multiple Risk Factor Intervention study.' Further- decreasing plasma triglyceride concentration, the more, the study of populations with plasma bulk of evidence implicates LDL as the major cholzsterol concentrations much below those seen atherogenic particle. Recent angiographic studies in Western industrialized societies has pointed to a suggest that radical alteration ofplasma lipids and continuous gradient of CHD risk with increasing lipoproteins by lifestyle, pharmacological and sur- plasma cholesterol.2 The value of measurement of gical measures can retard the progression of http://pmj.bmj.com/ individual plasma lipoproteins in defining CHD atherosclerotic lesions, delay the appearance of risk more closely is now well established. Low new lesions and in some patients lead to lesion density lipoprotein (LDL) cholesterol, is the major regression8'-2 (Table I). transporter of plasma cholesterol, and largely Advances in the cell and molecular biology of accounts for the relationship between total lipoprotein cell interactions have provided new cholesterol and CHD.3 In contrast, high density insights into the mechanisms ofatherosclerosis and lipoprotein (HDL), the other major cholesterol- much is now known about the regulation ofplasma on September 24, 2021 by guest. Protected rich lipoprotein, is inversely related to CHD.4 The lipoprotein levels. The central role of the liver in role of plasma triglyceride as an independent risk these processes has been identified. The seminal factor for CHD remains controversial,' although work of Goldstein and Brown,'3 which identified there is no doubt of the atherogenicity of some the LDL receptor pathway, provided the found- triglyceride-rich lipoproteins, namely chylomicron ation for major advances in this field. This work remnant particles and intermediate density lipo- has not only enabled the identification of genetic proteins (IDL). Very high concentrations of abnormalities underlying some of the primary plasma triglycerides, reflecting the accumulation of hyperlipidaemias but also has led to an under- chylomicrons which transport exogenous fat from standing of the mechanism of action of some the intestine, are associated with risk of pan- lipid-modifying drugs and the logical development creatitis. of new therapeutic agents. Correspondence: D.J. Betteridge, B.Sc., Ph.D., M.D., Various consensus committees have reviewed F.R.C.P., Department of Medicine, University College recent developments and have furnished guidelines London Medical School, The Middlesex Hospital, for optimal lipid and lipoprotein concentrations Mortimer Street, London WIN 8AA, UK. for the population as a whole in an attempt to Accepted: 11 January 1993 reduce the burden of CHD.4" 5 In addition, 360 D.J. BETTERIDGE et al. Postgrad Med J: first published as 10.1136/pgmj.69.811.359 on 1 May 1993. Downloaded from Table I Differences between changes in patients in treatment and control groups in angiographic trials of lipid-lowering therapy LDL-C HDL-C Prog Reg A% A% A% A% NHLBI Type II8 (Ch) -20 + 6 -17 0 CLAS9 Co+NA -36 +35 -22 + 14 FATSI' L+Co -39 + 11 -25 +21 NA + Co -25 + 38 -21 + 28 UCSF" Co+NA±L -28 +28 -21 +20 STARS'2 Diet - 13 0 - 31 + 34 Diet + Ch -33 - 4 -34 + 29 Ch = cholestyramine; Co = colestipol; NA = nicotinic acid; L = lovastatin; NHLBI = National Heart Lung and Blood Institute; CLAS = Cholesterol Lowering Atherosclerosis Study; FATS = Familial Atherosclerosis Treatment Study; UCSF = University College San Francisco; STARS = St Thomas' Atherosclerosis Regression Study; Prog = progression; Reg = regression; LDL-C = LDL cholesterol; HDL-C = HDL cholesterol. Reproduced from Thompson, G.R. Progression and regression of coronary artery disease. Curr Opinion Lipidol 1992, 4, 263-267, with permission. guidelines for the identification by screening and with the clinical stigmata of hyperlipidaemia; withcopyright. treatment of hyperlipidaemia have been pub- a strong family history of premature CHD or lished.6"7 This review provides the current consen- hyperlipidaemia; and those with other risk factors sus of the views of the British Hyperlipidaemia for CHD such as hypertension, diabetes mellitus Association, which consists ofphysicians and other and obesity. It is recognized that not all individuals health professionals involved in the management of with significant hyperlipidaemia will be identified lipid disorders. Hopefully general physicians, by these measures and more general screening may whether in hospital or the will find it of community, be appropriate on an opportunistic basis, as http://pmj.bmj.com/ benefit in guiding their own practice. resources permit. For general screening purposes a random, non- fasting plasma cholesterol measurement is appro- Screening for hyperlipidaemia priate. If this falls outside our previously published guidelines,'8 a full lipid profile including plasma Hyperlipidaemic individuals may be identified by cholesterol, plasma triglyceride and HDL-chol- plasma lipid measurements performed because esterol should be obtained following an overnight they have clinically overt vascular disease. Others fast (12-14 hours). LDL-cholesterol can then be on September 24, 2021 by guest. Protected may have the clinical stigmata of hyperlipidaemia calculated using the Friedewald equation:'9 (premature arcus, xanthelasma, xanthomata) and many will be identified in screening programmes. LDL cholesterol (mmol/l) = The question of which individuals should have Total cholesterol - HDL cholesterol trgl2ceride plasma lipid measurements performed has led to (applicable when total triglyceride < 4.5 mmol/l). much debate within the profession. Certain coun- tries such as the United States of America have Measurements are best performed in hospital instigated well-publicised cholesterol education chemical pathology departments. Care is required programmes designed to ensure that every adult in venepuncture techniques as prolonged venous has their cholesterol measured by opportunistic occlusion may increase cholesterol concentrations screening.'7 Although it is possible that other significantly. Posture also affects cholesterol levels countries will adopt similar strategies in the future, with a significant fall on sitting and a further fall on a strategy of selectively screening only high risk lying down. It is recommended therefore that blood individuals seems to prevail in the UK. The should be taken with minimal venous occlusion presence of hyperlipidaemia should be sought in after the subject has been sitting for 10 minutes. individuals with clinically overt vascular disease; Office-based machines employing dry chemistry GUIDELINES IN MANAGEMENT OF HYPERLIPIDAEMIA 361 Postgrad Med J: first published as 10.1136/pgmj.69.811.359 on 1 May 1993. Downloaded from technology have a role in screening as long as the disorders by genotype as opposed to laboratory instrument operator has received proper training phenotype. There is no doubt that lipoprotein and appropriate quality assurance is performed. phenotyping introduced in the early 1970s and However, it is inappropriate to make management adopted by the WHO2' gave a major impetus to the decisions based solely on these tests. understanding of the hyperlipidaemias. However, In high risk groups it is advisable to perform a this was a laboratory classification and has obvious full fasting profile in the first instance as abnor- drawbacks in the sense that it does not point to malities of triglyceride and HDL cholesterol con- aetiology; for example, type Ila hyperlipidaemia centrations may otherwise be missed. Long-term (increased LDL cholesterol) can be the result of plans should not be made without at least two hypothyroidism or familial hypercholesterolaemia. measurements. An important