APRIL 2014 A REGULAR CASE-BASED SERIES ON PRACTICAL PATHOLOGY FOR GPs Contents: • Interpreting lipid results • Non-HDL cholesterol • Case studies • Key points Lipid and lipoprotein testing A JOINT INITIATIVE OF ©The Royal College of Pathologists of Australasia Author: David Sullivan MBBS FRACP FRCPA, Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Missenden Rd, Camperdown, NSW 2050. This issue of Common Sense Pathology is a joint initiative of Common Sense Pathology editor: Australian Doctor and the Royal College of Pathologists of Dr Steve Flecknoe-Brown Australasia. Email: [email protected] It is published by Cirrus Media Australian Doctor Tower 2, 475 Victoria Ave, Locked Bag 2999 Co-editor: Megan Howe Chatswood DC NSW 2067. Email: [email protected] Ph: (02) 8484 0888 Fax: (02) 8484 8000 E-mail: [email protected] Reviewer: Dr Tanya Grassi Website: www.australiandoctor.com.au Email: [email protected] (Inc. in NSW) ACN 000 146 921 ABN 47 000 146 921 ISSN 1039-7116 Sub-editor: Gill Canning Email: [email protected] © 2014 by the Royal College of Pathologists of Australasia www.rcpa.edu.au Graphic designer: Edison Bartolome CEO Dr Debra Graves Email: [email protected] Email: [email protected] While the views expressed are those of the authors, modified by Production coordinator: Eve Allen expert reviewers, they are not necessarily held by the College. Email: [email protected] For an electronic version of this and previous articles, you can visit www.australiandoctor.com.au or download an ebook version from www.australiandoctor.com.au/ebooks You can also visit the Royal College of Pathologists of Australasia’s web site at www.rcpa.edu.au Click on Library and Publications, then Common Sense Pathology. This publication is supported by financial assistance from the Australian Federal Department of Health. 2 Some clinical situations such as long- standing diabetes or chronic renal impairment ... warrant an aggressive approach to risk factor intervention irrespective of calculated risk. Introduction These results are unchanged compared to a previous Plasma lipid and lipoprotein levels affect the risk of test three months ago. Does her hypercholesterolaemia serious cardiovascular events and acute pancreatitis. warrant further evaluation or intervention? Guidelines concerning testing and utilisation of results The absolute risk of a cardiovascular event (CVD) have been provided by the National Vascular Disease within the next five years, according to NVDPA Prevention Alliance (NVPDA) (see Online resources). (or equivalent) guidelines, should be calculated The Royal College of Pathologists has embarked on a to assist decision making in primary prevention review of the reporting of lipid and lipoprotein results (primary prevention is for people in whom a clinical because more detailed interpretations may be required atherothrombotic coronary or cerebrovascular event has in particular circumstances. Lipid guidelines in other not yet occurred). countries have diverged recently.1,2 As a consequence, One would think that the clinical information and practitioners now require a greater level of sophistication laboratory results should be sufficient to calculate this in their understanding and use of these tests. patient’s absolute risk. On the other hand, some clinical situations, such as CASE 1 long-standing diabetes or chronic renal impairment, A 57-year-old woman, Mrs PS, returns for review of a pose a sufficiently high risk in themselves to warrant lipid profile, which revealed: an aggressive approach to risk factor intervention • Total cholesterol = 8.2mmol/L irrespective of calculated risk. This is because the risk • Triglycerides = 1.1mmol/L calculator only considers diabetes as a categorical risk • HDL cholesterol = 2.9mmol/L factor, while renal status is completely omitted. • The laboratory has calculated the LDL cholesterol = Similar logic applies in the case of patients in whom 4.8mmol/L. there is a likelihood of genetic predisposition, or those in She is asymptomatic and has never suffered serious whom risk factor levels are extreme. In the former group, illness, including cardiovascular disease. She is non- there is concern that the risk is likely to have prevailed diabetic and other results are free from any suggestion since birth. In the latter, the epidemiological studies on of alterations in renal, hepatic or thyroid function. which absolute risk calculations are based contain very She is slightly overweight (BMI = 27) but there are no few individuals with such severe risk factor profiles, and features to suggest diabetes. She is a non-smoker, and hence there is uncertainty concerning the calculation. her untreated blood pressure is 125/85. Her diet is Consequently the fact that this patient’s total cholesterol appropriate in terms of trans and saturated fat avoidance. exceeds 7.5mmol/L would be taken as evidence of very 3 Figure 1: Non-HDL cholesterol = total cholesterol minus HDL cholesterol In the case of Mrs PS, LDL cholesterol is 4.8 mmol/L and non-HDL cholesterol (estimated as total minus HDL cholesterol) is 5.3 mmol/L. Severe elevations of these fractions are a risk for future CVD, even in the presence of elevated HDL.4 On the other hand, this usually applies to higher levels than those seen in this patient, whose levels remain below the thresholds suggested by NVDPA guidelines (LDL cholesterol >5mmol/L, non-HDL cholesterol >5.5 mmol/L). So on this basis, diet could be further intensified by addition of plant sterol foods, which might reduce total cholesterol by approximately 10%. This could result in a total cholesterol close to the 7.5 mmol/L threshold, but LDL cholesterol and non-HDL cholesterol would have declined also, to approximately 4.4 mmol/L and 4.8 mmol/L respectively. The question of whether or not to resort to pharmacological therapy could rest on the choice between the confounded total cholesterol result or the more specific LDL or non–HDL cholesterol levels. The latter are more appropriate. high risk necessitating an aggressive approach to risk CASE 2 factor control. Mr TS is the husband of Mrs PS in case 1. He is a However, this approach is not above criticism. 59-year-old man who has had this lipid test at his wife’s Clinicians would recognise that the picture of elevated recommendation. She made this suggestion because she total cholesterol with well sustained HDL cholesterol is was aware that his mother died of a coronary event when common, particularly among postmenopausal women. she was 58 years old. Mr TS’s results include: In cases such as this, the use of the relevant total and • Total cholesterol = 8.7 mmol/L HDL cholesterol levels in an absolute risk calculator • Triglycerides = 1.4 mmol/L results in a surprising low level of risk which in many • HDL cholesterol = 1.1 mmol/L. • The laboratory has calculated the LDL cholesterol as instances is consistent with clinical experience. This 6.9 mmol/L. reflects the fact that total cholesterol is a confounded He is asymptomatic, has no history of serious illness measurement because it combines pro- and anti- and there is nothing to suggest renal, hepatic or thyroid atherosclerotic lipoprotein fractions. This patient dysfunction. He is non-diabetic and he does not smoke. does not have any risk due to low HDL cholesterol His weight is normal (BMI 24) and he shares the same levels. The question is the degree to which the pro- diet as his wife. There is a faint corneal arcus superiorly, atherosclerotic fractions (reflected by LDL cholesterol, but the rest of the physical examination is normal and his or the more simply calculated non-HDL cholesterol) blood pressure is 145/90. Does his hypercholesterolaemia are increased. warrant further investigation or intervention? A4 The family history raises the possibility of inherited risk of premature cardiovascular disease. As was the case for his wife, Mr TS’s total cholesterol of the possibility of underlying FH. The guidelines will exceeds 7.5 mmol/L, so a case can be made for regarding recommend the use of the Dutch Lipid Clinic Score, him as having a high absolute risk for cardiovascular which incorporates details concerning personal and disease. Unlike his wife, he does not have high levels of family history of hypercholesterolaemia and premature HDL cholesterol, so his LDL and non–HDL cholesterol cardiovascular disease (Table 1).4 The likelihood of FH levels are considerably higher (his non–HDL cholesterol is categorised as “definite”, “probable”, “possible” or is 7.6 mmol/L). “unlikely”. Mr TS’s Dutch Lipid Clinic Score is 6, which The family history raises the possibility of inherited suggests “probable” FH. risk of premature cardiovascular disease. One prevalent The use of total cholesterol level to flag the possible cause of inherited risk of premature cardiovascular p r e s e n c e o f F H p o s e s t h e s a m e p r o b l e m t h a t a r o s e i n disease is familial hypercholesterolaemia (FH). This case 1 concerning the calculation of absolute risk. The dominantly inherited disturbance of the function of LDL underlying question is the degree to which the pro- receptors leads to an approximate doubling of total and atherosclerotic fractions (reflected by LDL cholesterol, or LDL cholesterol levels, resulting in an acceleration of cardiovascular disease by 20 to 40 years. The prevalence Table 1: Dutch Lipid Clinic criteria for Familial of FH is approximately 1:500 to 1:200, which implies Hypercholesterolaemia that it affects nearly 40,000 Australians. Models of Care recommend family cascade screening of first- 8 points DNA Mutation, or LDL-C >8.5 degree relatives to detect undiagnosed cases and to offer 6 points Tendon xanthomas preventive therapy (see Online resources).