Clinical Evolving worldwide approaches to lipid management and implications for Australian general practice Tom Brett, Jan Radford, GUIDELINES on assessing and managing CVD accounted for 14% of Australia’s Nadeem Qureshi, Jing Pang, lipid disorders are constantly evolving as total burden of disease in 2015, with 27% Gerald F Watts new knowledge and treatments emerge of deaths attributed to CVD in 2017.8 to help health professionals and patients Raised blood lipids are just one of multiple Background decide the best course of disease modifiable risk factors for CVD, all of Guidelines on lipid disorders are management. which deserve appropriate consideration constantly evolving. General practitioners As the point of first contact with the for treatment.9 regularly face critical decisions about the health system, general practitioners The aim of this article is to review best treatment strategies for individual (GPs) are uniquely placed to see, assess international lipid management guidelines patients. Cardiovascular disease (CVD) and prevent disease in the early stages of focusing on recommendations of is common, with most morbidity and development.1 The care provided by GPs relevance to the primary care management mortality due to atherosclerosis. Raised low-density lipoprotein cholesterol can extend to families and communities of lipid disorders. (LDL-C) is the most atherogenic and involves contact across multiple component – lowering it lowers the generations, yielding opportunities for risk of future cardiovascular events. unique insights into the family histories Lipid disorders and the biopsychosocial dynamics Lipid disorders are increasingly Objective The aim of this article is to provide affecting individual patient risk and prevalent in the modern world, due an evidence-informed summary of disease presentations.2 primarily to poor diet and unhealthy, national guidelines and recent research Lipid disorders are commonly managed sedentary lifestyles; they can also be to help clinicians reduce the risk of in general practice but their severity secondary to other disease conditions atherosclerotic CVD and improve health and optimum treatment options may and treatments. Left untreated, lipid service delivery through improved lipid not always be appreciated or updated. disorders can progress to severe CVD management strategies. As patients progressively age, many and predispose to other conditions such Discussion develop multiple chronic conditions, as diabetes, non-alcoholic fatty liver Elevated plasma lipids, especially LDL-C, with multimorbidity the norm as people disease, chronic kidney disease (CKD) increase the likelihood of a CVD event progress beyond their middle years.3,4 and pancreatitis. over time. Knowledge of family and Younger people gain most if signs and Lipids are a component of plasma personal histories plus other risk factors for CVD should alert clinicians to the need for risk factors of cardiovascular disease (CVD) lipoproteins and can be subject to treatment. The greater the overall burden are detected early and preventive actions abnormalities in their metabolism due of combined risk factors, the greater the tailored to their overall risk are enacted.5 to genetic and environmental factors lifetime risk. This update provides new Lower-risk patients can be advised of diet resulting in elevated levels of cholesterol information that informs future approaches and other lifestyle strategies to maintain or triglycerides. Such abnormalities can for improving lipid management in their status quo while those with lipid occur at any stage of the continuum, Australian general practice. disorders often need additional strategies.6,7 from synthesis through processing and © The Royal Australian College of General Practitioners 2021 Reprinted from AJGP Vol. 50, No. 5, May 2021 297 Clinical Evolving worldwide approaches to lipid management and implications for Australian general practice clearance, resulting over time in increased familial hypercholesterolaemia affecting 20% of the population. A high risk of CVD.10 (HeFH) is an often-missed, autosomal level (>50 mg/dL) increases the risk of Cholesterol and triglyceride are the two dominant, hereditary disorder with high coronary and peripheral artery disease, major forms of lipid found in the body. phenotypic penetrance that is present calcific aortic stenosis and strokes. Testing Both are carried in lipoproteins in the in approximately 1:250 people in the is not listed on the Medical Benefits blood. Cholesterol is used mainly in cell general population.5,13,14 Dominant Schedule in Australia and is currently membrane formation as well as in bile forms of familial hypercholesterolaemia undertaken mostly by lipid specialists if acids and in steroid hormones. are also caused by APOB mutations and there is a family history of heart disease. Hypertriglyceridaemia has strong proprotein convertase subtilisin/kexin type Up to 30% of patients with HeFH environmental and genetic causes. High 9 (PCSK9) gain-of-function mutations have elevated lipoprotein(a).17 There is triglyceride levels can lead to increased causing markedly elevated low-density currently no specific treatment other than CVD risk, pancreatitis and hepatic lipoprotein cholesterol (LDL-C) levels lipoprotein(a) apheresis but RNA-based steatosis.11 Levels up to 1.7 mmol/L are related to defective LDL receptor activity in therapies that target the hepatic normal while >10 mmol/L increases risk liver cells, leading to premature CVD and over-production of apolipoprotein(a) and of pancreatitis and hepatic steatosis. It death if untreated.13–16 HeFH is recognised the formation of lipoprotein(a) particles is important that fasting blood levels are worldwide as a major public health are under investigation.17,18 taken, as levels are highest after meals. problem13,14 with 50% of first-degree A comparison of heritable lipid After a trial period of diet and exercise, it relatives harbouring the disease. disorders, including prevalence, mutations is recommended that a fasting triglyceride Homozygous familial and epidemiology, is presented in Table 1. test is repeated.11 hypercholesterolaemia (HoFH) is a Common causes are sugary foods, much more serious condition affecting inactivity, excess alcohol/binge drinking, 1:300,000 people. It results from the Cardiovascular disease risk smoking, certain conditions (eg diabetes, union of two HeFH carriers, with 25% of assessment kidney and thyroid disorders), their offspring inheriting the homozygous Approaches to assessing cardiovascular medications such as thiazide diuretics, form.13,14 Such children have markedly risk have moved from determining steroids, oestrogen and tamoxifen, and elevated LDL-C from birth and rarely individual risk factors to a more global inheritance. Obesity and the metabolic survive beyond teenage years unless perspective involving absolute risk syndrome are other complicating factors aggressively treated from infancy.5,13,14 calculations.6,19 Absolute risk determines that need to be considered.11,12 Elevated lipoprotein(a) is a dominantly the percentage probability of an individual Among the inherited inherited disorder leading to accumulation having a major cardiovascular event in hypercholesterolaemias, heterozygous in plasma of lipoprotein(a) particles17,18 the next 5–10 years. The target group are Table 1. Summary of inherited lipid disorders Heterozygous Type III familial Familial (Homozygous familial Familial combined Familial hypertri- dysbetalipo- chylomicronaemia Type hypercholesterolaemia) Lipoprotein(a) hyperlipidaemia glyceridaemia proteinaemia syndrome Inheritance Monogenic co-dominant Polygenic with variable penetrance and secondary causes, Monogenic, environmental factors recessive Prevalence 1 in 250 1 in 5 1 in 100 1 in 500 1 in 5000 13 per million (1 in 300,000) Effect on lipids Elevated LDL Elevated Elevated LDL-C, Elevated Elevated Elevated lipoprotein(a) triglyceride, ApoB VLDL intermediate chylomicrons density lipoprotein Clinical features Premature CAD CAD Premature CAD CAD, acute CAD Recurrent acute pancreatitis pancreatitis Gene variants LDLR, APOB, PCSK9 APOA Several gene APOE2/E2 Deficiency lipoprotein variants lipase or APOC-11 APO, apolipoprotein; CAD, coronary artery disease; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; LDLR, low-density lipoprotein receptor; PCSK9, proprotein convertase subtilisin/kexin type 9; VLDL, very low-density lipoprotein 298 Reprinted from AJGP Vol. 50, No. 5, May 2021 © The Royal Australian College of General Practitioners 2021 Evolving worldwide approaches to lipid management and implications for Australian general practice Clinical those with no known or overt CVD and intermediate risk where a high CAC score The risk of CVD is no longer seen as usually in the 45–74 years age range. re-classifies them at higher risk, whereas a an ‘LDL-hypothesis’ as the evidence Risk calculators were originally zero score reflects low disease probability.28 increasingly shows LDL-C values are developed using specific variables As well as elevated LDL-C, lipid causally related to CVD, and the lower based on Framingham data to estimate disorders (apolipoprotein B and the LDL-C level achieved, the better 10-year risk of developing coronary heart lipoprotein(a)) are attracting increasing the outcome.15,38,39 For each 1 mmol/L disease.20 The original cohort involved attention in overall risk estimation and reduction in LDL-C achieved, there patients to age 70 years, but other versions