Lucan · Conditions

Dyslipidaemia

Australian guidance: Heart Foundation Cholesterol Guidelines + eTG Cardiovascular

1. Definition and epidemiology

Dyslipidaemia refers to abnormal concentrations of lipids or lipoproteins in the blood, encompassing elevated low-density lipoprotein cholesterol (LDL-C), elevated triglycerides, reduced high-density lipoprotein cholesterol (HDL-C), or combinations thereof. In Australia, over one-third of adults have abnormal lipid levels, making it among the most prevalent modifiable cardiovascular risk factors nationally. Familial hypercholesterolaemia alone affects more than 100,000 Australians and accelerates atherosclerotic cardiovascular disease (ASCVD) by 20 to 40 years compared with the general population, yet it remains substantially underdiagnosed and undertreated.

2. Pathophysiology

The central mechanism linking dyslipidaemia to ASCVD involves LDL-C entry into the subendothelial space of arterial walls, where oxidative modification triggers monocyte recruitment and foam cell formation, the hallmark of the early atheromatous plaque (Robbins Ch 11). Elevated LDL-C provides a concentration gradient that drives this process; because LDL receptors on hepatocytes normally clear circulating LDL-C, defects in receptor number or function (as in familial hypercholesterolaemia due to LDL receptor, APOB, or PCSK9 gain-of-function mutations) dramatically amplify risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of LDL receptors after endosomal recycling; pharmacological PCSK9 inhibition therefore increases receptor density and accelerates LDL-C clearance. Very low-density lipoprotein cholesterol (VLDL-C) and its remnants contribute to the non-HDL-C pool, which is atherogenic particularly when triglycerides are elevated. HDL-C mediates reverse cholesterol transport, removing excess cholesterol from peripheral tissues back to the liver; reduced HDL-C independently correlates with increased ASCVD risk. Severely elevated triglycerides (above 10 mmol/L) additionally predispose to acute pancreatitis via chylomicron-induced pancreatic duct obstruction and lipase activation.

3. Clinical presentation and diagnostic criteria

Most patients with dyslipidaemia are asymptomatic and are identified only through screening or incidental blood tests. Clinical signs, when present, suggest severe or longstanding disease: tendon xanthomata (particularly over the Achilles tendon and extensor tendons of the hands) are nearly pathognomonic for familial hypercholesterolaemia, while xanthelasma palpebrarum and corneal arcus may also appear. Symptomatic presentation reflects end-organ complications including angina, acute coronary syndrome, stroke, transient ischaemic attack, or peripheral arterial disease. Familial hypercholesterolaemia should be suspected when LDL-C is severely elevated, tendon xanthomata are present, or there is a strong family history of premature cardiovascular events (males younger than 55 years, females younger than 60 years). Diagnosis is clinical and biochemical, supported by the Dutch Lipid Clinic Network Score when familial hypercholesterolaemia is suspected, after excluding secondary causes.

4. Investigations and AU-specific cutoffs

A full lipid assessment comprises total cholesterol, HDL-C, and triglycerides measured directly; LDL-C is calculated (Friedewald equation or directly measured when triglycerides exceed 4.5 mmol/L); non-HDL-C is derived by subtracting HDL-C from total cholesterol and captures all atherogenic particles including VLDL remnants. Only total cholesterol and HDL-C are required to calculate ASCVD risk using the Australian cardiovascular disease risk (Aus CVD Risk) calculator, but the full panel guides treatment targets. Lipid-modifying therapy is warranted if total cholesterol exceeds 7.5 mmol/L irrespective of calculated ASCVD risk. AU-specific lipid targets stratified by ASCVD risk tier are as follows:

• Established ASCVD or very high risk: LDL-C at least 50% reduction from baseline AND less than 1.4 mmol/L; non-HDL-C less than 2.2 mmol/L; triglycerides less than 1.7 mmol/L.
• High ASCVD risk: LDL-C at least 50% reduction from baseline AND less than 1.8 mmol/L; non-HDL-C less than 2.6 mmol/L.
• Intermediate risk: LDL-C less than 2.6 mmol/L; non-HDL-C less than 3.4 mmol/L.
• Low risk: LDL-C less than 3.0 mmol/L; non-HDL-C less than 3.8 mmol/L.

Secondary causes must be excluded: hypothyroidism, nephrotic syndrome, cholestasis, type 2 diabetes (particularly if poorly controlled), chronic kidney disease, obesity, alcohol excess, and drugs including thiazide diuretics, beta-blockers, oral oestrogens, some antipsychotics, and antiretroviral agents. Recheck lipid concentrations 6 weeks after initiating or adjusting therapy. Coronary artery calcium scoring should not be used to assess treatment response.

5. Management

All patients receive lifestyle counselling at diagnosis and continuing after drug initiation. For elevated LDL-C, dietary interventions include reducing saturated and trans fat intake, replacing saturated fats with mono- and polyunsaturated fats, increasing soluble fibre, and reducing alcohol. Plant sterol enriched foods can reduce LDL-C by 10 to 15%. For elevated triglycerides, restricting added sugars, refined carbohydrates, alcohol, and total fat is effective; weight loss and increased physical activity also raise HDL-C.

Drug therapy initiation is guided by ASCVD risk category per the Aus CVD Risk Calculator, as detailed in the Heart Foundation Australian Guideline for assessing and managing cardiovascular disease risk. Pharmacotherapy is prescribed for high-risk patients (estimated 5-year CVD risk 10% or more) and considered at intermediate risk (5 to less than 10%); it is not routinely recommended at low risk (less than 5%). Patients known to be at clinically determined high risk irrespective of calculator output include those with familial hypercholesterolaemia, moderate-to-severe chronic kidney disease, and established ASCVD.

For triglycerides above 4 mmol/L, fish oil (4 g omega-3 fatty acids daily) is added to statin therapy; fenofibrate 145 mg daily (eGFR above 60 mL/min) is added if triglycerides remain elevated. Severely elevated triglycerides (above 10 mmol/L) require fenofibrate plus fish oil simultaneously to prevent pancreatitis. Gemfibrozil should not be combined with statins due to significantly increased myositis risk.

6. Pharmacology and AU PBS notes

Statins are first-line therapy for LDL-C reduction and ASCVD risk reduction in all risk tiers where drug therapy is indicated. High-intensity statins for secondary prevention or high primary-prevention risk include atorvastatin 40 to 80 mg orally daily, rosuvastatin 20 to 40 mg orally daily (CrCl 30 mL/min or more), or simvastatin 80 mg orally daily (the last carries a higher myopathy risk than equivalent alternatives). Lower starting doses are titrated upward to achieve targets.

Ezetimibe 10 mg orally daily is added when the LDL-C target is not met after 6 weeks on maximally tolerated statin; it further reduces LDL-C by 20 to 25%. Ezetimibe is PBS listed and reduces cardiovascular events in secondary prevention when combined with statin therapy.

PCSK9 inhibitors (alirocumab, evolocumab) are monoclonal antibodies reducing LDL-C by 50 to 60%. Alirocumab 75 to 150 mg subcutaneously every 2 weeks (or 300 mg every 4 weeks) and evolocumab 140 mg subcutaneously every 2 weeks (or 420 mg every 4 weeks) are PBS subsidised for nonfamilial hypercholesterolaemia when LDL-C remains above 1.8 to 2.6 mmol/L (depending on indication) despite maximally tolerated statin plus ezetimibe, and when initiated by a specialist. Inclisiran (small interfering RNA targeting PCSK9 hepatic production) is PBS listed as an alternative to PCSK9 inhibitors in patients who have not achieved LDL-C targets on statin plus ezetimibe.

Fenofibrate 145 mg daily (eGFR above 60 mL/min) or 48 to 96 mg daily (eGFR 20 to 60 mL/min) targets hypertriglyceridaemia and is also indicated to slow diabetic retinopathy progression irrespective of lipid levels. Fish oil (omega-3 fatty acids 4 g daily) is used for moderate-to-severe hypertriglyceridaemia; note a dose-dependent increased risk of atrial fibrillation.

7. Complications and monitoring

Major vascular complications include coronary artery disease, acute coronary syndrome, ischaemic stroke, peripheral arterial disease, and aortic stenosis secondary to atherosclerotic plaque. Severe hypertriglyceridaemia (above 10 mmol/L) independently causes acute pancreatitis. Familial hypercholesterolaemia causes premature ASCVD, with events occurring 20 to 40 years earlier than expected; cascade screening of first-degree relatives is essential once a proband is identified.

Monitoring after initiating statin therapy: recheck fasting lipids and alanine aminotransferase (ALT) at 6 weeks, then every 12 months once targets are stable. Creatine kinase (CK) should only be measured if muscle symptoms develop. ALT elevation of 0.5 to 2% occurs with statins but clinically significant hepatotoxicity is rare; routine monitoring is not required. Statin-associated muscle symptoms affect a small minority; most patients who cease due to symptoms can tolerate rechallenge. CK exceeding 5 times the upper limit of normal with symptoms warrants statin cessation; rhabdomyolysis (CK at least 10 times the upper limit of normal with myoglobinuria) contraindicates statin rechallenge. Statin therapy causes a small increase in new-onset diabetes, primarily in patients with pre-existing prediabetes risk factors; this risk is outweighed by cardiovascular benefit and does not alter the prescribing decision. Patients with familial hypercholesterolaemia require review every 2 years when at possible-risk status and should ideally be referred to a lipid specialist.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.