Hypercholesterolaemia

CVD risk is related to LDL-C concentration, particularly when HDL-C is low. Start therapy based on calculated CVD risk: if high risk, statin therapy is recommended (≥10% 5-year risk on the Aus CVD Risk Calculator, per the 2023 guideline). If low/ moderate risk, the benefits of lowering cholesterol are smaller — consider drug therapy if lifestyle modification isn’t improving CVD risk on its own.

CVD risk may be over-estimated with a high HDL-C and under-estimated with high triglycerides — non-HDL-C better reflects CV risk in these cases.

Targets: LDL < 2.0mmol/L (general — the 2023 guideline is risk-based rather than target-based for primary prevention, so treat this as a rough guide, not a hard number), < 1.8 (secondary prevention — current target is tighter still, see below, tightening further to <1.4mmol/L and ≥50% reduction from baseline after ACS per the 2025 NHFA/CSANZ guideline). Non-HDL < 2.5mmol/L. Total cholesterol < 4.0mmol/L. HDL > 1.0mmol/L. Triglycerides < 2.0mmol/L.

Secondary causes of dyslipidaemia

Condition	Cholesterol	Triglycerides	HDL cholesterol
Diabetes mellitus		↑↑/↑	↓
Untreated hypothyroidism	↑↑
Alcohol excess		↑↑/↑	↑
Obesity		↑	↓
Chronic renal failure	↑	↑↑	↓
Nephrotic syndrome	↑↑	↑
Cholestasis	↑↑
Gout		↑
Pregnancy	↑/−	↑/↑↑
Anorexia nervosa	↑
Hypopituitarism	↑/↑↑↑	↑↑/↑	↓

Long-term drug treatment causes: anticonvulsants (HDL ↑/↑↑), androgens (HDL ↓/−−), atypical antipsychotics (cholesterol ↑/↑↑↑, triglycerides ↑/↑↑↑, HDL ↓), beta-blockers (triglycerides ↑), corticosteroids (cholesterol ↑, triglycerides ↑, HDL ↓), ciclosporin (cholesterol ↑, triglycerides ↑, HDL ↓), HIV/antiretroviral drugs (triglycerides ↑/↑↑), oral oestrogens (triglycerides ↑, HDL ↑), retinoids (triglycerides ↑↑/↑, HDL ↓).

Non-pharmacological modification

Dietary: reduce saturated/trans fats (deep-fried foods); replace saturated fats with mono/polyunsaturated fats (e.g. a handful of almonds/day); increase soluble fibre (rolled oats, beans, peas, apples); plant sterols (proactive butter, heart-active milk, avocados). Also: exercise, limit alcohol, lose weight.

Drug therapy

Statins are first-line, with a more aggressive approach in patients with established CVD or at very high CVD risk. If target isn’t achieved on maximum-dose statin, add ezetimibe. If statin is not tolerated, ezetimibe is a reasonable alternative.

Could consider adding a PCSK9 inhibitor instead of ezetimibe — evolocumab and alirocumab are PBS-funded for secondary prevention not at target on maximal statin + ezetimibe; the PBS criteria were expanded in December 2022 to a lower LDL-C threshold, widening access. A third option, inclisiran, is TGA-approved — a long-acting small interfering RNA (siRNA) rather than a monoclonal antibody, reducing LDL-C by roughly 50%. Neither ezetimibe nor PCSK9 inhibitors have been studied in primary prevention.

Bile acid resins, fibrates, and nicotinic acid improve lipid abnormalities but have only limited evidence of CVD risk reduction. If triglycerides remain > 4.0mmol/L despite max-dose statin, add a fibrate.

Statins

Low rates of serious adverse events with long-term use, and a significant CVD risk reduction. Should be started in patients with established CVD and those at high CVD risk. Atorvastatin and rosuvastatin are the high-potency statins.

Adverse effects:

• Myalgia — check CK only if it develops (no need to check routinely). Typically starts 4–6 weeks after starting the statin, affecting large muscle groups bilaterally with aching/stiffness. CK falls with stopping the statin.
• Rhabdomyolysis — 1–3 per 100,000 patients/year; severe myalgia and generalised muscle weakness. Necrotising autoimmune myopathy is rarer, also severe.
• Glucose metabolism/diabetes — a small increase in progression to diabetes, but the CVD risk benefit outweighs this.

Triglycerides

Elevated triglycerides increase CVD risk, usually alongside low HDL. Severely elevated triglycerides (> 10mmol/L) increase the risk of acute pancreatitis. Poorly controlled diabetes commonly contributes to elevated triglycerides.

Treatment:

• Triglycerides ≤ 4mmol/L → statin therapy.
• Triglycerides > 4.0mmol/L → combination statin and fenofibrate.
• Triglycerides > 10mmol/L → fenofibrate + 2–4g fish oil daily.