High Cholesterol
Written by Dr Tashi Zhaxiduojie FRACP PhD · Updated June 2025
Elevated LDL cholesterol is a major, modifiable cause of heart attack and stroke. Specialist management — particularly for familial hypercholesterolaemia, statin intolerance, and advanced lipid-lowering therapy — significantly reduces cardiovascular risk.
Overview
What is high cholesterol?
Cholesterol is a waxy lipid essential for cell membrane integrity and hormone synthesis. Dyslipidaemia — abnormal blood lipid levels — is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD), which remains the leading cause of death in Australia.
The primary target for cardiovascular risk reduction is LDL cholesterol (LDL-C). LDL-C deposits in arterial walls, forming atherosclerotic plaques that narrow and destabilise coronary and cerebral arteries, leading to heart attacks and strokes.
Lipid reference ranges (Australian guidelines)
| Lipid | Desirable | High-risk target |
|---|---|---|
| Total cholesterol | <5.0 mmol/L | <4.0 mmol/L |
| LDL-C | <3.0 mmol/L | <1.8 mmol/L (ASCVD) / <1.4 mmol/L (very high risk) |
| HDL-C (men) | >1.0 mmol/L | >1.0 mmol/L |
| HDL-C (women) | >1.2 mmol/L | >1.2 mmol/L |
| Triglycerides | <1.7 mmol/L | <1.7 mmol/L |
Causes & Why It's Hidden
High cholesterol is almost always asymptomatic. Most patients are diagnosed incidentally on blood testing. Xanthelasma (eyelid deposits) or tendon xanthomata may be seen in severe familial hypercholesterolaemia.
Causes of high LDL-C
- Familial hypercholesterolaemia (FH): Autosomal dominant. Heterozygous FH affects 1 in 250 Australians. LDL-C typically 5–10 mmol/L. Massively elevated atherosclerotic risk from birth.
- Polygenic hypercholesterolaemia: Most common cause. Multiple common genetic variants + lifestyle factors.
- Secondary causes: Hypothyroidism, nephrotic syndrome, diabetes, medications (thiazides, glucocorticoids, immunosuppressants).
Elevated Lipoprotein(a)
Lp(a) is a genetically inherited lipoprotein independent of LDL-C. Elevated in ~20% of the population, it promotes atherosclerosis and thrombosis and is not adequately lowered by standard lipid therapies. Lp(a) should be measured once in all adults. Specialist management is required for Lp(a) above 50 mg/dL (125 nmol/L).
Investigations
- Fasting lipid profile: LDL-C, HDL-C, total cholesterol, triglycerides. Fasting for 12 hours gives the most accurate triglyceride level.
- Lipoprotein(a): Should be measured at least once. Genetic — does not change significantly with diet or most medications.
- ApoB: Reflects total atherogenic particle number. More predictive than LDL-C in patients with metabolic syndrome or hypertriglyceridaemia.
- Non-HDL cholesterol: Total cholesterol minus HDL. Includes all atherogenic lipoproteins. Useful when triglycerides >4.0 mmol/L.
- Dutch Lipid Clinic Network (DLCN) score: Validated scoring tool for familial hypercholesterolaemia diagnosis using LDL-C level, clinical features, family history and genetic testing.
- Coronary calcium score: CT-based measurement of calcified coronary plaque burden. Reclassifies intermediate-risk patients and guides intensity of treatment.
Treatment Options
Lifestyle modification
- Mediterranean or portfolio diet (plant sterols, soluble fibre, nuts, plant protein) reduces LDL-C by up to 30%
- Weight loss — every 1 kg reduces triglycerides and improves HDL-C
- Aerobic exercise 150 min/week
- Alcohol reduction — lowers triglycerides
Medication options
- Statins (atorvastatin, rosuvastatin): First-line. Reduce LDL-C by 40–60%. Proven mortality benefit in primary and secondary prevention.
- Ezetimibe: Add-on to statin. Reduces LDL-C by a further 15–25%. IMPROVE-IT trial: further CV event reduction.
- Bempedoic acid: Oral, non-statin. Reduces LDL-C ~20%. CLEAR Outcomes trial: reduces CV events. PBS-listed for statin-intolerant patients.
- PCSK9 inhibitors — evolocumab (Repatha), inclisiran (Leqvio): Reduce LDL-C by 50–60% on top of statin therapy. Injectable. PBS-subsidised in Australia for eligible ASCVD or FH patients. Specialist initiation required.
PCSK9 Inhibitor PBS Assessment
Dr Tashi offers a dedicated PCSK9i PBS eligibility assessment service for GPs and their patients. Check eligibility →
Statin Intolerance
Statin intolerance — defined as the inability to tolerate two or more statins due to adverse effects — affects up to 10% of treated patients. Myalgia (muscle aching) is the most common complaint.
Management of statin intolerance
- Confirm true intolerance — exclude other causes (vitamin D deficiency, hypothyroidism, drug interactions)
- Trial a different statin at lower dose (rosuvastatin or pravastatin — lower myalgia risk)
- Alternate-day or twice-weekly dosing
- Ezetimibe monotherapy
- Bempedoic acid (not metabolised in muscle — avoids myopathy)
- PCSK9 inhibitors
- Inclisiran (siRNA — twice-yearly injection)
Familial Hypercholesterolaemia
FH is a genetic disorder causing severely elevated LDL-C from birth. Despite affecting 1 in 250 people, it remains significantly underdiagnosed and undertreated in Australia.
- LDL-C typically ≥5.0 mmol/L (HeFH) or ≥13 mmol/L (HoFH)
- Risk of premature MI 10–20 times higher than general population if untreated
- Cascade screening of first-degree relatives is essential — 50% chance of FH in each child
- Treatment requires high-intensity statins plus ezetimibe; most require PCSK9 inhibitors to achieve LDL targets
- Genetic testing aids diagnosis and family screening
See a specialist cardiologist in Perth
HeartWise Cardiology — GP referral required.