1. Definition and clinical relevance
- Absolute cardiovascular (CV) risk describes a person's probability of experiencing a cardiovascular event (myocardial infarction, stroke or cardiovascular death) over a defined period, typically the next 5 years.
- It integrates multiple risk factors rather than treating any single factor (such as cholesterol or blood pressure) in isolation.
- This matters because a person with only mildly abnormal individual values may still carry high absolute risk when factors combine, while a person with one strikingly abnormal value may have low overall risk.
The practical purpose is to direct the intensity of intervention: who should receive lipid-lowering therapy, blood pressure treatment and aggressive lifestyle change, and how low to drive lipid targets. Two broad clinical situations are distinguished:
- Primary prevention: no established cardiovascular disease. Treatment decisions are guided by calculated absolute risk plus lifestyle.
- Secondary prevention: established macrovascular disease (coronary artery disease, transient ischaemic attack or stroke, peripheral arterial disease). These patients are automatically high risk and warrant intensive lipid lowering irrespective of baseline cholesterol level.
- Statins are the cornerstone of pharmacological risk reduction.
- Their benefit is well established: lowering LDL-C reduces adverse cardiovascular outcomes across people with acute coronary syndrome (ACS) and other vascular disease.
2. Key values, thresholds and decision rules
- Lipid targets differ markedly between primary and secondary prevention.
- In primary prevention lifestyle is first line, with drugs added when risk or lipid levels justify them; in secondary prevention high-potency statin therapy is warranted regardless of the starting level.
| Setting | Target | Notes |
|---|---|---|
| Secondary prevention (established macrovascular disease) | Total cholesterol < 4.0 mmol/L and LDL-C < 2.0 mmol/L (ideally < 1.5 mmol/L) | Use high-dose, high-potency statin |
| Post-ACS LDL-C target | LDL-C < 1.4 mmol/L and at least a 50% reduction from baseline | Further benefit from treating to the lowest achievable level |
| LDL target after starting/intensifying therapy | LDL < 1.8 mmol/L within 1 to 3 months (in the stroke context) | Achieve with maximally tolerated statin +/- ezetimibe |
| Statin vs fibrate as first line for hypertriglyceridaemia | Statin first line if triglycerides < 8 mmol/L; fibrate first line if higher | Combination therapy is often required |
| Triglyceride threshold for drug therapy | TG persistently > 6.0 mmol/L despite lifestyle | Warrants drug therapy |
- LDL-C lowering magnitude: lowering LDL-C by approximately 1.0 mmol/L is associated with a substantial reduction in adverse cardiovascular outcomes.
- In ACS, high-dose versus no- or low-dose statins reduced the combined outcome of death, recurrent MI and stroke by 28% beyond 30 days.
Timing of reassessment: re-check total cholesterol and LDL-C approximately 4 to 6 weeks after starting or intensifying lipid-lowering therapy, and adjust the statin dose or add non-statin therapy accordingly.
Blood pressure targets (relevant when managing overall CV risk, especially with chronic kidney disease):
| Population | BP target |
|---|---|
| Chronic kidney disease (general) | 140/90 mmHg or lower |
| CKD with micro- or macroalbuminuria | 130/80 mmHg or lower |
3. Approach: presentation and differential
Absolute CV risk assessment is usually a proactive, asymptomatic activity in general practice rather than a response to symptoms.
History
- Established cardiovascular disease: prior MI, angina, coronary revascularisation, TIA or stroke, peripheral arterial disease. Any of these places the patient immediately in the secondary-prevention (high-risk) group.
- Modifiable risk factors: smoking, diet, physical activity, alcohol.
- Diabetes and glycaemic control; a long-term HbA1c target below 53 mmol/mol (< 7%) applies in patients with ischaemic stroke and diabetes.
- Family history of premature cardiovascular disease or familial hypercholesterolaemia.
- Medications that can worsen lipids, including high-dose thiazides, oestrogens and glucocorticoids, which can raise triglycerides in susceptible patients.
- Adherence and psychosocial factors: identify and manage depression, which limits adherence. The Heart Foundation has a depression screening tool for patients with coronary artery disease.
Examination
- Blood pressure (correctly measured, repeated).
- Body habitus and waist circumference.
- Signs of hyperlipidaemia: tendon and tuberous xanthomas (for example behind the elbow), lipid deposits in the hand creases (remnant hyperlipidaemia), and xanthelasma.
- Evidence of established vascular disease: peripheral pulses, carotid bruits.
Differential
- Familial hypercholesterolaemia: consider in markedly elevated LDL-C, premature vascular disease or characteristic physical signs. May require specialist agents.
- Secondary hyperlipidaemia: hypothyroidism, nephrotic syndrome, cholestasis, diabetes, alcohol excess and drug effects.
- Predominant hypertriglyceridaemia versus combined hyperlipidaemia versus predominant hypercholesterolaemia, as first-line drug choice differs (see Management).
4. Investigations
Bedside
- Blood pressure measurement.
- Body mass index and waist circumference.
- Smoking status.
Bloods
- Fasting lipid profile: total cholesterol, LDL-C, HDL-C and triglycerides. These values feed directly into risk calculation and target setting.
- Blood glucose / HbA1c to identify diabetes.
- Liver function tests (LFTs) before and during therapy, particularly with fibrates, which require LFT monitoring and predispose to gallstones and myopathy.
- Renal function and urine albumin-to-creatinine ratio (UACR): identifies chronic kidney disease and albuminuria, which tighten the blood pressure target (UACR > 3.5 mg/mmol in women, > 2.5 mg/mmol in men indicating micro/macroalbuminuria).
Imaging and other
- Investigations are directed by the clinical picture. In the context of stroke work-up, sleep apnoea assessment may be relevant (polysomnography is the gold standard for calculating the apnoea-hypopnoea index; overnight oximetry is less sensitive and will not differentiate central sleep apnoea).
- Cancer screening or body imaging is only pursued where symptoms, laboratory findings or multiterritory infarcts suggest malignancy.
5. Management
Management is stepwise: quantify absolute risk, optimise lifestyle, then add drug therapy targeted to the lipid abnormality and the prevention setting.
- Step 1: Lifestyle (all patients).
- Diet and lifestyle change is first line before drugs in primary prevention.
- Plant sterols have supporting evidence for lowering cholesterol.
- There is insufficient evidence to recommend vitamin E, garlic or lecithin.
- Reinforce lifestyle advice at every follow-up visit and build a long-term therapeutic relationship to maximise adherence.
Step 2: Choose drug therapy by lipid pattern.
| Predominant abnormality | First-line agent |
|---|---|
| Predominant hypercholesterolaemia | Statin (moderate dose in primary prevention; highest tolerated dose in secondary prevention) |
| Combined hyperlipidaemia | Statin |
| Predominant hypertriglyceridaemia (TG < 8 mmol/L) | Statin |
| Severe hypertriglyceridaemia (TG > 8 mmol/L) | Fibrate |
Step 3: Secondary prevention and ACS.
- Initiate or continue high-potency statin therapy (for example atorvastatin or rosuvastatin) as early as possible during an ACS admission, irrespective of baseline LDL-C.
- For patients already on lipid-lowering therapy before ACS, consider intensifying the existing regimen.
- Aim for LDL-C < 1.4 mmol/L with at least a 50% reduction from baseline, treating to the lowest achievable level.
- Reassess total cholesterol and LDL-C at 4 to 6 weeks and adjust. Additional non-statin therapies are frequently required to reach target.
Step 4: When statins are insufficient or not tolerated.
- Resistant LDL-C elevation: combine a statin with ezetimibe 10 mg daily (inhibits dietary and biliary cholesterol absorption), or combine a statin with a bile-acid resin such as cholestyramine 4 to 8 g orally.
- In ACS with suboptimal LDL-C despite statin therapy, or in statin intolerance, add ezetimibe.
- In ACS with suboptimal LDL-C despite maximally tolerated statin plus ezetimibe, add a PCSK9 inhibitor (a strong recommendation supported by high-quality evidence). Monoclonal antibody agents are also used for familial hypercholesterolaemia and muscle-related statin intolerance.
- Step 5: Statin intolerance.
- Use the maximally tolerated dose, or trial the alternative high-intensity statin (rosuvastatin).
- Muscle symptoms are common: in a large meta-analysis nearly half of participants reported at least one episode of muscle pain or weakness over a median of 4.3 years, corresponding to only a small (about 3%) relative increase attributable to statins, so most muscle symptoms are not caused by the drug.
- Step 6: Triglyceride management.
- For moderate to severe (isolated or predominant) triglyceride elevation, options include a fibrate (gemfibrozil 600 mg orally twice daily or fenofibrate 145 mg orally daily), and/or n-3 fish oil concentrate 6 g orally daily in divided doses up to a maximum of 15 g/day, adding nicotinic acid if the response is insufficient.
- Monitor LFTs; fibrates have a slow response and predispose to gallstones and myopathy.
- Note that statins are not effective at reducing triglycerides but may still be indicated to reduce overall cardiovascular risk.
- Step 7: Address other risk factors together.
- Combine lipid lowering with blood pressure control.
- In chronic and diabetic kidney disease, an ACE inhibitor or ARB is first line (do not combine both), targeting BP at or below 140/90 (or 130/80 with albuminuria).
- Optimise glycaemic control (HbA1c below 53 mmol/mol / 7% in ischaemic stroke with diabetes).
6. Australian-specific considerations
- Statins are available on the PBS and are among the most commonly prescribed medicines in Australian general practice; atorvastatin and rosuvastatin are the preferred high-potency agents.
- PCSK9 inhibitors are accessed via specialist services and have specific PBS eligibility criteria, generally reserved for familial hypercholesterolaemia or established disease with LDL persisting above target despite maximally tolerated statin and ezetimibe.
- Ezetimibe is PBS-listed and widely used as add-on or in statin intolerance.
Clinical pearls
- Absolute risk trumps single values: a mildly elevated cholesterol in a person with multiple risk factors may warrant statin therapy, while a markedly elevated cholesterol in isolation may not, until absolute risk is calculated.
- Secondary prevention is automatic high risk: any established macrovascular disease (coronary artery disease, TIA, stroke, peripheral arterial disease) places a patient in the high-risk category, and intensive statin therapy is warranted regardless of baseline LDL-C.
- Start statins early in ACS: high-potency statin therapy (atorvastatin or rosuvastatin) should be initiated as early as possible during an ACS admission, irrespective of the presenting cholesterol level.
- Reassess at 4 to 6 weeks: re-check total cholesterol and LDL-C after starting or intensifying therapy, and escalate to ezetimibe or a PCSK9 inhibitor if targets are not met.
- Most muscle symptoms on statins are not statin-caused: nearly half of patients report muscle pain or weakness, but only approximately 3% of this is attributable to the statin itself; trial the alternative high-intensity statin before abandoning the class.
- Fibrate, not statin, is first line for severe hypertriglyceridaemia: when triglycerides exceed 8 mmol/L, fibrates are the preferred initial agent; statins do not meaningfully reduce triglycerides.
- Fibrate monitoring is mandatory: LFTs must be checked before and during fibrate therapy, given the risk of myopathy, hepatotoxicity and gallstone formation.
- Do not overlook adherence: depression limits adherence to lipid-lowering and other preventive therapies; the Heart Foundation depression screening tool is a practical resource for patients with coronary artery disease.