Dyslipidaemia
Summary
Dyslipidaemia refers to abnormalities in plasma lipid levels, most commonly elevated LDL-cholesterol ("bad cholesterol"), low HDL-cholesterol ("good cholesterol"), or elevated triglycerides. It is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD). Primary causes include genetic disorders (e.g., familial hypercholesterolaemia) and lifestyle factors (diet, obesity). Secondary causes include hypothyroidism, diabetes, nephrotic syndrome, and medications. Treatment involves lifestyle modification and lipid-lowering therapy, primarily statins. QRISK assessment guides primary prevention decisions.
Key Facts
- LDL-C: "Bad cholesterol" - drives atherosclerosis
- HDL-C: "Good cholesterol" - protective
- Triglycerides: >10 mmol/L = Pancreatitis risk
- Familial Hypercholesterolaemia (FH): TC >7.5, Tendon xanthomas, Early MI
- Treatment: Statins (HMG-CoA reductase inhibitors) are first-line
- QRISK: 10-year CVD risk ≥10% = Statin indicated (primary prevention)
Clinical Pearls
"LDL is the Culprit": Lowering LDL-C reduces cardiovascular events. The lower the better for high-risk patients.
"Suspect FH if TC >7.5": Total cholesterol >7.5 or LDL-C >4.9 with family history of early CVD should prompt FH screening.
"Triglycerides >10 = Pancreatitis": Very high triglycerides cause acute pancreatitis. Requires urgent treatment.
"Statins Save Lives": Statins reduce myocardial infarction and stroke by 25-35% in high-risk patients.
Prevalence
- 50% of adults have elevated cholesterol
- FH affects 1 in 250 (underdiagnosed)
Risk Factors for Elevated LDL
- High saturated fat diet
- Obesity
- Sedentary lifestyle
- Genetic factors (FH)
- Secondary causes
Causes
| Primary | Secondary |
|---|---|
| Familial hypercholesterolaemia | Hypothyroidism |
| Familial combined hyperlipidaemia | Diabetes mellitus |
| Familial hypertriglyceridaemia | Nephrotic syndrome |
| Polygenic hypercholesterolaemia | Chronic kidney disease |
| Cholestasis | |
| Medications (steroids, thiazides, beta-blockers) | |
| Alcohol (triglycerides) |
Lipid Classes
| Lipoprotein | Main Lipid | Function |
|---|---|---|
| LDL | Cholesterol | Delivers cholesterol to tissues; atherogenic |
| HDL | Cholesterol | Reverse cholesterol transport; protective |
| VLDL | Triglycerides | Delivers TG to tissues |
| Chylomicrons | Triglycerides | Dietary fat transport |
Atherosclerosis Mechanism
- LDL particles enter arterial intima
- Oxidation of LDL
- Uptake by macrophages → Foam cells
- Fatty streak formation
- Smooth muscle proliferation, fibrosis
- Atherosclerotic plaque
- Plaque rupture → Thrombosis → MI/Stroke
Familial Hypercholesterolaemia (FH)
- Autosomal dominant
- LDL receptor mutations (most common)
- Very high LDL from birth
- Early atherosclerosis and MI
Usually Asymptomatic
Clinical Signs (Severe/FH)
| Sign | Description |
|---|---|
| Tendon xanthomas | Cholesterol deposits in tendons (Achilles, extensor tendons of hands) |
| Xanthelasma | Yellow plaques around eyelids |
| Corneal arcus | White ring around iris (<45 years = suspicious for FH) |
| Eruptive xanthomas | Yellow papules (very high TG) |
| Lipaemia retinalis | Pale retinal vessels (severe hypertriglyceridaemia) |
Complications at Presentation
General
- Often normal
- Obesity, central adiposity
Specific Signs
- Tendon xanthomas (palpate Achilles)
- Xanthelasma
- Corneal arcus (especially if <45 years)
- Signs of CVD (absent pulses, carotid bruits)
Lipid Profile (Fasting Not Essential)
| Test | Desirable Level |
|---|---|
| Total cholesterol | <5.0 mmol/L |
| LDL-cholesterol | <3.0 mmol/L (lower targets for high risk) |
| HDL-cholesterol | >1.0 mmol/L (men), >.2 mmol/L (women) |
| Triglycerides | <1.7 mmol/L |
| Non-HDL-C | <4.0 mmol/L (TC minus HDL; includes all atherogenic lipoproteins) |
FH Criteria (Simon Broome / Dutch)
- LDL-C >4.9 or TC >7.5
- Family history of early MI (<60 1st degree, <50 2nd degree)
- Tendon xanthomas
- Genetic testing
Secondary Causes Workup
| Test | Excludes |
|---|---|
| Thyroid function (TSH) | Hypothyroidism |
| Fasting glucose/HbA1c | Diabetes |
| U&E, Urine protein | Nephrotic syndrome |
| LFTs | Cholestasis |
CVD Risk Assessment
- QRISK3: 10-year cardiovascular risk calculator
- Inform shared decision-making
Treatment Approach
┌──────────────────────────────────────────────────────────┐
│ DYSLIPIDAEMIA MANAGEMENT │
├──────────────────────────────────────────────────────────┤
│ │
│ STEP 1: LIFESTYLE MODIFICATION (All patients) │
│ • Diet: Reduce saturated fat, increase fibre, fruits │
│ • Exercise: 150 min/week moderate intensity │
│ • Weight loss if overweight │
│ • Smoking cessation │
│ • Reduce alcohol (especially for TG) │
│ │
│ STEP 2: ASSESS CVD RISK │
│ • QRISK3 for primary prevention │
│ • Consider statin if QRISK ≥10% │
│ │
│ STEP 3: STATIN THERAPY │
│ PRIMARY PREVENTION (QRISK ≥10%): │
│ • Atorvastatin 20mg │
│ │
│ SECONDARY PREVENTION (Established CVD): │
│ • Atorvastatin 80mg │
│ │
│ STEP 4: ADD-ON THERAPY (If targets not met) │
│ • Ezetimibe 10mg (intestinal absorption inhibitor) │
│ • PCSK9 inhibitors (Evolocumab, Alirocumab) for FH/ │
│ very high risk │
│ • Bempedoic acid (if statin intolerant) │
│ │
│ SEVERE HYPERTRIGLYCERIDAEMIA (TG >10): │
│ • Fibrates (Fenofibrate) │
│ • Omega-3 fatty acids │
│ • Urgent if pancreatitis risk │
│ │
└──────────────────────────────────────────────────────────┘
Statin Side Effects
- Myalgia (5-10%; true myopathy rare)
- Elevated LFTs (check before and at 3 months)
- Diabetes risk (slight increase)
- Rhabdomyolysis (very rare)
Monitoring
- Re-check lipids at 3 months
- Target: ≥40% reduction in non-HDL-C
- Annual review
Of Dyslipidaemia
- Myocardial infarction
- Stroke (ischaemic)
- Peripheral arterial disease
- Acute pancreatitis (severe hypertriglyceridaemia)
Of Treatment
- Statin myopathy
- Statin-associated muscle symptoms (SAMS)
- Hepatotoxicity (rare)
With Treatment
- Statins reduce CVD events by 25-35%
- FH patients have excellent outcomes if treated early
Without Treatment
- FH: 50% of untreated men have CHD by age 50
- High LDL accelerates atherosclerosis
Key Guidelines
- NICE CG181: Cardiovascular Disease Risk Assessment
- NICE NG238: Cardiovascular Disease Prevention
- ESC/EAS Guidelines on Dyslipidaemias
Key Evidence
Primary Prevention
- CTT meta-analysis: Statins reduce major CV events
Secondary Prevention
- Landmark trials: 4S, HPS, PROVE-IT
PCSK9 Inhibitors
- FOURIER, ODYSSEY: Further LDL reduction reduces events
What is Dyslipidaemia?
Dyslipidaemia means abnormal levels of fats (lipids) in your blood. The main concern is high "bad cholesterol" (LDL), which can build up in your arteries and cause heart attacks or strokes.
What Causes It?
- Diet high in saturated fat
- Being overweight
- Not exercising enough
- Genetic conditions (familial hypercholesterolaemia)
- Other conditions like thyroid problems or diabetes
How Do I Know If I Have It?
High cholesterol usually has no symptoms. It's picked up on a blood test. Your doctor may calculate your heart disease risk using a tool called QRISK.
How is it Treated?
- Lifestyle changes: Healthy diet, exercise, weight loss, stop smoking
- Statins: Tablets that lower cholesterol (very effective and safe for most people)
- Other medications: If statins aren't enough or don't suit you
Are Statins Safe?
Yes, for most people. Some get muscle aches, but serious side effects are rare. The benefits for your heart far outweigh the risks.
Primary Guidelines
- NICE Guideline [CG181]. Cardiovascular Disease: Risk Assessment and Reduction. 2014, updated 2023.
- ESC/EAS Guidelines. Management of Dyslipidaemias. Eur Heart J. 2019.
Key Studies
- CTT Collaboration. Efficacy and safety of LDL-lowering therapy. Lancet. 2010;376(9753):1670-1681. PMID: 21067804