• Raised total cholesterol is estimated to cause 4.4 million deaths/year globally (WHO 2023).
• Mean population TC has been declining in Western countries over recent decades (due to statin use and dietary shifts) but rising in East and Southeast Asia.

• The Population Health Survey 2020/22 (HK Department of Health) found that ~49.5% of persons aged 15–84 had TC ≥ 5.2 mmol/L — making hypercholesterolaemia the single most prevalent metabolic risk factor in Hong Kong.
• Prevalence of hypertriglyceridaemia (TG ≥ 1.7 mmol/L) is approximately 25–30% in HK adults.
• Familial hypercholesterolaemia (FH) — estimated prevalence of heterozygous FH is ~1 in 300 individuals ^[3][4]. HK has a dedicated FH registry at Queen Mary Hospital.
• Coronary heart disease remains the 3rd leading cause of death in HK (after cancer and pneumonia), and dyslipidaemia is its most important modifiable metabolic risk factor after smoking.

• Chinese heterozygous FH patients usually do not have a markedly elevated LDL — environmental factors (traditional lower-fat diet) modulate phenotype expression, but this is changing rapidly with Westernisation of diet ^[4][5].
• Chinese homozygous FH patients are severely affected — similar severity to Western counterparts ^[5].

A lipoprotein particle is essentially a micelle:

• Core: hydrophobic lipids — triglycerides (TG) and cholesterol esters (CE)
• Surface: amphipathic monolayer of phospholipids + free cholesterol + apolipoproteins (the functional "address labels" and enzyme cofactors)

Lipoprotein(a) is a subclass of LDL-C — it consists of an LDL particle covalently bound to apolipoprotein(a). Normal is < 30 mg/dL. It is largely genetically determined and not well-modified by statins ^[6].

This is a critical table to know — examiners commonly give you a patient with dyslipidaemia and ask you to identify/exclude secondary causes before diagnosing primary dyslipidaemia.

Clinical approach: always exclude secondary causes by ordering TFT, liver/renal function tests, glucose, and urine protein ^[2][8]

^[5][7][9]

This is a purely biochemically descriptive classification. It provides no information about aetiology. It does NOT affect treatment or management. ^[2]

However, it is still referenced in exam questions and provides a useful framework:

The clinical approach to dyslipidaemia ^[2][8]:

1. Identify the pattern: Is it ↑cholesterol, ↑TG, or both (mixed)?
2. Look for secondary causes: TFT, liver function, renal function, glucose, urine protein
3. Look for primary causes if clinically likely: Lipoprotein electrophoresis, family/genetic studies
4. Look for other CVD risk factors: DM, HT, obesity, smoking, pre-existing cardiovascular disease
5. Manage accordingly

A standard lipid profile consists of: Total cholesterol (TC), HDL cholesterol (HDL-C), Total triglycerides (TG), and LDL cholesterol (LDL-C) — usually estimated by the Friedewald equation ^[2]

Friedewald Equation: $LDL\text{-}C = TC - HDL\text{-}C - \frac{TG}{2.2} \quad (\text{in mmol/L})$

Limitations:

• Invalid when TG > 4.5 mmol/L (because the TG/2.2 assumes a fixed VLDL cholesterol:TG ratio which breaks down in hypertriglyceridaemia)
• Invalid in Type III hyperlipidaemia
• Must be fasting sample (non-fasting TG elevates VLDL → overestimates VLDL-C → underestimates LDL-C)

When Friedewald is invalid, direct LDL-C measurement or ultracentrifugation can be used.

^[2]

Fatty plaque formation starts from age 20 onwards, as a result of high circulating LDL cholesterol, genetic factors, and inflammation ^[6]

1. Endothelial dysfunction: Turbulent flow at branch points + risk factors (smoking, HTN, DM, dyslipidaemia) → endothelial injury → ↑permeability to LDL
2. LDL infiltration: LDL particles enter the subendothelial space (intima) and become trapped in the extracellular matrix
3. Oxidation of LDL: Trapped LDL undergoes oxidative modification by ROS → oxidised LDL (oxLDL) — this is the critical step that makes LDL "toxic"
4. Inflammatory response: OxLDL activates endothelial cells → expression of adhesion molecules (VCAM-1, ICAM-1) → recruitment of monocytes
5. Foam cell formation: Monocytes enter intima → differentiate into macrophages → engulf oxLDL via scavenger receptors (SR-A, CD36) — these are NOT downregulated by intracellular cholesterol (unlike LDLr) → unregulated uptake → foam cells (lipid-laden macrophages)
6. Fatty streak: Accumulation of foam cells = fatty streak (earliest visible lesion, present from age 20)
7. Plaque progression: Smooth muscle cell migration + proliferation + ECM deposition + lipid core formation → fibrous cap over a necrotic lipid core = mature atherosclerotic plaque
8. Plaque rupture: Thinning of fibrous cap (by MMPs from inflammatory cells) → plaque rupture → exposure of thrombogenic material → platelet adhesion + coagulation cascade → thrombus formation → acute coronary syndrome or stroke

Rupture of plaque results in coagulation and artery blockage ^[6]

• LDL is the dominant cholesterol carrier in plasma (~60–70% of total cholesterol)
• It is the lipoprotein that infiltrates the arterial wall
• Epidemiological, genetic (Mendelian randomisation), and interventional (statin trials) data all converge on LDL-C as a causal factor in ASCVD
• Every 1 mmol/L reduction in LDL-C reduces ASCVD events by ~22% (CTT meta-analysis)

• Relationship between TG and ASCVD is less direct than LDL
• Hypertriglyceridaemia is a marker of TG-rich remnant lipoproteins (chylomicron remnants, VLDL remnants/IDL) which are atherogenic
• Also associated with small dense LDL (more atherogenic) and low HDL (less protective)
• Very high TG ( > 10 mmol/L) → major risk of acute pancreatitis (TG-related, not ASCVD-related)

• HDL mediates reverse cholesterol transport (as described above)
• HDL also has anti-oxidant, anti-inflammatory, and anti-thrombotic properties
• Low HDL is an independent ASCVD risk factor
• However, pharmacologically raising HDL (e.g. with niacin, CETP inhibitors) has NOT consistently reduced ASCVD events → HDL is a marker of risk but raising it may not be the right therapeutic target

Metabolic syndrome: a cluster of metabolic disorders due to insulin resistance. The likely cause is central obesity — adipocytes release large amounts of FFA and adipokines → insulin resistance. ^[10]

Manifestations include ^[10]:

• Hypertension
• Dyslipidaemia (↑LDL-C, ↑TG, ↓HDL-C)
• Type 2 DM
• Polycystic ovarian syndrome (PCOS)
• Non-alcoholic fatty liver disease (NAFLD)

Obesity, diabetes, and hyperlipidaemia are the three most common comorbidities of hypertension — they come like a bundle deal ^[11]

Formal ASCVD risk assessment is indicated if ≥ 40 years old + ≥ 1 ASCVD risk factor (HK Consensus 2016) ^[8]

Not needed if: overt ASCVD, or DM, or ≥ 1 major risk factor (e.g. moderate/severe HT, severely elevated lipid) — these patients automatically meet the threshold for treatment ^[8]

Coronary heart disease risk equivalents (automatically high-risk) ^[8]:

• Clinical coronary heart disease
• Symptomatic carotid artery disease
• Peripheral arterial disease
• Abdominal aortic aneurysm
• Diabetes mellitus

Risk assessment tools ^[8]:

• Chinese Multiprovincial Cohort Study (CMCS) (2005)
• Joint British Societies (JBS2) risk charts (2005)
• Framingham risk assessment (2008)
• ACC/AHA ASCVD risk calculator (2013)
• Joint British Societies (JBS3) risk calculator (2014)
• SCORE/SCORE2 risk charts (ESC 2016/2021)

These tools generally consider: age, gender, smoking, systolic BP, TC/HDL-C ratio, family history, ± BMI ^[8].

Importance: guide necessity and goal of lipid-lowering therapy ^[8].

Dyslipidaemia itself is almost always asymptomatic — it is a silent condition discovered on blood testing. However, its consequences and complications can produce symptoms:

Controversial — some recommend lipid profile in ALL individuals vs only in high-risk groups ^[8]

The rationale for universal paediatric screening is to identify FH early (before cumulative LDL burden causes irreversible ASCVD). Current approach in most guidelines:

• Screen children age 2+ with a family history of premature ASCVD or known FH
• Consider cascade screening of first-degree relatives when an index case of FH is identified

Indication: patient with existing CVD, DM, or family history/clinical evidence of familial hyperlipidaemia (Department of Health 2013) ^[8]

In practice:

• All adults ≥ 40 years should have a fasting lipid profile as part of CVD risk assessment
• Younger adults should be screened if they have risk factors (DM, HT, obesity, FHx of premature ASCVD, clinical signs of FH)

This is the pattern where LDL-C is elevated but triglycerides are within normal range. Think of it as a problem with cholesterol clearance or overproduction without a major triglyceride component.

Elevated TG reflects either overproduction of TG-rich lipoproteins (chylomicrons, VLDL) or impaired TG hydrolysis (LPL pathway dysfunction).

Both cholesterol and TG are elevated. This can be primary or secondary.

Note from the Teaching Clinic slides: FCH has no distinctive clinical features — you cannot diagnose it by looking at the patient. Diagnosis requires demonstration of multiple lipid phenotypes within the same family. ^[7]

Low HDL ( < 1.03 mmol/L in men, < 1.29 mmol/L in women) is often part of the "metabolic syndrome" picture rather than an isolated finding.

Think FH first.

Key questions:

• Family history of premature ASCVD (Male < 55y, Female < 65y) ^[8]
• Physical signs: tendon xanthomas (Achilles, knuckles, elbows), corneal arcus, xanthelasma ^[5]
• LDL-C level: ≥ 4.9 mmol/L without FHx, ≥ 6.2 mmol/L with FHx before treatment; patient aged < 20y with LDL-C > 6.2 mmol/L is definite for FH ^[5][8]

But also exclude:

• Hypothyroidism — check TFT! The 28-year-old teaching clinic case normalised completely with thyroxine ^[12]
• Nephrotic syndrome — check urine protein
• Cholestasis — check LFT

Screen for secondary causes of hyperlipidaemia before initiating treatment, particularly hypothyroidism which elevates LDL through downregulation of LDL receptors. ^[12]

Think severe hypertriglyceridaemia (TG > 10 mmol/L) causing acute pancreatitis.

Differential for the severe hypertriglyceridaemia itself:

• Poorly controlled DM (the 22-year-old diabetic presenting with abdominal pain and lipaemic serum ^[12])
• Familial chylomicronaemia (Type I/V)
• Alcohol excess
• Drugs (oestrogen, retinoids, protease inhibitors)
• Often multifactorial — genetic predisposition + an acquired "second hit"

Metabolic syndrome = cluster of metabolic disorders linked by insulin resistance and associated with accelerated atherosclerosis ^[13]

The dyslipidaemia pattern is typically: ↑TG, ↓HDL, small dense LDL (even if LDL-C number may appear "normal", the particles are more atherogenic).

Diagnosis of metabolic syndrome requires presence of 3 or more of ^[13]:

• Glucose intolerance / Type 2 DM
• Hypertension
• Hypertriglyceridaemia
• Low HDL cholesterol
• Central obesity

Renal transplant recipients are prone to multiple cardiovascular risk factors including diabetes, hypertension, and hyperlipidaemia — related to immunosuppressive drugs (ciclosporin, tacrolimus, corticosteroids) and the underlying renal disease ^[14]. This is an important secondary cause in the post-transplant setting.

In PBC (primary biliary cholangitis), cholesterol may be markedly elevated. However: Increased cholesterol will not increase atherosclerosis risk if the rise is due to HDL / Lipoprotein X ^[15]. Lp-X is an abnormal lipoprotein formed in cholestasis that is NOT atherogenic — so don't reflexively start a statin in PBC.

A standard lipid profile consists of: Total cholesterol (TC), HDL cholesterol (HDL-C), Total triglycerides (TG), and LDL cholesterol (LDL-C) — usually estimated by the Friedewald equation ^[2][9]

$LDL\text{-}C = TC - HDL\text{-}C - \frac{TG}{2.2} \quad \text{(mmol/L)}$

Why it works: VLDL-C is roughly one-fifth of TG (in mmol/L, one-2.2th). So: TC = LDL-C + HDL-C + VLDL-C; rearrange to solve for LDL-C.

When it fails:

• Invalid when TG > 4.5 mmol/L — the assumed VLDL-C:TG ratio breaks down ^[9]
• Invalid in Type III dyslipidaemia (abnormal IDL)
• Must be a fasting sample (non-fasting chylomicrons inflate the TG denominator → underestimates LDL-C)

When Friedewald fails, use: direct LDL-C measurement, or Martin-Hopkins equation (more accurate at moderate TG), or ultracentrifugation (gold standard) ^[2][9].

• Fasting for ≥ 9–12 hours is recommended for standard lipid profile — chylomicrons clear within ~12 hours post-prandially
• Non-fasting lipid profiles are increasingly accepted for screening (ESC 2019, ACC/AHA) — TC, HDL-C, and non-HDL-C are minimally affected by fasting state; only TG and calculated LDL-C are meaningfully affected
• If non-fasting TG > 5 mmol/L → repeat fasting
• Post-prandial sample is a common secondary cause of apparently elevated TG — always confirm with a proper fasting sample ^[9]

Lipoprotein electrophoresis: different lipoproteins have different charge-to-mass ratios ^[2]

• Separates lipoproteins into bands: α (HDL), pre-β (VLDL), β (LDL), chylomicrons (origin)
• Key finding: broad beta band = Type III dysbetalipoproteinaemia (IDL/remnant accumulation due to ApoE2/E2)
• Helps classify the Fredrickson phenotype

• Each VLDL and LDL particle contains exactly one ApoB-100 molecule
• ApoB is therefore a direct measure of the total number of atherogenic particles — arguably better than LDL-C (which measures cholesterol content per particle, not particle number)
• Useful when LDL-C is discordant with clinical risk (e.g. patient has "normal" LDL-C but small dense LDL with high particle number)

Lipoprotein(a) is a subclass of LDL-C — normal is < 30 mg/dL ^[6]

• Genetically determined (> 90% heritable), largely unmodifiable by lifestyle or statins
• Independent ASCVD risk factor
• Measure at least once in a lifetime in all patients being assessed for ASCVD risk (ESC 2019)
• Particularly important in patients with premature ASCVD or FH-like phenotype without identifiable LDLr/PCSK9/ApoB mutation

Genetic testing for FH: presence of causal mutation — mutation identification rate can be as high as 86% ^[5]

• Indicated when clinical criteria suggest FH (see Dutch Criteria below)
• Tests for mutations in: LDLR (most common), PCSK9 (gain-of-function), APOB (familial defective ApoB)
• Also tests for AR causes: LDLRAP1, ABCG5/8 (sitosterolaemia), CYP7A1
• Depth of genetic sequencing affects the prevalence of disease detected in a population ^[3] — more comprehensive panels detect more cases

Dutch criteria is the most important scoring algorithm for FH ^[3]

• When an index case of FH is identified, first-degree relatives should be screened with a fasting lipid profile ± genetic testing
• Diagnosis of FCH requires demonstration of multiple phenotypes in family ^[7] — you cannot diagnose FCH from one individual's lipid profile alone

Dutch Lipid Clinic Network criteria: > 8 = definite FH, 6–8 = probable FH, 3–5 = possible FH ^[3][8]

Interpretation:

• > 8 points: Definite FH
• 6–8 points: Probable FH
• 3–5 points: Possible FH
• < 3 points: Unlikely FH

Only the highest scoring criterion from each category is used (i.e., you do not add multiple items within the same category).

Simon Broome diagnostic criteria: 1+2 or 3 = definite FH; 1+4 or 1+5 = probable FH ^[8]

Interpretation:

• Definite FH: Criterion 1 + 2 (xanthomas), OR Criterion 3 (genetic confirmation)
• Probable FH: Criterion 1 + 4 (FHx of MI), OR Criterion 1 + 5 (FHx of raised TC)

Patient aged < 20 years old with LDL-C > 6.2 mmol/L is definite for FH ^[5]

Grossly elevated LDL-C: generally ≥ 4.9 mmol/L (without FHx) or ≥ 6.2 mmol/L (with FHx) before treatment ^[8]

These thresholds serve as "red flags" even without scoring criteria — any young patient with LDL-C of this magnitude warrants FH workup.

The treatment target (how low to drive LDL-C) depends on the patient's total ASCVD risk, not just the LDL-C number. A person with LDL-C of 4.0 mmol/L and diabetes + hypertension + smoking needs much more aggressive treatment than someone with LDL-C of 5.0 mmol/L who is otherwise healthy.

Formal ASCVD risk assessment is indicated if ≥ 40 years old + ≥ 1 ASCVD risk factor (HK Consensus 2016) ^[8]

Not needed if: overt ASCVD, or DM, or ≥ 1 major risk factor (e.g. moderate/severe HT, severely elevated lipids) — these patients automatically meet the threshold for treatment ^[8]

For ACS secondary prevention, LDL target is 1.4–1.8 mmol/L with aggressive statin therapy ^[20]

Diabetes is a coronary heart disease risk equivalent — meaning a diabetic patient without established ASCVD is treated as if they already have ASCVD ^[8][21]

Tools generally consider: age, gender, smoking, systolic BP, TC/HDL-C ratio, family history, ± BMI ^[8]

• CT-based measurement of calcified plaque in coronary arteries
• Heterozygous FH: early ( < 23y) coronary artery calcification is a useful marker ^[8]
• Useful for reclassifying intermediate-risk patients (CAC = 0 is very reassuring; high CAC may upgrade risk)
• NOT a lipid test per se, but directly assesses the consequence of dyslipidaemia on the coronary vasculature

• Ultrasound-based; measures subclinical atherosclerosis
• Less commonly used now than CAC score (less robust evidence for risk reclassification)

Ultracentrifugation: different lipoproteins have different densities — gold standard for lipoprotein quantification ^[2]

• Separates lipoproteins by density using a high-speed centrifuge
• Allows direct measurement of VLDL-C, LDL-C (not estimated), HDL-C
• Also useful when TG is very high and Friedewald equation is invalid
• Used to prepare samples for accurate amylase/lipase measurement in lipaemic serum ^[12]

Management of dyslipidaemia rests on three pillars, applied in a stepwise fashion:

1. Treat the underlying cause (if secondary dyslipidaemia)
2. Lifestyle modification (universal, for ALL patients)
3. Pharmacological therapy (guided by ASCVD risk category and LDL-C target)

The overarching goal is to reduce ASCVD events — not simply to "normalise" a lab number. Every treatment decision should be framed by the patient's total cardiovascular risk.

Supervised exercise programme recommended as part of CV risk factor modification ^[23]

• Stop smoking — smoking ↓HDL-C by ~5–10%, ↑oxidation of LDL, ↑thrombogenicity ^[20]
• Weight loss — 5–10% body weight reduction significantly improves all lipid parameters; weight loss of 5–7% is already sufficient for non-fibrosis MASLD patients, 10% for fibrosis patients ^[22]
• Moderate alcohol intake — small amounts may ↑HDL, but excess ↑TG; advise moderation or abstinence
• Coffee → beneficial for fatty liver ^[22]

Lifestyle modification works — the hardest part is always going to be ADHERENCE ^[24]

Secondary prevention: always indicated in those with existing ASCVD ^[8]

Primary prevention: controversial — consider when 10-year risk > 20% despite non-drug measures for ≥ 3 months (DH 2013); ALL if high risk vs not meeting target after 6 months if low/moderate risk (HK 2016) ^[8]

Statin therapy with a documented history of coronary, cerebral, or peripheral vascular disease, unless the patient's status is end-of-life or established moderate or severe frailty ^[25]

Aggressive lipid lowering with statin — LDL 1.4–1.8 for secondary prevention of ACS ^[20]

5 ways to control risk factors in the secondary prevention of ACS ^[20]:

1. Stop smoking
2. Optimal glycaemic control in diabetic patients → HbA1c < 7%
3. Blood pressure control in hypertensive patients
4. Aggressive lipid lowering with statin — LDL 1.4–1.8
5. Diet and weight control

Refer patients to Cardiac Rehabilitation programmes, educate them ^[20]

Manage risk factors: Lipids — ↓LDL to < 1.8 mmol/L with lifestyle and drug ^[29]

DM: aim HbA1c < 7%, consider SGLT2i or GLP-1RA ^[29]

CKD 3–5 patients aged > 50 years have high risk of coronary deaths or incident MI → 10 per 1000 patient years, regardless of cholesterol level ^[26]

Treatment recommended with statin only, or statin + ezetimibe. Basically every patient in this group is started on a statin. ^[26]

If patient already on dialysis, no recommendation to START a statin ^[26]

Therapeutic objectives for CKD include: control lipid and CV risk ^[26].

Stepwise approach ^[8]:

1. Risk factor control (lifestyle, treat comorbidities)
2. Intensive lipid-lowering therapy:
   • Statin: 1st line, prefer atorvastatin or rosuvastatin
   • 2nd line: majority will not achieve LDL-C target → add ezetimibe or PCSK9 inhibitor
   • 3rd line: consider investigational Tx — LDL apheresis, liver transplantation, partial ileal bypass surgery
3. Cascade family screening — first-degree relatives

This is a medical urgency because of pancreatitis risk.

• Immediate: NPO (nil by mouth if acute pancreatitis), IV fluids
• Fibrate (fenofibrate preferred) — start immediately
• Strict dietary fat restriction ( < 15% of calories from fat)
• Treat underlying cause: DM control, stop alcohol, stop offending drugs
• Insulin infusion — can rapidly ↓TG by activating LPL (insulin-dependent enzyme); used in acute setting
• Fish oil in pharmacological doses (adjunct) ^[8]
• Dietary restriction is the cornerstone for familial chylomicronaemia ^[8]

CV risk factor modification: statin — regardless of lipid level for overall CVS protection ^[23]

This is an important principle — in patients with established atherosclerotic disease (PAD, carotid disease, etc.), statin is indicated for its pleiotropic effects even if LDL-C appears "normal."

IHD accounts for 70% of deaths in diabetes mellitus ^[30] — and dyslipidaemia is one of the key drivers

Risk of MI is 3–5× higher in DM patients ^[30]

Complications of MI (i.e. complications of a complication):

• Post-infarct angina — residual stenosis or re-occlusion ^[32]
• Mechanical complications — free wall rupture, VSD, papillary muscle rupture → acute MR
• Arrhythmias — VF/VT (most common cause of early death), heart blocks
• Pump failure — cardiogenic shock
• Pericarditis — Dressler syndrome (autoimmune, 2–10 weeks post-MI)

Fatty plaque streaks in coronary arteries begin from age 20 onwards ^[6] — atherosclerosis is a lifelong process that begins decades before clinical events

Risk of stroke is 2.5× higher in DM patients ^[30] — dyslipidaemia + DM + HT together accelerate cerebrovascular atherosclerosis synergistically

Hypercholesterolaemia is a risk factor that only increases the risk of arterial thrombosis, but NOT venous thrombosis ^[33]

This is an important distinction: ischaemic stroke from atherosclerosis is an arterial thrombotic event. Dyslipidaemia does NOT increase the risk of cerebral venous thrombosis, DVT, or PE.

Conservative management of PAD includes statin — regardless of lipid level — for overall CVS protection ^[23]

The rationale is that PAD is a systemic atherosclerotic marker — if a patient has PAD, they almost certainly have coronary and cerebrovascular atherosclerosis too. The statin is for its pleiotropic effects on ALL atherosclerotic beds, not just to "lower cholesterol."

• Atherosclerosis weakens the aortic wall → aneurysmal dilatation (typically infrarenal)
• AAA is a coronary heart disease risk equivalent — patients are treated as very high ASCVD risk ^[8]
• Risk of rupture increases exponentially with aneurysm diameter ( > 5.5 cm → indication for repair)

• Atherosclerosis of the renal arteries → renal artery stenosis → renovascular hypertension and ischaemic nephropathy
• Not uncommon — renal artery stenosis is often found in patients with other stenoses of either the carotids or coronary arteries ^[26]
• Can be unilateral (→ hypertension from RAAS activation) or bilateral (→ renal failure)

1. TG-rich lipoproteins (chylomicrons, VLDL) circulate in the pancreatic microcirculation
2. Pancreatic lipase (normally secreted into the duodenum) has some activity within the pancreatic capillary bed
3. It hydrolyses TG from the lipoproteins → releases toxic free fatty acids (FFAs) locally
4. FFAs are cytotoxic → direct acinar cell injury and capillary endothelial damage → local inflammation → acute pancreatitis
5. FFAs also activate trypsinogen → autodigestion cascade

• Severe epigastric pain radiating to the back
• Nausea, vomiting
• Lipaemic (milky/turbid) serum — visible on inspection
• Amylase may be falsely low — TG interferes with the amylase assay → measure lipase on ultracentrifuged sample ^[12]
• Eruptive xanthomas may be present on examination
• Hepatosplenomegaly (from reticuloendothelial TG-rich lipoprotein engorgement)

• Hypertriglyceridaemia-induced pancreatitis can be severe (10–15% mortality in severe cases)
• Recurrent if TG not controlled