Overview.
Dyslipidaemia affects approximately 86 million US adults and is a major modifiable risk factor for atherosclerotic cardiovascular disease (ASCVD) — the leading cause of death globally. The traditional focus on LDL-C is being replaced by ApoB (apolipoprotein B), which directly counts all atherogenic particles and better predicts cardiovascular risk. Additionally, Lp(a) — a genetically determined and underrecognised risk factor — should be measured at least once in every adult's life. Understanding which lipid markers matter most is key to appropriate risk stratification and treatment.
Dyslipidaemia encompasses a spectrum of abnormal lipid profiles: elevated LDL-C, elevated triglycerides, low HDL-C, elevated non-HDL-C, elevated ApoB, or elevated Lp(a). Each represents a different facet of atherogenic risk. LDL particles penetrate arterial walls, become oxidised, and trigger the inflammatory cascade that builds atherosclerotic plaque. ApoB is the structural protein on all atherogenic particles — counting ApoB particles captures total atherogenic burden more accurately than measuring cholesterol content (LDL-C) alone.
Prevalence: ~86 million US adults have elevated LDL-C (>130 mg/dL). Lp(a) is elevated (>50 mg/dL) in 20-25% of the global population — most people are never tested. Only 48% of adults who could benefit from statins are currently taking them. Triglyceride-rich lipoprotein excess (hypertriglyceridaemia) affects ~25% of adults.
Medical name: Dyslipidaemia / Hyperlipidaemia
Symptoms.
Early warnings
- Elevated LDL-C or total cholesterol on routine blood work
- Family history of early heart attack or stroke
- Corneal arcus (white arc around iris in adults <45)
- Xanthomas or xanthelasmas (cholesterol deposits in tendons or eyelids)
- Elevated fasting triglycerides (>150 mg/dL)
- Low HDL-C (<40 mg/dL men, <50 mg/dL women)
Classic symptoms
- Dyslipidaemia is entirely asymptomatic until a cardiovascular event occurs
- First presentation may be: myocardial infarction, ischaemic stroke, transient ischaemic attack, peripheral arterial disease
- Severe hypertriglyceridaemia (>500-1000 mg/dL): can cause acute pancreatitis — abdominal pain, nausea
- Familial hypercholesterolaemia: tendon xanthomas (Achilles tendon), xanthelasmas, premature ASCVD
Progression
Atherosclerosis begins silently in childhood and progresses over decades. LDL and ApoB particles accumulate in arterial intima, becoming oxidised and phagocytosed by macrophages, forming foam cells and fatty streaks. These progress to fibrous plaques. When plaques rupture, thrombosis causes acute MI or stroke. The lifetime duration of LDL exposure (cumulative burden) — not just current levels — determines ASCVD risk, which is why earlier treatment reduces lifetime events more than late treatment.
Risk factors.
- Family history of premature ASCVD (men <55, women <65) or familial hypercholesterolaemia (FH)
- Diet high in saturated fat, trans fats, and refined carbohydrates
- Physical inactivity
- Obesity and insulin resistance (drives atherogenic dyslipidaemia: high TG, low HDL, elevated ApoB)
- Type 2 diabetes and metabolic syndrome
- Hypothyroidism (secondary dyslipidaemia — elevated LDL-C and TG)
- MASLD/NAFLD (excess VLDL-TG production)
- CKD and nephrotic syndrome
- Genetic predisposition: familial hypercholesterolaemia (FH) — LDL-C ≥190 mg/dL
- High Lp(a): genetically determined (70-90% heritable), independent of lifestyle
Lab interpretation.
Key biomarkers
- LDL-C (LDL Cholesterol) — Primary guideline target. Goal: <100 mg/dL standard risk; <70 mg/dL high risk (clinical ASCVD or diabetes); <55 mg/dL very high risk (recurrent ASCVD events). Calculated or directly measured. Accuracy reduced by elevated triglycerides (Friedewald equation unreliable when TG >400 mg/dL). (primary)
- ApoB (Apolipoprotein B) — Counts all atherogenic particles: LDL, VLDL, IDL, Lp(a). Superior to LDL-C for risk prediction, especially in insulin resistance and hypertriglyceridaemia ('discordance' states). Target: <80 mg/dL standard risk; <70 mg/dL high risk; <60 mg/dL very high risk. Often underused — must be specifically requested. (primary)
- Non-HDL-C — Total cholesterol minus HDL-C. Captures all atherogenic cholesterol including VLDL-C. Goal = LDL-C goal + 30 mg/dL. Better than LDL-C when TG elevated. Calculated from standard lipid panel — no additional cost. (primary)
- Lp(a) (Lipoprotein little a) — Measure once per lifetime — 70-90% genetically determined; stable from early adulthood; not meaningfully altered by diet, exercise, or statins. High risk: >50 mg/dL (>125 nmol/L). Elevated in 20-25% of adults. Associated with 2-3x increased ASCVD risk and aortic valve stenosis. (primary)
- Triglycerides — Normal: <150 mg/dL. Borderline high: 150-199. High: 200-499. Very high (pancreatitis risk): ≥500 mg/dL. Driven by carbohydrate excess, alcohol, insulin resistance, genetic lipoprotein lipase deficiency. Requires fasting sample for accuracy. (primary)
- HDL-C (HDL Cholesterol) — Low HDL (<40 mg/dL men, <50 mg/dL women) = cardiovascular risk factor. HDL-C correlates inversely with ASCVD risk but attempts to raise HDL pharmacologically (niacin, CETP inhibitors) have not reduced ASCVD events — HDL function, not quantity, may matter more. (secondary)
Diagnostic criteria
- No single threshold defines 'dyslipidaemia' — risk is continuous and context-dependent (absolute ASCVD risk matters more than isolated lipid values)
- Familial hypercholesterolaemia (FH): LDL-C ≥190 mg/dL with Dutch Lipid Clinic or Simon Broome criteria (family history, tendon xanthomas, corneal arcus)
- AHA/ACC 2018: four statin benefit groups (see nextSteps)
- Hypertriglyceridaemia: TG 150-499 (moderate); ≥500 (severe, pancreatitis risk)
- Elevated Lp(a) (>50 mg/dL): reclassifies borderline-risk patients to higher risk
- ApoB ≥130 mg/dL with low LDL-C = atherogenic dyslipidaemia of insulin resistance
Recommended panels
When & next steps.
When to test
- All adults: fasting lipid panel every 5 years starting age 20 (AHA recommendation)
- More frequent testing (annually): established ASCVD, diabetes, FH, metabolic syndrome, CKD
- Lp(a): measure once in every adult's lifetime; earlier if family history of premature ASCVD or FH
- ApoB: request alongside lipid panel for anyone with insulin resistance, diabetes, metabolic syndrome, or TG >150 mg/dL
- Non-fasting lipid panel: acceptable for initial screening; TG accuracy requires fasting (8-12 hours)
- Children with family history of FH or premature ASCVD: screen at 9-11 years and 17-21 years
If suspected
- Fasting lipid panel: total cholesterol, LDL-C, HDL-C, triglycerides
- Request ApoB alongside lipid panel (especially if TG elevated or metabolic syndrome present)
- Lp(a): measure once; flag if >50 mg/dL (>125 nmol/L)
- Non-HDL-C: calculated from panel result (total cholesterol − HDL-C)
- TSH: exclude secondary dyslipidaemia from hypothyroidism
- Fasting glucose/HbA1c: metabolic syndrome and insulin resistance assessment
- CMP: liver enzymes (baseline before statin) and renal function
- Calculate 10-year ASCVD risk using ACC/AHA Pooled Cohort Equations (age 40-75)
If confirmed
- Lifestyle: Mediterranean or plant-based diet reduces LDL-C 10-15%; aerobic exercise raises HDL-C and lowers TG
- 4 AHA/ACC statin benefit groups: (1) clinical ASCVD; (2) LDL-C ≥190 mg/dL; (3) diabetes aged 40-75 with LDL-C 70-189; (4) 10-year ASCVD risk ≥7.5% with LDL-C 70-189
- Statin intensity: high-intensity (atorvastatin 40-80mg, rosuvastatin 20-40mg) for clinical ASCVD and very high risk; moderate-intensity for other groups
- If LDL-C goal not met on maximally tolerated statin: add ezetimibe (further 20-25% LDL-C reduction)
- PCSK9 inhibitors (evolocumab, alirocumab): for very high-risk patients not at goal on statin + ezetimibe; reduce LDL-C by 50-60%
- Severe hypertriglyceridaemia (TG ≥500): fibrates or icosapent ethyl (EPA) — omega-3 at 4g/day
- Lp(a) >50 mg/dL with high ASCVD risk: more aggressive LDL-C/ApoB targets; RNA-targeted therapies in clinical trials
- Repeat lipid panel 4-12 weeks after starting or changing therapy; annually when stable
FAQs.
My LDL-C is normal — why do I need ApoB?
LDL-C measures cholesterol content inside LDL particles, not the number of particles. In insulin resistance, patients often have many small, dense LDL particles (high particle count = high ApoB) despite normal LDL-C cholesterol content. This 'discordance' means LDL-C underestimates risk. ApoB directly counts atherogenic particles and is the better predictor. It's especially important if you have metabolic syndrome, elevated triglycerides, low HDL, or diabetes.
Why does Lp(a) only need to be measured once?
Lp(a) levels are 70-90% determined by your genetics (specifically the LPA gene). Unlike LDL-C, Lp(a) is minimally affected by diet, exercise, statins, or other lifestyle factors. Levels are stable throughout adult life after a developmental increase in childhood. Therefore, one measurement identifies your genetic risk burden — it does not need to be repeated unless transitioning to a kidney or liver condition that could affect levels.
What does it mean if I have elevated Lp(a)?
Elevated Lp(a) (>50 mg/dL or >125 nmol/L) means you carry a genetically elevated ASCVD risk that statins cannot lower. It affects approximately 20-25% of people and confers a 2-3x increased risk of heart attack and aortic valve stenosis. Management focuses on lowering all other modifiable risk factors more aggressively (LDL-C <70 mg/dL, ApoB <70 mg/dL, blood pressure control, no smoking). RNA-targeted therapies specifically reducing Lp(a) are in late-stage clinical trials and may become available in the next few years.
Are statins safe long-term?
Yes — statins are among the most studied medications in medical history. Large meta-analyses involving hundreds of thousands of patients confirm their safety profile. The most common side effect is muscle discomfort (myalgia) in 5-10% of patients — usually manageable with dose reduction or switching statins. Serious myopathy (rhabdomyolysis) is rare (<0.01%). The small increase in T2D risk with statins is outweighed by the cardiovascular benefit in almost all patients with elevated ASCVD risk.