Overview.
Dyslipidaemia is the most modifiable cardiovascular risk factor, yet lipid assessment remains stuck in the LDL-C era for most patients. ApoB (apolipoprotein B) counts all atherogenic particles and is a better predictor of cardiovascular events than LDL-C — discordance between the two occurs in 20-30% of patients, particularly those with insulin resistance. Lp(a) is a genetic risk factor that should be tested once in every adult's lifetime. Modern lipid management targets ApoB, not just LDL-C.
Dyslipidaemia encompasses elevated LDL-C, elevated triglycerides, low HDL-C, and elevated atherogenic particle counts (ApoB). Atherosclerosis is driven by the number of ApoB-containing particles that cross the endothelium and deposit in arterial walls — not by the amount of cholesterol per particle. This is why ApoB (particle count) outperforms LDL-C (cholesterol content) for risk prediction.
Prevalence: ~38% of US adults have elevated LDL-C (≥130 mg/dL). ~25% have elevated triglycerides (≥150 mg/dL). Familial hypercholesterolaemia affects ~1 in 250 (heterozygous) — most undiagnosed. Elevated Lp(a) (>50 mg/dL) affects ~20% of the population and is entirely genetic.
Medical name: Hyperlipidaemia / Dyslipidaemia
Symptoms.
Early warnings
- LDL-C >160 mg/dL in young adults (<35 years) — suspect familial hypercholesterolaemia
- Triglycerides >500 mg/dL — pancreatitis risk; requires urgent treatment
- Family history of heart attack in first-degree relative before age 55 (men) or 65 (women)
- Discordance: LDL-C looks acceptable but ApoB is elevated (common in metabolic syndrome)
- Elevated Lp(a) — independent, genetic, and not modifiable by lifestyle
Classic symptoms
- Completely asymptomatic in the vast majority — this is the danger
- Xanthelasma (yellowish deposits around eyelids) — uncommon, suggests FH or chronic dyslipidaemia
- Tendon xanthomas (especially Achilles tendon) — pathognomonic for FH
- Corneal arcus before age 45 — suggests FH
- Symptoms only appear when atherosclerosis causes end-organ damage: angina, claudication, TIA/stroke
Progression
Atherogenesis begins in the teens with fatty streak formation. By the 40s-50s, plaques are established. Plaque rupture causes acute events (heart attack, stroke). The process is driven by cumulative ApoB exposure over time — 'area under the curve'. Lower ApoB earlier means less cumulative exposure and lower lifetime risk. This is why longevity physicians advocate for early, aggressive lipid management.
Risk factors.
- Family history of premature cardiovascular disease (<55 men, <65 women)
- Familial hypercholesterolaemia (suspect if LDL-C >190 mg/dL without secondary cause)
- Obesity and insulin resistance (atherogenic dyslipidaemia pattern: high TG, low HDL, small dense LDL)
- Type 2 diabetes (dyslipidaemia in 70-80% of patients)
- Hypothyroidism (elevated LDL-C; check TSH before starting statin)
- CKD (dyslipidaemia worsens with declining eGFR)
- Sedentary lifestyle
- High saturated fat and trans fat diet
- Smoking (lowers HDL, increases oxidised LDL)
- Medications: thiazides, beta-blockers, corticosteroids, retinoids
Lab interpretation.
Key biomarkers
- ApoB — Single best predictor of cardiovascular risk. >80 mg/dL = elevated. Each ApoB-containing particle carries exactly one ApoB molecule — it's a true particle count. (primary)
- LDL-C — Standard lipid marker. <100 mg/dL (general); <70 mg/dL (high risk); <55 mg/dL (very high risk). Discordant with ApoB in ~25% of patients. (primary)
- Lp(a) — Genetic; test once in lifetime. >50 mg/dL (>125 nmol/L) = elevated risk. Not modifiable by diet, exercise, or statins. Identifies patients needing earlier, more aggressive intervention. (primary)
- Triglycerides — <150 mg/dL (standard); <100 mg/dL (optimal). >500 mg/dL = pancreatitis risk. Elevated TG with low HDL = atherogenic dyslipidaemia of insulin resistance. (secondary)
- HDL-C — >40 mg/dL (men), >50 mg/dL (women). Low HDL is a risk marker but RAISING HDL pharmacologically has not reduced events in trials. (secondary)
Diagnostic criteria
- Standard lipid panel: total cholesterol, LDL-C, HDL-C, triglycerides (fasting preferred but non-fasting acceptable)
- ApoB: should be measured in all patients with metabolic syndrome, diabetes, elevated triglycerides, or discordant risk
- Lp(a): test once in every adult's lifetime (EAS/ESC recommendation); retest not needed (genetic, stable)
- 10-year ASCVD risk calculation (Pooled Cohort Equations) guides statin eligibility
- Coronary artery calcium (CAC) score: refines risk in borderline cases (5-20% 10-year risk)
Recommended panels
When & next steps.
When to test
- All adults ≥20 years (AHA/ACC recommend lipid panel every 4-6 years if normal)
- Annually if: on lipid-lowering therapy, diabetes, metabolic syndrome, family history of premature CVD
- Lp(a): once in lifetime for every adult (EAS/ESC); especially if family history of premature CVD
- ApoB: with any lipid panel when insulin resistance, diabetes, or metabolic syndrome is present
- Before starting or adjusting statin therapy
- When hypothyroidism is newly diagnosed (LDL normalises with thyroid treatment)
If suspected
- Full lipid panel (fasting preferred): LDL-C, HDL-C, triglycerides, total cholesterol
- Add ApoB (the single most informative lipid test)
- Add Lp(a) if never tested (one-time test)
- Calculate 10-year ASCVD risk (Pooled Cohort Equations)
- Rule out secondary causes: TSH (hypothyroidism), fasting glucose (diabetes), eGFR (CKD), liver panel (biliary obstruction)
If confirmed
- Lifestyle: Mediterranean diet, regular exercise, smoking cessation, weight loss if overweight
- Statins: first-line pharmacotherapy. High-intensity (atorvastatin 40-80mg, rosuvastatin 20-40mg) for high-risk patients.
- Ezetimibe: add if statin alone doesn't reach target (10-15% additional LDL reduction)
- PCSK9 inhibitors (evolocumab, alirocumab): for very high risk or statin-intolerant patients (50-60% LDL reduction)
- Target: ApoB <80 mg/dL (general) or <60 mg/dL (high risk); LDL-C <70 mg/dL (high risk) or <55 mg/dL (very high risk)
- Triglycerides >500 mg/dL: icosapent ethyl (Vascepa) or fibrate to reduce pancreatitis risk
- Elevated Lp(a): consider earlier, more aggressive ApoB lowering. Specific Lp(a)-lowering therapies (pelacarsen, olpasiran) are in Phase 3 trials.
FAQs.
Why is ApoB better than LDL-C?
LDL-C measures the amount of cholesterol carried by LDL particles. ApoB counts the actual number of atherogenic particles. In ~25% of people (especially with metabolic syndrome), LDL-C underestimates risk because particles are small and dense — carrying less cholesterol per particle but being MORE atherogenic. ApoB catches what LDL-C misses.
What is Lp(a) and should I test it?
Lp(a) is a genetic variant of LDL that is independently atherogenic and thrombogenic. It's determined by your genes, not your diet or exercise. Test once in your lifetime — if elevated (>50 mg/dL), it means your cardiovascular risk is higher than standard lipid panels suggest. This changes how aggressively other risk factors should be managed.
Do I really need a statin?
Statins are among the most evidence-based medications in medicine. For patients with established CVD, statins reduce heart attack and stroke risk by 25-35%. For primary prevention, the benefit depends on your 10-year ASCVD risk. At ≥7.5% risk, most guidelines recommend statin therapy. Discuss your individual risk-benefit with your doctor.
Can I lower cholesterol with diet alone?
Diet can reduce LDL-C by 10-15% (Mediterranean diet, reduced saturated fat, increased fibre, plant sterols). For mild dyslipidaemia with low ASCVD risk, this may be sufficient. For higher levels or higher risk, lifestyle plus medication is more effective. Genetics account for ~80% of LDL-C variation — diet is important but not always sufficient.