Dyslipidaemia

• Dyslipidaemia means abnormal blood lipids, especially low-density lipoprotein cholesterol (LDL-C), which is a causal driver of atherosclerotic cardiovascular disease (ASCVD).
• It is usually silent: plaques build over decades, while very high LDL-C or high triglycerides can produce physical signs (xanthomas, xanthelasma, arcus) or pancreatitis.
• Risk is estimated first (SCORE2, the pooled cohort equations, QRISK3), then risk category sets the LDL-C target, from under 116 mg/dL in low risk to under 40 mg/dL in extreme risk.
• Statins are first-line. Ezetimibe, bempedoic acid, the PCSK9 inhibitors evolocumab and alirocumab, and inclisiran are added when targets are not met.
• Lifestyle, treatment of secondary causes and familial cascade screening prevent disease rather than just lower numbers.

By the end of this page you should be able to:

1. Describe how LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) and apolipoprotein B (apoB) relate, and which are causal for ASCVD.
2. Classify primary and secondary dyslipidaemias and list the conditions and drugs that cause secondary disease.
3. Recognise xanthomas, xanthelasma, arcus cornealis and pancreatitis, and interpret a lipid profile.
4. Estimate 10-year cardiovascular risk with SCORE2, the pooled cohort equations and QRISK3, and choose the appropriate LDL-C target.
5. Apply the ESC/EAS 2019/2025 and AHA/ACC 2018 treatment thresholds, including the primary and secondary prevention approaches.
6. Plan lifestyle and drug therapy: statin intensity and dose, monitoring, adverse effects, and add-on drugs.
7. Manage special groups (children, pregnancy, older adults, chronic kidney disease, diabetes), familial screening, prognosis and low-resource care.

Dyslipidaemia is primary (genetic) or secondary (acquired). Most patients have a mixture: a polygenic tendency made worse by weight gain, diet, alcohol or another disease. Heart failure can follow long-standing dyslipidaemia when ASCVD is untreated; dyslipidaemia itself rarely causes symptoms.

Dietary and liver-made lipids are carried in particles called lipoproteins, each made of cholesterol and triglycerides inside a shell of apolipoproteins. The relevant particles are:

• LDL (low-density lipoprotein). LDL delivers cholesterol to tissues. It contains one copy of apolipoprotein B-100 (apoB), so the apoB concentration counts atherogenic particles. LDL-C (the cholesterol mass within them) is the main treatment target.
• HDL (high-density lipoprotein). HDL removes cholesterol from peripheral tissues. Low HDL-C marks metabolic and inflammatory disease, but drugs that raise HDL-C have not reduced events.
• Triglycerides (TG). Carried mainly by very-low-density lipoprotein (VLDL) and remnants. Hypertriglyceridaemia marks a higher burden of triglyceride-rich lipoproteins.
• Remnant cholesterol is the cholesterol within VLDL, intermediate-density lipoprotein (IDL) and chylomicron remnants.
• Lipoprotein(a) (Lp(a)). An LDL-like particle with a second protein, apolipoprotein(a), attached to its apoB. Its level is largely genetic and promotes atherosclerosis, aortic valve stenosis and events in men and women across ethnic groups.
• Apolipoprotein B (apoB). The structural protein of every atherogenic particle (LDL, VLDL, IDL, Lp(a)). It measures particle number, which becomes clinically useful when LDL-C and particle number disagree, as in diabetes, obesity and metabolic syndrome.

Atherosclerosis is driven by atherogenic particles entering the arterial wall, which is proportional to LDL-C. Meta-analyses and Mendelian randomisation show a log-linear relation between LDL-C and risk, and between LDL-C and plaque progression in established disease. ^[1]

LDL can be measured directly; many laboratories still calculate it:

Friedewald formula: LDL-C (mg/dL) = total cholesterol − HDL-C − (TG ÷ 5). It assumes a fixed cholesterol:TG ratio in VLDL and is invalid when fasting TG > 400 mg/dL (4.5 mmol/L), so direct measurement is used then. Non-fasting samples are acceptable in practice and have equal prognostic value. Conversion: LDL-C (mg/dL) = mmol/L × 38.67. ^[1]

ASCVD is the leading cause of death worldwide, and dyslipidaemia is causal. Hypercholesterolaemia is common and underdiagnosed: a German survey (DEGS1) reported dyslipidaemia in about 64.5% of men and 65.7% of women. ^[1] Only about 30% of high- and very-high-risk secondary prevention patients reach guideline LDL-C targets, and only about 27% of primary prevention patients managed by office cardiologists do. ^[1] The burden is rising in low- and middle-income countries. ^[1]

Deaths attributable to high LDL-C: the world rate fell about 15% from 2010 to 2021, while the total number rose 17%. ^[2] Average total cholesterol in the US fell from 197 mg/dL (2007–2008) to 189 mg/dL (2017–2018), with LDL-C ≥ 130 mg/dL in about 25.5%. ^[2]

Primary dyslipidaemia results from genetic defects in lipid synthesis, transport or clearance. Published cases and reviews divide it as follows. ^[9][4]

Diagnosis of suspected FH uses the Dutch Lipid Clinic Network score, Simon Broome or MEDPED (Make Early Diagnosis to Prevent Early Death) criteria, integrating LDL-C level, clinical signs and family history. Genetic testing (LDLR, APOB, PCSK9) is not required for the clinical diagnosis but confirms it, helps counselling and can stratify risk; mutations in LDLR underlie more than 90% of cases. ^[9] Cascade screening of relatives is the most cost-effective way to find more cases. ^[9]

Polygenic hypercholesterolaemia (common, smaller LDL elevations without a single mutation) accounts for most patients seen in clinic and behaves similarly to mild HeFH.

A secondary cause should be sought in every adult with new dyslipidaemia, because treatment of the cause may correct it. Common secondary causes: ^[8]

Drug-induced dyslipidaemia is common and under-recognised. Selected drug effects from the 2024 KSoLA consensus: ^[8]

When a high-risk drug is being started, measure lipids before therapy and again after a few weeks, and reassess whether it can be stopped or substituted. ^[8]

Dyslipidaemia is asymptomatic most of the time. Symptoms arise from complications.

History. Family history of premature ASCVD (men <55, women <60), early myocardial infarction, strokes in relatives, known familial dyslipidaemia, diabetes, obesity, alcohol. In HeFH 50% of men and 30% of women develop CAD by ages 50–60 without treatment. ^[9] Ask about drugs, alcohol, thyroid symptoms and renal disease.

Physical signs of cholesterol deposition.

• Xanthomas: cholesterol-laden nodules. Tendon xanthomas on the Achilles and extensor tendons are pathognomonic for FH. Planar xanthomas and tuberoeruptive xanthomas occur in severe hyperlipidaemia.
• Xanthelasma: yellow plaques on the eyelids. Common, but not specific for FH.
• Arcus cornealis: lipid ring at the corneal periphery. Suggests FH when present before age 45; an arcus in an older adult is often physiological.
• Lipaemia retinalis when TG are very high.

Pancreatitis. Severe hypertriglyceridaemia (>500 mg/dL, 5.6 mmol/L) gradually increases the risk of pancreatitis. ^[1][8] Patients with fasting TG >500 mg/dL require urgent attention to prevent pancreatitis. ^[1]

ASCVD manifestations. Angina, myocardial infarction, stroke, peripheral arterial disease, aortic aneurysm or stenosis can be the first clue. ECG interpretation is part of the work-up for chest pain.

Establish whether the patient has:

• primary vs secondary dyslipidaemia (screen for the causes above);
• isolated hypercholesterolaemia vs mixed vs hypertriglyceridaemia;
• inherited disorder vs polygenic/metabolic;
• ASCVD already present (secondary prevention).

The main mimics are poorly controlled diabetes in mixed hyperlipidaemia, nephrotic syndrome in marked hypercholesterolaemia and thyroid disease. When an LDL-C is >190 mg/dL (4.9 mmol/L) in an adult, FH is likely. ^[9]

A full lipid profile is total cholesterol, HDL-C, TG, with calculated LDL-C and non-HDL-C. ^[10] Hypertriglyceridaemia is diagnosed when fasting TG exceed 150 mg/dL (1.7 mmol/L). ^[1] Non-fasting samples are adequate. Repeat fasting TG if >4.5 mmol/L.

Before starting therapy, collect a baseline profile and screen secondary causes: TSH/free T4, glucose/HbA1c, creatinine and albumin, LFTs. Lipids should be rechecked on the drugs listed. ^[10]

Measure Lp(a) at least once in every adult: Lp(a) <30 mg/dL (<75 nmol/L) roughly “rules out” an important risk modifier, >50 mg/dL (>125 nmol/L) “rules it in”; the 30–50 mg/dL (75–125 nmol/L) range is a grey zone. ^[1] Lp(a) should be considered significant above 50 mg/dL (>105 nmol/L) in the 2025 ESC update. ^[3] Repeat Lp(a) only if levels may have changed (CKD, liver disease, after menopause). ^[1]

ApoB is rarely the first test, but is more accurate than LDL-C when discordance is expected: use it in metabolic syndrome, diabetes, obesity and hypertriglyceridaemia. ^[1] If TG >400 mg/dL and LDL cannot be calculated, use non-HDL-C (total cholesterol − HDL-C) or direct ApoB. ^[1]

ESC/EAS 2025 (via SCORE2 and SCORE2-OP). For apparently healthy adults without ASCVD, diabetes, CKD or FH: use SCORE2 for adults 40–69 years and SCORE2-OP for adults ≥70 years to estimate 10-year fatal and non-fatal CVD risk. Categories: low risk <2%, moderate ≥2% and <10%, high ≥10% and <20%, very high ≥20%. ^[3]

Risk can be refined by modifiers: family history of premature CVD, South Asian ethnicity, obesity or inactivity, chronic inflammatory disease or HIV, history of pre-eclampsia or premature menopause, psychosocial stress, a raised hs-CRP >2 mg/L, Lp(a) >50 mg/dL, imaging (CAC, carotid/femoral plaque, CT angiography). ^[3]

Pooled cohort equations (PCE, “ASCVD risk estimator”). US equations based on age, sex, race, lipids, blood pressure, diabetes and smoking. They estimate 10-year risk and categorise it as low <5%, borderline 5–7.5%, intermediate 7.5–20%, high >20%. ^[6][2]

PREVENT equations. The 2023 AHA equations (which remove race and include BMI, eGFR and statin use) give risk estimates roughly 40–50% lower than PCE for the same profile; future guidelines are expected to use lower thresholds for them. ^[2]

QRISK3. The UK prediction model (used by NICE) for 10-year CVD risk in adults aged 25–84, including additional factors such as corticosteroid or antipsychotic use, migraine, systemic lupus erythematosus, severe mental illness and erectile dysfunction. QRISK2 underestimates in those groups. ^[10] QRISK3-lifetime is used to illustrate long-term risk and motivate lifestyle change, especially with 10-year risk under 10% and in under-40s with risk factors. ^[10]

When ASCVD, FH, type 1 diabetes, eGFR <60 or albuminuria is present, risk tools are not used; patients are at least high risk by definition. ^[10]

The LDL-C targets (2025 ESC update; 2019 ESC/EAS unchanged):

• Extreme risk: LDL-C <40 mg/dL (<1.0 mmol/L).
• Very-high risk: LDL-C <55 mg/dL (<1.4 mmol/L) (and ≥50% reduction from baseline).
• High risk: LDL-C <70 mg/dL (<1.8 mmol/L) (and ≥50% reduction).
• Moderate risk: LDL-C <100 mg/dL (<2.6 mmol/L).
• Low risk: LDL-C <116 mg/dL (<3.0 mmol/L).

Extreme risk defined = recurrent ASCVD events on maximally tolerated statin therapy and/or polyvascular disease. ^[1][3][2]

AHA/ACC 2018/Multisociety uses a % reduction approach for primary prevention and LDL-C goals for secondary prevention: ^[2][6]

• clinical ASCVD, very-high risk or FH: LDL-C <70 mg/dL (<1.8 mmol/L), non-HDL-C <100 mg/dL (<2.6).
• severe hypercholesterolaemia (LDL-C ≥190 mg/dL): high-intensity statin to lower LDL-C by ≥50%.
• diabetes 40–75 years: at least moderate-intensity statin, lowering LDL-C ≥30%–50% (≥50% if multiple risk factors or risk >20%).
• 40–75 years, LDL-C 70–189 without diabetes: statin if 10-year ASCVD risk ≥7.5%, lowering LDL-C ≥30% (≥50% if risk ≥20% or additional risk-enhancing factors).

European and US targets differ in both wording (absolute vs percentage reduction) and numerical threshold. After an event, “the sooner, the lower, the better” applies. ^[1][3]

1. Confirm dyslipidaemia and screen/treat secondary causes. ^[10]
2. Calculate risk if appropriate, assign a risk category, set the LDL-C target.
3. Start with lifestyle and, if needed, pharmacotherapy.
4. Add drugs in a stepwise fashion (statin → ezetimibe → bempedoic acid/PCSK9/inclisiran) or, after ACS, use upfront combination when the target is unlikely to be met with a statin alone. ^[3]

• Diet: Mediterranean or DASH pattern; reduce saturated and trans fats, refined carbohydrate, added sugars; increase vegetables, fruit, whole grains, legumes and nuts; soluble fibre target >25 g/day; plant sterols/stanols are not advised by NICE. Saturated fat <7% of energy if possible. ^[1][10]
• Activity: ≥150 minutes of moderate-intensity (or 75 minutes vigorous) aerobic activity weekly. ^[1]
• Weight: loss of 5–10% reduces LDL-C 3–5% (and ~20% TG for 5–10% loss in obesity). ^[8]
• Alcohol: mild-moderate only; complete abstinence if hypertriglyceridaemia is present. ^[8]
• Smoking cessation and control of hypertension and diabetes. ^[1]

The main lipid-lowering classes are compared in the table below and described one by one after it. UK names are given first, with US names in brackets.

Highly potent statins (atorvastatin, rosuvastatin) are preferred to lower potency statins (simvastatin, fluvastatin). High-intensity therapy reduces LDL-C by about 50% and, per 40 mg/dL of LDL-C lowered, reduces relative risk of major adverse cardiac events by ~25%. ^[1]

Intensity categories (2018 AHA/ACC; NICE intensity doses similar): ^[5][6][10]

• High intensity: atorvastatin 40–80 mg daily, rosuvastatin 20–40 mg daily, LDL-C reduction ≥50%.
• Moderate intensity: atorvastatin 10–20 mg, fluvastatin 80 mg, pitavastatin 1–4 mg, pravastatin 40–80 mg, rosuvastatin 5–10 mg, simvastatin 20–40 mg; LDL-C reduction 30–49%.
• Low intensity: fluvastatin 20–40 mg, pravastatin 5–40 mg, simvastatin 10 mg; reduction <30%.

NICE dosing points used in UK practice: atorvastatin 20 mg for primary prevention, 80 mg for secondary prevention (lower doses if interacting drugs, high adverse-effect risk or patient preference); after an ACS measure the full profile on admission and at 2–3 months. ^[10]

After initiation or a dose change, remeasure lipids and transaminases at 2–3 months (NICE) and yearly; AHA/ESC practice remeasures at 4–12 weeks, then 3–12 months. ^[6][10]

Adverse effects and monitoring:

• Muscle symptoms (SAMS). Myalgia is the most common, usually without marked CK rise. SAMS in ~4.9% in RCTs but ~17% in real-world data, partly due to the nocebo effect. ^[1] Muscle pain/tenderness/weakness → measure CK; if CK ≥5× ULN stop or adjust; asymptomatic patients do not need CK screening. ^[10]
• Hepatotoxicity. Monitor transaminases; mild elevation is not a reason to stop; statins are generally contraindicated in active liver disease. ^[1]
• Diabetes risk. Statins slightly increase diabetes risk in prediabetes; therapy should continue because the net benefit is much greater. ^[6][10]
• Interactions. Cyclosporine increases myopathy risk; fluvastatin/pravastatin are preferred with transplant patients; pravastatin/fluvastatin are also preferred with HIV protease inhibitors. ^[1]

In confirmed statin intolerance, bempedoic acid and ezetimibe are the usual first alternatives.

Inhibits NPC1L1 in the small intestine, reducing cholesterol absorption. Lowers LDL-C by ~20% alone; combined with a high-intensity statin lowers LDL-C by ~65%. ^[1] Typical dose 10 mg daily. ^[9] AHA 2018 adds ezetimibe when LDL-C remains >70 mg/dL on maximal tolerated statin in very high-risk ASCVD, and for severe hypercholesterolaemia with LDL-C >100 mg/dL on statin. ^[6] It is available in fixed combination with rosuvastatin. ^[1]

Inhibits ATP citrate lyase, upstream of HMG-CoA reductase. Active in liver but not muscle, so muscle-related adverse effects are not increased. Lowers LDL-C by 20–25% and, in CLEAR Outcomes, reduced major adverse events in statin-intolerant patients by 13% (primary endpoint) and 30% in the primary prevention subgroup. ^[1][2] Typical dose 180 mg daily, or 180/10 mg with ezetimibe (LDL-C ~38% reduction). ^[9] Recommended (class IIa) in the 2025 ESC update for statin intolerance or failure to reach target. ^[3] Adverse effects: hyperuricaemia/gout, cholelithiasis, slight rise in LFTs, renal impairment cautions. ^[2]

Monoclonal antibodies bind PCSK9 to prevent degradation of the LDL receptor. Given subcutaneously, they lower LDL-C 50–60% and reduce ASCVD risk by ~15% (FOURIER, ODYSSEY OUTCOMES). ^[1][2] Evolocumab is given 140 mg subcutaneously every 2 weeks or 420 mg once monthly. ^[7] Alirocumab is given subcutaneously every 2 weeks. ^[1] Inclisiran is a small interfering RNA given by subcutaneous injection and, after the second dose, administered twice yearly; it lowers LDL-C ~50–52%. ^[1][2] PCSK9 inhibitors may also be prioritised when Lp(a) is elevated (Lp(a) falls ~20–25%). ^[2]

ESC guidance (2025 update) supports evinacumab in homozygous FH ≥5 years not at target on maximal therapy (class IIa); evolocumab (Repatha) is FDA approved from age 10 years in HoFH. ^[3][7]

Fenofibrate and gemfibrozil lower TG via PPAR-α. Fenofibrate is preferred with statins because gemfibrozil increases myopathy/rhabdomyolysis risk in combination. ^[8] NICE: do not routinely offer fibrates for CVD prevention; ESC recommends statins first in hypertriglyceridaemia, fibrates in severe elevation when ASCVD prevention is aimed. ^[3][10]

High-dose icosapent ethyl (4 g daily) added to a statin reduced major events by 25% in REDUCE-IT in high/very-high-risk patients with fasting TG 135–499 mg/dL (1.52–5.63 mmol/L), despite a small increase in atrial fibrillation/bleeding. ^[2] The benefit may not be reproducible with mixed EPA/DHA (STRENGTH negative) and concerns exist about the mineral oil placebo in REDUCE-IT. ESC 2025: consider icosapent ethyl in high/very-high-risk patients with TG in this range despite statin (class IIa). ^[3] NICE allows icosapent ethyl per TA805 only. ^[10]

Extended-release niacin raises HDL and lowers TG but outcome trials (AIM-HIGH, HPS2-THRIVE) did not show ASCVD benefit. Current practice: do not offer niacin for CVD prevention. ^[10]

Lomitapide (MTP inhibitor) and evinacumab (ANGPTL3 inhibitor) are reserved for HoFH not at target on maximal therapy. Lomitapide requires a low-fat diet, liver monitoring and carries hepatotoxicity risk. ^[1][3] Funding restrictions apply. ^[1][3]

Apheresis for refractory hyperlipidaemia (HoFH or markedly raised Lp(a) with progressive ASCVD) is a last-resort specialist therapy; PCSK9 inhibitors have reduced its use. ^[1]

Post-ACS, initiate high-intensity statin plus, if the target is unlikely to be met, ezetimibe during index hospitalisation (class IIa). Intensify promptly in patients already on therapy. Follow-up lipid/LFT at 2–3 months. ^[3][10]

• Recheck lipids/LFTs after changes. ^[10]
• Measure CK if muscle symptoms occur; do not screen CK in asymptomatic patients. ^[10]
• Do not stop statins because of a rise in glucose/HbA1c. ^[10]
• Pregnancy: see Special groups.

• ASCVD: coronary, cerebral and peripheral events, heart failure.
• Pancreatitis and chylomicronaemia in severe TG elevation.
• Tendon and planar xanthomas, arcus; cosmetic and psychosocial impact.
• Severe childhood phenotype in HoFH.
• Drug side effects of lipid-lowering therapy (myopathy, hepatotoxicity, hyperuricaemia, diabetes risk).

The benefit of lowering LDL-C is proportional to the absolute reduction and duration: statin therapy reduces major adverse cardiac events by about 25% for every 40 mg/dL (1 mmol/L) of LDL-C lowered. ^[1] Lipid lowering early in life prevents more disease because of “cholesterol burden” (mg-years): younger adults gain more relative protection per mmol of LDL-C lowered. ^[1] Poor control in high/very-high-risk patients is common despite available drugs. ^[1]

• FH cascade screening: identify an index case, then screen first-degree relatives with lipids (± genetic testing). ^[9]
• Universal childhood screening. AHA advises risk factor assessment and family history for children 0–19. ^[6]
• Lp(a) once in a lifetime, ideally with a standardised assay in nmol/L. ^[1]
• Recheck lipids during routine physicals and after any change in condition or treatment.
• Lifestyle prevention across the life course, including in pregnancy where possible. ^[6]

• FH. LDL-C often >160 mg/dL even in children; diagnosis is usually clinical, and genetic testing is advised if FH is suspected because scoring systems lack sensitivity. ^[1][9]
• Treatment. Effective in children; evinacumab is ESC-supported in homozygous FH; lomitapide is reserved for HoFH; generally treat from about 8–10 years when levels and risk warrant it (specialist care). ^[1]
• Severe obesity → screen and intensive lifestyle therapy. ^[6]
• Exclude secondary causes (hypothyroidism, nephrotic syndrome, drugs).

• Statins are contraindicated in pregnancy; stop 1–3 months before conception and do not restart until breastfeeding ends; use effective contraception on lipid-lowering therapy. ^[6][10]
• FH in pregnancy: managed with bile acid sequestrants, lifestyle, and judgement; ezetimibe data limited.
• Hypertriglyceridaemia in pregnancy: if TG >225 mg/dL (2.5 mmol/L) monitor and modify lifestyle; if >500 mg/dL consider omega-3 fatty acids. Fibrate/nicotinic acid data limited. ^[8]

Age alone should not exclude statin therapy, especially for secondary prevention. In those ≥75, starting a statin is reasonable when life expectancy is at least ~2.5 years and after a clinician–patient discussion; stop when life expectancy <1 year. ^[2] Side effects are more common with frailty and polypharmacy; consider starting at half the usual dose. ^[1] ESC/EAS advise a low starting dose with renal impairment or drug interactions. ^[4]

Offer atorvastatin 20 mg for primary or secondary prevention; if the lipid target is not met and eGFR ≥30 mL/min/1.73 m², uptitrate; with eGFR <30 mL/min agree higher doses with a renal specialist. ^[10] In dialysis-dependent adults, recommendations are to continue but not initiate statins (outcome trials in dialysis not helpful). ^[2]

Type 2 diabetes is a major driver of atherogenic dyslipidaemia. Moderate-intensity statin is recommended regardless of 10-year risk; escalate to high intensity with multiple risk factors or risk >20%. 2025 ESC update: use SCORE2-Diabetes for type 2 diabetes 40–79 with ASCVD. ^[3][6]

HIV: ESC 2025 recommends statin therapy in all adults ≥40 years with HIV, irrespective of estimated risk or LDL-C (class I). ^[3] Adult patients at high risk for anthracycline cardiotoxicity are considered for statins (class IIa). ^[3]

• Measure what is available. Total cholesterol and HDL-C (or non-HDL-C) can guide treatment when LDL-C/apoB unavailable. If TG >4.5 mmol/L, treat LDL-C as unreliable and use non-HDL-C, or wait for fasting samples. ^[1]
• Fasting is unnecessary in most situations. ^[1]
• Pharmacology by impact and cost. Simvastatin and atorvastatin are inexpensive; ezetimibe cheap. Reserve bempedoic acid, PCSK9 antibodies, siRNA and lomitapide for very high-risk patients not at target; they are costly and often restricted.
• Screen secondary causes cheaply (TSH, glucose, creatinine, LFTs).
• Cascade screening can begin with family history and fasting lipids before genetic testing.
• Prevent pancreatitis by identifying TG >500 mg/dL and causes like alcohol and diabetes early.
• Manage CKD without dialysis with atorvastatin 20 mg before escalation, combined with BP control.
• If apheresis unavailable, refer HoFH patients early to a tertiary centre.

• Heart failure
• ECG interpretation
• Cardiac physical examination
• Chronic coronary syndrome and stable angina (planned); coronary atherosclerosis
• Pancreatitis and primary hypertriglyceridaemia (planned)
• Diabetes and obesity (planned)
• Chronic kidney disease (planned)
• Familial hypercholesterolaemia (see above)

• Dyslipidaemia is mostly asymptomatic; LDL-C is the causal atherogenic driver, with Lp(a) and apoB-containing particles also causal.
• Always exclude secondary causes before lifelong treatment.
• HeFH prevalence ≈1 in 250–300; HoFH ≈1 in 160,000–300,000; early treatment prevents premature CAD.
• Physical signs: tendon xanthomas (FH), xanthelasma (nonspecific), arcus before 45 (FH), very high TG → pancreatitis.
• Use a non-fasting full lipid profile; calculate LDL-C or use direct measurement if TG >400 mg/dL.
• Lp(a) should be measured once in life; interpret with rule-in/rule-out thresholds (30 and 50 mg/dL).
• Risk: SCORE2/SCORE2-OP in Europe; PCE and newer PREVENT in the US; QRISK3 in the UK, with appropriate risk category.
• Targets: extreme <40, very high <55, high <70, moderate <100, low <116 mg/dL (ESC/EAS); AHA/ACC uses % reduction or LDL-C <70 in ASCVD.
• First-line drugs: statins; escalate by LDL-C intensity categories.
• Add ezetimibe (cheap), then bempedoic acid, PCSK9 antibodies or inclisiran.
• Icosapent ethyl 4 g/day only for high/very-high risk with TG 135–499 mg/dL.
• Do not use niacin, routine fibrates or omega-3 for CVD prevention.
• Statins contraindicated in pregnancy; use with CKD and older adults with shared decision-making.
• Monitor lipids/LFTs at 2–3 months; CK only if symptomatic.
• Cascade screening and Lp(a) testing prevent disease in families.