Abnormal Lipid Profile Algorithm

Safety

Red Flags — When a Lipid Result Needs Action Today

Done

Most abnormal lipid results are incidental and are managed in a planned way. These are the exceptions. A lipid result never lowers the urgency of symptoms, and a normal result never reassures about them.

Acute, ongoing or recent chest pain Possible acute coronary syndrome, whatever the cholesterol shows → call 999. Do not wait for, or be reassured by, a lipid result.

Raised triglycerides with abdominal pain or vomiting Possible acute pancreatitis, at any triglyceride level (it can occur below 10 mmol/L) → same-day hospital assessment, 999 if unwell. Do not wait for a fasting repeat. Use the High triglycerides pathway.

Triglycerides above 20 mmol/L Not explained by excess alcohol or poor glycaemic control → urgent specialist review (NICE NG238); same-day assessment if there is abdominal pain, vomiting or systemic illness.

LDL cholesterol above 13 mmol/L in an adult Consider homozygous familial hypercholesterolaemia (NICE CG71) → offer referral to a specialist FH centre without delay. Do not wait to apply the Simon Broome or DLCN criteria.

Heavy proteinuria, oedema and low albumin Nephrotic syndrome as the cause of the lipid result → urgent medical assessment; same-day hospital assessment if there is acute kidney injury, severe oedema, thrombosis, infection or instability. Do not treat the cholesterol in isolation.

Raised triglycerides with thirst, polyuria, weight loss or vomiting New or uncontrolled diabetes, possibly DKA or HHS → check capillary glucose and blood ketones now; same-day hospital assessment if ketones are raised or the patient is unwell.

Lipid results arrive in the inbox detached from the patient. The two harms are opposite: over-reacting to an asymptomatic high cholesterol (which is a long-term risk factor, not an emergency) and under-reacting to symptoms because the lipid result looks "fine". Chest pain is assessed on its own merits. Very high triglycerides are the one lipid result that carries a direct short-term danger, through pancreatitis, and they have their own pathway. Homozygous FH is rare but needs specialist treatment from childhood or as soon as it is found.

Diagnose

Is It Real? — Sample, Repeat and Secondary Causes

Done

Fasting or not

A non-fasting full lipid profile (total cholesterol, HDL, non-HDL cholesterol, triglycerides) is sufficient for CVD risk assessment and for most decisions (NICE NG238). Fasting matters only for triglycerides: repeat a fasting sample when triglycerides are 4.5 mmol/L or more, when the result is unexpected, or when chylomicronaemia is suspected. Calculated LDL cholesterol is unreliable when triglycerides are above 4.5 mmol/L — use non-HDL cholesterol (total minus HDL) or a direct LDL.

Repeat before labelling

Do not label a patient on one unexpected result. Repeat it, with the secondary-cause tests, before a diagnosis such as familial hypercholesterolaemia (FH): NICE CG71 asks for at least 2 LDL cholesterol measurements before a clinical FH diagnosis. Triglycerides 10–20 mmol/L: repeat a fasting sample after at least 5 days but within 2 weeks.

When the result misleads

Acute illness, infection, recent surgery or a recent heart attack can lower cholesterol for a time — recheck when the patient is well. Pregnancy raises cholesterol and triglycerides physiologically. A binge or a heavy fatty meal can raise a single triglyceride result.

Secondary causes — before you label it primary

Hypothyroidism (TSH) · diabetes, especially poorly controlled (HbA1c) · CKD and nephrotic syndrome (eGFR, urine ACR) · liver disease and cholestasis (LFTs; cholestatic liver disease can cause very high cholesterol) · alcohol excess (AUDIT-C, GGT) · obesity and metabolic syndrome · pregnancy · drugs: antipsychotics, corticosteroids, retinoids (isotretinoin, acitretin), HIV antiretrovirals, ciclosporin, amiodarone, thiazides and beta-blockers, oestrogens. Treat the cause, then recheck the lipids — but never delay a statin in established CVD.

NICE NG238 recommends a non-fasting sample because total and HDL cholesterol change very little after a meal, and non-HDL cholesterol captures all the atherogenic particles without the Friedewald calculation. Triglycerides are the exception: they rise after food, and the Friedewald LDL estimate (total minus HDL minus TG/2.2) fails once they are above 4.5 mmol/L. The NICE quality standard on CVD risk assessment asks for secondary causes to be checked before a statin is offered, because treating an untreated thyroid, uncontrolled diabetes, nephrotic syndrome or heavy drinking can correct the lipid result, and because a hidden secondary cause also needs treatment in its own right.

Diagnose

Result Bands — What Each Number Means and What to Do

Done

There is no single "normal" cholesterol for treatment decisions: in most people the decision rests on overall CVD risk (step 5), not on the lipid number. The numbers below are the ones that change the pathway. Use your laboratory's reference ranges.

Total cholesterol (TC)

Below 7.5 mmol/L interpret through CVD risk (QRISK3, step 5) · >7.5 mmol/L in an adult assess for FH (step 4), especially with premature CHD in the patient or a first-degree relative · >9.0 mmol/L specialist assessment, even without a family history (NICE NG238). TC:HDL ratio is the cholesterol input to QRISK3.

LDL cholesterol

>4.9 mmol/L in an adult Simon Broome lipid criterion → assess for FH (step 4) · >13 mmol/L in an adult consider homozygous FH → specialist FH centre without delay · Unreliable if triglycerides are above 4.5 mmol/L — use non-HDL cholesterol.

Non-HDL cholesterol

Total minus HDL cholesterol; no fasting sample needed. >7.5 mmol/L specialist assessment, even without a family history (NICE NG238). On treatment it is the measure of success: primary prevention >40% reduction; secondary prevention ≤2.6 mmol/L (step 6).

HDL cholesterol

<1.0 mmol/L (men) or <1.2 mmol/L (women) low — a marker of higher CVD risk that QRISK3 already counts through the TC:HDL ratio. No specific drug treatment; see step 7.

Triglycerides (TG)

<4.5 mmol/L assess overall CVD risk · 4.5–9.9 mmol/L fasting repeat, secondary causes; CVD risk may be underestimated; specialist advice if non-HDL >7.5 mmol/L · 10–20 mmol/L fasting repeat after 5 days but within 2 weeks; still >10 → specialist advice · >20 mmol/L urgent specialist review if not explained by alcohol or poor glycaemic control · Full detail: High triglycerides pathway.

Cholesterol is a continuous risk factor, and the same total cholesterol carries very different risk in a 30-year-old non-smoker and a 70-year-old smoker with diabetes. NICE NG238 therefore bases the statin decision on QRISK3, not on a cholesterol cut-off. The exceptions are the very high values, which suggest a genetic disorder that QRISK3 cannot capture: TC >7.5 mmol/L (or LDL >4.9 mmol/L) prompts FH assessment, and TC >9.0 mmol/L or non-HDL >7.5 mmol/L needs specialist assessment whatever the family history. The HDL figures are the commonly used markers of increased risk (ESC/EAS); they are not treatment targets.

Diagnose

Suspected Familial Hypercholesterolaemia (FH)

Done

Suspect FH (NICE CG71)

Adults with total cholesterol >7.5 mmol/L, or LDL >4.9 mmol/L, and/or a personal or family history of premature coronary heart disease (an event before 60 in the patient or a first-degree relative). Also tendon xanthomata, and corneal arcus or xanthelasma in a young patient. Use the whole clinical picture, not a lipid cut-off alone.

Assess

Exclude secondary causes (step 2), take at least 2 LDL cholesterol measurements, take a family history of premature CHD and raised cholesterol, examine for tendon xanthomata, then apply the Simon Broome or Dutch Lipid Clinic Network (DLCN) criteria. Do not use QRISK3 — it underestimates risk in FH.

Simon Broome (adults)

TC >7.5 mmol/L or LDL >4.9 mmol/L, plus: definite FH — tendon xanthomata in the patient or a first- or second-degree relative, or a DNA-confirmed mutation; possible FH — MI before 60 in a first-degree relative or before 50 in a second-degree relative, or TC >7.5 mmol/L in an adult first- or second-degree relative.

Refer

Possible or definite FH on Simon Broome, or a DLCN score >5 → refer to the specialist FH service for DNA testing (NICE CG71). Cascade testing of first-, second- and, where possible, third-degree relatives is arranged through the specialist FH service.

Specialist assessment without FH features

TC >9.0 mmol/L or non-HDL >7.5 mmol/L → specialist assessment even in the absence of a first-degree family history of premature CHD (NICE NG238).

Records search

Search practice records for adults under 30 with TC >7.5 mmol/L and adults aged 30 or over with TC >9.0 mmol/L (NICE CG71), and assess them for FH.

FH affects about 1 in 250 people in the UK, and most are undiagnosed. Each affected person's first-degree relatives have a 50% chance of carrying the variant, which is why one diagnosis in primary care can protect a whole family through cascade testing. FH treatment is not decided by QRISK3: people with FH are offered a high-intensity statin and are managed with the lipid clinic. Treatment detail is in the Familial hypercholesterolaemia protocol.

Diagnose

Cardiovascular Risk Assessment — Who Gets a Statin

Done

Frame the patient first

Established CVD (MI or ACS, angina, stroke or TIA, peripheral arterial disease, revascularisation) → secondary prevention; no risk score. Suspected FH → step 4; no risk score. Type 1 diabetes, CKD (eGFR <60 and/or albuminuria) → disease-specific criteria, not QRISK3. Aged 85 or over → QRISK3 is not appropriate; individualise. Everyone else aged 25–84 → QRISK3.

QRISK3 ≥10%

Offer atorvastatin 20 mg for primary prevention after an informed discussion of risks and benefits (NICE NG238). Discuss lifestyle first, but do not delay treatment if the patient prefers to start.

QRISK3 <10%

Lifestyle advice. Do not rule out a statin if the patient has an informed preference for one, or if their risk may be underestimated.

When QRISK3 may underestimate

Severe mental illness, HIV, autoimmune and inflammatory disease, antipsychotics, corticosteroids or immunosuppressants, and triglycerides 4.5–9.9 mmol/L. Treat the score as a starting point.

Other groups

Secondary prevention: atorvastatin 80 mg (lower dose if interactions, adverse-effect risk or patient preference). CKD: atorvastatin 20 mg for primary or secondary prevention. Type 1 diabetes: offer atorvastatin 20 mg if older than 40, diabetes for more than 10 years, nephropathy or other CVD risk factors. Aged 85 or over: consider a statin after individual assessment. Doses per the SPC and local formulary.

QRISK3 is validated for primary prevention in people aged 25–84 without CVD. It is not used where risk is already known to be high (established CVD) or where the tool is not designed for the group (FH, type 1 diabetes, CKD), because it would underestimate their risk. NICE NG238 uses a 10-year risk of 10% or more as the point at which to offer a statin, and asks clinicians to keep the door open below that threshold for people who want treatment after an informed discussion.

Treat

Primary vs Secondary Prevention — Targets and First Steps

Done

Primary prevention target

A reduction in non-HDL cholesterol of more than 40% from baseline, measured at 2–3 months (NICE NG238). There is no absolute LDL target in primary prevention.

Secondary prevention target

LDL cholesterol ≤2.0 mmol/L or non-HDL cholesterol ≤2.6 mmol/L (NICE NG238).

Aim for at least a 50% reduction in LDL cholesterol from the untreated baseline (NICE CG71); managed with the lipid clinic.

Lifestyle — alongside, not instead

Cardioprotective (Mediterranean-style) diet; swap saturated for unsaturated fat; do not recommend plant sterols or stanols to prevent CVD; at least 150 minutes a week of moderate activity; weight loss if overweight; alcohol ≤14 units a week; stop smoking.

Not at target

Check adherence, lifestyle and secondary causes, then step up the statin, then ezetimibe, as set out in the High cholesterol protocol, which holds the full treatment ladder, doses and NICE technology-appraisal options.

Next steps: see High cholesterol (lipids) protocol · Familial hypercholesterolaemia · High triglycerides · Metabolic syndrome

Each 1 mmol/L fall in LDL cholesterol lowers major cardiovascular events by about a fifth, so the measured response matters more than the starting value. In primary prevention NICE uses a relative target (more than 40% fall in non-HDL), which is what a high-intensity statin taken regularly should achieve; a smaller fall usually means missed doses. In secondary prevention NICE NG238 sets absolute targets and advises escalation when they are not reached.

Diagnose

Low HDL and Mixed Patterns

Done

Isolated low HDL

HDL <1.0 mmol/L (men) or <1.2 mmol/L (women) with otherwise normal lipids: no specific drug treatment. Look for the drivers — smoking, inactivity, obesity, insulin resistance or type 2 diabetes, high triglycerides, anabolic steroids — and address lifestyle. Let QRISK3 (which includes the TC:HDL ratio) decide on a statin.

Low HDL + high triglycerides

The pattern of insulin resistance and metabolic syndrome: check HbA1c, waist circumference, BP and LFTs (fatty liver). It indicates higher cardiovascular risk. The statin remains the main lipid treatment when risk is raised; manage triglycerides on the High triglycerides pathway.

Mixed hyperlipidaemia

Raised LDL (or non-HDL) and raised triglycerides together: exclude secondary causes (diabetes, hypothyroidism, alcohol, drugs). With premature CVD in the family, think of familial combined hyperlipidaemia → lipid clinic. Use non-HDL cholesterol, not calculated LDL, when triglycerides are above 4.5 mmol/L.

Very high HDL

A high HDL does not cancel a raised LDL or non-HDL, and it is not a reason to withhold a statin when risk is raised.

Low HDL is strongly linked with cardiovascular risk, but trials of drugs that raise HDL have not reduced events, so HDL is treated as a risk marker rather than a target. Its usefulness lies in what it signals (insulin resistance, smoking, inactivity) and in its contribution to the QRISK3 calculation.

Safety

Follow-Up and Statin Monitoring

Done

Before a statin

Full lipid profile, renal function, liver transaminases (ALT or AST), HbA1c where clinically appropriate, TSH if symptoms or signs of hypothyroidism. Ask about unexplained muscle pain: measure CK only if there are muscle symptoms — not routinely. Baseline CK >5× ULN → re-measure after 7 days; still >5× ULN → do not start; raised but below 5× ULN → start at a lower dose.

Lipids

Full lipid profile at 2–3 months after starting or changing treatment, against the target in step 6. Then consider an annual medicines review, with a non-fasting non-HDL cholesterol to inform it.

Liver transaminases

Baseline, within 3 months (with the 2–3 month lipid check) and at 12 months; then not routinely unless clinically indicated (NICE NG238). Transaminases raised but below 3× ULN are not a reason to withhold or stop a statin. At 3× ULN or more → recheck and review; stop only if they stay above 3× ULN.

No routine CK in people without symptoms. Muscle symptoms → check CK. Severe pain, weakness or dark urine → stop the statin and check CK and renal function the same day; CK >10× ULN or suspected rhabdomyolysis → urgent assessment. CK 4–10× ULN or intolerable symptoms → stop for 4–6 weeks, then rechallenge. Below 4× ULN → usually reassure and look for other causes.

Not on a statin

Reassess QRISK3 and lipids periodically, and sooner if risk factors change.

The 2–3 month check is the point where most treatment failures (often missed doses) are found and corrected. Mild transaminase rises are common on statins and are not harmful; stopping a statin for them removes protection without benefit. Routine CK testing in people without symptoms finds exercise-related rises and leads to needless statin avoidance, which is why CK is measured only when there are muscle symptoms. These rules match the site's High cholesterol protocol.

Refer

Referral Pathways

Done

999 / same-day hospital

Acute, ongoing or recent chest pain → 999 · Raised triglycerides at any level with abdominal pain or vomiting → same-day hospital assessment · Suspected DKA or HHS → same-day hospital assessment

Urgent

Triglycerides >20 mmol/L not explained by alcohol or poor glycaemic control → urgent lipid specialist review · LDL >13 mmol/L in an adult (possible homozygous FH) → specialist FH centre without delay · Nephrotic syndrome → urgent medical assessment

Specialist FH service

Possible or definite FH on Simon Broome, or DLCN score >5 → DNA testing and cascade testing of relatives

Lipid specialist

TC >9.0 mmol/L or non-HDL >7.5 mmol/L, even without a family history · Triglycerides still >10 mmol/L on fasting repeat · Triglycerides 4.5–9.9 mmol/L with non-HDL >7.5 mmol/L · Suspected familial combined hyperlipidaemia · Not at target on maximum tolerated treatment, or statin intolerance (per the local lipid pathway)

Primary care manages

Polygenic hypercholesterolaemia once secondary causes are excluded and FH criteria are not met · primary prevention with QRISK3 ≥10% · secondary prevention reaching target · isolated low HDL · secondary causes (thyroid, diabetes, alcohol, drugs)

Most abnormal lipid profiles are polygenic or secondary and are managed well in primary care. Specialist input is reserved for genetic disorders (FH, familial combined hyperlipidaemia, chylomicronaemia), very high values that suggest one, severe triglycerides, and patients who do not reach target on maximum tolerated treatment. Follow the local lipid pathway for how to refer.