Dyslipidaemia

Dyslipidaemia is an abnormal blood lipid profile: raised low density lipoprotein cholesterol (LDL-C), raised triglycerides, low high density lipoprotein cholesterol (HDL-C), raised lipoprotein(a), or combinations of these. It is a major modifiable cause of atherosclerotic cardiovascular disease and, when triglycerides are very high, of acute pancreatitis.

• Primary (genetic) forms: familial hypercholesterolaemia (about 1 in 250 people), familial combined hyperlipidaemia, familial hypertriglyceridaemia, dysbetalipoproteinaemia, and elevated lipoprotein(a) (about 1 in 5 people, with levels above 125 nmol/L or 50 mg/dL adding risk).
• Secondary causes: obesity, diabetes, hypothyroidism, nephrotic syndrome, chronic kidney disease, cholestatic liver disease, alcohol, pregnancy, Cushing syndrome, anorexia nervosa; drugs including thiazides, beta blockers, oestrogen, oral retinoids, corticosteroids, ciclosporin, protease inhibitors, antipsychotics, and antiepileptics.
• Dietary factors: saturated and trans fats, refined carbohydrate, alcohol excess.
• Usually asymptomatic until complications occur.
• Targets depend on cardiovascular risk: very high risk (established disease, diabetes with organ damage, estimated 10 year risk 20 percent or more) LDL-C below 1.4 mmol/L (55 mg/dL) with at least a 50 percent reduction; high risk below 1.8 mmol/L (70 mg/dL); moderate risk below 2.6 mmol/L (100 mg/dL); low risk below 3.0 mmol/L (116 mg/dL). Non-HDL-C targets are 0.8 mmol/L higher.

• Usually none. Signs of severe or genetic disease: tendon xanthomas (Achilles, extensor tendons of the hands), xanthelasma, arcus cornealis before age 45, eruptive xanthomata (very high triglycerides), palmar xanthomata, lipaemia retinalis.
• Family history of premature cardiovascular disease (men under 55, women under 65) or high cholesterol.
• Symptoms of consequences: angina, claudication, stroke or transient ischaemic attack; abdominal pain from pancreatitis (triglycerides above 10 mmol/L or 885 mg/dL).
• Features of secondary causes: weight gain, cold intolerance, oedema, jaundice, polyuria.

• Non-fasting lipid profile is acceptable (total cholesterol, HDL-C, calculated LDL-C, triglycerides, non-HDL-C). Fasting sample for triglycerides above 4.5 mmol/L (400 mg/dL) or when LDL-C is calculated and triglycerides are high.
• Repeat to confirm, and when an acute illness, recent pregnancy, or weight change might distort results.
• Secondary screen: thyroid stimulating hormone, HbA1c or fasting glucose, urea, creatinine and eGFR, urine albumin to creatinine ratio, liver function tests (ALT, alkaline phosphatase), full blood count, and alcohol history.
• Lipoprotein(a) once in a lifetime for all adults (family history, premature disease, or borderline risk).
• Apolipoprotein B when triglycerides are high.
• Familial hypercholesterolaemia suspected with LDL-C above 4.9 mmol/L (190 mg/dL), or above 4.0 mmol/L in a child, with family history or xanthomas: arrange genetic testing and family cascade testing.
• Calculate 10 year cardiovascular risk; consider coronary calcium scoring in intermediate risk.
• Differentials for markedly abnormal results: nephrotic syndrome, hypothyroidism, obstructive jaundice, anorexia nervosa, pregnancy.

Lifestyle (everyone)

• Diet: reduce saturated fat to under 10 percent of energy (replace with unsaturated fats), avoid trans fats, increase fibre to 30 g daily including 5 to 10 g of soluble fibre (oats, beans), add plant sterols or stanols 2 g daily to lower LDL-C by about 7 to 10 percent, eat fish twice weekly, restrict refined carbohydrate and added sugar when triglycerides are high, alcohol under 14 units per week (none if triglycerides are very high).
• Activity: 150 minutes a week of moderate aerobic exercise.
• Weight loss of 5 to 10 percent when overweight; stop smoking.

Statins (main treatment when risk is raised)

• Atorvastatin 20 mg (20 to 80 mg) orally at night; rosuvastatin 5 to 10 mg (up to 40 mg); simvastatin 20 to 40 mg at night (maximum 20 mg with amlodipine, 10 mg with diltiazem or verapamil; not with clarithromycin, itraconazole or ciclosporin); pravastatin 20 to 40 mg. Intensity: high (atorvastatin 40 to 80 mg, rosuvastatin 20 to 40 mg) lowers LDL-C by 50 percent or more; moderate by 30 to 49 percent.
• Start atorvastatin 20 mg for primary prevention when 10 year risk is 10 percent or more, and for type 1 diabetes, chronic kidney disease, or LDL-C above 4.9 mmol/L; use 80 mg after myocardial infarction or stroke. Rosuvastatin in chronic kidney disease: maximum 20 mg if eGFR below 30 (not above 10 mg in Asian patients initially).
• Baseline ALT and lipids; recheck lipids and ALT at 8 to 12 weeks, then yearly. Stop only if ALT above three times the upper limit; creatine kinase only for symptoms.
• Muscle symptoms: check for hypothyroidism, vitamin D deficiency, and drug interactions; stop for 2 to 4 weeks, then restart a different or lower dose statin (rosuvastatin 5 mg or alternate day dosing). Rhabdomyolysis (creatine kinase above 10 times normal with symptoms) requires admission.

Add on treatment if the target is missed on maximum tolerated statin

• Ezetimibe 10 mg once daily (lowers LDL-C a further 15 to 20 percent); can be used alone in statin intolerance.
• Bempedoic acid 180 mg daily (not with simvastatin above 40 mg; raises uric acid); PCSK9 inhibitors (evolocumab 140 mg subcutaneously every 2 weeks, alirocumab 75 to 150 mg every 2 weeks, or inclisiran 284 mg subcutaneously at 0 and 3 months, then every 6 months) by specialist.
• Fenofibrate 145 mg daily for triglycerides above 5.6 mmol/L; omega-3 (icosapent ethyl 2 g twice daily) for triglycerides 1.7 to 5.6 mmol/L in high risk patients on a statin.
• Colesevelam 3.75 g daily is used rarely.

Special groups

• Pregnancy and breastfeeding: stop statins before conception, and use resins or fish oil if essential, with specialist advice.
• Familial hypercholesterolaemia: statins start at 8 to 10 years (children), high intensity in adults, and screen relatives.
• Older adults over 75: continue if already treated, and start after discussion in established disease.
• Hypothyroidism: levothyroxine often normalises lipids (recheck after 3 months).
• Diabetes: statin if age over 40, or younger with risk factors.

Follow up

• Annual lipid profile and adherence review; refer for LDL-C above 5 mmol/L despite treatment, triglycerides above 10 mmol/L, suspected genetic disease, or statin intolerance with a high risk.