High Cholesterol — Symptoms, Causes & Treatment | MyMedicPlus

High cholesterol (hypercholesterolemia/dyslipidemia) refers to elevated levels of LDL cholesterol ('bad cholesterol'), reduced HDL cholesterol, or elevated triglycerides in the blood. Approximately 39% of adults globally have elevated total cholesterol. Elevated LDL-C is a major causal risk factor for atherosclerosis — the buildup of arterial plaque leading to heart attacks and strokes. High cholesterol is largely asymptomatic ('silent'), underscoring the importance of routine blood testing to detect and treat it before cardiovascular events occur. Cholesterol is transported in the blood as lipoproteins: LDL (low-density lipoprotein) transports cholesterol from the liver to peripheral tissues and is the primary atherogenic lipoprotein; HDL (high-density lipoprotein) participates in reverse cholesterol transport back to the liver; and VLDL carries triglycerides. Non-HDL cholesterol (total cholesterol minus HDL) captures all atherogenic lipoproteins including VLDL and IDL and is a superior cardiovascular risk predictor to LDL-C alone in patients with elevated triglycerides. Lipoprotein(a) — Lp(a) — is an independent causal risk factor for cardiovascular disease affecting 1 in 5 people and is not reduced by statins; RNA-targeting therapies (pelacarsen, olpasiran) are in late-stage trials specifically targeting elevated Lp(a).

Primary (genetic) causes include familial hypercholesterolemia (FH) — autosomal dominant disorder affecting 1 in 250 people, causing very high LDL-C from birth due to LDL receptor mutations. Secondary causes include poor diet (high saturated and trans fats), sedentary lifestyle, obesity, hypothyroidism, type 2 diabetes, chronic kidney disease, obstructive liver disease, and certain medications (corticosteroids, antiretrovirals, progestins). Risk factors for cardiovascular complications include male sex, age, smoking, hypertension, family history of premature cardiovascular disease, and diabetes. Polygenic hypercholesterolemia accounts for the majority of elevated LDL-C in the general population — multiple small-effect genetic variants combine with lifestyle factors. Familial Combined Hyperlipidaemia (FCHL) — the most common familial dyslipidaemia, affecting 1 in 200 — causes elevated LDL, VLDL, and triglycerides through apolipoprotein B overproduction. Nephrotic syndrome causes hyperlipidaemia through reduced oncotic pressure driving increased hepatic lipoprotein synthesis.

High cholesterol is typically asymptomatic — most people have no symptoms until a cardiovascular event (heart attack or stroke) occurs. Physical signs are rare and appear in severe cases: xanthelasma (yellowish cholesterol deposits around the eyelids), xanthomas (cholesterol deposits in tendons, particularly the Achilles tendon — characteristic of familial hypercholesterolemia), and corneal arcus (white ring around the cornea in those under 45 suggesting hyperlipidemia). These physical signs prompt investigation of the lipid profile. Tendon xanthomas — yellowish nodular deposits at the Achilles tendon, patellar tendon, or extensor tendons of the fingers — are pathognomonic of familial hypercholesterolemia (LDL receptor deficiency). Xanthelasma palpebrarum (yellowish plaques at the inner canthi of the eyelids) may indicate FH in patients under 45. Arcus cornealis (grey-white ring around the cornea) before age 45 is a clinical indicator of severe hyperlipidaemia warranting lipid profile and cascade family screening.

Fasting lipid profile is the standard diagnostic test: total cholesterol, LDL-C, HDL-C, triglycerides, and non-HDL-C are measured. Target LDL-C values differ by cardiovascular risk category: below 2.6 mmol/L for moderate risk, below 1.8 mmol/L for high risk, below 1.4 mmol/L for very high risk (established ASCVD, familial hypercholesterolemia). Cardiovascular risk calculators (SCORE2, Framingham, ACC/AHA Pooled Cohort Equations) estimate 10-year risk to guide treatment intensity. Genetic testing confirms familial hypercholesterolemia. Thyroid function, renal function, liver enzymes, and glucose are checked to exclude secondary causes. Framingham Risk Score, ACC/AHA Pooled Cohort Equations, and QRISK3 (UK — includes additional risk factors such as Townsend deprivation score, rheumatoid arthritis, chronic kidney disease, and prior corticosteroid use) stratify patients for statin initiation decisions. Coronary artery calcium (CAC) score on non-contrast CT: a CAC score of zero substantially reduces MACE risk and may allow reclassification of some intermediate-risk patients to lower treatment intensity, while high CAC scores (above 400 Agatston units) support aggressive lipid-lowering. The Simon Broome criteria and Dutch Lipid Clinic Network criteria are validated tools for diagnosing familial hypercholesterolemia clinically.

Statins (atorvastatin, rosuvastatin, simvastatin) are the cornerstone of LDL-C reduction — high-intensity statin therapy (atorvastatin 40–80 mg or rosuvastatin 20–40 mg) reduces LDL-C by 50–55% and reduces cardiovascular events by 25–35% per mmol/L LDL reduction. Ezetimibe (10 mg daily) inhibits intestinal cholesterol absorption and adds a further 15–20% LDL reduction when combined with statins. PCSK9 inhibitors (evolocumab, alirocumab — subcutaneous injection every 2 or 4 weeks) reduce LDL-C by 50–60% on top of statins and are indicated for very high-risk patients or statin-intolerant patients. Inclisiran, a small interfering RNA given twice yearly, is a newer option with equivalent PCSK9 inhibition. Bempedoic acid (Nexletol) — an ATP-citrate lyase inhibitor — lowers LDL-C by 18–25% and is an alternative for patients intolerant to statins; the CLEAR Outcomes trial showed cardiovascular benefit in statin-intolerant patients. Alirocumab and evolocumab — PCSK9 inhibitors — are proven to reduce major adverse cardiovascular events (FOURIER and ODYSSEY OUTCOMES trials) with LDL reductions of 50–60% and excellent safety profiles. Fasting triglycerides above 10 mmol/L (900 mg/dL) require urgent treatment to prevent pancreatitis: fenofibrate, omega-3 fatty acids (4 g/day of icosapentaenoic acid — Vascepa), and very low fat diet.

Uncontrolled high LDL-C leads to progressive atherosclerosis causing coronary artery disease (angina, myocardial infarction), stroke and transient ischemic attacks, peripheral artery disease (leg ischemia), and aortic aneurysm. In familial hypercholesterolemia, coronary artery disease may develop by the third or fourth decade of life without statin treatment. Very high triglyceride levels (above 10 mmol/L or 880 mg/dL) cause acute pancreatitis, which can be severe and life-threatening. Statin-related complications include myopathy and rare rhabdomyolysis (muscle breakdown), elevated liver enzymes, and new-onset diabetes in predisposed individuals.

Adopt a heart-healthy diet: reduce saturated fat (limit red meat, full-fat dairy, tropical oils) and eliminate trans fats (partially hydrogenated oils, processed foods), increase dietary fiber (oats, legumes, fruits, vegetables), and include omega-3 fatty acid sources (oily fish, flaxseed, walnuts). Regular aerobic exercise (150+ minutes per week of moderate-intensity activity) raises HDL-C and reduces triglycerides. Achieve and maintain healthy body weight. Quit smoking. Screen for familial hypercholesterolemia in first-degree relatives of affected patients. Check lipid profile every 5 years from age 20, or annually if on treatment or with elevated risk.

Call emergency services immediately for: chest pain, pressure, or tightness spreading to the jaw or left arm (possible heart attack — call 999 or 911, do not drive yourself); sudden numbness or weakness of the face, arm, or leg, sudden difficulty speaking, or sudden severe headache (possible stroke — act FAST). See your GP within 2 weeks if you have visible cholesterol deposits — xanthelasma (yellowish deposits around the eyelids) or xanthomas (lumps in tendons, particularly the Achilles) — these strongly suggest familial hypercholesterolemia, which requires urgent diagnosis and treatment from an early age due to high cardiovascular risk. Ask your GP for a fasting lipid profile if you have any of: a first-degree relative with heart attack under 55 (men) or 65 (women); a first-degree relative diagnosed with FH; or personal history of cardiovascular disease, type 2 diabetes, hypertension, CKD, or obesity — annual cholesterol monitoring and cardiovascular risk stratification is recommended. If you are already on a statin and develop new unexplained muscle pain, weakness, or dark-coloured urine (possible rhabdomyolysis), stop the statin and seek urgent medical review — a creatine kinase level is needed.