Overview
Definition
Staging and classification
Primary hypercholesterolemia
Secondary hypercholesterolemia
Morbidity
A national survey in China in 2012 showed that the prevalence of hypercholesterolemia in adults in China was 4.9% [2].
Etiology
Causes of the disease
The development of hypercholesterolemia is associated with the following factors [1]:
Primary hypercholesterolemia
The cause of primary hypercholesterolemia is unknown and is the result of an interaction between genetic and environmental factors.
Genetic factors
Caused by mutations in a single gene, usually in the LPL, ApoC2 or ApoA5 genes involved in TG metabolism, and manifests as severe hyper-TGemia (TG > 10 mmol/L).
Environmental factors
Including long-term poor dietary habits, insufficient exercise, obesity, age, smoking and alcohol abuse.
Secondary hypercholesterolemia
Mainly caused by disease and drug factors.
Disease factors
Disease factors such as hypothyroidism, Cushing’s syndrome, hepatic and renal diseases, systemic lupus erythematosus, myeloma, polycystic ovary syndrome, excessive alcohol consumption, etc. can affect the synthesis, transport or metabolism of lipids or lipoproteins through different mechanisms, causing secondary hypercholesterolemia.
Drugs
Long-term use of thiazide diuretics (e.g., hydrochlorothiazide, furosemide, etc.), beta-blockers (e.g., metoprolol, bisoprolol), and glucocorticosteroids (e.g., prednisone, dexamethasone, etc.) can cause lipid metabolism abnormality, leading to secondary hypercholesterolemia.
Risk factors
People with any one or more of the following risk factors are at high risk for hypercholesterolemia. Regular physical examination and lipid screening are recommended [2].
Symptoms
Main symptoms
Usually there are no obvious symptoms, most often detected on physical examination, and a few patients may present with the following symptoms:
Yellow tumor
It presents as a limited abnormal elevation of the skin, mostly nodular, plaque or papule-like, with a soft texture.
Commonly found in the skin and subcutaneous tissue, the most common site is around the eyelids, but also seen in the tendon area, the extensor side of the body, the palm of the hand and other parts of the body.
The color is yellow, orange or brownish red.
Corneal Arch
Also known as senile ring.
Most commonly seen in familial hypercholesterolemia.
It is characterized by grayish-white or white deposits of corneal lipids located at the outer edge of the cornea.
Complications
Atherosclerotic cardiovascular disease
Hypercholesterolemia leads to lipid deposition in blood vessels, causing atherosclerotic cardiovascular disease.
Atherosclerotic cardiovascular disease can further lead to coronary heart disease, stroke, and atherosclerotic occlusion of the lower extremities.
When coronary heart disease is caused, symptoms such as chest tightness, palpitations, shortness of breath and chest pain can occur.
Stroke can lead to dizziness, headache, hemiplegia, aphasia and other symptoms.
Intermittent claudication (i.e., pain, cramping and weakness of the lower limbs after walking for a period of time, and the need to stop and rest for a period of time before continuing to walk) can occur when arteriosclerosis occlusion of the lower limbs is caused.
Wandering arthritis
Severe hypercholesterolemia can lead to cholesterol deposition in the joint cavity, causing an inflammatory response and inducing wandering arthritis.
Wandering pain in joints throughout the body may occur.
Lipemic retinal changes
Severe hypercholesterolemia leads to deposition of lipoproteins on small arteries in the fundus.
Symptoms such as loss of vision and hemorrhages in the fundus may occur.
Acute pancreatitis
Severe hypercholesterolemia can lead to acute pancreatitis.
Symptoms such as abdominal pain, nausea, and vomiting can occur [7-8].
Consultation
Department of Medicine
Endocrinology
Prompt medical attention is recommended in case of xanthomas and corneal bowing.
If cholesterol is elevated on physical examination, prompt medical attention is recommended.
Cardiovascular Medicine
If symptoms such as chest tightness, palpitations, shortness of breath, or chest pain occur, it is recommended to consult a doctor promptly.
Neurology
If symptoms such as dizziness, headache, hemiplegia, aphasia, etc. occur, it is recommended to consult a doctor promptly.
Preparation for medical treatment
Preparation for medical consultation: registration, preparation of documents, common problems
Tips for medical treatment
Lipid test requires a blood draw on an empty stomach, so it is recommended to visit the doctor on an empty stomach.
Preparation List
Symptom list
Pay particular attention to the time of onset of symptoms, special symptoms, etc.
Medical history checklist
Checklist
Test results of the last six months, which can be brought to the doctor’s office
Lipid test.
Medication List
Medication used in the last 3 months, if available in boxes or packages, can be brought to the doctor’s office
Diagnosis
Diagnosis is based on
Medical history
May be seen in people with a family history of hypercholesterolemia.
Prevalent in people with atherosclerotic cardiovascular disease with chronic high cholesterol, high saturated fatty acid intake, smoking, alcohol abuse, lack of exercise and other poor lifestyle.
There may be underlying diseases such as atherosclerotic cardiovascular disease, acromegaly, hypothyroidism, nephrotic syndrome, renal failure, acute hepatitis, cirrhosis, non-alcoholic fatty liver disease, etc. before the onset of the disease.
Thiazide diuretics (e.g., hydrochlorothiazide, furosemide, etc.), beta-blockers (e.g., metoprolol, bisoprolol), glucocorticoids (e.g., prednisone, dexamethasone, etc.), and other medications may be used prior to the onset of the disease.
Clinical manifestations
Symptoms
Usually there are no obvious symptoms, and some of them may present with yellow tumors and corneal bowing.
Signs
The disease itself usually does not cause abnormal signs. Some patients may present with limited abnormal skin elevations and grayish-white or white corneal lipid deposits on the outer edge of the cornea.
Auxiliary tests
Lipid profile
It is an important basis for confirming the diagnosis of the disease.
China’s 2016 revised Guidelines for Prevention and Control of Dyslipidemia in Chinese Adults states that cholesterol <5.2 mmol/L is within the normal range, between 5.2 and 6.2 mmol/l is borderline elevated, and ≥6.2 mmol/L is elevated.
In addition to the blood cholesterol level, lipid determination can also understand the level of other lipid items such as triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and so on.
Cholesterol is not as accurate as LDL-C in assessing and predicting the risk of developing atherosclerotic cardiovascular disease.
Genetic Testing
Used to clarify the diagnosis of family history hypercholesterolemia.
Diagnostic Criteria
The diagnosis is confirmed by lipid measurements suggesting cholesterol ≥6.2 mmol/L [2].
Differential diagnosis
The disease can be diagnosed by measuring blood cholesterol levels, and usually no differential is needed.
Treatment
General treatment
Intervention Lifestyle
Stop smoking and drinking.
Eat a reasonable diet, avoid high-fat diet, eat more fresh fruits and vegetables, and take enough vitamins.
Increase exercise, maintain healthy weight, and control body mass index (BMI) at 20.0-23.9kg/m2.
Medication
Statins
are the drugs of choice and can significantly reduce the risk of cardiovascular events.
Commonly used drugs include atorvastatin and resuvastatin.
Can cause liver function abnormalities, rhabdomyolysis and other adverse reactions, but mostly seen in high-dose users, so liver function and creatine kinase should be regularly monitored during the use of drugs.
Children, pregnant and lactating women should not use.
Cholesterol absorption inhibitor
Can inhibit the absorption of cholesterol in the small intestine and can be used in combination with statins.
The commonly used drug is ezetimibe.
May cause transient pain, gastrointestinal symptoms (nausea, vomiting, dyspepsia, etc.) and other adverse reactions.
It is contraindicated in pregnant and lactating women.
Bile Acid Chelators
Can block the reabsorption of cholesterol in the intestines to achieve the effect of lowering cholesterol levels in the blood.
Commonly used drugs include colestipol and colestipol.
Can cause nausea, vomiting, bloating, constipation and other gastrointestinal reactions.
Contraindicated for those with TG>4.5mmol/L and abnormal β-lipoproteinemia.
PCSK9 Inhibitors
PCSK9 inhibitors are currently recommended for very high-risk cardiovascular patients and familial high cholesterol patients who are unable to achieve LDL-C after high-dose potent statin therapy, and for very high-risk cardiovascular patients and familial high cholesterol patients who are unable to tolerate statins.
Commonly used drugs include eloxacinumab injection and aliskirenumab injection.
It is contraindicated in people who have severe allergic reactions to the drug and children under 13 years of age, pregnant and lactating women, and people with severe hepatic impairment.
Probucol
It affects lipoprotein metabolism and makes LDL easy to be removed through non-receptor pathway.
Mainly indicated for hypercholesterolemia, especially in patients with familial hypercholesterolemia and xanthomas, and has been shown to reduce cutaneous xanthomas.
Contraindicated in ventricular arrhythmias, prolonged QT interval, and low blood potassium.
Prognosis
Cure
Hypercholesterolemia is often effectively controlled with aggressive treatment and has a favorable prognosis.
Some patients with mild disease may recover spontaneously after active lifestyle intervention.
If untreated, it may lead to complications such as coronary heart disease and stroke, and the prognosis is poor.
Some of the very severe pureblooded hereditary hypercholesterolemia lacks effective treatment measures and has a poor prognosis.
Harmfulness
It can cause cardiovascular diseases, resulting in symptoms such as chest tightness, palpitations, shortness of breath, chest pain, and even acute myocardial infarction, affecting the quality of life and life expectancy.
It can induce stroke, leading to sequelae such as paralysis, limb dysfunction, intellectual disability, affecting normal life and work.
It can induce atherosclerotic occlusion of the lower limbs, leading to activity limitation and even necrosis of the limbs, seriously affecting the quality of life [9-10].
Daily
Daily management
Dietary management
Low-fat diet: Reduce the intake of foods high in cholesterol and saturated fatty acid intake, such as fried foods, animal oils, offal, etc. Daily cholesterol intake should be less than 300mg.
Eat more dietary fiber-rich carbohydrates: e.g. fresh fruits, vegetables, grains, potatoes, etc.
Exercise management
Moderate-intensity aerobic exercise (e.g., brisk walking, jogging, playing badminton, etc.) is recommended for 5 to 7 days per week for not less than 30 minutes each time.
People with cardiovascular disease should be evaluated and guided by a physician.
Lifestyle management
Stop smoking completely and effectively avoid exposure to second-hand smoke.
Stop drinking alcohol.
Maintain a good lifestyle.
Disease monitoring
Patients with hypertension and diabetes should learn how to measure blood pressure and blood glucose correctly, and regularly monitor and record changes in blood pressure and blood glucose.
Follow-up and review
Patients with hypercholesterolemia should have their blood cholesterol levels monitored on a regular basis (usually once every 3 to 6 months, depending on the patient’s condition and as determined by the specialist), so that the doctor can assess their condition and make timely adjustments to the treatment plan.
Prevention
Adopt good living habits
Eat a reasonable diet and avoid a high-fat diet.
Stop smoking and limit alcohol consumption.
Strengthen physical exercise and avoid obesity.