Blood Lipids (Hyperlipidemia)

Blood lipids are the general term for neutral fats in the blood plasma and are widely present in the human body. They are essential substances for the basic metabolism of life’s cells. Generally, the main components of blood lipids are triglycerides and cholesterol. Triglycerides are involved in energy metabolism in the body, while cholesterol is mainly used for the synthesis of cell plasma membranes, steroid hormones, and bile acids. Hyperlipidemia refers to excessively high levels of blood lipids, a systemic disease where fat metabolism or transport is abnormal, causing plasma lipids to be higher than normal values.[1][2] This refers to high levels of cholesterol or triglycerides in the blood, or low levels of high-density lipoprotein cholesterol, which modern medicine calls dyslipidemia.

Hyperlipidemia is also divided into primary and secondary types.[2] The former is related to environmental factors and family genetics, while the latter is caused by conditions such as diabetes, hypothyroidism, obesity, and pancreatitis. Furthermore, because hyperlipidemia has no obvious symptoms in its early stages, it is easily overlooked by patients and often develops unknowingly, only to be discovered during a health check-up.[1]

Causes

Western Medicine Perspective

Pathogenesis:

The low-density lipoprotein (LDL) receptor, also known as the ApoB/E receptor, is a cell surface glycoprotein, most abundant in liver cells. The gene for the LDL receptor is located on human chromosome 19. The cause of familial hypercholesterolemia is a natural mutation in the LDL receptor gene, including deletions, insertions, nonsense mutations, and missense mutations.[4] Dozens of LDL receptor gene mutations have been discovered and can be divided into five main classes:[5]

• Class I mutation: Characterized by the mutant gene not producing a measurable LDL receptor. There are no LDL receptors on the cell membrane. This is the most common type of mutation.

• Class II mutation: Characterized by impaired maturation and transport of the LDL receptor synthesized by the mutant gene within the cell. The number of LDL receptors on the cell membrane is significantly reduced, which is also a common type.

• Class III mutation: Characterized by the LDL receptor synthesized by the mutant gene being able to reach the cell surface but unable to bind with the ligand.

• Class IV mutation: In this type of mutation, the mature LDL receptor, after reaching the cell surface, can bind to LDL but cannot be internalized.

• Class V mutation: Characterized by normal synthesis of the LDL receptor, binding with LDL, and subsequent internalization, but the receptor cannot be recycled back to the cell membrane.

The occurrence of LDL receptor mutations varies among different ethnic groups. For example, in heterozygous familial hypercholesterolemia among French-Canadians, mutations caused by receptor gene deletion account for 60%. The most prominent abnormality of an LDL receptor defect is the slowed breakdown of LDL from the plasma. When the LDL receptor is normal, part of the intermediate-density lipoprotein (IDL) can be directly taken up and broken down by the liver’s LDL receptors. In familial hypercholesterolemia, LDL cannot be broken down, causing more IDL to be converted into LDL, thus increasing LDL production.[6]

Traditional Chinese Medicine (TCM) Perspective

• Constitutional Factors: The unique constitution of an individual means that their internal organs and tissues have different degrees of resilience. Due to these constitutional peculiarities, there is often a susceptibility to certain pathogenic factors or diseases. For instance, the Lingshu (Spiritual Pivot) states: “If the flesh is not firm and the skin texture is loose, one is susceptible to wind diseases… If all five zang-organs are soft, one is prone to wasting-thirst disorder (Xiao Dan),” and “Those with small bones and weak flesh are prone to chills and fever.”

• Behavioral Factors: Good habits are an important guarantee of health. The Suwen (Basic Questions) says: “Diet is regulated, daily life is regular, and one does not work recklessly, thus the form and spirit are in harmony, and one can live out their natural lifespan.” “Going against the joy of life,” meaning unhealthy habits and lifestyle, is an important factor in the onset of internal diseases.

Prevention

1. Adjust to a reasonable diet: Eat less animal fat and organ meats, sweets, and starchy foods. Eat more plant-based protein, oils, vegetables, fruits, and fish.[7]

2. Adjust lifestyle and work habits: Actively participate in physical activities, avoid prolonged sitting, and control weight.[8] Quit smoking and limit alcohol consumption.[8]

3. Regular check-ups: Individuals with a family history of coronary heart disease, diabetes, or primary hyperlipidemia should have regular comprehensive examinations including blood lipids, blood sugar, and liver function annually.

4. Early detection for at-risk groups: Patients with hyperlipidemia, especially men over 40, postmenopausal women, or those with risk factors like hypertension, diabetes, and coronary heart disease, should have their blood lipids checked regularly for early prevention and treatment.

5. Screening: To enable early and timely detection of hyperlipidemia, it is recommended that all adults over 20 years of age have their plasma total cholesterol levels checked regularly. All patients with pancreatitis should have their plasma triglyceride levels measured.

Precautions
Adjust the diet structure to be reasonable and reduce the intake of saturated fatty acids and cholesterol.

Common Symptoms

Typical Symptoms: Arteriosclerosis, yellow nodules (xanthomas), high blood pressure, unstable angina, and [diabetes].[9]

I. Symptoms
The clinical manifestations of hyperlipidemia are mainly xanthomas caused by lipid deposition in the dermis and arteriosclerosis caused by lipid deposition in the vascular endothelium.[10] Although hyperlipidemia can cause xanthomas, their incidence is not very high; and the occurrence and development of atherosclerosis is a slow and gradual process. Therefore, under normal circumstances, most patients have no obvious symptoms or abnormal signs.[10] Many people only discover they have elevated plasma lipoprotein levels during a blood biochemistry test for other reasons.

• Age of onset, gender, and race: Although homozygous familial hypercholesterolemia is very rare, its age of onset is early, and patients can show clinical symptoms and signs of coronary heart disease before the age of 10. Without timely and effective treatment, patients often die of myocardial infarction around the age of 20. Lipoprotein lipase deficiency can manifest as chylomicronemia syndrome from infancy or childhood. Familial defective apolipoprotein B-100 is mainly seen in Caucasian populations. LDL-cholesterol levels begin to rise in childhood or adolescence. With increasing age, plasma total cholesterol and LDL-cholesterol levels will continue to rise. Not all primary hyperlipidemias start in childhood. Most patients with familial combined hyperlipidemia develop hyperlipidemia after adulthood, although a few may develop it in childhood.[11]

• Premature cardiovascular disease: There is often a family history of premature coronary heart disease. The incidence of premature coronary heart disease in familial defective apolipoprotein B-100 is similar to that of heterozygous familial hypercholesterolemia. About one-third of patients develop coronary heart disease before the age of 60. Those who develop peripheral vascular disease are often complicated by hypertension. 48% of patients have carotid atherosclerosis. Early-onset vascular lesions are more common in type III hyperlipoproteinemia.

• Pancreatitis: Patients with familial lipoprotein lipase deficiency can suffer from recurrent pancreatitis due to chylomicron emboli obstructing the pancreatic capillaries, causing localized pancreatic cell necrosis. One-third to one-half of patients may develop acute pancreatitis.

• Xanthomas:

  • Xanthelasma (Plane xanthoma): Mainly seen around the eyelids, hence also called xanthelasma palpebrarum, which is relatively common clinically.[12]

  • Palmar xanthoma: Distributed in the creases of the palms and fingers, appearing as orange-yellow linear, flat, slightly raised lesions.[13]

  • Tuberous xanthoma: Occurs on the extensor surfaces of elbows, knees, finger joints, as well as ankles, hips, and buttocks.[14]

  • Eruptive xanthoma: Appears as small orange or brownish-yellow papules with a whitish center and an inflammatory base, resembling acne.[15]

  • Tuber eruptive xanthoma: More common on the extensor surfaces of the limbs, such as the elbows and buttocks, appearing as orange-yellow nodules.

  • Tendon xanthoma: A special type of nodular xanthoma that occurs in the tendons, commonly in the Achilles tendon, extensor tendons of the hand or foot, quadriceps femoris at the knee, and deltoid tendon at the shoulder.[14]

• Other manifestations: Corneal arcus, also known as arcus senilis, if it appears in people under 40, is often accompanied by hyperlipidemia. Severe hypertriglyceridemia can cause lipemia retinalis. Triglyceride deposition in the reticuloendothelial cells can also cause hepatosplenomegaly. Chylomicronemia can also lead to dyspnea and neurological symptoms.

II. Diagnostic Criteria for Hyperlipidemia
Currently, there is no unified international or domestic standard. To prevent and treat atherosclerosis and coronary heart disease, a suitable plasma cholesterol level is below 5.17 mmol/L (200 mg/dL).[1] The new standards recommend starting drug therapy when LDL-C concentration is >130 mg/dL, with a treatment goal of LDL-C <100 mg/dL.[7]

• Classification of Hyperlipidemia:

  • Hypercholesterolemia: Elevated plasma Total Cholesterol (TC) levels.

  • Mixed hyperlipidemia: Elevated plasma TC and Triglyceride (TG) levels.[16]

  • Hypertriglyceridemia: Elevated plasma TG levels.[17]

  • Low high-density lipoproteinemia: Decreased plasma HDL-C levels.

  • Primary hyperlipidemia: Lipid metabolism abnormality caused by genetic defects or mutations, dietary habits, lifestyle, and other environmental factors.[3]

  • Secondary hyperlipidemia: Caused by a specific underlying disease.[3]

• Coronary Heart Disease Risk Factors Other Than High Cholesterol:

  • Gender: The incidence rate in men is higher than in women.

  • Age: The incidence of coronary heart disease increases with age.

  • Hypertension: Long-term elevation of either systolic or diastolic blood pressure increases the risk.

  • Smoking: The degree of risk is related to the amount of smoking.[8]

  • Family history of coronary heart disease.

  • Diabetes and impaired glucose tolerance.

  • Premature menopause.

  • Obesity.

Clinical Examination

1. Full lipid profile measurement: Including fasting TC, TG, LDL-C, and HDL-C.

2. Presence of chylomicrons in plasma: A simple method is to place the plasma in a 4°C refrigerator overnight and observe if there is a “creamy” top layer.

3. Plasma LDL-C concentration: Can be calculated using the Friedewald formula: LDL-C (mg/dL) = TC – (HDL-C + TG/5) or LDL-C (mmol/L) = TC – (HDL-C + TG/2.2).

4. Special tests for lipid metabolism:

   • Apolipoprotein measurement: Measuring plasma ApoB and ApoAⅠ levels is significant for predicting the risk of coronary heart disease.

   • In vivo lipoprotein metabolism tests.

5. Other examinations: Patients with familial combined hyperlipidemia and familial hypertriglyceridemia have insulin resistance, and their plasma insulin levels are elevated, which can manifest as abnormal glucose tolerance clinically.

Differential Diagnosis

When diagnosing hyperlipidemia, it is necessary to clarify the type of lipid metabolism abnormality the patient has. Because the treatment methods for hyperlipidemia caused by different reasons are also different, it is necessary to distinguish between primary and secondary hyperlipidemia and further determine the specific cause.

Complications

• Premature coronary heart disease is more common in familial hypercholesterolemia.

• Significant hypertriglyceridemia can cause acute pancreatitis.

Treatment

Western Medicine Treatment

The goal of treating hyperlipidemia is to reduce the incidence of coronary heart disease and cardiovascular events by lowering blood lipid levels. Treatment for primary hyperlipidemia mainly includes adjusting lifestyle and diet, lipid-lowering drug therapy, plasma purification therapy, surgical treatment, and gene therapy.

• Weight control: Many epidemiological data show that the average plasma cholesterol and triglyceride levels of obese people are significantly higher than those of non-obese people of the same age.

• Exercise: Physical activity can not only enhance cardiopulmonary function, improve insulin resistance and glucose tolerance, but also reduce weight, lower plasma triglyceride and cholesterol levels, and increase HDL cholesterol levels.

• Smoking cessation: Smoking can increase plasma cholesterol and triglyceride levels and decrease HDL-cholesterol levels.[8]

• Dietary therapy: Plasma lipids mainly come from food. By controlling the diet, plasma cholesterol levels can be reduced by 5%-10%.[8]

• Drug therapy:

  • Statins: HMG-CoA reductase inhibitors are a class of lipid-lowering drugs with good efficacy and are currently the most widely used.[19]

  • Fibrates: Phenoxy-aromatic acid derivatives.

  • Niacin: Belongs to the B vitamins, but has a lipid-regulating effect when the dosage exceeds that of a vitamin.

  • Resins (bile acid sequestrants): These drugs include cholestyramine and colestipol.

  • Probucol.

  • Fish oil – Omega-3 fatty acids.

• Non-drug treatment for severe hyperlipidemia: For a very small number of patients with extremely high blood lipid levels, often due to genetic abnormalities, treatment methods such as plasma purification, surgical treatment (such as partial ileal bypass, portacaval shunt), can be considered.

Traditional Chinese Medicine (TCM) Treatment

• Main syndrome: The treatment should focus on regulating the liver and spleen.

• Treatment principle: Resolve dampness and promote digestion.

• Formula: Modified San Xian Jiang Zhi Fang:

  • Malt (Mai Ya), Medicated Leaven (Shen Qu), Dried Tangerine Peel (Chen Pi), Hawthorn Fruit (Sheng Shan Zha), Goji Berry (Gou Qi Zi), Red Sage Root (Dan Shen), Licorice Root (Gan Cao).

Nursing Care

1. Dietary control: Since most of the lipids in the human body come from food, people with hyperlipidemia should have a controlled diet. The staple food should be matched with some coarse grains, and the non-staple food should be mainly fish, lean meat, beans and bean products, various fresh vegetables, and fruits.

2. Beneficial foods: Seaweed, laver, black fungus, enoki mushroom, shiitake mushroom, garlic, and onion are beneficial for lowering blood lipids and preventing atherosclerosis and can be eaten often.

3. Cooking methods: Use vegetable oil for cooking and eat less fried food. Eat fewer peanuts because they contain a lot of oil, but you can eat walnuts, sunflower seeds, and other nuts.

4. Foods to limit: Those with high cholesterol should eat less egg yolk, meat (especially fatty meat), animal organs, chicken skin, duck skin, shrimp skin, fish roe, brain, and other foods with high cholesterol content. Those with high triglycerides should avoid sugar and sweets and limit their total food intake.

Dietary Health

Suitable Foods:

1. Eat more vegetables and fruits.

2. Eat more plant-based protein.

3. Eat more tubers.

Foods to Avoid:

1. Avoid high-salt diets.

2. Avoid high-fat diets.