Hypercholesterolemia

Hypercholesterolemia is defined as an increase in cholesterol levels in the blood. Cholesterol is a lipid present in all cells, which the body uses to form cell membranes and produce certain hormones, bile acids, and vitamin D. However, excess cholesterol can be very harmful as it increases the risk of developing cardiovascular diseases by promoting cholesterol accumulation in the arterial walls (atherosclerosis).

Cholesterol is naturally produced in the liver, but a significant portion also comes from food. Since it is insoluble in water, it is transported by lipoproteins. The types of cholesterol are classified according to these lipoproteins:

• LDL (low-density lipoproteins): These transport cholesterol to the tissues. Known as "bad cholesterol," LDL cholesterol can penetrate the arterial wall from the bloodstream. Most cholesterol in the blood is LDL cholesterol.
• HDL (high-density lipoproteins): These collect cholesterol from the tissues and carry it to the liver for elimination as bile. This is referred to as "good cholesterol."

Cholesterol levels are measured in milligrams per deciliter (mg/dL). Healthy HDL values are above 45 mg/dL, while LDL levels should be below 100 mg/dL. The optimal total cholesterol value should be below 200 mg/dL.

Elevated cholesterol levels are those at which lipid-lowering treatment is recommended, depending on each person’s baseline risk. The cholesterol level at which treatment is advised depends on the patient’s risk of developing cardiovascular complications. The higher the risk, the lower the cholesterol level at which treatment is recommended, and the lower the target LDL cholesterol level.

Depending on its origin, hypercholesterolemia is classified into the following types:

• Secondary hypercholesterolemia: Results from an underlying condition.
• Primary hypercholesterolemia:
• Familial hypercholesterolemia: Genetic in origin. It can be inherited from both parents (homozygous familial hypercholesterolemia) or just one (heterozygous familial hypercholesterolemia).
• Polygenic hypercholesterolemia: Combines genetic and environmental factors. This is the most common type of primary hypercholesterolemia.

Additionally, depending on whether other elevated substances are present in the blood, it is classified as:

• Pure hypercholesterolemia: Only cholesterol levels are elevated.
• Mixed dyslipidemia: Both cholesterol and triglyceride levels are elevated.

Symptoms

Primary hypercholesterolemia does not produce any symptoms other than elevated blood cholesterol levels. Familial hypercholesterolemia, however, may sometimes present symptoms such as:

• Xanthomas: Yellow or orange plaques or nodules on the skin due to cholesterol accumulation. Commonly found on the elbows, knees, fingers, and tendons, particularly the Achilles tendon.
• Corneal arcus: A white or gray ring around the iris caused by cholesterol buildup.
• Xanthelasmas: Xanthomas that appear on the eyelids.

Causes

Familial hypercholesterolemia is caused by a mutation in the LDL receptor gene, preventing normal cholesterol elimination and leading to its accumulation in the blood. Other mutations responsible for elevated cholesterol levels have been identified in the apolipoprotein B gene, which binds to the LDL receptor gene, and the PCSK9 gene, a key protein in cholesterol degradation in the liver.

Secondary hypercholesterolemia is caused by diseases such as hypothyroidism, diabetes mellitus, or chronic kidney disease. It can also be due to certain medications, including cancer treatments, acne medications, antihypertensives, or antiarrhythmics. Polygenic hypercholesterolemia is primarily caused by an unhealthy diet rich in lipids and cholesterol.

Risk Factors

The main risk factors for increased cholesterol levels include:

• Poor diet: Saturated and trans fats increase cholesterol levels.
• Sedentary lifestyle: Exercise helps increase HDL levels.
• Overweight or obesity.
• Smoking: Can lower HDL levels.
• Alcohol consumption: Excessive alcohol increases total cholesterol levels.
• Family history.
• Age: More common after age 40 as liver function declines.

Complications

Hypercholesterolemia can lead to various conditions, including:

• Atherosclerosis: Excess cholesterol accumulates in the arterial walls, forming plaques that narrow and harden the arteries, reducing blood flow and limiting oxygen and nutrient delivery to organs.
• Angina or heart attack: Due to reduced blood supply.
• Stroke: Caused by insufficient oxygen reaching the brain.
• High blood pressure.
• Kidney failure.
• Early death in cases of homozygous familial hypercholesterolemia, as cholesterol levels often exceed 500 or 600 mg/dL, significantly increasing the risk of heart disease.

Prevention

The key to preventing high cholesterol is diet and physical activity:

• Eat foods rich in fiber and antioxidants, such as vegetables, legumes, fruits, and whole grains (cereal, rice, and pasta).
• Increase intake of monounsaturated fats, such as olive oil, avocado, and nuts.
• Consume Omega-3 and Omega-6: sardines, mackerel, anchovies, salmon, walnuts, sunflower oil, corn, and soy.
• Avoid foods high in saturated and trans fats: butter, aged cheese, fatty meats, processed meats, industrial baked goods, fried foods, and snacks.
• Cook food by boiling, baking, steaming, or grilling instead of frying or breading.
• Exercise several days a week.
• Avoid smoking.
• Reduce alcohol consumption.

Which Doctor Treats Hypercholesterolemia?

Hypercholesterolemia is usually diagnosed by family medicine, internal medicine, or preventive medicine units. Familial hypercholesterolemia requires genetic specialists. Endocrinologists may also be involved in treatment.