Hypercholesterolemia: Definition, Symptoms

Brief overview

• Symptoms: Initially no symptoms, but in the long term possibly serious consequences such as vascular calcification.
• Treatment: Among other things, changes in lifestyle and dietary habits, drug treatment of high cholesterol levels and existing underlying diseases.
• Causes and risk factors: Among other things, high cholesterol diet, heredity, other underlying diseases or certain medications.
• Diagnostics: Blood test, medical history and physical examinations

What is hypercholesterolemia?

Hypercholesterolemia is a disorder of fat metabolism in the body. The disease is characterized by an increased amount of cholesterol in the blood. Cholesterol (cholesterol) is a vital natural substance of animal cells.

Only a small proportion of cholesterol is ingested with food. A much larger proportion is produced by the body itself, mainly in the liver and the intestinal mucosa. This process is called cholesterol biosynthesis. The intermediate product is 7-dehydrocholesterol. This substance is the precursor to the vital vitamin D.

Lipoproteins

Only about 30 percent of cholesterol occurs freely in the human body. The remaining 70 percent is associated with fatty acids (cholesterol esters). As a fat-like substance, cholesterol is not water-soluble. However, it must be water-soluble for transport in the blood.

Depending on their composition, a distinction is made between different lipoproteins. The most important of these are chylomicrons, VLDL (“very low density lipoproteins”), LDL (“low density lipoproteins”) and HDL (“high density lipoproteins”). There are also IDL (“intermediate density lipoproteins”), which stands between LDL and VLDL, and lipoprotein a, which is similar in structure to LDL.

In hypercholesterolemia, the lipoproteins LDL and HDL play a crucial role. They consist largely of cholesterol and keep the cholesterol balance in equilibrium. LDL transports cholesterol from the liver via the blood to the other cells of the body.

The lipoprotein HDL counteracts this. It transports excess cholesterol back to the liver and thus prevents elevated cholesterol levels.

This is why LDL is also known as “bad” cholesterol and HDL as “good cholesterol”.

Hypercholesterolemia in the group of lipid metabolism disorders

How does hypercholesterolemia manifest itself?

Hypercholesterolemia, i.e. elevated cholesterol levels in the blood, does not cause any symptoms itself. Rather, hypercholesterolemia is a sign of other diseases and a certain lifestyle. In the long run, however, high blood cholesterol has potentially serious consequences.

Arteriosclerosis

The result is hypercholesterolemia. The excess cholesterol is deposited in the walls of the blood vessels. This sets off a process that ultimately damages the vessels (arteries).

This is because fats, carbohydrates, blood components, fibrous tissue and lime are deposited in the vessel wall along with the cholesterol, resulting in arteriosclerosis.

CHD and heart attack

For example, the risk of heart attack is about doubled at a total cholesterol level (HDL plus LDL) of 250 mg/dl. At a total value of over 300 mg/dl, it is four times as high as in people with normal cholesterol levels.

PAVK and stroke

If hypercholesterolemia damages the arteries of the legs, this may lead to so-called window-shopping disease. Doctors refer to this as pAVK (peripheral arterial occlusive disease). Patients then suffer from painful circulatory disorders, especially under stress (for example, when walking).

Xanthomas

Xathomas are fatty deposits in the tissues, primarily in the skin. Due to hypercholesterolemia or hypertriglyceridemia, fats and cholesterol are deposited, for example, on the trunk or hands, forming yellow-orange skin thickenings (plane xanthomas). If elevated cholesterol is deposited in the eyelids, doctors speak of xanthelasmata.

Typical of hypertriglyceridemia are also yellowish nodules on reddened skin, especially on the buttocks and the extensor sides of the arms and legs. Physicians refer to these skin manifestations as eruptive xanthomas. Fat deposits on the hand lines usually indicate an increase in IDL and VLDL.

Hypercholesterolemia at the eye

How is hypercholesterolemia treated?

The aim of hypercholesterolemia therapy is primarily to reduce the risk of dangerous vascular calcification and thus of cardiovascular disease. Treatment can lower LDL and HDL cholesterol as well as triglycerides within a certain target range.

For triglycerides, the target value is below 150 mg/dl. HDL cholesterol is ideally above 40 mg/dl in men and above 50 mg/dl in women.

According to the ESC, patients can also be divided into four risk categories according to their cardiovascular risk:

Risk

low

moderate

high

very high

In the case of patients at very high risk, experts advise a target LDL cholesterol level of 55 mg/dl, and in the case of high risk, a target level of 70 mg/dl. In the case of moderate risk, an LDL cholesterol level of 100 mg/dl is recommended, and in the case of low risk, a target value of below 116 mg/dl.

• Prevention or therapy of inflammation of the pancreas (pancreatitis).
• Prevention or elimination of xanthomas, a fatty liver, etc.

Stages of hypercholesterolemia treatment

In case of hypercholesterolemia, the first priority is to change lifestyle habits as well as diet. For overweight patients, experts recommend achieving a normal body weight. Normal weight patients, on the other hand, are advised by doctors to maintain their weight.

Do sports or consciously make your everyday life active.

For example, climb stairs instead of using the elevator! Ride your bike to work instead of taking the car! In this way, you not only counteract LDL hypercholesterolemia, but also lower your triglyceride level.

In addition, the “good” HDL increases. In addition, this is the most effective way to lose weight and prevent further cardiovascular diseases or diabetes.

Many sufferers are already helped by replacing butter with diet margarine and vegetable oils. In general, a high proportion of unsaturated fatty acids is beneficial. Saturated fatty acids, on the other hand, should be avoided.

For children and adolescents with hypercholesterolemia, doctors advise a daily intake of about one to three grams. Too much phytosterols, however, has the opposite effect. They bear a strong resemblance to cholesterol and may in turn trigger vascular calcification.

Avoid hidden fat.

Also choose lean meats and sausages that are low in saturated fats. These include low-fat fish such as trout or cod, game, veal and poultry.

Prepare your meals low in fat and eat fruits and vegetables daily.

Reduce cholesterol-rich foods.

These include, above all, egg yolks (and their further processing such as mayonnaise), offal or shellfish and crustaceans.

Pay attention to protein and fiber.

Vegetable protein in particular, found especially in soy products, is capable of potentially lowering hypercholesterolemia. This is because it increases the absorption of LDL and the high cholesterol level decreases.

If possible, stop smoking and drink alcohol only in moderation.

In the case of severe hypertriglyceridemia, doctors even recommend abstaining from alcohol completely. This will also prevent other health problems such as liver damage. It is also advisable to avoid sugary soft drinks if you have hypercholesterolemia with elevated triglycerides.

Give preference to “complex” carbohydrates.

Stay balanced.

Diets that are too hard do more harm to the body than good! Therefore, the point of a change is to train yourself other eating habits in the long term and not to abruptly give up everything.

Dietary composition

The German Society for Combating Lipid Metabolic Disorders and Their Consequential Diseases (Lipid League) advocates the following recommendation regarding daily dietary composition:

Nutrient	Amount or proportion of total energy intake per day	suitable food examples
Carbohydrates	50-60 percent	Fruit, potatoes, vegetables, cereals
Protein	10-20 percent	Fish, lean poultry, low-fat milk(products)
Dietary fiber	more than 30 grams/day
Bold	25-35 percent	Butter, frying fat, fatty meat and dairy products. Beware of hidden fat!
Fatty acids	saturated 7-10 percent	animal fat
monounsaturated 10-15 percent polyunsaturated 7-10 percent	Rapeseed, olive, soybean, corn germ, sunflower oil, diet margarine
Cholesterol	less than 200-300 grams/day	Egg yolk (no more than two per week), egg yolk products (e.g. egg pasta, mayonnaise), offal

Treatment of other diseases

Also, take your medications consistently to successfully counteract hypercholesterolemia. If you have any doubts or questions, do not hesitate to ask your doctor for advice.

Medication hypercholesterolemia treatment

At the beginning of a drug treatment for hypercholesterolemia, the doctor usually prescribes only one drug, usually statins. If the high cholesterol levels cannot be reduced sufficiently, the dose is increased.

If there is no significant improvement after three to six months, he extends the therapy with other hypercholesterolemia drugs.

Statins (CSE inhibitors)

As a result, more LDL receptors are formed in the cell envelope. These “tentacles” enable the cell to take up cholesterol from the blood. Hypercholesterolemia decreases.

Anion exchange resins – bile acid binders

Anion exchange resins or bile acid binders bind these bile acids in the intestine. As a result, they disappear with their cholesterol from the enterohepatic circulation.

To obtain new cholesterol for the bile, the liver cells stimulate their LDL receptors. Cholesterol passes out of the blood and the hypercholesterolemia improves.

Known active ingredients are colestyramine and colesevelam. However, both are now only rarely used in combination therapies.

The active ingredient is called ezetimibe and prevents the absorption of cholesterol from the intestine. For hypercholesterolemia treatment, there is a fixed combination with the CSE inhibitor simvastatin.

Fibrates

Physicians use fibrates, in addition to hypercholesterolemia therapy, primarily to treat elevated triglyceride and lowered HDL levels. The effect is complex. Among other things, the degradation of triglyceride-rich lipoproteins increases.

Nicotinic acid

Doctors also combine this drug with statins to treat hypercholesterolemia. However, a study conducted in the USA in 2011 with a specific nicotinic acid preparation in combination with statins did not confirm a benefit.

Omega-3 fatty acids

Omega-3 fatty acids are said to have numerous benefits. In 2010, the European Food Safety Authority (EFSA) published a report on the claimed effects of various omega-3 fatty acids, as there are many studies on this subject, some of which are contradictory.

According to the expert statements, the intake of omega-3 fatty acids supports normal heart function. However, the experts denied the positive effect on hypercholesterolemia.

PCSK9 inhibitors

After lengthy research, PCSK9 inhibitors were finally approved for the treatment of high cholesterol levels in Europe in the fall of 2015. The active ingredients in this group of drugs are proteins, or more precisely antibodies, that bind to PCSK9 enzymes, rendering them ineffective. This makes more LDL receptors available again to counteract hypercholesterolemia.

Doctors also have the option of prescribing this agent if the patient cannot tolerate statins. The physician usually administers PCSK9 antibodies every two to four weeks by means of an injection under the skin (subcutaneous). However, due to the high cost of treatment, the use of PCSK9 inhibitors is rather restrained.

LDL apheresis

In an artificial circuit, tubes guide the blood to a machine. This either divides it into plasma and cells or cleans LDL directly from it.

Tubes then return the now “clean” blood to the body. LDL apheresis can also be used to lower elevated levels of lipoprotein a, IDL and VLDL. The procedure is usually performed once a week. In parallel, physicians continue to treat hypercholesterolemia with medication.

Depending on the cause of hypercholesterolemia, different forms can be distinguished.

Reactive-physiological form

This group includes, for example, a cholesterol-rich diet. As a reaction to this, the fat metabolism in the human body is overloaded. The body no longer excretes increased cholesterol quickly enough, and high cholesterol levels develop.

Secondary form

In the secondary form of hypercholesterolemia, other diseases cause high cholesterol levels. These include diabetes mellitus, hypothyroidism, nephrotic syndrome or a buildup of bile in the bile ducts (cholestasis). In addition, certain drugs are able to trigger hypercholesterolemia.

Diabetes mellitus

The cholesterol therefore remains in the blood and the patient develops hypercholesterolemia. In obesity, the formation of LDL cholesterol is increased. In addition, insulin no longer works properly (insulin resistance, type 2 diabetes). Fatty acids enter the liver in increased amounts, causing VLDL to increase (hypertriglyceridemia).

Hypothyroidism

Nephrotic syndrome and cholestasis

Nephrotic syndrome results from damage to the kidneys. Typically, increased protein levels in the urine (proteinuria), decreased proteins in the blood (hypoproteinemia, hypalbuminemia) and water retention in the tissues (edema) are found.

In addition, hypercholesterolemia and triglyceridemia are among the classic signs of nephrotic syndrome. The “good” HDL cholesterol is often reduced.

Drugs

Numerous medications may also have an adverse effect on lipid metabolism. In most cases, cortisone preparations lead to hypercholesterolemia. Treatments with estrogens, the pill, water tablets (thiazides) or beta blockers usually increase triglycerides in the blood.

In addition, high cholesterol levels have been observed in pregnant women. In this case, however, hypercholesterolemia has little clinical significance.

Primary form

In polygenetic hypercholesterolemia, several errors in the building blocks of the human genome (genes) lead to slightly elevated cholesterol levels. External factors such as a poor diet and lack of exercise are usually added.

Familial monogenetic hypercholesterolemia

In monogenetic hypercholesterolemia, the defect lies solely in the gene that contains the information for the production of LDL receptors. They serve to eliminate LDL cholesterol from the blood.

Heterozygotes have one diseased and one healthy gene and usually suffer their first heart attacks in middle age unless they have their hypercholesterolemia treated. Familial hypercholesterolemia may be inherited to the next generation (autosomal dominant inheritance).

Hypercholesterolemia due to different apolipoproteins

Another genetic defect affects apolipoprotein B100. This protein is involved in the assembly of LDL and helps in the uptake of LDL cholesterol into the cell. More specifically, it accomplishes the binding of LDL to its receptor.

Medicine has found that hypercholesterolemia occurs mainly in people with apolipoprotein E 3/4 and E 4/4. They also have an increased risk of developing Alzheimer’s disease.

Hypercholesterolemia due to PCSK9

PCSK9 (proprotein convertase subtilisin/kexin type 9) is an endogenous protein (enzyme) found primarily in liver cells. This enzyme binds LDL receptors, whereupon their number is reduced.

Consequently, high cholesterol levels continue to rise. However, there are also known cases in which PCSK9 has lost its function due to mutations (“loss of function”), which reduces the risk of hypercholesterolemia.

Other inherited dyslipidemias

Other dyslipidemias may also be due to genetic defects. Affected individuals also usually have elevated blood cholesterol levels:

Disease	Disorder	Disease characteristics
Familial combined hyperlipoproteinemia
Familial dysbetalipoproteinemia
Hyperchylomicronemia
Familial hypoalpha-lipoproteinemia

In addition, lipoprotein a may be elevated. It is composed of LDL and apolipoprotein a. Among other things, it inhibits processes in blood clotting, especially in the dissolution of blood clots (plasminogen competitor).

Diagnosis and examination

The general practitioner or a specialist in internal medicine (internist) diagnoses hypercholesterolemia by a blood test. In many cases, the elevated cholesterol levels are noticed by chance.

If the values are elevated, the physician draws blood again, this time after food intake.

For healthy adults without risk factors for cardiovascular disease, the following target values apply according to European guidelines:

LDL cholesterol	< 115 mg/dl
HDL cholesterol	Women > 45 mg/dl, Men > 40 mg/dl
Triglycerides	< 150 mg/dl
Lipoprotein a (Lp a)	< 30 mg/dl

If the blood draw has revealed hypercholesterolemia, the doctor will check the levels after about four weeks.

In people who have no other risk factors for atherosclerosis (such as high blood pressure), experts advise an LDL/HDL quotient below four. In contrast, a quotient below three is recommended for people with such other risk factors, and a quotient below two is recommended for people who already have atherosclerosis, for example.

Since hypercholesterolemia is a symptom, it is important that physicians make a more precise diagnosis of the underlying disease. For this purpose, the German Society for Fat Science has published a scheme that can be used to assign hypercholesterolemia to a disease.

LDL cholesterol blood level	Family history of coronary artery disease (CAD)	Diagnosis
> 220 mg/dl	positive	Familial hypercholesterolemia
Negative	Polygenic hypercholesterolemia
190-220 mg/dl		Familial combined hyperlipidemia (esp. with elevated triglycerides)
negative	Polygenic hypercholesterolemia
160-190 mg/dl	positive	Familial combined hyperlipidemia (esp. with elevated triglycerides)
negative	Pure diet-induced hypercholesterolemia

Physicians code the diagnosis of hypercholesterolemia with the ICD-10 code E78 – “Disorders of lipoprotein metabolism and other lipidemias” or with E78.0 – “Pure hypercholesterolemia”.

Taking a medical history is of crucial importance in hypercholesterolemia. It provides the doctor with information about possible causes and risk factors.

The doctor will ask you about your dietary habits and alcohol or cigarette consumption. Also tell the doctor about any known diseases you suffer from, such as diabetes, thyroid or liver disease. Among other things, the doctor will ask you the following questions:

• Do you already suffer from any diseases? If yes, which ones?
• Do you take medication permanently and what is the name of it?
• Do you sometimes experience pain in your legs when walking, possibly so severe that you have to stop?
• Do you have any family members with hypercholesterolemia?

Physical examination

The doctor may calculate your BMI (body mass index) from body weight and height. In addition, he measures blood pressure and pulse and listens to the heart and lungs (auscultation).

Risk calculation

As part of the examinations of the body and blood, the physician determines a risk value for cardiovascular disease. The value indicates how high the risk is that the respective patient will suffer a heart attack in the next ten years.

Further examinations

Under certain circumstances, the doctor will carry out further examinations. If there are signs of diseases that cause hypercholesterolemia, these must be clarified. With the aid of ultrasound (sonography), the doctor also visualizes the condition of large arteries – for example, the carotid arteries – and assesses the degree of vascular calcification.

Course of the disease and prognosis

The course of hypercholesterolemia varies greatly from individual to individual. The extent of the elevated cholesterol level differs depending on the cause. For example, people with hereditary hypercholesterolemia have a significantly higher risk of dying from a heart attack.

Studies show that affected men and women often had a blood clot in their coronary arteries before the age of 60.

The individual forms of therapy respond differently to each patient. Ultimately, it is your personal commitment that decisively determines the success of the treatment and gives you the opportunity to prevent the dangerous secondary diseases of hypercholesterolemia.