Familial hypercholesterolemia is an inherited disorder by which blood cholesterol levels become abnormally elevated. The result is severe disorders of the blood circulatory system. Treatment is by medication and is supported by a healthy lifestyle.
What is familial hypercholesterolemia?
Familial hypercholesterolemia is the genetic elevation of blood cholesterol levels. The prefix hyper- means “over” and the suffix -emia stands for “blood”; consequently, hypercholesterolemia means something like: Excess of cholesterol in the blood. Cholesterol is an important building block in the body. It is involved in various bodily processes, including hormone formation and energy balance. Cholesterol is both produced in the body and ingested with food. In familial hypercholesterolemia, the metabolism is disturbed, resulting in far more cholesterol in the body than is healthy. A distinction is made between different forms. In polygenic familial hypercholesterolemia, it is not the genes alone that cause the increase in cholesterol, but also lifestyle and dietary style. Monogenic familial hypercholesterolemia is purely hereditary. It is divided into heterozygous and homozygous familial hypercholesterolemia, depending on whether only one parent (heterozygous) or both parents (homozygous) inherited the genetic alteration.
Causes
The cause of familial hypercholesterolemia is a change in genes responsible for cell metabolism and specifically for the uptake of LDL cholesterol. These so-called LDL receptors take up cholesterol produced by various organs from the blood into the cells. In familial hypercholesterolemia, the LDL receptors cannot pull enough cholesterol from the blood due to a disorder. As a result, it accumulates on the blood vessels and gradually leads to atherosclerosis, or calcification of the vessels. If only one parent has inherited the gene mutation, the disorder is much less severe, since more functioning LDL receptors are present here. If the homozygous form is present, in which both father and mother have passed on the altered gene, lipid metabolism is much more severely disturbed and massively elevated cholesterol levels occur.
Symptoms, complaints, and signs
Initially, there are no symptoms in familial hypercholesterolemia. Often, however, a highly elevated total cholesterol level is measured in young people as a result of an incidental finding. However, the typical symptoms of atherosclerosis develop early in affected individuals. The appearance of a large number of xanthomas and xanthelasmas also indicates a high cholesterol concentration in the blood. Xanthomas represent yellowish deposits of plaques in the skin. They appear as yellowish skin lesions that can take different forms. In xanthelasma, the yellowish deposits are located in the tissues of the upper and lower eyelids of the eyes. Arteriosclerosis develops very quickly and often leads to high-grade vasoconstriction and even vascular occlusion, causing heart attacks or strokes, even in young sufferers. In addition to cardiovascular disease, kidney damage is also common. Another common symptom in familial hypercholesterolemia is a ring- to arc-shaped degeneration of the cornea, also known as senile arch or arcus senilis. Arcus senilis usually occurs after age 80. In familial hypercholesterolemia, even young people show this feature. Overall, the life expectancy of affected individuals is greatly reduced due to the vascular occlusions and resulting complications. Even with the maximum possible lipid-lowering therapy, affected individuals reach an average age of only about 33 years.
Diagnosis and progression
Young people with familial hypercholesterolemia usually have no symptoms yet, and so the disease often remains undetected at first. The danger here is that although the elevated cholesterol does not yet cause noticeable symptoms, it still causes damage in the body. Arteriosclerosis begins unnoticed and progresses steadily. Fat is deposited in the walls of the vessels. The diameter of the vessels becomes smaller and smaller, which leads to an obstruction of the blood flow.If the blood supply is reduced, this causes a poorer supply to the organs and the entire body. Depending on which vessels are affected, the consequences can be angina pectoris (stenosis of the heart) and heart attacks, vascular occlusions in the legs with the development of a so-called smoker’s leg, and a stroke. Cholesterol can be deposited in the skin and lead to yellowish nodules, mostly on the eyelids and between the fingers. To diagnose familial hypercholesterolemia, blood is drawn from the patient and the levels of cholesterol and triglycerides are determined. Furthermore, cardiovascular functions and the general condition of the body are checked. With the help of a genetic test, the presence of familial hypercholesterolemia can be detected.
Complications
Because high cholesterol often causes no symptoms, familial hypercholesterolemia often goes unnoticed. This leads to progressive hardening of the arteries, which results in obstruction of blood circulation. Complications due to vasoconstriction or vascular occlusion (angina pectoris, heart attack, stroke) are possible at any age. If the homozygous form of the hereditary disease is present, fatal heart attacks can occur in early childhood. In heterozygous familial hypercholesterolemia, the time of first occurrence of cardiovascular complications varies widely. If other risk factors are present, early manifestation before 30 years of age is possible. Frequently, cardiovascular problems do not become apparent until the age of 50 or 60. Treatment of familial hypercholesterolemia is usually with cholesterol-lowering drugs (statins). A common side effect, in addition to an increase in liver values, is the risk of developing diabetes mellitus. Lipid apheresis (blood washing) carries the risk of acute and long-term complications. Side effects during therapy may include headache, dizziness, fatigue, drop in blood pressure or edema. Iron deficiency anemia is a possible consequence of treatment in the long term. Hemolysis, allergic reactions, and shock are very rarely observed as serious complications of blood washing.
When should you see a doctor?
In this disease, a visit to a doctor is always necessary. However, the symptoms of the disease can be relatively well limited by a healthy lifestyle with a healthy diet. Early diagnosis can have a very positive effect on the disease. A doctor should be consulted if the affected person suffers from heavy fat deposits under the skin. Heart problems or diseases of the circulatory system can also indicate this disease and should be examined. An elevated level of cholesterol in a blood test may also indicate this disease. Smokers in particular should therefore take part in regular examinations in order to detect the disease at an early stage. In most cases, this disease can be diagnosed by a general practitioner or by an internist. Further treatment, however, depends strongly on the severity of the symptoms and is carried out by different specialists. In acute emergencies, blood washing can also be performed if the level of cholesterol is very high. In addition to a healthy diet, those affected depend on taking medication to reduce or completely limit the symptoms of this disease.
Treatment and therapy
The goal of therapy for familial hypercholesterolemia is to bring blood cholesterol levels back down and keep them within a normal range. To do this, drugs are administered that, on the one hand, inhibit the body’s own production of cholesterol and, on the other hand, increase its absorption from the blood into the body’s cells. If there is a very massive elevation, sometimes blood washing is used outside the body to lower the cholesterol. In addition to these medical treatments, however, the patient himself must also contribute to an improvement in the values by changing his lifestyle and diet. The diet should be low in fat and healthy, which means plenty of fruits and vegetables, and little lean meat and fish. Sufficient exercise and light sports support the therapy. Since familial hypercholesterolemia is genetic, treatment must consist of both medication and dietary changes. Diet alone would not be sufficient for this form of the disease.
Outlook and prognosis
The gene disease is not curable according to current possibilities. Because of legal requirements, scientists and physicians are not allowed to make changes to a person’s genetics. As a result, there is no cure for familial hypercholesterolemia. The disease is treated symptomatically. It is possible to regulate the symptoms well, which leads to a significant improvement in health. The relief of the symptoms can be achieved by the administration of medications. The cholesterol level is regulated and reduces the symptoms. The patient has to undergo a lifelong therapy for this, because with the discontinuation of the medication an immediate regression of the symptoms occurs. The prognosis of the disease can be significantly influenced by the patient. With a healthy lifestyle and good nutrition, a positive course of the disease can be recorded. Sporting activities, avoidance of harmful substances and control of food intake must be well coordinated so that cholesterol levels do not become too high. If the affected person manages to take the necessary care, he or she will experience a considerable improvement in health and increase his or her quality of life. It should be taken into account in the case of familial hypercholesterolemia that cardiovascular disorders often develop in patients over the age of 50. This process has a negative impact on the overall prognosis.
Prevention
Because familial hypercholesterolemia is genetically caused, it cannot be prevented. The elevated cholesterol levels develop even with a healthy lifestyle. However, if it is known that one is affected by familial hypercholesterolemia, one should have one’s children examined with regard to the disease in order to be able to treat it early and avoid serious damage.
Follow-up
Because familial hypercholesterolemia is a genetic disease, regular follow-up should be sought. The patient must have regular blood checks with the primary care physician to monitor the levels of lipids in the blood. If they continue to be elevated, a new adjustment of the medication should be undertaken, for example by increasing the dose of statins or switching to fibrates or other drugs. The tolerability of the medication should also be investigated. Furthermore, typical secondary diseases of a too high cholesterol level should be examined. These include possible atherosclerosis, which represents a considerable risk of heart attack or stroke. For this purpose, regular ECG checks should be carried out by the physician, with intervention at the slightest suspicion. Xanthelasma, deposits of cholesterol in the skin, can be removed for cosmetic reasons. These yellowish plaques do not pose any further risk. A further step in follow-up care should be the examination of other family members, since the disease is passed on to them. If the disease is present, these should also be treated with medication and should also come regularly for follow-up care. The relatives should also be informed about the risk of the disease and its consequences, as well as about the hereditary nature of the disease. If necessary, genetic analysis should be performed.
What you can do yourself
Genetic familial hypercholesterolemia is characterized by an abnormally elevated level of LDL cholesterol in the blood, while the level for HDL cholesterol tends to remain within the normal range. The increased LDL concentration has to do with pathologically altered LDL receptors. They cause LDL to remain in the blood longer, which is associated with the risk of LDL being deposited in the walls of blood vessels. To curb the risk of developing atherosclerosis or coronary heart disease in adolescence or early adulthood, drugs are prescribed to lower LDL levels. Self-help measures include adherence to a strict diet to support drug therapy to lower LDL levels. However, the truth is that about 70 to 80 percent of cholesterol is synthesized in the body’s cells themselves, in the intestinal mucosa and especially in the liver. A diet that additionally increases the concentration of HDL cholesterols is very helpful. The risk of early coronary heart disease increases dramatically when a high LDL cholesterol level is accompanied by a low HDL level. The ratio of LDL to HDL is decisive.The quotient should preferably not be higher than 3.5. Some cold-pressed oil varieties with a high omega-3 fat content have a particularly favorable effect on increasing HDL levels and thus lowering the risk of atherosclerosis.
