Illustrations > Jean Lambert Illustrations graphic design > www.mine-de-rien.net graphic Chol/29/P030/01-01/10 NLA An educational booklet for patients with familial hypercholesterolemia This brochure was provided by Genzyme Corporation for use by the Foundation of the National Lipid Association. DR. LEIV OSE www.learnyourlipids.com CONTENTS PART 1 What will you learn from this booklet? 02 FAMILIAL HYPERCHOLESTEROLEMIA PART 1: FAMILIAL HYPERCHOLESTEROLEMIA 03 1 - What is Familial Hypercholesterolemia? 03 WHAT WILL YOU 2 - What is LDL-Cholesterol? 04 3 - What are the causes of FH? 05 LEARN FROM THIS GREAT GRANDMOTHER GREAT GRANDFATHER 4 - When should FH be suspected? 07 FH NON FH BOOKLET? 5 - How is FH diagnosed? 09 6 - How early can FH be diagnosed? 09 Woman You will learn about Familial PART 2: TREATMENT 10 GRANDMOTHER GRANDFATHER Hypercholesterolemia, NON FH FH Woman with FH 1 - How can LDL-Cholesterol be reduced? 10 its cause, and the potential 2 - Step 1: Dietary management of FH 11 Man consequences of this a) How does diet affect LDL-Cholesterol? 11 disease. You will learn b) What sort of diet? 11 Man with FH about high cholesterol 3 - Step 2: Using medication 12 AUNT MOTHER FATHER UNCLE and what this might mean a) How does medication affect LDL-Cholesterol? 12 NON FH FH NON FH FH for your heart and blood b) Which drug treatments reduce LDL-Cholesterol and how? 13 FIGURE 1: 4 - Why is lifelong treatment important? vessels. Most importantly 15 FH is an inherited disease, you will learn how to find PART 3: CARDIOVASCULAR DISEASE AND LIPOPROTEINS 16 which can usually be traced out whether someone in 1 - What is cardiovascular disease? 16 DAUGTER SON over several generations. your family has this disease 2 - What are risk factors? 17 NON FH FH and how you can reduce 3 - Is it possible to reduce the risk of cardiovascular disease in FH? 18 high cholesterol by adopting 4 - What are lipoproteins? 18 5 - What are lipids, cholesterol and triglycerides? 1 a healthy lifestyle and 20 What is Familial Hypercholesterolemia? receiving treatment. PART 4: OTHER QUESTIONS THAT YOU MIGHT HAVE 21 Familial Hypercholesterolemia (FH) is an inherited high blood cholesterol. The type of cholesterol that is This booklet can also serve 1 - Why is physical activity beneficial? 21 disease, where a genetic alteration causing high specifically increased in Familial Hypercholesterolemia as a starting point to help 2 - Does smoking affect lipids? 22 blood cholesterol is transmitted from generation to is Low Density Lipoprotein-Cholesterol (LDL-C). LDL- you discuss your disease What have you learned from this booklet? 23 generation (see figure 1). Familial means it runs in Cholesterol floats in the blood stream and transports and treatment with Glossary 24 families; sometimes it is possible to trace the disease cholesterol from one cell in your body to another cell your doctor. About the author 26 over several generations. Hypercholesterolemia means (see parts 1.2 and 3.4). 2 3 FH is one of the most common hereditary disorders. lifestyle factors such as diet, smoking and level of Approximately 1 in 500 people in the world has a physical activity, and whether you are male or female. IMPORTANT genetic alteration that causes FH1. If one parent has Women with FH are affected by cardiovascular FH, there is a 50% chance that their son or daughter disease approximately 10 years later than men with LDL-C transports cholesterol in your blood to cells. Cholesterol is needed to build cells, will also have it. FH2. With early and appropriate treatment the risk of make hormones and make bile acids. However, if there is too much LDL-Cholesterol cardiovascular disease can be reduced significantly. FH is associated with an increased risk of cardiovascular it will be deposited in blood vessel walls. This phenomenon is called atherosclerosis. disease1. Risk varies from family to family and is 1. Ose. Cardiovascular Drugs and Therapy 16 289–293 2002. influenced by cholesterol level, other hereditary factors, 2. Slack, Lancet 1969;2:1380. 3 What are the causes of FH? IMPORTANT FH is inherited and runs in families. It causes high blood cholesterol, specifically LDL-Cholesterol, and an increased risk of cardiovascular disease early in life. 2 What is LDL-Cholesterol? Cell Cell nucleus Chromosome DNA FIGURE 2: Low Density Lipoprotein-Cholesterol (LDL-C) is a To t ransport cholesterol into specific cells, the LDL-C DNA, which is over one meter in length, is packed in chromosomes. Chromosomes are packed into the cell nucleus, particle that floats in the blood stream and acts as an particle has a specific protein attached to it named which is inside the cell. efficient transport system that carries cholesterol from Apo-lipoprotein B or ApoB. ApoB acts as a bridge one cell to another in your body. Cholesterol is a fatty between the LDL-C particle and the cells in your The characteristics we inherit from our parents are within a specific gene can result in a hereditary illness. substance that is needed by your body to build cells, body that carry the LDL-receptor (which helps the determined by information carried on a strand of In FH there is a change in the gene that codes for the to make hormones, and to make bile acids in the liver cell recognize LDL-C). If the LDL-receptor or ApoB DNA that totals well over one meter in length. DNA LDL-receptor. This receptor sits on the surface of cells (see part 3.5). protein is not normal, the level of cholesterol in is organized into chromosomes found in the nuclei and can be thought of as a ‘tentacle’ that removes your blood will increase. This is the case in Familial of cells (figure 2). DNA consists of approximately cholesterol-containing LDL-C particles from the blood Too much LDL-Cholesterol in your blood stream is not Hypercholesterolemia. 3 billion building blocks, of which 25,000 specific (figure 3). The change in the LDL-receptor gene results good for you; excess cholesterol can be deposited in combinations make genes. Genes are a code for physical in abnormal LDL-receptors (‘tentacles’) making them the walls of blood vessels making them narrower and characteristics, such as eye and hair color, but also many unable to remove LDL-Cholesterol from the blood. causing the onset of atherosclerosis. Atherosclerosis diseases. A change in just one of these building blocks This is the cause of FH. can lead to cardiovascular diseases (see part 3). 4 5 Most people with FH have inherited one defective Normal Abnormal LDL-receptor gene from one of their parents, and cell LDL cell FIGURE 4: one normal LDL-receptor gene from the other LDL In FH (abnormal cell) there are LDL parent. Consequently, they have only approximately fewer LDL receptors able to 50% of the normal number of working LDL-receptors take LDL-Cholesterol out of (‘tentacles’) on the surface of cells (figure 4). This the blood. means that there is always an unnecessarily high LDL-receptor LDL-receptor amount of LDL-Cholesterol circulating in the blood. The problem is that excess LDL-Cholesterol can be Blood stream Cell LDL particle LDL-receptor Apo-B deposited in the blood vessel wall. IMPORTANT FH is caused by a change in the gene that codes for the LDL-receptor. The defective LDL-receptor LDL-receptor cannot take up LDL-Cholesterol from the blood into the cell. Excess cholesterol is deposited in blood vessel walls. 4 When should FH be suspected? FH is suspected if there is a family history of cardiovascular disease early in life. If a person suffers a heart Cell membrane attack before the age of 50-60, it may be due to high cholesterol and blood lipid profiles must be investigated in the family: FIGURE 3: Lipid profile means the assessment of the various types FH diagnosis at a young age is important. Treatment The LDL-receptor is attached at one end to of lipoproteins in the blood (see part 3.4) such as is more effective when started early and before the cell membrane. The other end binds to total cholesterol, LDL-Cholesterol, HDL-Cholesterol cholesterol deposition in the blood vessel wall becomes LDL-Cholesterol particles. and triglycerides. too advanced. 6 7 There are some physical signs (figure 5) that might raise eyes (xanthelasmas), but these are not always present 5 a suspicion of FH such as swollen tendons on the heels in patients with FH. How is FH diagnosed? and hands (xanthoma) or yellowish areas around the FH is usually first recognized by abnormally high levels of defects throughout the entire LDL-receptor gene in Xanthoma Xanthelasmas LDL-C as seen on a cholesterol test and other signs and chromosome 19. People who have the inherited gene symptoms. In addition, genetic testing may be performed defect will have FH. Close relatives, such as parents, to confirm the diagnosis3. A blood sample is taken so brothers and sisters and children of someone with FH, that DNA can be isolated from the cell nucleus of white have a 50% risk of also having inherited FH. Testing family blood cells. The DNA is then studied. FH is diagnosed members is crucial for early detection of the disease. by finding the defective gene for the LDL-receptor. Genetic testing involves a systematic search for gene 3. Schuster, Luft, Arteriosclerosis, Thrombosis, and Vascular Biology, 1998;18:331-332. FIGURE 5: Visible physical signs of FH include swollen tendons on the back of the heel (often observed in adolescents) IMPORTANT and yellow deposits in the skin around the eyes. A white deposit of cholesterol in the shape of an arc may also be seen at the edge of the colored part of the eye.