hormonal and metabolic disorders
Dyslipidemia
Causes of Dyslipidemia
Factors that cause dyslipidemia are categorized into Primary causes: Genetic (hereditary) causes Secondary causes: Lifestyle and other causes Both primary and secondary causes contribute to dyslipidemia in varying degrees. For example, a person with a hereditary hyperlipidemia may have even higher lipid levels if the person also has secondary causes of hyperlipidemia. Primary causes involve gene mutations that cause the body to produce too much LDL cholesterol or triglycerides or to fail to remove those substances. Some causes involve underproduction or excessive removal of HDL cholesterol. Primary causes tend to be inherited and thus to run in families. Some of the genetic causes of dyslipidemia are discussed here and Other Rare Hereditary Disorders of Lipid Metabolism . Cholesterol and triglyceride levels are highest in people with primary dyslipidemias, which interfere with the body’s metabolism and elimination of lipids. People can also inherit a tendency for HDL cholesterol to be unusually low. Consequences of primary dyslipidemias can include premature Atherosclerosis (in men 55 years old or younger, in women 60 years old or younger), which can lead to In people who have a genetic disorder that causes high triglyceride levels (such as familial hypertriglyceridemia or familial combined hyperlipidemia), certain disorders and substances can increase triglycerides to extremely high levels. Examples of disorders include poorly controlled Diabetes Mellitus (DM) and Symptoms can include fatty deposits (eruptive xanthomas) in the skin on the front of the legs and back of the arms, enlargement of the spleen and liver, abdominal pain, and decreased sensitivity to touch due to nerve damage. Primary dyslipidemias can cause Overview of Pancreatitis , which is occasionally fatal. Limiting fat intake (to less than 50 grams a day) can help prevent nerve damage and pancreatitis. Losing weight and not drinking alcohol can also help. Lipid-lowering drugs may be effective. In familial combined hyperlipidemia, the levels of cholesterol, triglycerides, or both may be high. This disorder affects about 1 to 2% of people. The lipid levels typically become abnormal after age 30 but sometimes at a younger age, especially in people who are overweight, who have a diet that is very high in fat, or who have Metabolic Syndrome . Treatment of familial combined hyperlipidemia involves limiting intake of saturated fat, cholesterol, and sugar as well as exercising and, when applicable, losing weight. Many people with this disorder need to take lipid-lowering drugs. In familial dysbetalipoproteinemia, levels of very low density lipoprotein (VLDL) cholesterol, total cholesterol, and triglycerides are high. These levels are high because an unusual form of VLDL accumulates in the blood. Fatty deposits (eruptive xanthomas) may form in the skin over the elbows and knees and in the palms, where they can cause yellow creases. This uncommon disorder results in the early development of severe atherosclerosis. By middle age, Atherosclerosis often produces blockages in the coronary and peripheral arteries. Treatment of familial dysbetalipoproteinemia involves achieving and maintaining recommended body weight and limiting intake of cholesterol, saturated fats, and carbohydrates. A lipid-lowering drug is usually needed. With treatment, lipid levels can be improved, the progression of atherosclerosis may be slowed, and the fatty deposits in the skin may become smaller or disappear. In familial hypercholesterolemia, the total cholesterol level is high. People may have inherited one abnormal gene or they may have inherited two abnormal genes, one from each parent. People who have two abnormal genes (homozygotes) are more severely affected than people who have only one abnormal gene (heterozygotes). About 1 in 200 people are heterozygotes, and 1 in 250,000 to 1 in 1 million people are homozygotes. Affected people may have fatty deposits (eruptive xanthomas) in the tendons at the heels, knees, elbows, and fingers. Rarely, xanthomas appear by age 10. Familial hypercholesterolemia can result in rapidly progressive atherosclerosis and early death due to Overview of Coronary Artery Disease (CAD) . Children with two abnormal genes may have a heart attack or angina by age 20, and men with one abnormal gene often develop coronary artery disease between ages 30 and 50. Women with one abnormal gene are also at increased risk, but the risk usually starts about 10 years later than in men. People who smoke or have high blood pressure, diabetes, or obesity may develop atherosclerosis at even younger ages. Treatment of familial hypercholesterolemia begins with following a diet that is low in saturated fats and cholesterol. When applicable, losing weight, stopping smoking, and increasing physical activity are advised. One or more lipid-lowering drugs are usually needed. Some people require Plasma exchange , a method of filtering the blood to lower LDL cholesterol levels. Some people with homozygous familial hypercholesterolemia may benefit from In familial hypertriglyceridemia, triglyceride levels are high. This disorder affects about 1% of people. In some families affected by this disorder, Atherosclerosis tends to develop at a young age, but in others, it does not. Losing weight, if necessary, and limiting alcohol and carbohydrate consumption often lower triglyceride levels to normal. If these measures are ineffective, use of a lipid-lowering drug can help. For people who also have Diabetes Mellitus (DM) , good control of the diabetes is important. In hypoalphalipoproteinemia, the HDL cholesterol level is low. Many different genetic abnormalities can cause the low HDL level. Since medications that raise HDL cholesterol do not decrease the risk of atherosclerosis, hypoalphalipoproteinemia is treated by lowering LDL cholesterol. Lipoprotein lipase deficiency and apolipoprotein CII deficiency are rare disorders caused by the lack of certain proteins needed for the removal of triglyceride-containing particles. In these disorders, the body cannot remove chylomicrons from the bloodstream, resulting in very high triglyceride levels. Without treatment, levels are often considerably higher than 1,000 mg/dL (11 mmol/L) and can cause Overview of Pancreatitis . Symptoms appear during childhood and young adulthood. They include Recurring bouts of abdominal pain Enlargement of the liver and spleen Pinkish yellow bumps in the skin on the elbows, knees, buttocks, back, front of the legs, and back of the arms These bumps, called eruptive xanthomas, are deposits of fat. Eating fats worsens symptoms. Although this disorder does not lead to Atherosclerosis , it can cause People who have these disorders must strictly limit the amount of all types of fat—saturated, unsaturated, and polyunsaturated—in their diet. People may need to take vitamin supplements to make up for nutrients missing from their diets. There are some therapies in development for treatment of lipoprotein lipase deficiency and apolipoprotein CII deficiency. Secondary causes contribute to many cases of dyslipidemia. Themost important secondary causeof dyslipidemia is A sedentary lifestyle with excessive dietary intake of total calories, saturated fat, cholesterol, and trans fats (see sidebar) Someother common secondary causesinclude the following: Having Diabetes Mellitus (DM) None Consuming large amounts of alcohol Having Chronic Kidney Disease None Having Hypothyroidism None Having Primary Biliary Cholangitis (PBC) None Using certain medications Some people are more sensitive to the effects of diet than others, but most people are affected to some degree. One person can eat large amounts of animal fat, and the total cholesterol level does not rise above desirable levels. Another person can follow a strict low-fat diet, and the total cholesterol does not fall below a high level. This difference seems to be mostly genetically determined. A person’s genetic makeup influences the rate at which the body makes, uses, and disposes of these fats. Also, body type does not always predict levels of cholesterol. Some overweight people have low cholesterol levels, and some thin people have high levels. Eating excess calories can result in high triglyceride levels, as can consuming large amounts of alcohol. Body type does not predict cholesterol levels. Some overweight people have low cholesterol levels, and some thin people have high cholesterol levels. Some disorders cause lipid levels to increase. Diabetes Mellitus (DM) that is poorly controlled or , and antiviral drugs used to treat Human Immunodeficiency Virus (HIV) Infection (HIV) infection and AIDS can cause cholesterol and/or triglyceride levels to increase. Cigarette smoking, HIV infection, poorly controlled diabetes, or kidney disorders (such as nephrotic syndrome) may contribute to a low HDL cholesterol level. Medications such as beta-blockers and anabolic steroids can lower the HDL cholesterol level. 