Lipoprotein Metabolism Disorder

Lipoprotein metabolism disorders are conditions where your body cannot properly process fats in the blood, leading to abnormal levels of cholesterol and triglycerides that can increase your risk of heart disease, stroke, and other serious health problems.

Table of contents

• What Are Lipoprotein Metabolism Disorders?
• Understanding Lipoproteins
• Types of Lipoprotein Disorders
• What Causes These Disorders?
• Signs and Symptoms
• How Are These Disorders Diagnosed?
• Treatment Options
• Lifestyle Changes

What Are Lipoprotein Metabolism Disorders?

Lipoprotein metabolism disorders, also called dyslipoproteinemias (a group of conditions affecting fat levels in blood), occur when something goes wrong with how your body handles fats^[1]. Metabolism is the process your body uses to make energy from the food you eat. When you have a metabolic disorder, this process doesn’t work correctly^[1].

These disorders involve problems with how your body processes lipids, which are fats or fat-like substances that include oils, fatty acids, waxes, and cholesterol^[1]. If you have one of these disorders, you may not have enough enzymes (chemicals that help break down food) to break down lipids, or the enzymes may not work properly. As a result, your body can’t convert the fats into energy, causing harmful amounts of lipids to build up in your body^[1].

Over time, this buildup can damage your cells and tissues, especially in the brain, peripheral nervous system, liver, spleen, and bone marrow^[1]. These disorders can lead to serious health problems, including cardiovascular disease, which is the leading cause of death worldwide^[4].

Understanding Lipoproteins

Lipoproteins are round particles made of fat and proteins that travel in your bloodstream to carry cholesterol and triglycerides to cells throughout your body^[3]. They are complex molecules with a central core made of triglycerides and cholesterol esters, surrounded by a mix of phospholipids, free cholesterol, and special proteins called apolipoproteins^[2].

Your body makes different types of lipoproteins^[3]. There are five main classes:

• High-density lipoprotein (HDL) is the “good cholesterol.” It carries cholesterol back to your liver to be flushed out of your body. High levels of HDL reduce your risk of heart disease^[3].
• Low-density lipoprotein (LDL) is the “bad cholesterol.” It increases your risk of heart attacks and stroke. LDL carries cholesterol that accumulates as plaque inside blood vessels, making them too narrow for blood to flow freely^[3].
• Very low-density lipoproteins (VLDL) are another type of “bad cholesterol.” VLDLs carry triglycerides and, to a lesser degree, cholesterol to your tissues^[3].
• Intermediate-density lipoproteins (IDL) are created when VLDLs give up their fatty acids^[3].
• Chylomicrons are very large particles that transport triglycerides from the intestine through the bloodstream^[3].

Cholesterol plays a vital role in your body. Your liver makes cholesterol, and you also get it from food such as meat and dairy products. This fat helps your body produce vitamin D and hormones like estrogen and testosterone. It also helps build cells in your nervous system^[3].

Triglycerides are another type of fat. Your liver and intestines make them. When you eat a lot of fat and calories, your body produces even more triglycerides and stores the excess in fat cells^[3].

Types of Lipoprotein Disorders

Disorders of lipoprotein metabolism can be classified based on the primary problem, such as high or low levels of certain lipoproteins^[5]. The main disorders include:

• LDL-hypercholesterolemia: This means you have too much bad cholesterol (LDL) in your blood. High LDL cholesterol makes fat collect in your arteries, which puts you at higher risk of heart attack and stroke^[14].
• Hypertriglyceridemia: This involves high levels of triglycerides in the blood^[7].
• Mixed hyperlipoproteinemia: This is a combination of high LDL cholesterol and high triglycerides^[7].
• Low HDL cholesterol: This means having too little “good cholesterol”^[7].

Another important disorder involves lipoprotein(a), or Lp(a), which is a type of LDL cholesterol with an extra protein attached. High levels of Lp(a) can double or even triple a person’s risk of heart attack^[18]. Unlike other types of cholesterol, your genes determine your Lp(a) levels, and diet and exercise have virtually no effect on them^[18].

What Causes These Disorders?

Numerous genetic and environmental factors contribute to differences between people in their levels of lipids and lipoproteins^[5]. Disorders with a genetic basis typically present earlier in life, while those that present later also have genetic determinants but depend more on interactions with environmental or lifestyle factors^[5].

These disorders are inherited, meaning they are passed down through families^[1]. Some people inherit gene changes that make them more prone to certain disorders. For example, high Lp(a) levels are determined by your genes, and some people inherit mutations that give them higher risk of heart disease at a young age^[3].

In Western countries specifically, lifestyle has been identified as an important factor in these disorders^[2]. Causes of hypercholesterolemia include^[14]:

• A diet that includes a lot of saturated and trans fats
• Lack of exercise
• Tobacco products
• Diabetes
• Hypothyroidism (underactive thyroid)
• Chronic kidney failure
• Certain medications

Triglyceride elevation may occur in association with diabetes, alcoholism, obesity, and hypothyroidism^[10].

Signs and Symptoms

There are no symptoms of hypercholesterolemia in most people^[14]. This is why regular testing is important. However, if you have severe hypercholesterolemia, you may have cholesterol deposits on your eyelid skin or in your eye, or on connective tissue^[14].

Many lipid metabolism disorders can be very serious, or sometimes even fatal^[1]. Over time, excess cholesterol in the blood can damage cells and tissues, especially in the brain, peripheral nervous system, liver, spleen, and bone marrow^[1].

High levels of bad cholesterol are a known risk factor in cardiovascular disease as they lead to premature atherosclerotic (hardening of the arteries) changes of vessels^[2]. This condition, called atherosclerosis, is the main cause of cardiovascular disease^[14].

How Are These Disorders Diagnosed?

Healthcare providers order lipid blood tests, also called lipid panels, to measure total cholesterol in your blood^[3]. The tests provide individual results for HDL, LDL, triglycerides, and total cholesterol^[3].

Any cholesterol test is a simple blood draw that takes fewer than five minutes. You may get the test at your healthcare provider’s office, blood testing lab, or hospital. For the most accurate results, you need to fast for eight to 12 hours before getting this blood test^[3].

Health experts recommend that total cholesterol and HDL cholesterol levels be measured every five years beginning at age 20 in patients who do not have coronary heart disease or other atherosclerotic disease^[10]. Testing for Lp(a) is not yet routine in the United States, but international consensus groups recommend one-time Lp(a) testing for everyone^[18].

Once your provider rules out other causes of your disorder, they can do genetic testing. Newborn babies get screened for some of these disorders using blood tests. If there is a family history of one of these disorders, parents can get genetic testing to see whether they carry the gene^[1].

Usually at your annual physical exam, your healthcare provider will ask you about your medical history and your family’s health, do a physical exam, and order blood tests^[14].

Treatment Options

Early diagnosis is central to specific dietary, lifestyle, and pharmacological interventions to delay death, disability, and medical complications^[5]. There is a causal relationship between hypercholesterolemia and the risk of heart and vascular events. Reducing LDL cholesterol lessens the risk of cardiovascular events^[7].

According to current European recommendations, an LDL-cholesterol target value should be defined based on the overall cardiovascular risk. If this risk is very high, as in patients with documented atherosclerosis, the target value should be set at less than 70 mg/dL. If the risk is lower, higher target values can be set^[7].

The most commonly used options for drug treatment include^[1][7]:

• Statins: Lowering the LDL-cholesterol concentration with statins is by far the most important type of drug therapy. Statins target a specific enzyme to lower high LDL-cholesterol^[2].
• Ezetimibe: Patients who cannot tolerate statins or whose cholesterol level is not adequately lowered can be given this medication instead^[7].
• PCSK9 antibodies: These medications can lower the LDL-cholesterol level by more than 50 percent. At present, they should only be given to carefully selected patients^[7].
• Fibrates and omega-3 fatty acids: These have been found to prevent cardiovascular events in some trials^[7].

Enzyme replacement therapies can help with a few of these disorders. For others, there is no treatment. Medicines, blood transfusions, and other procedures may help with complications^[1].

Lifestyle Changes

Lifestyle changes that involve diet and exercise are often the first treatment for metabolic syndrome^[15]. Lifestyle changes are an effective treatment mainly for patients with hypertriglyceridemia and mixed disorders of lipid metabolism^[7].

Health experts recommend getting at least 30 minutes of exercise, such as brisk walking, daily. Look for ways to increase activity any chance you get, such as walking instead of driving and using the stairs instead of an elevator^[15].

Losing 3 to 5 percent of body weight can reduce insulin resistance (when cells don’t respond well to insulin) and lower the risk of diabetes and heart disease^[15].

A few changes in your diet can reduce cholesterol and improve your heart health^[22]:

• Reduce saturated fats, found primarily in red meat and full-fat dairy products. Decreasing your consumption of saturated fats can reduce your LDL cholesterol^[22].
• Eliminate trans fats, sometimes listed on food labels as “partially hydrogenated vegetable oil.” Trans fats raise overall cholesterol levels^[22].
• Eat foods rich in omega-3 fatty acids. Foods with omega-3 fatty acids include salmon, mackerel, herring, walnuts, and flaxseeds^[22].
• Increase soluble fiber, found in foods such as oatmeal, kidney beans, Brussels sprouts, apples, and pears. Soluble fiber can reduce the absorption of cholesterol into your bloodstream^[22].

A heart-healthy diet low in saturated fat, trans fat, and cholesterol is ideal for lowering lipoprotein(a). A high-fiber diet is also therapeutic^[10].

If lifestyle changes aren’t enough, medicines may help you manage blood pressure, cholesterol, and blood sugar levels^[15].