What Is Familial Hypertriglyceridemia?

Your body uses lipids like cholesterol or triglycerides to make cell walls, form hormones, as well as for energy utilization and storage. However, cholesterol can be used for cell walls because it’s hydrophobic, meaning it doesn’t like interacting with water.

Triglyceride-rich lipoprotein particles can stem from both eFamilial hypertriglyceridemia may sound scary and complicated, but if you’ve recently been told you might have inherited this condition, don’t worry.

This article will explain exactly what familial hypertriglyceridemia is, when you should go to a doctor, and how you can help manage your condition.

What is it?

A familial hypertriglyceridemia is a form of dyslipidemia. If we break that word down, it means dysregulation of lipids. As a result, some triglycerides cannot be regulated appropriately in people with familial hypertriglyceridemia. 

To be more accurate, familial hypertriglyceridemia is known as type IV familial dyslipidemia, according to the Frederickson Classification of Dyslipidemias. These concepts are complicated, so we will go back quite a few steps to ensure you understand exactly what is happening within your body.

Endogenous and exogenous sources. Exogenously dietary fats are absorbed from the gut and secreted as triglyceride-rich chylomicrons, then cleared by the liver. The liver also endogenously produces triglyceride-rich very-low-density lipoprotein (VLDL), which in peripheral tissues are metabolized by lipoprotein lipases for energy utilization or storage in muscles and adipose tissue.

Ultimately, both chylomicrons and VLDL are cleared by a pathway using tissue lipases. If the activity of this lipase is reduced, clearance of these particles becomes impaired, and they accumulate. This susceptibility is modulated by genetic influences that reduce VLDL use through impaired lipoprotein lipase activity.

There are several different lipoproteins, but for familial hypertriglyceridemia, the lipoprotein we are interested in is very low-density lipoprotein (VLDL). This lipoprotein is overproduced in people with this form of dyslipidemia. Or in other cases, the body may not be able to clear VLDL efficiently, enabling it to accumulate.

Unlike other lipoproteins, VLDL transports triglycerides (fats) around the cells instead of transporting cholesterol around the body.

Symptoms

Unfortunately, people with familial hypertriglyceridemia are often unaware they have it until a family member is diagnosed.

Hypertriglyceridemia is typically clinically silent and detected by lipid screening. It can be inherited in an autosomal dominant pattern, but it’s linked more to polygenic inheritance.

Essentially, this means that the person with the disorder has likely passed on the potential to have familial hypertriglyceridemia to any children, regardless of whether they are male or female.

If one of your first-degree relatives has been diagnosed with familial hypertriglyceridemia, you aren’t guaranteed to have it, but you should bring it up with a doctor so they can check for you.

The presence of high levels of triglycerides doesn’t lead to any symptoms straight away. Instead, people are at higher risk of forming plaques in their arteries in a process known as atherosclerosis, where the fats transported by VLDL collect in the artery and harden.

This restricts blood flow and can cause heart attacks. People with familial hypertriglyceridemia are also more likely to have other comorbidities, such as obesity and hypertension (high blood pressure). 

One main secondary effect of familial hypertriglyceridemia is pancreatitis. Hypertriglyceridemia is a strong risk factor for pancreatitis, and a patient with recurrent pancreatitis likely has hypertriglyceridemia and possibly bouts of chylomicronemia.

Although the exact mechanism of how hypertriglyceridemia causes acute pancreatitis has not been elucidated, it is thought that the high levels of lipids passing through the pancreas cause premature activation of the enzymes made for digesting foods. When this occurs while still inside the pancreas, it can produce toxic fatty acids that are then secreted into the pancreatic circulation, leading to endothelial injury and an ischemic insult to the pancreatic cells.

People with familial hypertriglyceridemia have high levels of fats and are at a higher risk of acute pancreatitis.

Diagnosis

The good news is a diagnosis of familial hypertriglyceridemia is quite simple and relatively painless. Your doctor will aim to assess the level of triglycerides in your blood, which can be done through a simple blood test.

The doctor can then classify your disease as mild, moderate, severe, or very severe. You may also have some signs, such as ‘foamy’ looking, small yellowish papules surrounded by a reddened base on the skin, particularly on the buttocks or elbows, which are known as eruptive xanthoma. These can form due to the deposition of excessive amounts of chylomicrons in cutaneous cells, and if you notice them, you should see a doctor.

However, these aren’t standard symptoms of familial triglyceridemia because most people don’t have triglyceride levels this high.

A person can also develop lipemia retinalis, where excessive amounts of lipids in the blood make the retina appear pale and the retinal vessels appear white.

Your doctor will also monitor you for other comorbidities that can often be found alongside familial hypertriglyceridemia, such as obesity, hypertension, insulin resistance or diabetes, or metabolic disorder. 

Often, they will check your BMI and blood pressure and may also add additional blood tests, like glucose testing for diabetes. 

For doctors, the different types of hypertriglyceridemia can be difficult to distinguish. DNA testing may be utilized in familial hypertriglyceridemia.

Although unlikely to change the management, it can be useful, particularly in the context of suspicion of monogenic chylomicronemia or people with hypertriglyceridemia with first-degree relatives with hypertriglyceridemia-induced acute pancreatitis.

Although this might seem alarming, the DNA test looks for specific mutations in the genes responsible for causing familial hypertriglyceridemia. They won’t be looking at your entire gene sequence.

These kinds of genetic tests can be best done from any source in your body. However, most laboratories prefer blood specimens, although cheek (buccal) swabs and saliva samples may be an option for certain types of genetic testing. Your doctor will most likely refer you to a geneticist if they decide there’s ample suspicion that a genetic test will be useful.

This is just so they can best treat you and rule out any other types of triglyceridemia that may have different treatments. 

Causes

Familial hypertriglyceridemia is prone to occurring simultaneously with disorders such as obesity, hypertension, and diabetes. This disease also has a genetic component, meaning that your chance of having the disease comes partially from your parents. 

Essentially, the genes on your chromosomes come from your parents, half from your mother and a half from your father. A parent with familial hypertriglyceridemia will likely pass on the genes responsible for this condition. 

However, multiple genes govern hypertriglyceridemia (known as polygenic inheritance), and you might not inherit all of them from one parent. So, you could have some genes that predispose you to hypertriglyceridemia, but not all of them. There are also variants of the condition based on the genes you inherit from each parent. 

This means that some genes you might inherit are big contributors to familial hypertriglyceridemia, and some are minor. This leads to the disease being mild, moderate, severe, or very severe, depending on your particular gene combination.

Since hypertriglyceridemia relates to the level of fats in the blood, it can also be aggravated by what you eat and how much exercise you do. The same risk factors for heart disease (obesity, high blood pressure, diabetes, lack of exercise) can also be risk factors when predisposed to familial hypertriglyceridemia. 

Treatment

Luckily, the aim of treatment for familial hypertriglyceridemia is just to lower the total levels of triglycerides in the blood. Unless you have severely elevated triglyceride levels, lifestyle changes should likely be enough to help lower the risk of adverse effects like pancreatitis.

Lifestyle modifications can include stopping alcohol consumption, eating a low-fat diet, and losing weight alongside physical activity. The goal is to reduce the intake of saturated fats to <7% of total calories and cholesterol to <200mg daily. 

Your doctor may also try lowering the level of another lipoprotein, low-density lipoprotein (LDL). Like VLDL, LDL has a specific role. It functions to transport cholesterol around the body. Because LDL increases the amount of cholesterol in the body, it is often thought of as the ‘bad’ cholesterol. 

The increased blood lipids increase atherosclerotic lesions, whereby macrophages take up the excess oxidized LDL and transform it into foam cells. These can then rupture, leading to further damage of the vessel wall and, ultimately, sequelae such as heart attacks if it happens in the coronary arteries. 

So, if you have severe familial hypertriglyceridemia and already have high levels of VLDL, your doctor may also want to lower the amount of LDL in your blood. To do this, they may use a pharmaceutical known as a statin. 

Statins are used to lower the amount of cholesterol made and thus lower the amount of LDL required in the bloodstream. However, simple lifestyle changes and weight loss will be enough for most people to manage the condition.  

Depending on your TG levels, your doctor may also utilize medications called fibrates, marine omega-3 fatty acids, and niacin. There’s also a new generation of drugs approved for use in Europe but not yet in the US called volanesorsen.

Prevention

The best way to prevent familial hypertriglyceridemia from causing issues is to modify your diet, exercise, moderate your alcohol intake, and lose weight to reduce the risk of triglycerides in the blood. However, additional therapies are currently in the works. 

Some studies¹ have found high doses of an existing pharmaceutical—icosapent ethyl (IPE), a highly purified form of marine omega-3 fatty acid, to effectively reduce patients' triglyceride levels. It can also effectively lower the risk of atherosclerosis or type 2 diabetes.

It is already available pharmaceutically, so your doctor may prescribe this if you have moderate to severe familial triglyceridemia. 

When you should see a doctor

You should see a doctor for familial hypertriglyceridemia if one of your first-degree relatives has been found to have this condition. Because it can be inherited, it is possible that you could have the condition as long as the family member is biologically related to you. 

However, just because a family member has the condition doesn’t mean that you definitely will, so there is no need to panic. 

You should also see a doctor for familial hypertriglyceridemia if you have concerns about your heart health or weight. 

As obesity and atherosclerosis are often found simultaneously in people with familial hypertriglyceridemia, if your family has a history of obesity or bad heart health, it might be a good idea to get checked out. 

Your doctor will be able to counsel you appropriately on whether you have any risk factors for heart or arterial diseases.

You should always consult a doctor before starting a large lifestyle change, so if you have concerns about familial hypertriglyceridemia and want to make lifestyle changes like increasing exercise and monitoring your diet, a health professional will also be able to counsel you.

Diet and exercise should be done appropriately for your weight or health level, and doctors or physiotherapists may be able to help with additional exercises or medicines to manage other issues, like high blood pressure.

The lowdown

Familial hypertriglyceridemia is inherited in a complex genetic pattern, and just because one parent has the condition doesn’t necessarily mean you will inherit it.

However, you may be predisposed to the condition. You should use non-medical interventions like weight management and dietary monitoring to ensure that you are on top of maintaining your heart health.

This is because familial hypertriglyceridemia is a condition that can exacerbate other risk factors, like high BMI, high blood pressure, or type two diabetes.

If you have familial hypertriglyceridemia, support can be found through your doctor, who will be able to counsel you on the potential medications to support your heart health, as well as start you on your journey to having a heart-healthy lifestyle. These simple lifestyle changes have been shown to have a big impact and can make having familial hypertriglyceridemia much less of a concern.