What is Familial Combined Hyperlipidemia (Elevated Cholesterol)?
Familial combined hyperlipidemia (FCH) is a common inherited disorder affecting the levels of fats in the blood. This disorder is named for its unpredictable occurrence of raised cholesterol and triglyceride (a type of fat) levels in at least two family members. First identified in 1973, FCH was initially believed to be passed down through a single gene. However, later research discovered it is likely related to multiple genes and has a complex inheritance pattern.
FCH can increase the amount of cholesterol and/or triglycerides in the blood. Alternatively, it might only cause a rise in a certain protein called apolipoprotein B while keeping other blood fat levels normal. This disorder affects roughly 0.5 to 4% of people, yet scientists are still trying to understand the genetics behind it. FCH is associated with dysfunctional metabolism, leading to increased levels of certain fats in the blood, and it can slow down the removal of other types of cholesterol-rich fats.
Due to the abnormal increase in blood fat levels, individuals with FCH have a higher risk of heart disease and related mortality. This risk is particularly increased in individuals with metabolic-related disorders such as type 2 diabetes, obesity, alcohol addiction, thyroid deficiencies and liver disease. FCH is often found in people who already have heart disease or patients who have suffered a heart attack.
In managing FCH, patients receive treatments aimed to reduce cholesterol and triglyceride levels to prevent heart diseases. Approved treatments include statins, fibrates, and other cholesterol-lowering drugs, as well as niacin and ezetimibe. In addition, omega-3 fatty acids (found in fish oil) and MTTP inhibitors (such as lomitapide) are also used in treatment.
What Causes Familial Combined Hyperlipidemia (Elevated Cholesterol)?
The genetics behind familial combined hyperlipidemia (FCH) are not entirely clear. Initially, it was thought that this condition was passed down from parents to their children in a pattern known as autosomal dominant inheritance, as suggested by a study from 1973. Further research, however, indicated that FCH could be either familial (passed down through families) or non-familial, meaning it involves various genes and has a complex pattern of inheritance.
In addition to genetic factors, other risks potentially contributing to the development of FCH include environmental influences. The impact of these factors leads to a disruption in the body’s metabolism. As a result, the body can produce an excess amount of very low-density lipoprotein (VLDL), a kind of protein that carries bad cholesterol. Additionally, the removal process of bad cholesterol and other fat-rich proteins from the body might slow down. Also, there might be an uncontrolled production of a type of protein known as apo-B in the liver, all of which are involved in lipid balance and can influence FCH.
Risk Factors and Frequency for Familial Combined Hyperlipidemia (Elevated Cholesterol)
Familial combined hyperlipidemia (FCH) affects around 0.5% to 4% of the population. It’s found in about 10% to 20% of people who have had a premature heart attack. According to research, the likelihood of having FCH can vary among different racial groups.
- The study conducted by Paramsothy et al in 2009 found that Hispanics have higher rates of FCH than white people.
- On the other hand, despite having higher levels of body mass and abdominal fat, African-Americans have lower rates of FCH than white people.
- This suggests that African-Americans are less likely to develop FCH than white people.
Signs and Symptoms of Familial Combined Hyperlipidemia (Elevated Cholesterol)
Familial combined hyperlipidemia (FCH) is a condition that often runs in families and can lead to severe heart disease or stroke. Individuals with FCH may have relatives with abnormal cholesterol and lipid (fat) levels, early heart issues, and a history of dying young from heart conditions or strokes. Symptoms seen in FCH patients could include chest discomfort, shortness of breath, or leg pain during walking. They may also be at risk for heart-related conditions because they may have high blood pressure, diabetes, and obesity.
FCH can vary a lot in its effects, and can begin or become severe at different ages across relatives in the same family. That’s why it’s crucial to fully understand a patient’s family history of high fat or cholesterol levels, heart disease, and early deaths, especially in the case of immediate family members.
Typically, if a doctor physically examines a person with FCH, they might not find any out-of-the-ordinary signs specifically linked to this condition. However, this person might show signs of heart-related diseases, like high blood pressure, peripheral arterial disease (which affects the blood vessels in the limbs), or whooshing sounds heard in the neck arteries. Although it’s not a common phenomenon, an examination of the skin might uncover yellowish deposits (xanthomas) which are often linked to high cholesterol or fat levels in the blood. These deposits, although rare, can shed light on underlying metabolic disorders like FCH or a similar condition called familial hypercholesterolemia.
- Family history of abnormal cholesterol and lipid levels, early heart problems, and premature death
- Symptoms such as chest discomfort, difficulty breathing, or leg pain while walking
- Presence of risk factors such as high blood pressure, diabetes, and obesity
- Variable effects and symptom severity across family members
- No specific abnormal findings at a physical examination, but potential signs of heart diseases may be visible
- Possibility of skin deposits (xanthomas) indicating high blood cholesterol or fat levels
Additionally, a thorough heart check would determine other underlying issues like murmurs noticeable due to diseases affecting the heart valves, or signs of a failing heart, such as swelling in the extremities, distended neck veins, and an enlarged liver. A neurological assessment may expose specific areas of weakness, which could mean there’s a disease in the blood vessels of the brain.
Testing for Familial Combined Hyperlipidemia (Elevated Cholesterol)
Familial combined hyperlipidemia can show different lab results in various people and even different members within the same family. You might find higher levels of things such as total cholesterol, serum triglycerides (a type of fat in the blood), very-low-density lipoproteins (VLDLs), low-density lipoproteins (LDLs), and apolipoprotein B (apo-B). In contrast, high-density lipoprotein (HDL or ‘good cholesterol’) might be lower than usual. The values of triglycerides and apo-B can reach up to 1.5 mmol/L and 1.2 g/L, respectively.
Interestingly, people with this disorder have also been seen to have a thicker carotid artery wall (carotid intima-media thickness or IMT), indicating early signs of plaque buildup or atherosclerosis. So, if you have familial combined hyperlipidemia, a carotid ultrasound, which can measure this thickness, might be suggested to detect the onset of this artery-clogging disease.
Treatment Options for Familial Combined Hyperlipidemia (Elevated Cholesterol)
Familial combined hyperlipidemia is the most common genetic disorder that affects cholesterol levels, making you more likely to develop heart disease early in life. Controlling this condition involves reducing the amount of fat in your bloodstream and continually monitoring your heart health. This is done similar to other cholesterol-related disorders through a combination of medication and lifestyle changes, such as a healthy diet and regular exercise.
There are multiple medications approved by the FDA to help manage this condition. These include types of drugs known as statins, fibrates, bile acid sequestrants, PCSK9 inhibitors, adenosine triphosphate-citrate lyase inhibitors, niacin, and ezetimibe. Additionally, treatments may include omega-3 fatty acids (commonly found in fish oil) and MTTP inhibitors, one of which is the medication lomitapide.
Statins are a group of medications that include drugs like atorvastatin and simvastatin. These work by blocking a specific enzyme in liver cells which reduces the amount of cholesterol your body makes. With less cholesterol internally synthesized, your liver takes more out of your bloodstream, lowering your overall cholesterol levels.
Fibrates are another class of drugs, including gemfibrozil and fenofibrate. These stimulate certain receptors in your body, leading to a reduction in the fatty acids in your blood. By doing so, these drugs help break down the particles that carry fat in your bloodstream, reducing the risk of them building up in your blood vessels and leading to heart disease.
Bile acid sequestrants, such as cholestyramine, work by reducing the absorption of cholesterol in your gut and increasing its removal from your body in feces.
PCSK9 inhibitors, such as evolocumab, are a new class of drugs that regulate how much cholesterol circulates in your body. By blocking this inhibitor, shuttling cholesterol out of your bloodstream and into the liver is optimized, leading to lower cholesterol levels in the bloodstream.
The medication bempedoic acid is an adenosine triphosphate-citrate lyase inhibitor. It works by blocking a liver enzyme, reducing the amount of cholesterol produced in the liver.
Niacin, ezetimibe, omega-3 fatty acids (from fish oil), and the medication lomitapide can also be used to manage cholesterol levels effectively.
What else can Familial Combined Hyperlipidemia (Elevated Cholesterol) be?
Doctors need to keep in mind a range of possible causes when diagnosing familial combined hyperlipidemia, a condition that results in high lipid levels in the blood. These can include both inherited genetic disorders and other non-genetic factors.
Inherited disorders causing high lipid levels may include:
- Familial hypercholesterolemia
- Abetalipoproteinemia
- Hypobetalipoproteinemia
- Chylomicron retention disease
- Hypertriglyceridemia
In comparison to familial hypercholesterolemia, familial combined hyperlipidemia may display lower total cholesterol levels and LDL-C (bad cholesterol) levels. This may be because the full effect of familial combined hyperlipidemia typically develops in adulthood.
However, the risk of developing atherosclerosis (hardening of the arteries) from an early age is the same for both conditions. This early onset atherosclerosis is due to a combination of factors. These include not only lipid levels but also insulin resistance, issues with glucose metabolism, fatty liver, high blood pressure, high uric acid levels, and increased levels of inflammation markers in the blood.
What to expect with Familial Combined Hyperlipidemia (Elevated Cholesterol)
The outlook for Familial Combined Hyperlipidemia (FCH) depends on many elements. These include when it began, how severe the lipid abnormalities are, any other medical conditions, and if the patient sticks to treatment. FCH is tied to a higher risk of early onsets of atherosclerotic cardiovascular disease (ASCVD). This disease can lead to significant health issues and even death if it’s not treated.
So far, there haven’t been any suitably designed studies to figure out the unique risk of heart disease for patients with familial combined hyperlipidemia. However, some researchers suggest that their risk might be at least as high as those patients with a condition called heterozygous familial hypercholesterolemia.
Possible Complications When Diagnosed with Familial Combined Hyperlipidemia (Elevated Cholesterol)
Familial combined hyperlipidemia, a condition related to cholesterol and fat levels in your blood, can increase the possibility of developing a disease called atherosclerosis, which is the hardening of the arteries. Some people may not show any signs, but medical professionals can estimate the risk by checking the thickness of the wall of your neck artery, known as the common carotid artery.
There’s also a notable relationship between familial combined hyperlipidemia and an increased risk of developing coronary artery disease or CAD. This disease affects the vessels supplying blood to your heart. Men with familial combined hyperlipidemia have a higher chance of having CAD compared to women, regardless of their fat and cholesterol levels and other potential risks.
Familial combined hyperlipidemia is also one of the leading causes of heart attacks, especially in young people. In fact, a study shows that almost 40% of heart attack patients, who are under 40, have familial combined hyperlipidemia.
Preventing Familial Combined Hyperlipidemia (Elevated Cholesterol)
Doctors should make clear how FCH, a genetic disorder, is passed down the family line. By knowing about the genetic aspect of FCH, patients can better grasp their chances of getting heart disease and why taking action early matters. Along with information about genetics, patients should be taught how changing their lifestyle can help manage FCH. Changes such as eating correctly, exercising routinely, and maintaining a healthy weight are important. Moreover, doctors should also discuss other changeable risk factors like quitting smoking, moderating alcohol use, and managing stress.
Besides this, doctors might recommend medicine to help lower cholesterol levels, lowering the chance of heart disease for those with FCH. It’s important that doctors and patients talk about the possible benefits and risks linked with the use of such medicine, and keep an eye out for any unwanted side effects. Regular check-ups should be planned to keep track of the patient’s condition and update the treatment plan as needed. Continuing support and learning can help patients deal with FCH effectively and look after their overall health.
