Familial Combined Hyperlipidemia

Familial Combined Hyperlipidemia

Heart & Vascular Health
Nutrition & Dietetics
Contributed byKrish Tangella MD, MBAMay 26, 2018

What are the other Names for this Condition? (Also known as/Synonyms)

  • Familial Combined Hypercholesterolemia-Hypertriglyceridemia
  • Multiple Lipoprotein-Type Hyperlipidemia
  • Multiple Phenotype Familial Hyperlipidemia

What is Familial Combined Hyperlipidemia? (Definition/Background Information)

  • Familial Combined Hyperlipidemia (FCH) is a familial (running in families) metabolic disorder. Its main features are:
    • High levels of cholesterol and/or high levels of triglycerides in blood, in at least 2 members of the same family (including the affected individual)
    • Increased risk for young age or premature coronary heart disease (CHD)
    • Variations in lipid abnormalities is common within the individual or family
  • Among the different familial blood lipid abnormality disorders, FHC is the most common one. Other disorders that belong to this group are:
    • Familial defective apolipoprotein B-100
    • Familial hypertriglyceridemia
    • Familial hypercholesterolemia
    • Familial dysbetalipoproteinemia          
  • Although Familial Combined Hyperlipidemia is a familial disorder, environmental interactions may play a role in the manifestations of the disorder
  • FHC is frequently associated with other disorders such as metabolic syndrome, high blood pressure (hypertension), diabetes mellitus type 2, obesity, etc., and together may contribute to the development of coronary heart disease (heart attacks)
  • The main goal in treating individuals with FCH is to decrease the occurrence of early coronary heart disease. To achieve this, lifestyle changes, medications such as statins, and/or treatment of associated conditions may be used
  • The prognosis is favorable if Familial Combined Hyperlipidemia is diagnosed early and treated promptly. However, these individuals are at a higher risk for coronary heart disease than the general population

Who gets Familial Combined Hyperlipidemia? (Age and Sex Distribution)

  • Although Familial Combined Hyperlipidemia (FCH) is usually diagnosed in adulthood, up to half of the individuals may have had FCH during their childhood
  • It can occur in both men and women
  • Most of the major research studies about FCH are from Europe and US; however, the condition may also occur in other regions, and may involve all ethnicities and races. It is estimated that up to 2% of the population in the US and Europe have Familial Combined Hyperlipidemia

What are the Risk Factors for Familial Combined Hyperlipidemia? (Predisposing Factors)

The risk factors of Familial Combined hyperlipidemia include:

  • Individuals with a positive family history of FCH
  • Individuals with a family history of heart attacks at a young age

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Familial Combined Hyperlipidemia? (Etiology)

Familial Combined Hyperlipidemia is passed down through the families. It is the most common genetic disorder causing abnormal lipid levels in blood. Researchers believe that FCH occurs due to multiple factors including genetic and environmental mechanisms. The genetic mechanisms suggested are

  • Autosomal dominant inheritance
  • Upstream transcription Factor 1 (USF1): The gene encoding this protein has been shown to be associated with FCH
  • Chromosome locus (specific region) 1q21-q23  has been linked to FCH
  • APOA5 gene association with APOA1/CIII/AIV has also been linked to FCH

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly functioning gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Familial Combined Hyperlipidemia?

Individuals with Familial Combined Hyperlipidemia (FCH) are usually not diagnosed early, even though they might have the abnormality since childhood, because most often they do not present any signs or symptoms.

  • They develop symptoms related to clogging of the arteries, especially of the coronary and other peripheral arteries. These symptoms are:
    • Chest pain and heart attack
    • Transient stroke or full-blown stroke with symptoms such as paralysis, speech difficulty, and other presentations
    • Decreased blood flow to the lower body causing foot sores, pain on walking, male erection problems, etc.
  • Signs and symptoms of associated conditions such as metabolic syndrome, high blood pressure (hypertension), diabetes mellitus type 2, and obesity are frequently seen in individuals with FCH

How is Familial Combined Hyperlipidemia Diagnosed?

The following procedures may be used to diagnose Familial Combined Hyperlipidemia:

  • Thorough evaluation of the individual’s medical history and a complete physical examination
  • During history taking the healthcare provider may want to know the following:
    • About the presence of symptoms pertaining to the heart and arteries, when they began, and if they are becoming worse
    • About one’s personal and family medical history of heart attacks, abnormal blood lipid levels, diabetes mellitus, obesity, etc.
  • FCH is usually diagnosed based on the presence of family history of cardiovascular diseases, physical examination findings, and blood workup. The condition is characterized by the following:
    • high levels cholesterol and/or triglycerides in blood, in minimum 2 family members (can include the affected individual)
    • history of premature coronary heart diseases      
  • Initial blood tests done may include lipid profile, which are done 3 times every 15 days, before a diagnosis of FCH is made. The tests may show all or some of the following abnormalities:

    • Increased LDL, triglycerides, and
    • Decreased HDL levels in blood
  • Additional testing may be undertaken depending on the results of the above tests:
    • Apolipoprotein B100 blood levels
    • Small and dense LDL particles
    • Genetic testing may be performed, if other familial lipid abnormalities are suspected             
  • Carotid ultrasound is a good test to predict the likelihood of future heart attacks or stroke
  • Diagnostic testing of associated conditions such as metabolic syndrome, high blood pressure, type 2diabetes, obesity, and other related conditions may be undertaken in these individuals

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Familial Combined Hyperlipidemia?

Familial Combined Hyperlipidemia causes hardening of the arteries (atherosclerosis), which may lead to the following complications:

  • Early coronary heart disease (heart attacks); the coronary arteries are blood vessels supplying the heart
  • Stroke

How is Familial Combined Hyperlipidemia Treated?

The treatment options of Familial Combined Hyperlipidemia include:

  • The main treatment goal of FCH is to reduce the risk of early heart disease and stroke
  • It is initially treated through dietary and lifestyle modifications, which include:
    • Consultation with dietitians and nutrition experts to devise a dietary plan
    • Decreased consumption of saturated fat; reducing total fat intake to less than 30% of the total calories
    • Completely avoiding consumption of trans fat present in packaged foods
    • Limiting the amount of cholesterol consumption
    • Decreasing the consumption of sugars
    • Regular exercise   
    • Enrolling in weight loss programs if one is obese or overweight
    • Smoking cessation   
    • Limiting the amount of alcohol consumption
    • Undertaking the treatment of FCH associated conditions that include metabolic syndrome, hypertension, type 2 diabetes, etc., to decrease the overall risk of heart attacks
  • If dietary and lifestyle modifications are not helpful in treating Familial Combined Hyperlipidemia, then medications may be taken along with the above alterations to one’s lifestyle and dietary habits. These medications may include:
    • Statins
    • Bile acid resins
    • Fibrates
    • Niacin          

How can Familial Combined Hyperlipidemia be Prevented?

  • Currently, there are no specific methods or guidelines to prevent Familial Combined Hyperlipidemia, since it is a genetic condition
  • Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
  • If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
  • Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Nevertheless, the following measures may be taken to decrease the risk of heart disease in the affected individuals and their family members:

  • In individuals diagnosed with FCH, dietary modifications, such as low-cholesterol, low-saturated fat, and lifestyle modifications, such as smoking cessation and limiting the amount of alcohol, can prevent premature development of plaque (cholesterol-thickening of inner layer of blood vessels), and thereby prevent early heart attacks and stroke
  • Early blood lipid screening of family members including children of the affected individuals

What is the Prognosis of Familial Combined Hyperlipidemia? (Outcomes/Resolutions)

  • Individuals with Familial Combined Hyperlipidemia have an increased risk of atherosclerosis (thickening of the arteries). If the condition is diagnosed early during one’s life and if the treatment and lifestyle changes are appropriately followed, then the outcome is generally favorable
  • A delay in diagnosis and/or treatment can lead to complications such as premature heart attack, stroke, or even death at a young age
  • It is important to note that FCH-affected individuals are at a higher risk for coronary heart diseases than the general population despite treatment

Additional and Relevant Useful Information for Familial Combined Hyperlipidemia:

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Krish Tangella MD, MBA

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