Introduction:
Familial combined hyperlipidemia is one of the most common familial genetic disorders that shoot up blood fats. Disorders like diabetes, hypothyroidism and habits like alcoholism worsen the condition. The disease is associated with
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An increase in blood cholesterol and triglyceride levels in more than two members of the same family.
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The affected individuals may show a variable lipid profile.
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There is an increased risk of premature coronary artery disease.
It is one of the most common inherited hyperlipidemias in the general population and is frequently observed in clinical practice. The disorder is often highly prevalent in patients with coronary heart disease and young survivors of acute myocardial infarction. Familial combined hyperlipidemia is a prevailing hereditary disease that increases blood fats. It causes untimely heart attacks. Alcoholism, diabetes, and hypothyroidism worsen the condition. Risk factors include a family history of high blood cholesterol and untimely coronary artery disease. However, the patients often show variable laboratory parameters in testing. The features of familial combined hyperlipidemia frequently overlap with the characteristics of the metabolic syndrome, leaving the severe disease unrecognized and unattended.
How Are the Metabolism of Lipoproteins Affected in Familial Combined Hyperlipidemia?
An abnormal lipid profile is always observed in familial combined hyperlipidemia. It includes increased blood cholesterol and triglyceride levels, high levels of very-low-density lipoproteins, and low-density lipoproteins. However, a few patients also presented a decrease in blood levels of high-density lipoproteins and plasma cholesterol with increased triglyceride plasma levels.
The structural and metabolic changes in the lipoproteins are given below.
Very low-density lipoproteins (VLDLs):
The plasma VLDLs shoot up high in familial combined hyperlipidemia, but the exact mechanism behind the increase is yet to be understood. Some researchers suggest the elevation is due to the altered incorporation of fatty acids in the triglycerides or altered post-prandial metabolism of the very low-density lipoproteins. A reduced turnover rate of the VLDLs is also observed in the disease. Several other studies suggest that a defective activity of the enzyme lipoprotein lipase is also observed in the disease.
Low-density lipoproteins (LDLs):
An increase in the plasma levels of small and dense low-density lipoproteins is observed. However, significant alterations in the liver catabolic rates of low-density lipoproteins have not been described. The activity of LDL receptors is regular. The use of lipid-lowering drugs and diet can reduce plasma lipid levels. However, it cannot rectify the structural defects of low-density lipoproteins in a large percentage of the population. Moreover, their abundance makes the low-density lipoproteins of familial combined hyperlipidemia patients more prone to oxidative damage.
High-density lipoproteins (HDLs):
The high-density lipoproteins or the good cholesterol decreases in familial combined hyperlipidemia patients. The decrease can be attributed to the enhanced activity of the enzyme hepatic lipase. Recent studies suggest that the reduction of high-density lipoprotein is often associated with an increase in small and dense low-density lipoprotein and very low-density lipoprotein. Thus the LDL pattern is the primary determinant in familial combined hyperlipidemia.
What Is the Genetic Basis of Familial Combined Hyperlipidemia?
Familial combined hyperlipidemia has an autosomal dominant pattern of inheritance. It means an abnormal gene from one parent is enough to inherit the disease. Because of the autosomal dominant nature, it has a wide prevalence and is seen in many members of the same family. It is a genetic disorder caused by a defect on chromosome number 19.
What Is the Incidence of Familial Combined Hyperlipidemia?
It is considered to be the most prevalent genetic hyperlipidemia in a community. The prevalence is estimated to be 0.5 percent to 2 percent. The incidence in patients with coronary heart disease is 10 percent, and in young survivors of acute myocardial infarction aged less than 60 years is 11.3 percent.
What Are the Clinical Features of Familial Combined Hyperlipidemia?
Patients are not presented with any symptoms at a young age. The clinical manifestations are often due to fat accumulation in the blood vessels blocking blood flow to different parts of the body. The commonly presented symptoms include
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Chest pain (angina) may occur due to fat deposition in the coronary artery.
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Coronary heart diseases will appear prematurely.
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Straining of the muscles of calves during walking.
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Non-healing sores on the toes.
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Sudden symptoms similar to a stroke may appear, including trouble speaking, weakness of arms and legs, loss of balance, and drooping of half of the face.
People affected with familial combined hyperlipidemia have a high plasma level of triglycerides and cholesterol in their teenage. Usually, the disease is diagnosed when a person is in their 20s or 30s. However, the lipid profile will remain high throughout the patient's life. In addition to the increased risk of heart disease, patients with familial combined hyperlipidemia are more prone to obesity and glucose intolerance as well.
How Is the Diagnosis of the Disease Made?
The patient's lipid profile can be used to check triglycerides and cholesterol levels. The blood test show
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An Increased level of low-density lipoproteins.
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Decreased levels of high-density lipoproteins.
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Increased level of apolipoprotein B100.
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Increased levels of triglycerides.
Genetic testing can determine the genetic basis and inheritance pattern of the disease in a family.
What Are the Treatment Strategies for Familial Combined Hyperlipidemia?
The main aim of treatment is to decrease the risk of coronary heart disease and other complications associated with increased fat deposition in the blood vessels and body.
Lifestyle change:
Diet changes can help a lot in keeping the disease at bay. Some of the diet changes that can be implemented are
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Reducing the consumption of refined sugar and saturated fat.
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Reduced consumption of red meat (beef).
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Consume low-fat dairy products.
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Avoid processed food containing trans fats.
Therapeutic approach:
Therapeutic drugs for managing familial combined hyperlipidemia depend on the patient's lipid profile. Different drugs are available based on their action. Some medications lower the low-density lipoproteins, some lowers the very low-density lipoproteins, whereas some medications will raise the high-density lipoproteins.
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The medication for lowering cholesterol are Nicotinic acids, Fibrates, and Ezetimibe.
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Medications for raising HDL levels are statins.
Conclusion:
Despite the fact that familial combined hyperlipidemia is a highly prevalent disease, it is often undiagnosed due to pure negligence. As discussed above, if left untreated, the condition may lead to severe complications like premature coronary heart disease and heart attacks. However, with ample modifications in an individual's lifestyle and optimal therapeutics, the disease can be controlled very well.
