Hypercholesterolemia is a disease in which the level of cholesterol in the blood rises to pathological levels. From the point of view of normal physiology, this compound is important and useful. Normally, most of it is produced by the body (up to 80%). Cholesterol ensures the stability of cell membranes and is involved in the synthesis of vitamins, bile acids, and hormones. However, with hypercholesterolemia, its level increases, it is deposited on the walls of blood vessels, affects metabolic processes and leads to the development of serious complications, including heart attack, stroke, hypertension, etc.
Classification
Most often in clinical practice, the Frederickson classification of hypercholesterolemia is used, which is based on the division according to the predominance of one or another cholesterol fraction:
- Type I – increased concentration of chylomicrons (CM).
- Type IIa – increased levels of low-density lipoproteins (LDL).
- Type IIb – high content of low and very low density lipoproteins (VLDL and LDL).
- Type III – increased levels of intermediate density lipoproteins (IDL).
- Type IV – increased VLDL values.
- Type V – high level of VLDL and cholesterol.
Based on its origin, hypercholesterolemia is divided into:
1. Primary
. This form is in turn divided into:
- Polygenic. The most common variety. Caused by a combination of genetic predisposition and exposure to exogenous factors (diet, smoking, etc.).
- Family. Caused by various hereditary disorders of lipid metabolism due to genetic mutations.
2. Secondary
. High levels of cholesterol in the blood, which develops against the background of certain diseases, endocrine disorders, or taking medications.
Based on the degree of increase in blood cholesterol levels, the following are distinguished:
- Mild hypercholesterolemia
– from 5.0 to 6.4 mmol/l. - Moderate hypercholesterolemia
– from 6.5 to 7.8 mmol/l. - High hypercholesterolemia
– 7.9 mmol/l and above.
Meaning of the term
Before looking at hypercholesterolemia, it is important to understand what cholesterol is. It is one of the many chemical compounds present in the human body that falls under the category of fatty substances or lipids. The word cholesterol consists of two Greek words “chole” - bile, “steros” - solid, which translates as “hard bile”. The substance is a natural fatty alcohol, which is why in many sources it is called “cholesterol”.
Cholesterol, from the point of view of the physiology of the body, is one of the necessary and very important components of cell membranes, which are responsible for their stability. More precisely, each cell membrane consists of cholesterol, and it is this that determines its permeability and rigidity. The described substance is part of bile acids, ensuring normal digestion, and also participates in the synthesis of vitamins and hormones (sex and adrenal).
Reference! In fact, the human body is capable of independently synthesizing the amount of cholesterol necessary for life. This function is performed by the main gland – the liver. In the body of a healthy person, 80% of cholesterol is produced by the liver and only 20% comes from the outside, that is, from food.
Since cholesterol is a fatty substance, it cannot but mix with blood, the main part of which is water, and dissolve in it. To ensure the possibility of circulation in the bloodstream, the substance is covered with a kind of shell formed by protein molecules - proteins. Lipids that have a protein shell are called lipoproteins.
At the same time, substances in this group are characterized by significant differences. Lipoprotein particles can be of four types: very low density (VLDL), low density (LDL), intermediate density (LDL) and high density (HDL). The first three listed varieties contain “bad” cholesterol, which can be deposited on the vascular walls, forming atherosclerotic plaques. And HDL contains “good” cholesterol.
They collect cholesterol from the walls of blood vessels and transport it to the liver. Then, as part of bile, it is excreted from the liver into the gastrointestinal tract. This is how the “good” form of cholesterol, which HDL contains, prevents the development and progression of atherosclerosis.
Causes of hypercholesterolemia
Physiological
Cholesterol values can also exceed normal levels in healthy people. For example, changes in the balance of female sex hormones during pregnancy cause an increase in cholesterol levels. After childbirth, the indicators return to normal. In case of improper preparation before taking a biochemical blood test (eating fatty foods on the eve of blood donation), cholesterol turns out to be higher than normal.
Hereditary disorders of lipid metabolism
This group of diseases is called “hereditary (familial) hypercholesterolemia.” They are caused by mutations in genes encoding the expression of lipoprotein receptors (LDLR, ApoB-100, PCSK9) or the lipoprotein lipase enzyme. This leads to disruption of catabolism and absorption of lipoproteins by cells, as a result of which the concentration of cholesterol in the blood begins to increase significantly.
A distinctive feature of familial forms of hypercholesterolemia is the detection of very high levels of cholesterol (in homozygous patients it can reach 20 mmol/l) already from early childhood (5-7 years). All this is associated with the rapid progression of atherosclerosis and the development of serious cardiovascular complications already at 20-25 years of age. Aggressive lipid-lowering therapy is required to normalize cholesterol levels.
Xanthelasma on the eyelids is a sign of hypercholesterolemia
Obesity
Excess weight ranks first among the etiological factors of hypercholesterolemia and accounts for more than 90% of all its cases. The pathogenesis of the effect of excess weight on cholesterol levels is as follows. Adipocytes secrete a large amount of biologically active substances that reduce the sensitivity of cells to insulin, and insulin resistance is formed.
As a result, lipolysis and the release of free fatty acids (FFA) are activated. From excess FFA entering the liver, a large amount of VLDL, one of the cholesterol fractions, is synthesized. Hypercholesterolemia increases slowly and is directly proportional to the degree of obesity; it can gradually return to normal with weight loss, but over a long period of time it becomes irreversible.
Kidney diseases
The cause of hypercholesterolemia can be kidney diseases accompanied by nephrotic syndrome: the initial stage of glomerulonephritis, diabetic or hypertensive nephropathy, nephropathy with multiple myeloma. An increase in cholesterol levels is associated with the loss in urine of carrier proteins and enzymes involved in lipid catabolism (lecithin-cholesterol acetyltransferases, lipoprotein lipases).
The severity of hypercholesterolemia correlates with the degree of proteinuria. After specific therapy for the underlying disease and relief of nephrotic syndrome, cholesterol levels usually normalize, but in some cases they remain elevated for a long time, which may require additional therapeutic measures to prevent the progression of atherosclerosis.
Endocrine disorders
Diseases of the endocrine system occupy a special place in the structure of the causes of hypercholesterolemia. Insufficiency or excess production of a particular hormone causes significant changes at different stages of lipid metabolism.
- Diabetes mellitus type 2.
The most common cause among endocrine diseases. The mechanism of development of hypercholesterolemia is the same as in obesity (relative insulin deficiency, increased synthesis of VLDL). The degree of increase in cholesterol corresponds to the severity of diabetes. To normalize indicators, both antidiabetic and lipid-lowering therapy are necessary. - Hypothyroidism.
Thyroxine and triiodothyronine stimulate the formation of VLDL receptors and regulate the activity of cholesterol-7-alpha-hydroxylase, the main enzyme in the synthesis of bile acids. A decrease in the concentration of thyroid hormones in hypothyroidism leads to a slowdown in the catabolism of VLDL and the conversion of cholesterol into bile acids. Hypercholesterolemia is moderate, completely reversible. Disappears along with other symptoms of the disease after hormone replacement therapy. - Cushing's disease/syndrome.
Primary and secondary hypercortisolism increase cholesterol levels both directly (adrenocortical hormones and glucocorticosteroids reduce the number of VLDL receptors) and indirectly (through the development of steroid-induced diabetes mellitus). Hypercholesterolemia is more pronounced and more persistent than with hypothyroidism.
Cholestasis
An increase in serum cholesterol levels can be observed in diseases of the liver and biliary tract, accompanied by intra- or extrahepatic cholestasis (stagnation of bile). Hypercholesterolemia is caused by impaired utilization of cholesterol for the production of bile acids. Its degree correlates with the severity of cholestasis.
The highest rates are observed in primary sclerosing cholangitis, primary and secondary biliary cirrhosis, less pronounced in parenchymal liver diseases (alcoholic, viral hepatitis, fatty liver). Elimination of cholestasis leads to a fairly rapid normalization of cholesterol.
Other reasons
- Autoimmune diseases:
systemic lupus erythematosus, hypergammaglobulinemia. - Metabolic disorders:
gout, storage diseases (Gaucher disease, Niemann-Pick disease). - Mental illness:
anorexia nervosa. - Taking medications:
oral contraceptives, beta-blockers, thiazide diuretics.
4.Treatment
In fact, the only way to medically influence the concentration of cholesterol in the blood (in the direction of reducing it) are drugs from the pharmacological group of statins. However, to date, extensive medical and statistical material has been accumulated, which reliably indicates, firstly, the insufficient effectiveness of these drugs (the so-called residual cardiovascular risk with such therapy remains at the level of 60-70%), and secondly, the unacceptably high likelihood of complications and side effects, incl. very heavy.
Therefore, one of the primary tasks of modern research medicine is the search and testing of alternative, more effective and safe ways to control the concentration of both total cholesterol and its individual fractions.
However, statins in any case play the role of ultima ratio (“last argument”), which should be resorted to only if there is no effect from all other measures. They always begin with examination and treatment of identified pathology, often latent or asymptomatic (chronic somatic diseases, endocrine-metabolic disorders, etc.), with the most serious correction of lifestyle and daily diet, cycle of rest and stress (physical and mental); with normalization of body mass index and categorical refusal of harmful habits.
With this approach, pharmacotherapy will most likely not be needed.
Diagnostics
Laboratory hypercholesterolemia is detected by examining venous blood. In addition to the concentration of total cholesterol, the determination of its fractions and triglycerides is of great information. For differential diagnosis, the patient’s age and other anamnestic data are important - taking medications, the presence of close relatives with a confirmed familial form of hypercholesterolemia. To clarify the etiological factor, the following examination is carried out:
- Routine laboratory tests.
The content of liver transaminases (ALT, AST), markers of cholestasis (alkaline phosphatase, gamma-glutamyl transpeptidase), and glucose are measured. If nephrotic syndrome is suspected, a general urinalysis, analysis for microalbuminuria, and daily proteinuria are performed. - Hormonal studies.
The concentration of TSH and thyroid hormones (free T4 and T3) is determined. To confirm hypercortisolism, the level of cortisol in the blood is checked after performing small and large dexamethasone tests. - Immunological tests.
Tests are performed for markers of viral hepatitis (HBsAg, HCV), antimitochondrial (AMA), antineutrophil (ANCA) antibodies. - Ultrasound.
An ultrasound of the abdominal organs may reveal gall bladder stones, wall thickening, and signs of fatty infiltration in the liver. - Genetic research.
If hereditary hypercholesterolemia is suspected, mutations in the LDLR, PSCK-9, and ApoB-100 receptor genes are detected using the polymerase chain reaction.
For drug correction of hypercholesterolemia, different groups of drugs are prescribed
Correction
Conservative therapy
If hypercholesterolemia is detected, it is imperative to consult a doctor to find out the cause of this laboratory phenomenon and select appropriate treatment. Much attention is paid to the fight against the underlying disease (immunosuppressive therapy for nephrotic syndrome, hormone replacement therapy for hypothyroidism, choleretic therapy for cholestasis), since its elimination can lead to normalization of cholesterol levels without additional intervention.
Non-drug methods for correcting hypercholesterolemia include complete smoking cessation and limiting alcohol consumption. Also, in order to reduce body weight, obese patients must follow a diet with a decrease in the proportion of animal fats in the diet (butter, fried meat, sausages) and an increase in vegetable fats (vegetables, seafood), fruits and whole grains, and regularly perform various physical exercises.
For the drug correction of hypercholesterolemia, the following drugs are used:
- Statins
(atorvastatin, rosuvastatin). The most effective and frequently prescribed means to reduce cholesterol levels. The mechanism of action is based on the suppression of cholesterol synthesis in the liver. - Fibrates
(clofibrate). These drugs stimulate the activity of the LPL enzyme, thereby accelerating the degradation of the drug. They reduce not only cholesterol, but also triglycerides, so they often become the drugs of choice for patients suffering from diabetes. - Ezetimibe
. Inhibits the absorption of cholesterol in the intestine. Used in combination with statins. - PCSK9 inhibitors
(alirocumab). These are monoclonal antibodies that bind to LDL receptors in the liver, which stimulates the breakdown of lipoproteins. Prescribed when statins are ineffective. - Bile acid sequestrants
(cholestyramine, colestipol). They are ion exchange resins that suppress the absorption of bile acids in the intestine. Depletion of FA reserves activates their synthesis from cholesterol in the liver. Used in patients with cholestasis. - A nicotinic acid
. This drug reduces the flow of fatty acids into the liver, which suppresses the synthesis of lipid. It has a weak hypocholesterolemic effect, therefore it is used as an addition to other drugs. - Omega-3 fatty acids
. Eicosapentaenoic acid and docosahexaenoic acid are components of fish oil. These substances bind to the nuclear PPAR receptors of liver cells, which leads to a decrease in serum lipid levels.
Surgery
One of the prerequisites for the effective treatment of hypercholesterolemia is normalization of body weight. For patients with morbid obesity (body mass index above 40), especially in combination with type 2 diabetes mellitus, if conservative methods are unsuccessful, bariatric surgery is indicated - gastric banding, gastric bypass or resection.
If hypercholesterolemia is caused by cholestasis due to cholelithiasis, surgical removal of the gallbladder (cholecystectomy) is performed. Patients with Cushing's disease undergo endoscopic transnasal adenomectomy (removal of the pituitary adenoma). For Itsenko-Cushing syndrome, bilateral adrenalectomy is used.
Forecast
Hypercholesterolemia leads to the deposition of cholesterol on the walls of arterial vessels, the formation of atherosclerotic plaques, narrowing of the lumen and deterioration of blood supply to organs and tissues. This is of primary clinical importance for the coronary and cerebral arteries. Therefore, a long-term increase in cholesterol concentration is an unfavorable prognostic factor for cardiovascular diseases and is associated with such serious complications as acute myocardial infarction and acute cerebrovascular accident.
Symptoms
The main insidiousness of dyslipidemia is that until a certain time a person does not notice signs of its presence. Therefore, he continues to live an ordinary life, without changing his ingrained habits. Meanwhile, the level of cholesterol in his blood increases. If high rates persist for a long time, then the first manifestations of this disorder will be:
- Xanthomas are relatively dense nodules in the tendon area.
- Xanthelasmas are subcutaneous deposits on the eyelids. Because of their yellow color, they can be difficult to distinguish from other areas of the skin.
- Lipoid arc - a rim of cholesterol on the cornea of the eye of a white or grayish-white hue.
With the development of atherosclerosis against the background of hypercholesterolemia, the clinical picture will be supplemented by symptoms of damage to the internal organs involved in the pathological process, and subsequently various complications may develop.
Xanthelasma of the eyelid with hyperlipidemia
