Dyslipidaemia

Dyslipidemia is an increase in plasma cholesterol and (or) a decrease in triglyceride or HDL levels, which contributes to the development of atherosclerosis. Dyslipidemia may be primary (genetically determined) or secondary. The diagnosis is established by measuring the levels of total cholesterol, triglycerides and lipoproteins in the blood plasma. Dyslipidemia is treated on the basis of compliance with a specific diet, exercise and taking medications that reduce the lipid content.

[1], [2], [3], [4], [5], [6],

Causes of the dyslipidemia

Dyslipidemia has primary causes of development - single or multiple genetic mutations, resulting in hyperproduction or deficiency in triglyceride and LDL cholesterol release, or excessive production of HDL. Primary lipid metabolism is suspected in patients when there are clinical signs of a condition such as dyslipidemia, early development of systemic atherosclerosis and ischemic heart disease (under 60 years of age), a family history of coronary heart disease or an established level of serum cholesterol> 240 mg / dl (> 6.2 mmol / L). Primary disorders are the most common cause of development in childhood and in a small percentage of cases in adults. Many names still reflect the old nomenclature, according to which lipoproteins were divided into a and chains by electrophoretic separation in the gel.

Dyslipidemia in adults is most often due to secondary causes. The most important factors in developing it in developed countries are a sedentary lifestyle, overeating, especially the abuse of fatty foods containing saturated fats, cholesterol and trans fatty acids (TFA). TLC are polyunsaturated fatty acids, to which hydrogen atoms have been added; they are most widely used in the process of food processing and are atherogenic, saturated fat. Other common secondary causes include diabetes mellitus, alcohol abuse, chronic renal failure or complete loss of kidney function, hypothyroidism, primary biliary cirrhosis and other cholestatic liver diseases, drug-induced pathologies (such as drugs such as thiazides, blockers, retinoids, highly active antiretroviral drugs, estrogen and progesterone and glucocorticoids).

Dyslipidemia often develops against the background of  diabetes mellitus, as patients with diabetes tend to have atherogenesis in combination with hypertriglyceridemia and high LDL levels with simultaneously low levels of HDL fractions (diabetic dyslipidemia, hypertriglyceridemia, hyperapo B). Patients with type 2 diabetes have a particularly high risk of developing a condition such as dyslipidemia. Clinical combinations can include severe obesity and (or) low control of diabetes, which can increase blood circulation in FFA, which leads to an increase in the production of VLDL in the liver. Triglycerides, rich in VLDL, then transfer these TG and cholesterol to LDL and HDL, helping to form rich TG, small, low-density LDL, and produce rich HDL-T. Diabetic dyslipidemia is often exacerbated by a significant excess of the patient's daily kallorazha and reduced physical activity, which are characteristic features of the lifestyle in patients with type 2 diabetes mellitus. Women with type 2 diabetes mellitus may have a specific risk of developing cardiovascular disease.

[7], [8], [9], [10], [11], [12]

Pathogenesis

There is no natural division into normal and abnormal lipid levels, because the very measurement of lipids is a lengthy process. There is a linear relationship between blood lipid levels and the risk of developing cardiovascular disease, so many people who have "normal" cholesterol levels make efforts to make it even smaller. Consequently, there is no specific range of digital values of levels indicating a condition such as dyslipidemia; this term is superimposed on those blood lipid levels that are amenable to further therapeutic correction.

Evidence of the benefit of such a correction is convincing enough for slightly elevated LDL levels and less convincing for the task of lowering elevated triglyceride levels and increasing low levels of HDL; in part because elevated triglyceride levels and low HDL-C levels are more potent risk factors for the development of cardiovascular pathology in women than in men.

[13], [14], [15], [16],

Symptoms of the dyslipidemia

Dyslipidemia itself does not have its own symptoms, but it can lead to the emergence of clinical symptoms of cardiovascular disease, including IHD and obliterating atherosclerosis of the vessels of the lower limbs. A high level of triglycerides [> 1000 mg / dL (> 11.3 mmol / l)] may be the cause of acute pancreatitis.

High levels of LDL can lead to xanthomatosis of the eyelids, the formation of corneal opacity and tendon xanthomas found on the Achilles, ulnar and knee tendons and around the metacarpal joints. In homozygous patients with the development of familial hypercholesterolemia, additional clinical signs in the form of plantar or cutaneous xanthomas may also occur. Patients with a marked elevation in triglyceride levels may have xanthomatous rashes on the skin of the trunk, back, elbows, buttocks, knees, forearms, and feet. Patients with a fairly rare dysbetalepoproteinemia may have palmar and plantar xanthomas.

Expressed hypertriglyceridemia [> 2000 mg / dl (> 22.6 mmol / l)] can lead to the appearance of white cream deposits (lipemia retinalis) on the retinal arteries and veins. Sudden rise in lipid levels in the blood clinically also manifests itself by the appearance of white, "dairy" inclusions in the blood plasma.

[17], [18], [19], [20]

Forms

Dyslipidaemia is traditionally classified according to the model of increasing the size of lipids and lipoproteins (Fredrickson classification). Dyslipidemia divides into primary and secondary and performs subdivision depending on the increase in only  cholesterol  (pure or isolated hypercholesterolemia) or depending on the increase in both cholesterol and triglycerides (mixed or combined hyperlipidemia). The above classification system does not affect the anomalies of specific lipoproteins (eg, a decrease in HDL or an increase in LDL), which can lead to a nosological disease, despite normal levels of cholesterol and triglycerides in the blood plasma.

[21], [22], [23]

Diagnostics of the dyslipidemia

Dyslipidemia is established based on measurement of serum lipid levels, although such a study may not be required due to the presence of a characteristic clinical picture in patients. Routine measurements (lipid spectrum) include determination of the level of total cholesterol (OX), triglycerides, HDL and LDL.

Direct measurement of total cholesterol, triglycerides and HDL in the blood plasma; the quantitative values of total cholesterol and triglyceride levels reflect the content of cholesterol and TG in all circulating lipoproteins, including chylomicra, VLDL, CAP, LDL and HDL. The level of oscillation of OX values is about 10%, and TG-up to 25% in everyday measurement even in the absence of a nosological form of the disease. OX and HDL can be measured and not fasted, however, in most patients, to obtain the most correct results, the study should be performed strictly on an empty stomach.

All measurements should be performed in healthy patients (outside acute inflammatory diseases), as in conditions of acute inflammation triglyceride levels increase, and cholesterol - falls. The lipid spectrum remains valid for the first 24 hours after the development of acute MI, and then changes occur.

The most frequently measured amount of LDL, reflecting the amount of cholesterol not contained in HDL and VLDL; the VLDL level is calculated from the triglyceride content (TG / 5), ie LDL = OX [HDL + (TG / 5)] (Friedland formula). The cholesterol contained in VLDL is calculated by the level of triglycerides (TG / 5), because the concentration of cholesterol in VLDL particles is usually 1/5 of the total lipid content in this particle. This calculation is correct only when the triglyceride level is <400 mg / dL and the patient is examined on an empty stomach because eating increases the triglyceride content in the blood. Calculate the amount of LDL is possible if you measure the amount of cholesterol contained in CSPP and apolipoproteins (bypassing HDL and chylomicrons).

LDL can also be measured directly in the blood using a plasma ultracentrifugation method, which separates the fractions of chylomicrons and VLDL from HDL and LDL, as well as by the method of enzyme immunoassay. Direct measurement in plasma may be useful in some patients with elevated triglyceride levels to determine if LDL is also elevated, but such direct research is not routine in clinical practice. The role of apo B determination is under study, as its levels reflect all non-HDL cholesterol (i.e., cholesterol contained in VLDLP, VLDL, VLDL, and LDL residues) and may be better predictors of CHD risk than only one LDL.

The long-term lipid spectrum should be determined in all adults> 20 years and repeated thereafter every 5 years. Measurement of lipid levels should be complemented by determining the presence of other cardiovascular risk factors, such as diabetes mellitus, tobacco smoking, hypertension and the presence of a family history of coronary artery disease in men of the first degree of relationship to 55 years of age or in women of the first degree of kinship up to 65 years of age.

A certain age, after which patients would not need further screening, is not present, but, obviously, the need for screening disappears when the patients reach the age of 80, especially if they have IHD.

The purpose of the screening examination is indicated for patients under the age of 20 who have risk factors for atherosclerosis, such as diabetes, hypertension, tobacco smoking and obesity, hereditary forms of IHD in close relatives, ancestors or siblings, or if the cholesterol level is increased by more than 240 mg / dl ( > 6.2 mmol / l), or dyslipidemia from relatives. In the event that information on kinship is not available, as in the case of adoption of children, screening is at the discretion of the attending physician.

Patients with hereditary forms of IHD and normal (or almost normal) lipid levels, in patients with a saturated family history of cardiovascular disease or high LDL-related refractory to drug therapy, nevertheless, levels of apolipoproteins [Lp (a)] should be measured. Levels of Lp (a) can also be directly measured in blood plasma in patients with borderline high LDL levels to address the issue of drug correction. In these same patients, the level of C-reactive protein and homocysteine can be determined.

Laboratory methods for investigating secondary causes that trigger a condition such as dyslipidemia, including fasting blood glucose, liver enzymes, creatinine, TSH levels, and urine proteins-should be performed in most patients for the first time identified dyslipidemia and in the case of unexplained negative dynamics of individual components lipidograms.

[24], [25], [26], [27]

Treatment of the dyslipidemia

Dyslipidemia is treated by prescribing all patients with IHD (secondary prophylaxis) and, in some cases, patients without IHD (primary prevention). The guidelines developed by the Commission for the Treatment of Atherosclerosis in Adults (ATP III), operating within the framework of the National Education Program (NCEP), is the most authoritative scientific and practical publication that directly identifies indications for prescribing therapy for adult patients. In the guide recommendations are reduced to a decrease in elevated levels of LDL and the implementation of secondary prevention, aimed at treating high levels of TG, low levels of HDL and metabolic syndrome. An alternative treatment guide (Sheffield table) uses the ratio of OX: HDL in conjunction with the verification of IHD risk factors for the prevention of cardiovascular risk, but this approach does not lead to the desired effect of preventive treatment.

Therapeutic tactics in children are not developed. Strictly adhere to a specific diet in childhood is a difficult task, and besides there is no reliable scientific evidence that the reduction in lipid levels in childhood is an effective method of preventing cardiovascular disease in these same patients in the future. In addition, the question of the appointment of lipid-lowering therapy and its effectiveness for a long time (for years) is quite controversial. Still, the American Pediatric Academy (AAR) recommends that this therapy be used in some children with elevated LDL.

The specific treatment scheme depends on the established anomaly of lipid metabolism, although there is often a mixed pattern of lipid metabolism disorders. And in some patients, single anomalies of lipid metabolism may require an integrated therapeutic approach, including the use of several types of treatment; in other cases, the use of the same therapeutic method with several types of lipid metabolism disorders can be quite effective. Therapeutic measures should always include the treatment of hypertension and diabetes, quitting and those patients who have a risk of developing MI or cardiovascular death within the next 10-year period of 10% or more (according to the evaluation of the Table of Framingham, Table. 1596 and 1597), the mandatory appointment of small doses of aspirin.

In general, the therapeutic regimens for both sexes are the same.

Elevated LDL levels

The ATP III guideline recommends treatment in adults with elevated LDL and history of coronary artery disease.

Clinical conditions on the basis of which the patient is considered to be at risk for developing cardiac events in the future are similar to the criteria for the risk of developing coronary heart disease (CHD equivalents, such as diabetes mellitus, abdominal aortic aneurysm, obliterating peripheral vascular atherosclerosis and carotid artery atherosclerosis, manifested by clinical symptoms); or the presence of 2 risk factors for the development of IHD. According to the recommendations in the ATP III guidelines, such patients should have an LDL level of less than 100 mg / dl, but it is clear that in practice the goal of therapy is even more severe - keeping the LDL level below 70 mg / dl, it is these figures that are optimal for patients with a very high risk (for example, with the established diagnosis of IHD and diabetes and other poorly controlled risk factors, with metabolic syndrome or acute coronary syndrome). When prescribing drug therapy, it is desirable that the dose of drugs provide a reduction in LDL levels by at least 30-40%.

AAR recommends the appointment of dietotherapy in children with an LDL level above 110 mg / dl. Drug therapy is recommended for children older than 10 years in case of a poor therapeutic response to diet therapy and a persisting LDL level of 190 mg / dL and above, without family history of hereditary cardiovascular diseases. Carrying out drug therapy is also recommended for children older than 10 years with an LDL-C level of 160 mg / dl and above and simultaneous presence of a family history of cardiovascular pathology or having 2 or more risk factors for the development of this pathology. Risk factors in childhood, in addition to family history and diabetes, include tobacco smoking, arterial hypertension, low HDL-C levels (<35 mg / dl), obesity and hypodynamia.

The therapeutic approach includes changing the habitual lifestyle (taking into account the diet and the need for physical activity), taking medications, food supplements, physiotherapy and other procedures, and experimental methods of treatment. Many of the above are also effective for the treatment of other disorders of lipid metabolism. Sufficient physical activity has a direct direct effect on lowering LDL levels in some patients, which is also useful for the ideal control of body weight.

The change in the habitual regimen and the nature of nutrition and physical activity should in any case be considered the initial elements of therapy, whenever it is conducted.

The therapeutic diet includes a reduction in the content of saturated fat and cholesterol; increase the content of monounsaturated fats, dietary fiber and common carbohydrates and achieve an ideal body weight. For these purposes, it is often very useful to consult a dietician, especially in elderly patients who have dyslipidemia.

The length of the period devoted to the change in the habitual lifestyle, used before the beginning of lipid-lowering therapy, is quite controversial. In patients with an average or low cardiovascular risk, it is prudent to allocate for this from 3 to 6 months. Usually 2-3 patient visits to the doctor are sufficient for 2-3 months in order to assess the motivation and determine the degree of adherence of the patient to the established dietary framework.

Drug therapy is the next step that is used when changing just one lifestyle is ineffective. However, for patients with significantly elevated LDL [> 200 mg / dL (> 5.2 mmol / l)] and a high cardiovascular risk, drug therapy should be combined with diet and exercise from the beginning of treatment.

Statins are the drugs of choice for correcting the level of LDL, they evidently reduce the risk of cardiovascular mortality. Statins inhibit hydroxymethylglutaryl CoA reductase, a key enzyme in cholesterol synthesis, by regulating LDL receptors and increasing LDL clearance. Drugs in this group reduce LDL levels by up to 60% and cause a slight increase in HDL and a moderate decrease in TG levels. Statins also contribute to the reduction of intra-arterial and (or) systemic inflammation by stimulating the production of endothelial nitric oxide; they can also reduce the deposition of LDL in endothelial macrophages and the content of cholesterol in cell membranes in the development of processes of systemic chronic inflammation. This anti-inflammatory effect is manifested as atherogenic even in the absence of lipid elevation. Side effects are nonspecific, but are manifested as an increase in hepatic enzymes and the development of myositis or rhabdomyolysis.

The development of muscle intoxication and without an increase in enzymes is described. The development of side effects is more typical for elderly and elderly people who have combined polyorganic pathology and receive multimedia therapy. In some patients, the replacement of one statin with another during treatment or a reduction in the dose of a prescribed statin eliminates all the problems associated with the side effect of the drug. Muscular intoxication is most pronounced when some of the statins are used together with drugs that inhibit cytochrome PZA4 (for example, together with antibiotic mikrolidami, antifungal drugs of the azole group, cyclosporins), and together with fibrates, especially gemfibrozil. The properties of statins are common to all drugs in the group and differ little for each particular drug, so its choice depends on the patient's condition, LDL level and medical staff experience.

Bile acid sequestrants (SLC) block the reabsorption of bile acids in the small intestine, exert a strong regulating influence on the liver's LDL receptors, facilitating the capture of circulating cholesterol for the synthesis of bile. Preparations of this group contribute to reducing cardiovascular mortality. To activate the reduction in LDL, bile acid sequestrants are usually used in conjunction with statins or nicotinic acid preparations and are the drugs of choice for prescribing in children and women planning a pregnancy. These drugs are a fairly effective group of lipid-lowering drugs, but their use is limited due to the side effects they cause in the form of flatulence, nausea, convulsions and constipation. In addition, they can also increase the level of TG, so their appointment is contraindicated in patients with hypertriglyceridemia. Cholestyramine and colestipol, but not colosseum, are incompatible (interfere with absorption) with the simultaneous administration of other drugs - all known thiazides, blockers, warfarin, digoxin and thyroxine - their effect can be smoothed out in the appointment of FFA 4 hours before or 1 hour after admission .

Ezetimibe (Ezetimibe) inhibits intestinal absorption of cholesterol, phytosterol. It usually lowers LDL only by 15-20% and causes a small increase in HDL and a moderate decrease in TG. Ezetimibe can be used as a monotherapy in patients with intolerance to drugs from the statin group or can be prescribed in combination with statins in patients who are at the maximum doses of drugs in this group and who have a persistent increase in LDL. Side effects are rare.

Supplement to the treatment in the form of lipid-lowering diet includes the use of dietary fiber and affordable margarine, containing vegetable fats (sitosterol and campesterol) or stanols. In the latter case, it is possible to achieve a decrease in LDL at a maximum of 10% without any effect on HDL and TG levels by competitive substitution of cholesterol on the villous epithelium of the small intestine. Adding garlic and walnuts as a food ingredient that reduces LDL levels is not recommended because of the apparent minimal effectiveness of such supplements.

Additional therapies are included in complex therapy in patients with severe hyperlipidemia (LDL <300 mg / dL), refractory to conventional treatment, for example, such as is observed with hereditary hypercholesterolemia. The complex of therapeutic measures includes apheresis (plasmapheresis) of LDL (in which all LDLs are removed by replacing with extracorporeal plasma), ileal bypass anastomosis (blocking the inverse absorption of bile acids) and portocaval shunting (resulting in reduced LDL synthesis, although the mechanism is unknown). Ateresis of LDL is the procedure of choice in most cases, when dyslipidemia as a result of the most effective treatment still can not achieve an adequate effect of reducing LDL. Ateresis of LDL is also commonly used in patients with a homozygous type of inheritance of familial hypercholesterolemia who have a limited response or no response at all to medical therapy.

Among the new methods currently being developed for reducing LDL levels in the near future is the use of peroxisome proliferator (PPAR) receptor agonists with thiazolidinedion-like and fibrate-like properties, LDL receptor activators, LPL activator and apo E recombinants. Vaccination with cholesterol preparations (for the purpose of inducing anti -LLNP antibodies and the acceleration of the clearance of LDL from serum) and transgenic engineering (gene transplantation) are conceptual areas of research Today they are at the stage of study, but the clinical realization of which is possible in a few years.

[28], [29], [30], [31], [32], [33],

Elevated levels of triglycerides

It is still unclear whether an increased level of  triglycerides has an  independent effect on the development of cardiovascular pathology, since the increase in triglycerides is associated with numerous metabolic abnormalities that result in the development of IHD (eg, diabetes, metabolic syndrome). According to consensus, the reduction in high triglyceride levels is clinically justified. There are no specific therapeutic goals for correcting hypertriglyceridemia, but triglyceride levels <150 mg / dL (1.7 mmol / L) are generally considered desirable. There are no specific recommendations for the treatment of elevated triglycerides in children.

Initial therapy includes lifestyle changes (metered exercise, combating excess body weight and refraining from eating refined sugar and alcohol). Adding fish dishes rich in 3 fatty acids to a diet (2 to 4 times a week) can be clinically effective, but the amount of 3 fatty acids in a fish is often lower than necessary, so you may need to resort to food supplements. In patients with diabetes and in whom dyslipidemia is observed, blood glucose levels should be closely monitored. If the above measures are ineffective, the use of lipid-lowering drugs should be considered appropriate. Patients with very high levels of triglycerides should be prescribed drug therapy from the time of diagnosis in order to reduce the risk of acute pancreatitis as soon as possible.

The intake of fibrates reduces the level of triglycerides by approximately 50%. They begin to stimulate endothelial LPL, which leads to an increase in the processes of oxidation of fatty acids in the liver and muscles and a decrease in intrahepatic synthesis of VLDL. Preparations of this group also increase A PVP by almost 20%. Fibrates can cause side effects from the gastrointestinal tract, including dyspepsia and abdominal pain. In some cases, they can cause cholelithiasis. Fibrates promote the development of muscle intoxication in cases when prescribed together with statins and potentiate the effects of warfarin.

The use of nicotinic acid preparations can also have a positive clinical effect.

Statins can be used in patients with a triglyceride level of <500 mg / dl if there is also an elevated LDL; they can reduce and LDL, and TG and still VLDL. Fibrates are the drugs of choice only in the case of a high level of triglycerides in the patient and which have dyslipidemia.

Omega-3 fatty acids in high doses [1-6 g / day of eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA)] can have a positive effect on reducing the level of triglycerides. 3 fatty acids EPA and DHA are contained as active ingredients in fish oil or capsules 3. Side effects include eructations and diarrhea and can be reduced by dividing the daily dose of fish oil capsules by taking 2 or 3 times daily with meals. The purpose of 3 fatty acids can be useful in the treatment of other diseases.

[34], [35], [36], [37], [38]

Low HDL

The result of therapeutic measures aimed at increasing the level of HDL, may be a reduction in the risk of death, but scientific publications on this topic are few. In the ATP III guidelines, low HDL is defined as <40 mg / dL (<1.04 mmol / L); the guidelines do not explicitly indicate the therapeutic goals of HDL-C levels, and it is recommended that drug-induced intervention be used to increase HDL levels only after reaching the LDL target. Treatment of elevated LDL and TG levels often leads to normalization of HDL levels, so that sometimes as a result of treatment, all 3 goals can be achieved simultaneously. There are no official guidelines for treating a low level of HDL in children.

Therapeutic measures include increasing physical exertion and adding monounsaturated fats to the diet. Alcohol increases the level of HDL, but its use is not recommended as a therapeutic because of the many other side effects of its intake. Drug therapy is recommended in cases where a change in lifestyle alone is not sufficient to achieve the goals.

Nicotinic acid (niacin) is the most effective drug for increasing the level of HDL. The mechanism of its action is unknown, but it has an effect on the increase in HDL, and on the inhibition of the clearance of HDL and can promote the mobilization of cholesterol from macrophages. Niacin also reduces the level of TG and in doses from 1500 to 2000 mg / day reduces LDL. Niacin causes a rush of blood (and associated redness of the skin), itchy skin and nausea; the prescription of small doses of aspirin can prevent the development of these side effects, and the slow impact of small doses divided into several doses per day is often the reason for a significant decrease in the severity of side effects. Niacin can cause increased hepatic enzymes and rarely liver failure, insulin resistance, hyperuricemia and gout. It can also help increase homocysteine levels. In patients with moderate LDL and below average levels of HDL, treatment with niacin in combination with statins can be very effective in preventing cardiovascular diseases.

Fibrates increase the content of HDL. Infusion of recombinant HDL cholesterol (eg, apolipoprotein A1 Milano, a special variant of HDL in which the amino acid cysteine is substituted for arginine in the 173rd position, which makes it possible to form a dimer) today are a promising method of treating atherosclerosis, but require further development. Torcetrapib, an inhibitor of CETP, significantly increases HDL and reduces LDL, but its effectiveness in atherosclerosis is not proven, and this drug also needs further study.

Elevated levels of lipoproteins (a)

The upper limit of the norm for lipoproteins (a) is about 30 mg / dL (0.8 mmol / L), but individual values among African and American populations are higher. To date, there are very few medicines that can affect the elevated levels of lipoproteins (a) or prove the clinical effectiveness of such effects. Niacin is the only drug that directly reduces the level of lipoproteins (a); when administered in high doses, it can reduce lipoproteins (a) by about 20%. The usual therapeutic tactics in patients with elevated levels of lipoproteins (a) is the active reduction in LDL levels.

[39], [40]

How is dyslipidemia treated?

Diabetic dyslipidemia is treated with a lifestyle change combined with a statin prescription to lower LDL and / or fibrate levels to reduce TG levels. Metformin reduces the level of TG, which may be the reason for the preferred choice of this drug among all antihyperglycemic agents in the appointment of treatment to a patient with diabetes. Some thiazolidinediones (TZDs) contribute to an increase in both HDL and LDL (probably, to a lesser extent, those that have an atherogenic effect). Some TZD also reduce TG. These drugs should not be selected as the main lipid-lowering drugs in the treatment of lipid metabolism disorders in patients with diabetes, but they can be useful as an additional therapy. Patients with very high TG levels and diabetes control other than optimal TG may have a better response to insulin therapy than oral hypoglycemic drugs.

Dyslipidemia in patients with hypothyroidism, kidney disease and / or obstructive liver disease, first involves therapy for underlying causes, and then anomalies of lipid metabolism. The changed levels of the lipid spectrum in patients with a slightly reduced thyroid function (level of TSH at the upper limit of the norm) are normalized with the appointment of hormone replacement therapy. It should be considered reasonable to reduce the dose or complete discontinuation of the drug, which caused a violation of lipid metabolism.

Monitoring of dyslipidemia 

The levels of the lipid spectrum after the start of therapy should be checked periodically. There are no data confirming the existence of special monitoring intervals, but measurement of lipid levels 2-3 months after the onset or change of treatment and then 1 or 2 times a year after the lipid level is stabilized is a common practice.

Despite rare cases of hepatotoxicity and accumulation of toxins by the muscles against the background of taking statins (0.5-2% of all cases), the most popular recommendations are in such a state as dyslipidemia, the baseline measurement of levels of hepatic and muscle enzymes at the beginning of treatment. Many specialists use at least one additional study of hepatic enzymes 4-12 weeks after the start of treatment and then annually on a background of therapy. Therapy with statins can be continued until the hepatic enzymes are more than 3 times higher than the upper limit of the norm. The level of muscle enzymes does not need to be monitored regularly until patients develop myalgia or other symptoms of muscle damage.

Forecast

Dyslipidemia has a variable prognosis, depends on the dynamics of the lipid spectrum and the presence of other risk factors for cardiovascular disease.

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