Gipertriglitseridemiya

Description:

Gipertriglitseridemiya is the increased content of triglycerides (TG) in a blood plasma on an empty stomach. As limits of norm of the TG level use the 95th percentile for this population depending on age and a floor. Gipertriglitseridemiya can be followed by quantitative or high-quality disturbances from lipoproteids which level and a ratio at the same time can change also significantly. TG indicators at various states can give in to considerable fluctuations: adequate metabolic tension with a moderate gipertriglitseridemiya can pass into heavy. The increased concentration of TG in a blood plasma increases risk of development of the cardiovascular diseases (CD) as an independent factor and in a complex with other connected risk factors, such as obesity, the metabolic syndrome (MS), the diabetes mellitus (DM), the increased levels of pro-inflammatory and prethrombotic biomarkers. At increase in the TG level (especially> 10 mmol/l) there is also a risk of development of the acute pancreatitis (AP).

Gipertriglitseridemiya's symptoms:

TG are brought out of composition of chylomicrons in fabrics (except a liver) by hydrolysis by lipoproteinlipazny system by means of a cofactor of apolipoprotein (Apo) of C-II. The hereditary chylomicronemia (a giperlipoproteinemiya of the I type) and primary mixed lipidemia (the V type) are characterized by pathological emergence of chylomicrons after 12-14-hour restriction of meal. Feature of the clinical manifestations observed at a hereditary chylomicronemia and primary mixed lipidemia, emergence of xanthomas, a lipemia of a retina of eyes, a gepatosplenomegaliya, symptoms from TsNS is, such as irritability, recurrent epigastric pain with the increased risk of development of OP. In samples of lipemichesky plasma after night cooling the dense layer emerging on a surface is formed. And at a hereditary chylomicronemia, and at the mixed lipidemia on an empty stomach in a blood plasma the TG level over 10 mmol/l is defined.
At a hereditary chylomicronemia the clinical symptomatology appears at children's age and is followed by deficit of lipoproteinlipase, decrease of the activity of Aro-CII, and also homozygous genovariations. At primary mixed lipidemia with infrequent genovariations symptoms appear at adult age with less heavy functional deficit and considerable the raised general cholesterol (OHS), than at a hereditary chylomicronemia. Prevalence of a hereditary chylomicronemia in population in comparison with primary mixed lipidemia is lower (about 1 on 10 million and 1 on 10 thousand respectively). At a family chylomicronemia during biochemical analysis activity of lipoproteinlipase of the plasma taken after intravenous administration of heparin decreases, however this test is carried out not in all laboratories.
The hereditary gipertriglitseridemiya (giperlipoproteinemiya of the IV type) is defined only by increase in the LPONP level which contain much less TG, than chylomicrons. Prevalence of this disturbance in population makes about 5-10%. As a rule, moderate increase in TG of a blood plasma (3-10 mmol/l), often with the LPVP low level is noted. The hereditary gipertriglitseridemiya is directly connected with the increased risk of development of SSZ, obesity, resistance to insulin, SD, the arterial hypertension (AH) and a hyperuricemia.
In separate group of hereditary diseases the combined giperlipoproteinemiya (IIb type) are combined with an autosomal and dominant mode of inheritance at variable penetrance. Prevalence of these diseases in population makes
2-5%. The main distinguishing character of this group of diseases is increase in LPONP fraction and lipoproteids of the low density (LPNP) with decrease in the LPVP level. These changes are connected with inheritance, at least, from one relative of the first degree of relationship at which similar disturbances of a lipidic profile were defined. It is supposed that disturbances are transmitted through a heterozygote in a random way, changing activity of lipoproteinlipase, or by APOC3 gene mutations, but the molecular basis which is the cornerstone of the combined hereditary giperlipoproteinemiya, as a rule, cannot be found. Recently the gene of USF1 which can code the starting factor, however was defined and other genes, including APOA5 and APOC3, can sometimes play a role in development of these disturbances.
There is also hereditary disbetalipoproteinemiya (a giperlipoproteinemiya of the III type) which population prevalence makes about 1-2 cases on 20 thousand population. The main symptom of a disease is increase in level of the lipoproteidovy remains rich with triglycerides known as lipoproteids of the average density (LPSP) or β-LPONP which lead to equimolar increase in the OHS and TG level in a blood plasma. People with this disturbance are most often homozygous on defective the APOE E2 isoform in which arginine is replaced with cysteine that distinguishes it from the E3 isoform in the rest 158. The phenotypical expression, however, usually demands concurrent factors, such as obesity, SD of the 2nd type or a hypothyroidism.
The LPNP level of plasma decreases owing to disturbance of metabolism of LPONP. Increase in level of cholesterol (XC) of LPONP is defined, at the same time diagnostic test is the ratio of TG and E2/E2 of a homozygote. Patients with these diseases often have the increased risk of development of SSZ. Characteristic clinical manifestation of disturbances are hilly xanthomas or rashes on extensor elbow surfaces of extremities and flat in the field of a palmar fold.

Secondary gipertriglitseridemiya.
Some states connected with metabolic disturbances, often (but not always) are connected with the increased TG level. It can mean that at persons insignificant hereditary metabolic defects can decide on a secondary gipertriglitseridemiya. Obesity is the most frequent metabolic stressful factor connected with a gipertriglitseridemiya. Similar communication is found also with badly controlled SD of the 2nd type and the excessive use of alcoholic drinks.

Obesity, metabolic syndrome, diabetes mellitus.
People at whom the increased content of visceral fatty tissue is defined have the increased TG level and the lowered LPVP level XC. Approximately at 80% of men with a waist circle> 90 cm and the blood plasma TG level ≥ 2 mmol/l the metabolic triad of nonconventional markers of SSZ is characteristic: a giperinsulinemiya, the increased Apo-B levels and LPNP. This triad can increase risk of development of SSZ by 20 times.
At SD of the 2nd type there is a deterioration in ability of absorption of glucose fabrics under the influence of insulin and there are no adequate mechanisms of replacement of this process. Besides, among persons without SD of the 2nd type, but with resistance to insulin the giperinsulinemiya is connected with a number of the metabolic frustration called MS. This syndrome is often observed at patients with obesity of the central genesis and is serious risk factor of development of SD of the 2nd type. It is characterized by existence of tolerance to glucose, a dislipidemiya (TG> of 1,7 mmol/l and with a low level of XC LPVP) and AG.
At MS and SD the gipertriglitseridemiya is shown by increase in the LPONP level in a blood plasma with/without chylomicronemia; decrease of the activity of lipoproteinlipase and increase in activity of the proteins which are responsible for cholesterol transport; the increased release and metabolism of free fatty acids. Clinically at such patients liver obesity is often noted.
There is several determination of MS which combines several risk factors in one concept. It is made to find out, whether above risk of cardiovascular events in the presence of a complex of factors, than from each factor separately. At the same time it is revealed that at obesity, SD of the 2nd type, MS control of weight and a glycemia leads to decrease in a gipertriglitseridemiya.

Alcohol.
At the excessive use of alcoholic drinks the gipertriglitseridemiya is connected with increase in LPONP with/without chylomicronemia. In certain cases TG of plasma can remain within normal range as a result of adaptive increase in lipolytic activity. However alcohol can worsen a lipolysis, especially when the patient has a functional deficit of lipoproteinlipase that leads to noticeable increase in TG.

Diseases of kidneys.
At a nephrotic syndrome increase in LPNP fraction XC is the main manifestation of a dislipoproteinemiya which often is followed by increase in Aro-V, including LPONP. The main mechanism of increase in TG is strengthening of function of a liver, at the same time there is also an increase in synthesis of albumine as compensation of renal proteinaceous exhaustion. Uraemia is associated with increase in the LPONP level that reflects decrease in a lipolysis as a result of toxic effect of uraemic metabolites.

Pregnancy.
During the third trimester of pregnancy of TG of a blood plasma often raise three times from initial level. As a rule, such changes are physiologic, are not shown clinically and completely disappear at normal lipoproteinlipazny activity. The chylomicronemia during pregnancy normal meets very seldom, and its emergence can demonstrate risk of development of OP which can be fatal both for mother, and for a fruit.

Not alcoholic steatosis of a liver.
These disturbances can occur approximately at a third of inhabitants of North America that reflects increase in frequency of obesity, resistance to insulin and MS. At a third of patients with a gipertriglitseridemiya it can be noted not alcoholic steatogepatit. Besides, toxic action of various fractions of lipids, an oxidatic stress, cytokines and pro-inflammatory mediators bring the contribution in progressing of a disease from fatty regeneration of a liver to not alcoholic steatogepatit. The main manifestations of a dislipidemiya at the disturbances connected with not alcoholic steatosis of a liver are increase in the TG level and decrease in the LPVP level XC. Small researches showed that treatment of such disturbances by statines more effectively in comparison with fibrata.

Other states.
The hypothyroidism usually is followed by increase in the LPNP level, at the same time the TG level can be also increased. Paraproteinemias (a hypergammaglobulinemia at a macroglobulinemia, a multiple myeloma, a lymphoma and lymphocytic leukoses) and autoimmune disorders (for example, a system lupus, эритематоз) can also cause a gipertriglitseridemiya, most likely, by impact on processes of a lipolysis.

Effect of medicines.
A large amount of medicines can increase concentration of TG in a blood plasma. In such cases it is necessary to consider the possibility of correction of a gipertriglitseridemiya. If it is impossible to lower a dosage, to change a way of administration of drug or to replace it with other class, then at identification of disturbances it is necessary to appoint either a diet, or the drugs reducing the TG level.
Patients to whom anti-retrovirus therapy, especially protease inhibitors is appointed often have a lipodystrophy, a dislipidemiya and resistance to insulin. At 80% from them the gipertriglitseridemiya and at 50% – a hypercholesterolemia develops. At a combination of these disturbances at persons to whom active anti-retrovirus therapy is carried out the relative risk of SSZ increases by 26%. Ritonavir and лопинавир most often cause a dislipidemiya, inhibitors of the return transcriptase (ставудин, not Virapinum and эфавиренз) – it is less. Often the TG level is normalized when drugs can temporarily be cancelled or replaced with others if there is no alternative to purpose of anti-retrovirus therapy. For example, in one of researches change of protease inhibitor on not Virapinum or эфавиренз reduced the TG level approximately by 25%, addition to therapy of a pravastatin or bezafibrat allowed to lower it approximately by 40%.

The secondary reasons leading to a gipertriglitseridemiya:
Obesity
MS with the TG level> 1,7 mmol/l
High-calorific diet with high content of fats and carbohydrates with positive power balance
Insufficient physical activity
Alcohol intake
SD of the 2nd type
Diseases of kidneys, uraemia or glomerulonephritis
Hypothyroidism
Pregnancy: physiological increase in the TG level throughout the third trimester
Autoimmune disorder (paraproteinemia, system lupus, эритематоз)
Any drug from the presented groups:
• corticosteroids
• peroral estrogen
• Tamoxifenum
• antihypertensives (non-selective β-blockers, tiazida)
• изотретиноин
• pitches of bile acids
• cyclophosphamide
• the anti-retrovirus drugs used at HIV infection
• psychotropic drugs (fenotiazina, anti-psychotics of the second generation)

Gipertriglitseridemiya's reasons:

The main sources of TG in a blood plasma can be divided on endogenous (from a liver) and exogenous (food fats). In the first case of TG arrive as a part of the particles containing lipoproteids of very low density (LPONP) in the second – as a part of chylomicrons. At receipt of lipoproteids and chylomicrons from capillaries in fatty or muscular tissue under the influence of lipoproteinlipase there is their hydrolysis in free fatty acids. After food of more than 90% of TG circulating in a blood plasma arrives from the digestive tract (DT) as a part of chylomicrons whereas during limited meal endogenous triglycerides cosecrete a liver and prevail as a part of LPONP. Thus, increase in the TG level in plasma results from their increased education in a GIT or a liver or owing to decrease in processes of a peripheral catabolism of fats (mainly, as a result of decrease in lipoproteidny activity of a lipase).

Gipertriglitseridemiya's treatment:

Patients with a gipertriglitseridemiya often have obesity, MS, AG or SD. All states are risk factors of development of SSZ. Therefore treatment has to include reduction of weight, correction of a diet and an exercise stress. Correction of a diet has to be directed to reduction of weight, general caloric content of food, the use of fats and pure carbohydrates (that is products with a high glycemic index). The use of alcoholic drinks should be limited. In cases of a heavy hyper chylomicronemia it is recommended to reduce consumption of fats in a total amount of food to 10-15% (about 15-20 g/days) with restriction of the saturated, unsaturated and combined fats. Consultation of the dietitian is recommended. In cases of a moderate gipertriglitseridemiya restriction of consumption of the sated and combined fats and increase in aerobic loading can lead to decrease in the TG level. According to the Canadian national educational program for cholesterol, consumption of carbohydrates in a daily diet has to make 55-60%, proteins – 15-20% whereas consumption of fats including saturated, should not exceed 30 and 7% respectively. Approximately at 25% of patients normalization of indicators of TG as a result of observance of a diet and weight reduction is noted.
Omega-3 fatty acids (eykozapentayenovy and dokozageksayenovy acids) are components of the Mediterranean diet which includes a large number of seafood. Daily consumption of 4 g the omega-3 of fatty acids along with restriction of the general caloric content of food and consumption of saturated fats can reduce the TG level by 20%. However at non-compliance with other recommendations use only an omega-3 of fatty acids ineffectively.

Medicamentous therapy for decrease in risk of SSZ
Drug treatment of a gipertriglitseridemiya needs to be begun with one medicine in a combination with correction of a diet. Purpose of two drugs is also more carried out at a heavy gipertriglitseridemiya and resistance to monotherapy and a diet under control of creatinine, a creatine kinase and transaminases.