The use of omega-3 PUFA in patients with arterial hypertension associated with metabolic syndrome and concomitant type 2 diabetes mellitus

Since the 1970s, omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have interested cardiologists after the publication of data from significant epidemiological studies in which a lower incidence of cardiovascular diseases (CVD) due to atherosclerosis and thrombosis was found in the population people eating seafood (Greenland Eskimos, indigenous people of Chukotka). The non-physiological nutrition of modern humans accelerates the development of coronary heart disease (IHD), exacerbating such potent risk factors for IHD as hyperlipoproteinemia, arterial hypertension (AH), and overweight.

In a number of clinical, experimental and epidemiological studies, results have been obtained proving that the intake of omega-3 polyunsaturated fatty acids has a beneficial effect on the course of atherosclerosis and slows its progression. Consumption per day of 1-2 g of ω-3 PUFA significantly reduced the risk of repeated myocardial infarction (MI).

To date, there has been ample evidence of interpopulation and intrapopulation epidemiological as well as clinical studies indicating that consumption of an increased amount of omega-3 polyunsaturated fatty acids is accompanied by a change in the serum lipid spectrum, mainly a decrease in the level of triglycerides (TG), and very low density lipoproteins (VLDL), as well as a decrease in thrombogenesis due to suppression of platelet aggregation due to congruence of omega-3 polyunsaturated fatty acids lot with arachidic acid, which leads to a decrease in mortality from CVD caused by atherothrombosis.

Nevertheless, despite favorable changes in lipid levels, prostaglandin and other tissue factors, there were some concerns about the use of omega-3 polyunsaturated fatty acids in patients with impaired glucose tolerance or type 2 diabetes mellitus (DM). In particular, a significant increase in plasma glucose in these patients was reported, which required an increase in the dose of insulin or oral hypoglycemic agents. Other studies have indicated that in humans, enrichment of omega-3 cell membranes with polyunsaturated fatty acids can improve insulin action on peripheral tissues.

The purpose of this study was to study the feasibility of using omega-3 polyunsaturated fatty acids as part of standard therapy in patients with Stage II AH associated with metabolic syndrome (MS) and concomitant type 2 diabetes mellitus.

42 patients with stage II arterial hypertension with MS and concomitant diabetes mellitus type 2 were examined. The mean age of patients was 58.0 ± 1.3 years, duration of hypertension - 8-10 years (9 ± 1.43), type 2 diabetes - 7-12 years (9 ± 3.8). The degree of increase in blood pressure was assessed according to the European Guidelines for Management of AH (2007). Diagnosis of type 2 diabetes was based on fasting blood glucose and glycosylated hemoglobin (HbAlc). The diagnosis of MS was determined according to the criteria of the Committee of Experts of the National Educational Program of the USA (Programs Adult Treatment Panel III - ATP III, 2001).

According to the scheme of treatment, patients were divided into 2 groups. Patients of group I (n = 21), along with standard therapy, were prescribed a drug containing omega-3 polyunsaturated fatty acids - omocor at a dose of 1 g / day. Patients of the II group (n = 21) received standard therapy for hypertension with concomitant diabetes mellitus. During the study, patients took nebivalol (nebilet), fosinopril (monopril), amaryl M (glimepiride and metformin). Duration of treatment was 4 months.

The criteria for exclusion from the study were the presence of a history of myocardial infarction; acute heart failure; anamnestic data on acute disturbance of cerebral circulation; kidney failure; allergy or intolerance of medications.

For a comparative assessment of the clinical efficacy of the drugs, the patients were examined prior to treatment and 4 months after the start of the drug (after treatment).

Patients underwent a medical examination and a physical examination. The following parameters were taken into account: date of birth (age), sex, weight, height, the Quetelet index - body mass index (BMI), the presence of CVD risk factors, duration of the underlying disease, concomitant therapy, systolic and diastolic blood pressure ), variability of SBP and DBP (VarSAD and Vardad), heart rate (HR) per minute.

BP was measured with a mercury sphygmomanometer in the patient's sitting position. 24-hour blood pressure monitoring was also performed with the help of Cardiette bp one.

All patients underwent a general analysis of blood and urine, determined the lipid profile of the blood: total cholesterol (OX, mg / dL), low density lipoprotein cholesterol (LDL cholesterol, mg / dl), high density lipoprotein cholesterol (HDL cholesterol, mg / dl) (VLDLP cholesterol, mg / dL) and TG, mg / dL, the atherogenicity index (IA) was calculated, fasting glucose (mg / dl) and HbAlc (%) were measured.

The study of functional and structural parameters of the heart was performed with the help of echocardiography.

For the analysis of data, descriptive statistics methods were used-mean (M) and standard deviation. To compare the quantitative variables, the Student's t-criterion for unrelated samples and the Fisher criterion for daily monitoring were used. A value of p <0.05 was taken as an indicator of the reliability of the differences.

In the dynamics, a change in the daily profile of blood pressure was followed. The circadian rhythm of blood pressure more intensively decreased in group I. As is known, lability and resistance - stabilization of blood pressure is established by means of the definition of the time index (IV), which according to different data in healthy individuals does not exceed 10-25%. Stable arterial hypertension is diagnosed with IV at least 50% during the day and at night.

The analysis of the data shows that the IVSAD, IVDAD (day and night) parameters in patients of the I group (when omocor is added to the standard therapy) and IVDADDN, IVDADN, IVSADDN in patients of the II group decrease statistically reliably (p <0.001). At the same time there is a tendency to stabilize normal BP in patients of Group I and a significant decrease in IVDADDN in both groups.

Reduction of blood pressure by 13% at night ("dipper") was noted in group I in 8 (38.95%) patients, in group II it was registered in 3 patients (14.3%). In group I, blood pressure declined slightly in one patient (4.8%) - "pop dipper", and in group II - in 2 (9.6%), excessive decrease ("over dipper") was recorded in 4 (19.2 %), exceeding the level of SBP at night time over day time ("night peaker") was observed in 9 (42.9%) patients.

In patients of group I, the variability of BP in the daytime was reliably (p <0.01) decreased, its decrease at night was not significant (p> 0.05).

In the II group of patients treated with complex standard drugs, despite the improvement in the variability of blood pressure, the obtained data were statistically insignificant.

When comparing the daily rhythm of BP before and after treatment, there was a significant decrease (P <0.001) in the SBP, DASr (day and night), VarSADD and VARDAD in group I, with a significant difference between the I and II groups. The observed decrease in VarSADD and VARDADn in patients of the I and II groups was found to be unreliable (p> 0.05).

At the beginning of treatment, along with an elevated daily BP profile, hypertriglyceridemia, an increase in OXC, LDL, VLDL, fasting glucose and HbAlc in the blood were recorded in both groups.

With the current therapy, a decrease in the level of OXC in all patients was revealed. The values of OXC in groups I and II decreased from 230.1 ± 6.2 to 202.4 ± 6.5 (p <0.01) and from 230.0 ± 6.2 to 222.1 ± 5.9 (p > 0.05), respectively.

Hypertriglyceridemia is one of the most characteristic quantitative changes in lipoproteins. According to some authors, there is a direct correlation between TG and VLDL, which was also discovered by us.

In conducting the study in both groups, violations of the lipid profile of the blood were detected in the form of qualitative and quantitative changes in lipoproteins. Conducted therapy in both groups reduced the level of OXC, LDL, VLDL, TG, increased the level of HDL cholesterol, while the patients received along with the standard therapy of omakor, the obtained data were reliable.

During the follow-up in group II, one patient registered MI, anginal pains acquired a progressive character and the level of AD did not respond to ongoing therapy. During the observation period, no mortality was observed in any of the groups.

The received results testify to positive influence of spent therapy on a BP in both groups. However, in patients receiving omakor along with standard therapy, blood pressure decreased to the target level.

It is known that the impaired vascular endothelial function is found in people with CVD risk factors caused by atherosclerosis, omega-3 polyunsaturated fatty acids have a direct effect on the vasomotor function of the endothelium and can cause a moderate decrease in blood pressure. Usually there is a decrease in blood pressure by 2-5 mm Hg. The effect can be stronger with a higher initial blood pressure level and be dose-dependent. The use of omega-3 polyunsaturated fatty acids reduces the vasospastic response to the action of catecholamines and, possibly, angiotensin. These effects supplement the decreasing effect on AD of antihypertensive drug therapy.

In our study, there was a significant decrease in the lipid profile and carbohydrate metabolism (glucose and HbAlc) levels when omega-3 polyunsaturated fatty acids - omacor. Conducted standard therapy in group II had no significant effect on serum concentration of OXC.

Omega-3 polyunsaturated fatty acids contribute to the functional activity of HDL in the reverse transport of cholesterol from tissues, including from the arterial wall, to the liver, where the cholesterol catabolizes to bile acids (LC). In VLDON, omega-3 PUFAs are enriched with TG, lipoproteins are the best substratum for the lipoprotein lipase enzyme, which explains the low level of TG in people who consume omega-3 polyunsaturated fatty acids. Thus, individuals from a population consuming more seafood seem to develop anti-atherogenic properties in the lipid transport system. Also, the presence of omega-3 polyunsaturated fatty acids in lipoprotein particles increases receptor removal from the bloodstream of VLDL both by the liver and peripheral tissues, and finally, increases the excretion of LC catabolism products of cholesterol with intestinal contents. At the heart of one of the mechanisms of omega-3 PUFAs is the effect on the synthesis in the liver of TG and enriched VLDL, resulting in a decrease in the plasma content of these potentially atherogenic lipid compounds with the incorporation of omega-3 PUFAs, which are mainly consumed with food . Higher doses have a stronger effect, for example, 4 g / day reduce the level of TG by 25-40%. The American Heart Association in the recommendations of 2003 indicates that daily supplementation of 2-4 g of eicosapentaenoic and docosalexenoic acids can reduce the TG level by 10-40%. It was noted that in patients with type 2 diabetes in the treatment of omega-3 with polyunsaturated fatty acids, the level of TG decreases. Along with a decrease in the level of TG, omega-3 PUFA causes an increase in anti-atherogenic HCVPV by 1-3%.

According to the laboratory data obtained at the end of our study, the changes in the glycemic control parameters in both groups were the same. It turned out that the drug omakor does not cause an increase in blood glucose in patients with type 2 diabetes mellitus with concomitant MS.

The report of the working group of the European Society of Cardiology on sudden death lists the medications that have a direct electrophysiological effect on the heart. Of these agents, only beta-blockers are comparable to highly purified ω-3 PUFAs due to the effect of reducing the frequency of sudden death after a previous myocardial infarction. The highly significant results of the Lyons dietary study of the heart and the Indian study convincingly confirmed the prophylactic effect of omega-3 polyunsaturated fatty acids, and their cardioprotective properties are also known.

Thus, our study shows that the drug may be used in the treatment of MS, which is a cluster of factors leading to CVD and sudden death, which are exacerbated by the presence of combined hyperlipidemia, arterial hypertension and concomitant type 2 diabetes mellitus. This treatment scheme may also reduce the development of various complications of arterial hypertension (myocardial infarction, GB crisis, ischemic stroke, diabetic coma, etc.). At the same time, the ease of treatment (1 capsule per day), the low frequency and the risk of side effects cause a small risk / benefit ratio and suggest that the treatment of omega-3 polyunsaturated fatty acids deserves widespread use in cardiac practice.

Sh. R. Guseinova. The use of omega-3 polyunsaturated fatty acids in patients with arterial hypertension associated with metabolic syndrome and concomitant type 2 diabetes mellitus // International Medical Journal No. 4 2012