Use of omega-3 PUFAs 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 PUFA) have attracted the interest of cardiologists after the publication of significant epidemiological studies that revealed a lower incidence of cardiovascular diseases (CVD) caused by atherosclerosis and thrombosis in the population of people who eat seafood (Greenland Eskimos, indigenous people of Chukotka). The non-physiological nutrition of modern humans accelerates the development of coronary heart disease (CHD), aggravating such powerful risk factors for CHD as hyperlipoproteinemia, arterial hypertension (AH) and excess weight.

A number of clinical, experimental and epidemiological studies have shown that omega-3 polyunsaturated fatty acid intake has a beneficial effect on the course of atherosclerosis and slows its progression. Daily intake of 1-2 g of omega-3 PUFA significantly reduced the risk of recurrent myocardial infarction (MI).

By now, sufficient data have been accumulated from interpopulation and intrapopulation epidemiological and clinical studies indicating that consumption of increased amounts of omega-3 polyunsaturated fatty acids is accompanied by a change in the spectrum of blood serum lipids, primarily a decrease in the level of triglycerides (TG) and very low density lipoproteins (VLDL), as well as a decrease in thrombogenesis due to the suppression of platelet aggregation due to the congruence of omega-3 polyunsaturated fatty acids with arachidic acid, which leads to a decrease in mortality from CVD caused by atherothrombosis.

However, despite the favorable changes in lipid, prostaglandin, and other tissue factors, some concerns have been raised about the use of omega-3 polyunsaturated fatty acids in patients with impaired glucose tolerance or type 2 diabetes mellitus (DM). In particular, significant increases in plasma glucose levels have been reported in these patients, requiring increased insulin or oral hypoglycemic agent doses. Other studies have indicated that in humans, enrichment of cell membranes with omega-3 polyunsaturated fatty acids can improve insulin action on peripheral tissues.

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

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

According to the treatment regimen, the patients were divided into 2 groups. Patients of group 1 (n = 21) along with standard therapy were prescribed a drug containing omega-3 polyunsaturated fatty acids - omacor at a dose of 1 g / day. Patients of group 2 (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). The duration of treatment was 4 months.

Exclusion criteria from the study were a history of myocardial infarction; acute heart failure; history of acute cerebrovascular accident; renal failure; allergy or intolerance to drugs.

For a comparative assessment of the clinical effectiveness of the drugs, patients were examined before treatment and 4 months after the start of taking the drug (after the end of treatment).

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

Blood pressure was measured using a mercury sphygmomanometer with the patient in a sitting position. Daily blood pressure monitoring was also performed using the Cardiette bp one device.

All patients underwent a complete blood count and urine analysis, blood lipid spectrum parameters were determined: total cholesterol (TC, mg/dl), low-density lipoprotein cholesterol (LDL-C, mg/dl), high-density lipoprotein cholesterol (HDL-C, mg/dl), VLDL-C (VLDL-C, mg/dl) and TG, mg/dl, the atherogenic index (AI) was calculated, fasting glucose levels (mg/dl) and HbAlc (%) were measured.

The study of functional and structural parameters of the heart was carried out using echocardiography.

Descriptive statistics methods were used for data analysis - mean (M) and standard deviation. For comparison of quantitative variables, Student's t-test for unrelated samples and Fisher's test for daily monitoring were used. The value p < 0.05 was accepted as an indicator of the reliability of differences.

The dynamics of the change in the daily profile of blood pressure were tracked. The daily rhythm of blood pressure decreased more intensively in Group I. As is known, lability and resistance - stabilization of blood pressure is established by determining the time index (TI), which, according to various data, does not exceed 10-25% in healthy individuals. Stable arterial hypertension is diagnosed with TI of at least 50% during the day and night.

Data analysis shows that the indices of IVSBP, IVDBP (day and night) in patients of group I (with the addition of omacor to the standard therapy) and IVDADDN, IVDADN, IVSADN in patients of group II decrease statistically significantly (p < 0.001). At the same time, there is a tendency to stabilization of normal blood pressure in patients of group I and a significant decrease in IVDADDN in both groups.

A 13% decrease in BP at night ("dipper") was observed in 8 (38.95%) patients in Group I, and was recorded in 3 patients (14.3%) in Group II. In Group I, BP decreased slightly in one patient (4.8%) - "pop dipper", and in Group II - in 2 (9.6%), an excessive decrease ("over dipper") was recorded in 4 (19.2%) patients, and an excess of SBP at night over the daytime level ("night peaker") was observed in 9 (42.9%) patients.

In patients of group I, the variability of blood pressure during the daytime significantly (p < 0.01) decreased, while its decrease at night was insignificant (p > 0.05).

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

When comparing the daily blood pressure rhythm indicators before and after treatment, a significant (p < 0.001) decrease in SBPcp, DBPcp (day and night), VarSBPdn and VarDABPdn was found in Group I with a significant difference between the data of Groups I and II. The observed decrease in VarSBPn and VarDABPn in patients of Groups I and II was insignificant (p > 0.05).

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

During the therapy, a decrease in the TC level was found in all examined patients. The TC indicators 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 we also found.

During the study, abnormalities in the blood lipid profile in the form of qualitative and quantitative changes in lipoproteins were detected in both groups. The therapy in both groups reduced the level of TC, LDL, VLDL, TG, increased the level of HDL, while in patients who took omacor along with standard therapy, the data obtained were reliable.

During the observation period, one patient in Group II developed MI, angina pain became progressive, and blood pressure did not respond to the therapy. No mortality was observed in any of the groups during the observation period.

The obtained results indicate a positive effect of the therapy on blood pressure in both groups. However, in patients who received omacor along with standard therapy, blood pressure decreased to the target level.

It is known that impaired vascular endothelial function is found in individuals with risk factors for CVD 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. A decrease in blood pressure of 2-5 mm Hg is usually observed, the effect may be stronger at higher initial blood pressure levels 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 complement the blood pressure-lowering effect of antihypertensive drug therapy.

In our study, a reliable decrease in lipid profile and carbohydrate metabolism (glucose level and HbAlc) was observed when using omega-3 polyunsaturated fatty acids - omacor. The standard therapy in Group II did not have a reliable effect on the serum concentration of TC.

Omega-3 polyunsaturated fatty acids promote the functional activity of HDL in the reverse transport of cholesterol from tissues, including the arterial wall, to the liver, where cholesterol is catabolized to bile acids (BA). In VLDL, omega-3 PUFAs enrich TG, lipoproteins with the best substrate for the enzyme lipoprotein lipase, which explains the low TG level in people consuming omega-3 polyunsaturated fatty acids. Thus, individuals from a population consuming more seafood apparently develop antiatherogenic properties in the lipid transport system. Also, the presence of omega-3 polyunsaturated fatty acids in lipoprotein particles increases the receptor removal of VLDL from the bloodstream by both the liver and peripheral tissues, and finally increases the excretion of BA products of cholesterol catabolism with intestinal contents. One of the mechanisms of omega-3 PUFA is the effect on the synthesis of TG and VLDL enriched with them in the liver, as a result of which the content of these potentially atherogenic lipid compounds in the blood plasma decreases when omega-3 PUFA, which are mainly consumed with food, are incorporated into them. Higher doses have a stronger effect, for example, 4 g / day reduce the TG level by 25-40%. The American Heart Association in its 2003 recommendations indicates that a daily supplement of 2-4 g of eicosapentaenoic and docosalexic acids can reduce the TG level by 10-40%. The work noted that in patients with type 2 diabetes mellitus, TG levels decrease during treatment with omega-3 polyunsaturated fatty acids. Along with a decrease in TG levels, omega-3 PUFAs cause an increase in antiatherogenic HDL-C by 1-3%.

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

The report of the European Society of Cardiology Task Force on Sudden Death lists medications that have a direct electrophysiological effect on the heart. Of these, only beta blockers are comparable to highly purified ω-3 PUFAs in reducing the incidence of sudden death after myocardial infarction. The highly significant results of the Lyon Heart Diet Study and the Indian Study have convincingly confirmed the preventive effect of omega-3 polyunsaturated fatty acids, and their cardioprotective properties are also known.

Thus, our study indicates that the drug omacor can be used in the treatment of MS, which is a cluster of factors leading to CVD and sudden death, which are aggravated by the presence of combined hyperlipidemia, arterial hypertension and concomitant type 2 diabetes mellitus. Such a treatment regimen may also reduce the development of various complications of arterial hypertension (myocardial infarction, hypertension crisis, ischemic stroke, diabetic coma, etc.). At the same time, the simplicity of treatment (1 capsule per day), low frequency and risk of side effects determine the low value of the risk/benefit ratio and allow us to consider that treatment with omega-3 polyunsaturated fatty acids deserves wide use in cardiology practice.

Sh. R. Guseynova. 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