L. Vlasyk¹, V. Taschuk², H. Khrebtii²

¹ “L.I. Medved Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health, Ukraine (State Enterprise)”, Kyiv, Ukraine
² Bukovinian State Medical University, Chernivtsi, Ukraine

SUMMARY. Hypertriglyceridemia is a characteristic feature of dyslipidemia in hypertension in patients with concomitant abdominal obesity. These individuals constitute an increased risk of cardiovascular complications, so optimizing their treatment is extremely important medical problem. The aim is to study the dynamics of the major lipid spectrum of the blood vessels and endothelial function as a marker of atherosclerosis, when you connect to the drug ω-3 polyunsaturated fatty acids to the standard combination of antihypertensive and lipid-lowering therapy in patients with hypertension and abdominal obesity. The analysis of the dynamics of lipidohramy and vascular endothelial function in patients with essential hypertension and abdominal obesity during the 6-month standard (basic) antihypertensive (lisinopril, amlodipine) and lipid-lowering therapy (atorvastatin) (group I) and accession thereto ω-3 polyunsaturated fatty acids (group II). When analyzing the results of 6 months of treatment in the studied patient groups in triglycerides reduction was significantly more pronounced when using combination antihypertensive and lipid-lowering therapy (-40,9+3,1% in group II and -22,7+2,3% in group I, p<0,001). Also in group II was marked significantly greater increase in HDL cholesterol (38,6+2,5% in group II and 28,7+2,6% in group I, p<0,05) and improved endothelium vasodilation (9,86+0,28% in group II and 6,8+0,23%, p<0,01). Thus, in patients with hypertension and concomitant abdominal obesity observed significant dyslipidemia, a characteristic feature of which is hypertriglyceridemia. Joining the standard antihypertensive and lipid-lowering therapy ω-3 polyunsaturated fatty acids contributes significantly more effective normalization of triglycerides. For persons with hypertension and concomitant abdominal obesity is characterized by endothelial dysfunction and significant additional purpose to standard therapy ω-3 polyunsaturated fatty acids leads to a significant improvement.

Key Words: arterial hypertension, obesity, dyslipidemia, endothelial function, free-3 polyunsaturated fatty acids.

Introduction. The influence of ω-3 polyunsaturated fatty acids (ω-3 PUFA) on blood lipid profile is well known [2]. Clinical reductions in triglycerides (TG) in a setting of therapy with ω-3 PUFAs is attributed to both an increased rate of conversion of very low-density lipoproteins into low-density lipoproteins and to direct inhibition of TG synthesis (possibly due to increased β-oxidation of fatty acids) [2, 3]. In clinical practice, diet and statins alone are not capable of bringing elevated TGs back to normal. Hypertriglyceridemia is a typical characteristic of dyslipidemia of hypertension (HT) in people with concomitant abdominal obesity (AO). These people are at increased risk for cardiovascular complications; this is why the maximum improvement of treatment in this patient population is a high-priority objective of preventive cardiology [1].

Objective of the study. To study the temporal patterns of indices reflecting lipid spectrum of blood and vascular endothelial function as markers of atherosclerosis adding a ω-3 PUFA product to the standard combination of antihypertensive and hypolipidemic therapy in subjects with HT and AO.

Materials and methods. The authors have conducted a 6-month program of treatment in 44 male patients with Stage II HT (diagnosed according to recommendations of the Ukrainian Association of Cardiologists) with comorbid Stage I AO; the age of the patients was 60 to 85 years (mean age 75 ± 8.5 years). Abdominal type of obesity was diagnosed by the ratio of waist circumference to thigh circumference ≥ 0.95, with body mass index (BMI) = 30.0–34.9 kg/m². Twenty-two patients obtained treatment under a standard protocol (basic therapy), which included antihypertensive therapy (lisinopril 10 mg QD, amlodipine 5 mg QD), hypolipidemic therapy (atorvastatin 10 mg QD). Twenty-two patients received ω-3 PUFA at 1,000 mg QD as an add-on to basic therapy. The lipid profile and vascular endothelial function were assessed before, 3 and 6 months after the onset of therapy.  The function of the endothelium was assessed with Doppler ultrasound of the brachial artery (BA) using ultrasound diagnostic scanner (LOGIQ 500 by General Electric, USA). Tests with reactive hyperemia (endothelial-dependent vasodilatation, EDVD) and nitroglycerin (endothelial-independent vasodilatation, EIVD) were used. The BA response is assessed as conventionally normal if its dilatation in a setting of reactive hyperemia is > 10 % of baseline diameter; lower dilation values or vasoconstriction is assessed as abnormal [3].

Statistical processing of data presented as М ± m was performed with methods of variation statistics using Student’s t-test on a personal computer using Microsoft Excel statistical analysis software. The difference was considered to be significant at p < 0.05.

Results and discussion. The baseline levels of total cholesterol (TC), TG, high-density lipoprotein cholesterol (HDL-C) did not differ in both groups of patients and were 6.47 ± 0.17; 2.64 ± 0.14; 1.01 ± 0.04 mmol/L in Group I and 6.48 ± 0.18; 2.59 ± 0.13; 1.01 ± 0.05 mmol/L in Group II (М ± m), respectively (р > 0.05). Changes in lipid transport function of the blood with the use of different hypolipidemic regimens were analyzed after 6 months. Changes in the main parameters of the lipid profile are given in the table below.

Table

Changes of lipid profile parameters with time in various options of hypolipidemic therapy in a setting of combination hypotensive therapy during 6 months of treatment (М ± m)

Note: Abbreviations: TC = total cholesterol, TG = triglycerides, HDL-C = high-density lipoprotein cholesterol; PUFA = polyunsaturated fatty acids, n = number of patients, р = the significance of differences of increase in indices when using various hypolipidemic options over appropriate observation time using exact Student t-test.

Analysis of treatment outcomes in test groups of patients has shown with high significance that TC and TG levels were lower with use of antihypertensive and combined hypolipidemic therapy (Group ІІ). In addition, in Group II of patients, in 6 months the levels of the anti-atherogenic cholesterol fraction (HDL-C) were significantly higher. Beyond doubt, this had a positive influence on the prevention of cardiovascular complications in this patient population. Pre-treatment EDVD was identical in both groups of patients, but with a significant deviation (–2.1 ± 0.29 % of the baseline diameter, р > 0.05); EIVD in response to nitrates remained unchanged in both groups.  After a 6-month treatment, EDVD improved in the group of patients receiving standard therapy; however, it was still far from normal values (6.8 ± 0.23 %, р < 0.01).  The group of patients receiving ω-3 PUFA had statistically significant improvements (compared to Group I) of EDVD (9.86 ± 0.28 %, р < 0.01). Improvements of lipid profile and reversal of endothelial dysfunction in patients at high cardiovascular risk are of fundamental importance because dyslipidemia, by deepening the remodelling of vascular wall and by increasing the expression of adhesion molecules on the surface of endothelial cells, creates a vicious pathogenetic circle, which causes the formation of an atheroma [2, 5]. Thus, adding ω-3 PUFA to standard antihypertensive and hypolipidemic therapy promotes more effective prevention of atherosclerosis in people with HT and AO.

Conclusions and prospects of further research

1. The group of patients with hypertension and comorbid abdominal obesity is found to have significant dyslipidemia; the characteristic sign of the latter is hypertriglyceridemia. Adding ω-3 polyunsaturated fatty acids to standard antihypertensive (lisinopril, amlodipine) and hypolipidemic (atorvastatin) therapy contributes to a significantly more effective reduction in the levels of total cholesterol, triglycerides and to an increase in the level of high-density lipoprotein cholesterol.
2. Endothelial dysfunction is a characteristic finding in people with hypertension and abdominal obesity. Adding ω-3 polyunsaturated fatty acids to standard antihypertensive and hypolipidemic therapy causes a significant improvement of endothelial dysfunction.
3. Prospects of further research: a study of the influence of a combination of hypolipidemic therapy with statins and ω-3 PUFA on other pathogenetic links of hypertension in order to optimize treatment and to reduce dose-dependent adverse effects of statins.

REFERENCES

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2. Omega-3 fatty acids and heart failure / R.J. Marchioli, M.G. Silletta, G.M. Levantesi, R. Pioggiarella // Curr. Atheroscler. Rep. – 2009. – No. 11(6). – P. 440–447.

3.The endothelial cell in health and disease: its function, dysfunction, measurement and therapy / B.G. Schwartz, C.S. Economides, G.S. Mayeda Burstein S, R.A. Kloner // J. Impot. Res. – 2009. No. 84(7). – P. 751–756.

Надійшла до редакції 22.05.2018 р.