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international Heart and Vascular Disease Journal • Volume 8, № 27, September 2020
Journal of the Cardioprogress Foundation
ORIGINAL ARTICLES
The new possibilities of dietary correction
of residual lipid metabolism disorders in patients with coronary artery disease
and obesity
Authors
Svetlana A. Derbeneva*, M.D., Ph.D., senior researcher of the Department of Cardiovascular Pathology of Federal State Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety", Moscow, Russia.
Vera E. Nesterova, M.D., Ph.D.-student of the Department of Cardiovascular Pathology of Federal State Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety", Moscow, Russia. Tatiana S. Zolotova, researcher of the Department of Cardiovascular Pathology of Federal State Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety", Moscow, Russia. Tatiana B. Feofanova, researcher of the Department of Cardiovascular Pathology of Federal State Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety", Moscow, Russia.
Acknowledgement
We are thankful to Bogdanov R. A., the head of the Department of Cardiology № 1 of City Clinical Hospital № 13, for the help in preparing this publication.
To estimate the dynamics of lipid panel in patients with coronary artery disease (CAD), obesity and residual dys-lipidemia, who receive optimal statin therapy and follow standard low-calorie diet with additional lipid-lowering product (LLP). Materials and methods
This study included 40 patients with severe coronary atherosclerosis manifestations, who were selected for surgical revascularization of myocardium due to multiple vascular lesions and / or stenosis of proximal segments of
Derbeneva S. A., Nesterova V. E., Zaletova T. S., Feofanova T. B.
Federal State Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety", Moscow, Russia
Objective
* Corresponding author. Tel.: +8-903-169-44-89. Е-mail: [email protected]
the coronary arteries and with non-target atherogenic lipoproteins levels during optimal statin therapy. We also
estimated additional effect of standard low-calorie diet (LCD) and LLP on the lipid panel.
Results
The results showed that 30-days follow-up of LCD could significantly decrease total cholesterol (TC) level by 15,7% (p=0,0003) and low-density lipoproteins (LDL) by 19,1 % (p=0,0024), and the additional intake of LLP increased the efficiency of LCD and contributed to the achievement of reliable reduction of TC by 32.9 % (p<0.0001), LDL by 38.1 % (p<0.0001), very low density lipoproteins (VLDL) by 44, 5 % (p= 0.013) and atherogenic coefficient of 35.2% (p= 0.003). Conclusion
Based on the obtained results we can conclude that low-calorie diet for the correction of residual dyslipidemia during the standard statin therapy was superior to statin therapy potentiation and was associated with lower drug-loading.
Key words: coronary artery disease, lipid metabolism, diet, obesity. Conflict of interests: None declared.
Received: 04.02.2020 Accepted: 15.04.2020
Introduction
Coronary artery disease (CAD) is the major cause of death and disability in developed countries [1]. It should be emphasized that Russia is the leading country by the matter of CAD morbidity and mortality — the prevalence is 13,5 % [2,3].
Modern approach to the pathogenesis of coronary artery disease is based on the idea of progressive occlusion of coronary arteries that develops over decades in response to the biological effects of various risk factors [4-6]. Hydroxymethylglutaryl-CoA reductase inhibitors (statins) are the basic modern treatment of atherosclerosis with powerful evidence base for their effectiveness for both primary and secondary prevention of the clinical manifestations of atherosclerosis [7,8]. At the same time, the indications fordrug treatmentare constantly expanding in evidence-based medicine, and decreasing fornon-drug approaches at the same time. However, there are still many issues on the treatment of CAD. Therefore, non-drug therapy is very promisingwhen used together with traditional statin therapy. The search for evidence of the efficacy of such approaches is extremely relevant nowadays.
The residual risk of cardiovascular complications in patients receiving optimal statin therapy is an issue of increasing concern. These patients cannot to achieve target values of atherogenic lipoproteins, including low density lipoproteins (LDL), despite receiving therapeutic doses of statins. Most often, high residual dyslipidemia occurs in patients with obesity,
and, therefore, is associated not only with the presence of severe metabolic disorders, but also with factors limiting the use of high statins doses, such as non-alcoholic fatty liver disease and steatohepatitis [9].
These patients are in need for new approaches that potentiate the effect of basic lipid-lowering therapy. Such approaches include both pharmacological and non-pharmacological treatment strategies. Pharmacological strategies include, for example, ezetimibe, bile acid sequestrants and some other drugs. However, these approaches are associated with high drug loading and have very limited effectiveness. Many cardiologists see hopes in the new class of targeted drugs, such as evalocumab, that consists of monoclonal antibodies to PCSK9 that decreases the number of LDL receptors [10,11]. The major disadvantage is their high cost.
Dietotherapy (DT) is the most effective and leading non-pharmacological treatment method. At the same time DT cannot be considered as an alternative for statins therapy thath as proven its effectiveness in many studies. However, it has been proven that adequate DT can significantly decrease the level of atherogenic lipids, and in some cases even reduce the dosage of statins [12].
A modern approach to DT is the use of lipid-lower-ing products (LLP) with known chemical composition enriched with lipotropic components.
Based on the analysis of published data, it is interesting to confirm the effect of new LLP in clinical
practice as an independent nutritional factor for the correction of blood lipid profile disorders in patients with CAD receiving optimal statin therapy.
The objective of this study was to estimate the dynamics of lipid panel characteristics in patients with CAD, obesity and residual dyslipidemia, who receive optimal statin therapy and follow standard low-calorie diet with additional lipid-lowering product.
Materials and methods
An open prospective observational study was carried out on the basis of the Department of Cardiovascular Pathology of Federal State Scientific Institution "Federal Research Centre of Nutrition, Biotechnology and Food Safety" from October 15, 2016 to March 15, 2017.
Characteristics of patients. The study included patients with severe manifestations of coronary atherosclerosis, selected for surgical myocardial revascularization due to multiple vascular lesions and / or stenosis of proximal segments of the coronary arteries. Inclusion criteria were non-target LDL values (over 1.5 mmol / L) during optimal statin therapy (rosuvastatin over 20 mg / day, atorvastatin and simvastatin over 80 mg / day), body mass index (BMI)> 30 kg / m2.
Given the non-interventional nature of this study, it was governed by the approval of the Ethics Committee of the Federal Research Centre of Nutrition, Biotechnology and Food Safety. All patients were informed of the purpose and nature of the observation and signed informed consent prior to the study. Patients were randomized into two groups by the method of nutritional treatment.
The study included 40 patients meeting the inclusion criteria. Age characteristics and clinical status of all participants are presented in Table 1. Most patients had severe cardiac status: 45-50 % of patients had class III angina, 85-90 %o patients revealed arterial hypertension (AH), 35-50 %o had clinical manifestations of chronic heart failure (CHF); 35-45 %o of patients had non-alcoholic fatty liver disease (NAFLD).
The study follow-up was 30 days and included 3 observation points.
Point 1 (Day 1). On the day of admission, in accordance with the study protocol, patients underwent physical examination, anthropometric, body composition studies, a 6-minute walk test, a study of energy expenditure and fats oxidation rates, proteins and carbohydrates metabolism, and blood sampling.
Point 2 (Day 15). A blood sampling was performed to analyze the blood lipid profile.
Table 1. Characteristic of studied groups
Parameters Studied groups №±m)
Main group Control group
Number of patients 20 20
Gender, anatomical and age characteristics
Average age, years 63.08±4.69 61.1 ±9.9
Men 9 10
Women 11 10
BMI, kg/m2 39.9±4.4 36.7± 5.0
Class of angina
I (% of patients) 3 (15 %) 2(10 %)
II (% of patients) 7 (35 %) 9(45 %)
III (% of patients) 10(50 %) 9(45 %)
IV (% of patients) 0 0
Comorbidities
I -III grade arterial hypertension 18(90 %) 17(85 %)
Clinical manifestations of Chronic Heart Failure with over 2ndFunctional Class (% of patients) 10(50 %) 7(35 %)
Type 2 diabetes mellitus 13(65 %) 15(75 %)
NAFLD (% of patients) 7 (35 %) 9(45 %)
Point 3 (Day 30) On the day of discharge. Patients underwent anthropometric studies, a study of body composition, basal metabolism, and blood sampling.
Patients from the main group (MG) (N=20) received a standard low-calorie diet (LCD) for 30 days with the additional LLP of 36 g / day (174.6 kcal / day).
Patients from the control group (CG) (N=20) — received LCD only for 30 days.
LCD is a diet with significant reduction of fats and easily digestible carbohydrates, normal protein and complex carbohydrates with increased amount of dietary fiber. Salt is usually limited (3-5 g / day). Dishes should be steamed, stewed, baked, mashed or not mashed. Food temperature — from 15 ° to 60-65 °C. Fluid consumption — 0.8-1.5 liters per day. Fractional nutrition — 4-6 times a day. Chemical composition: proteins — 70-80 g, including animal proteins — 40 g; general fats — 60-70 g, including vegetable — 25 g; total carbohydrates — 130-150 g, dietary fiber—30 g. Energy value: 1350-1550 kcal.
LLP "Dietary Oil" ("SOYUZ-M") is a fat product with the additional skimmed milk powder, with a mass fraction of fat of 53 %o. The fatty acid (FA) composition of the LLP "Dietary oil" is presented in table 2.
Chemical composition of both group's diets are presented in table 3.
Biochemical studies were performed using «Konelab 30i» analyzer (ThermoClinicalLabsystems, Finland). Biochemical markers of lipid metabolism were total cholesterol (TC), (s 5.0 mmol / L), triglycerides (TG), (s 1.7 mmol / L), high density lipoprotein cholesterol (HDL) (s 1.0 mmol / L). Very low-density
Table 2. The fatty acid composition of the LLP "Dietary oil"
used, and the data are presented as mean± standard deviation or % of the total number of patients. The significance level was set as p<0.05.
FA name FA index FA composition, %
Caprylic 8:0 0.15
Capric 10:0 0.14
Lauric 12:0 2.29
Myristic 14:0 1.57
Palmitic 16:0 35.74
Hexadecenoic 16:1 0.04
Palmitoleic 16:1 7-cys 0.14
Margaric 17:0 0.10
Heptadecene 17:1 0.04
Stearic 18:0 4.44
Elaidic 18:1 9-trans 1.83
Oleic 18:1 9-cys 36.05
Vaccenic 18:1 11-trans 0.89
Iso-octadecanoic 18:2i 0.11
Linoleic 18:2 14.13
Y-linolenic 18:3 œ-6 0.09
a-linolenic 18:3 œ-3 0.90
Arachidonic 20:0 0.48
Gondoic 20:1 0.18
Eicosapentaenoic 20:5 0.23
Docosapentaenoic 22:5 0.07
Docosahexaenoic 22:6 0.35
Table3. The comparison of the chemical composition of LCD and a modified diet with additional LLP
Diet composition parameters LCD LCD+LLP
Energyvalue, kcal / day 1350-1550 1524,6-1724,6
Proteins, g/day 70-80 70,2-80,2
Fats, g/day 60-70 79-89
Carbohydrates, g/day 130-150 130,3-150,3
lipoprotein cholesterol (VLDL) was determined by dividing the number of TG by 2.2 (ls 0.77 mmol / L); low density lipoprotein cholesterol (LDL) by subtracting the summary of HDL and VLDL from the amount of TC (s 2.8 mmol / l). The atherogenic coefficient (AC) was calculated by the formula of A. N. Klimova (s 3.5 mmol / l).
Statistical analysis was performed using the STATISTICA 10.0 software. When analyzing the main characteristics of patients, parametric criteria were
Table 4. The comparison of blood lipid
and, therefore, these indicators were not included in the subsequent analysis.
The analysis of TC level revealed its significant decrease in patients with low-calorie diet (Fig. 1, 2). At the same time, additional inclusion of LLP into the diet allowed to obtain an additional reduction of TC: in patients from the MG the level of TC decreased by 1.13± 0.56 mmol / L (-20.3 %, p<0.0001) in 2 weeks, and by 1.80± 1.09 (-32.9 %, p<0.0001) in 4 weeks, while in patients from the CG its level only had insignificant tendency to decrease by 0.15± 0.46 mmol / l (p= 0.16) in 2 weeks of treatment and significantly decreased by 0.90± 0.93 mmol / L (-15.7 %, p= 0.0003) in 4 weeks.
The intergroup statistical analysis found that the differences were highly significant at the second and third observation points: after 2 weeks the level of total cholesterol in the MG was 4.34± 0.58 mmol / l, in CG — 5.56± 0.79 mmol / l (p<0.0001), after 4 weeks: in
spectrum parameters during treatment
Blood lipid spectrum parameters Initially After 2 weeks After 4 weeks
MG CG P MG CG P MG CG P
TC, mmol/l 5.47±0.85 5.71 ±1.13 0.463 4.34±0.58 5.56±0.79 <0.0001 3.67±0.73 4.80±0.64 <0.0001
LDL, mmol/l 3.62±0.69 3.56± 1.03 0.823 2.68±0.51 3.25±0.71 0.006 2.24±0.72 2.88±0.59 0.003
HDL, mmol/l 1.05±0.28 1.49±0.33 0.007 0.98±,25 1.37±0.31 0.0008 0.99±0.18 1.20±0.31 0.015
VLDL, mmol/l 0.83±0.57 0.81 ±0.35 0.88 0.59±0.21 0.79±0.34 0.029 0.45±0.22 0.71 ±0.35 0.009
TG, mmol/l 3.03±0.80 1.42±0.49 <0.01 2.22±0.37 1.49±0.50 <0.0001 1.86±0.60 1.51 ±0.80 0.124
AC, kg/m2 2.21 ±0.81 2.04±0.85 0.52 1.77±0.57 1.95±0.74 0.4 1.42±0.72 1.94±0.90 0.05
Total cholesterol
Main Group
Control Group
E 6
T T
■ - J
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Visit 1 Visit 2 Visit 3
■ Mean □ Mean±SD H Mean±1,96*SD
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Visit 1 Visit 2 Visit 3
■ Mean □ Mean±SD Mean±1,96*SD
LDL
Main Group
Control Group
MG-1 MG-2 MG-3
■ Mean □ Mean±SD I Mean±1,96*SD
CG-1 CG-2 CG-3
■ Mean □Mean±SD I Mean±1,96*SD
VLDL
Main Group
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1,4
1,2
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0,6
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0,4
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1,4
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7
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4
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Figure 1. Diagrams of lipid spectrum parameters in patients during treatment
Main Group
I
Y T
MG-1 MG-2 MG-3
HDL
■ Mean □ Mean±SD Mean±1,96*SD
Control Group
CG-1 CG-2 CG-3
■ Mean □ Mean±SD Mean±1,96*SD
Main Group
MG-1 MG-2 MG-3
TG
T I — ■
[ T [
■ Mean □ Mean±SD Mean±1,96*SD
Control Group
T X ■ ■
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CG-1 CG-2 CG-3
■ Mean □ Mean±SD Mean±1,96*SD
Main Group
MG-1 MG-2 MG-3
AC
■ Mean □ Mean±SD
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8 15
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Control Group
CG-1 CG-2 CG-3
■ Mean □ Mean±SD I Mean±1,96*SD
2,4
2,4
2,2
2,2
2,0
2,0
1,8
1,8
1,6
1,6
,4
,4
I 1,2
I 1,2
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,0
0,8
0,8
0,6
0,6
0,4
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5
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3,5
3,5
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2,5
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2,0
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1,0
0,5
0,0
0,0
0,5
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Figure 2. (continuation) Diagrams of lipid spectrum parameters in patients during treatment
MG — 3.67± 0.73 mmol / l, in CG — 4.80± 0.64 mmol / l (p<0.0001).
Average LDL values, despite the ongoing DT, were higher than the target values during the entire observation period, thus, it was not possible to achieve the main goal of diet therapy during this study. At the same time, different nutritional approaches have shown different levels of efficacy. Standard LKD revealed the decrease of LDL by 0.31 ± 0.43 mmol / L (8.7 %, p= 0.0046) in 2 weeks andin 4 weeks — by 0.68± 0.87 mmol / L (19.1 %, p= 0.0024). The additional LLP intake showed even more pronounced reduction of LDL level — by 0.94± 0.48 mmol / L (-25.9 %, p<0.0001) in 2 weeks and by 1, 38±0.96 (-38.1 %, p<0.0001) in 4 weeks.
Intergroup statistical analysis revealed significant differences during the dynamic observation: at the second observation point the values were 2.68± 0.51 and 3.25± 0.71 mmol / L in the MG and CG, respectively (p= 0.006), at the third point — 2, 24±0.72 and 2.88± 0.59 mmol / L, with p= 0.003.
The dynamics of VLDL level were similar to LDL. VLDL level decreased in both groups during treatment: in the MG it decreased in 2 weeks by 0.24± 0.40 (-28.9 %, p= 0.015) mmol / L and amounted to 0.59± 0. 21 mmol / L, and in 4 weeks — by 0.37± 0.61 mmol / L (-44.5 %, p=0.013) and amounted to
0.45. 0.22 mmol / L. In the CG, the level of VLDL did not change significantly during the entire observation period — / here was only tendency to decrease in 2 weeks by 0.015± 0.1 mmol / L (p= 0.5), and in 4 weeks — by 0.09± 0.2 mmol / l (p= 0.058).
Intergroup statistical analysis revealed significant differences in VLDL level, after 2 (at p= 0.029), and 4 (p= 0.009) weeks of treatment.
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The analysis of the AC dynamics showed its significant decrease in the MG, as well as the presence of a strong tendency (but unreliable) to decrease in the CG. In the MG, it decreased after 2 weeks from 2.21 ± 0.81 kg / m2 to 1.77± 0.57 kg / m2 — by 0.44± 0.58 kg / m2 (-19.9 %, p= 0.003), and after 4 weeks —up to 1.42± 0.72 kg / m2 (-35.2 %, p= 0.003). In the CG, the AC value decreased insignificantly by 0.09± 1.1 kg / m2 (p= 0.3) and did not change by the end of the observation.
Conclusion
The results obtained in this study allow us to conclude that it should be recommended to use the possibilities of both low-calorie diet and LLP with antiatherogenic effect in patients with coronary artery disease, obesity, and non-target atherogenic lipoproteins level during standard statin therapy. This approach allows achieving an additional decrease in LDL by more than 44 % without increasing the drug load that is potentially more effective than using other lipid-lowering medications — cholesterol absorption inhibitors or sources of highly purified polyunsaturated fatty acids of the omega-3 family.
Conflict of interests: None declared.
The source of funding
Federal budget. The study was carried out as part of the Federal Research Centre of Nutrition, Biotechnology and Food Safety program-research topic No. 0529-2014-0048 "Development of technology for dietary correction of metabolic disorders in patients with coronary artery disease during complex preoperative preparation".
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