Vol 87, No 9 (2015)


Comorbidity of cardiovascular diseases and cancers: Problems in the diagnosis of cardiotoxic effects of chemo- and radiation therapy

Chazova I.E., Oshchepkova E.V., Kantorova A.Y.


Cardiovascular diseases (CVD) and cancers are the leaders in their prevalence and the major causes of death in economically developed countries, determining their high sociomedical significance in society. Improvement of methods for the early diagnosis and treatment of cancers has contributed to increases in relapse-free survival and life expectancy in these patients. At the same time, the new problems have emerged particularly in the development of various cardiovascular events/diseases when treating cancer, which may predict worse prognosis in patients and be an independent cause of death. To search for new markers of cardiotoxicity at early stages and to develop effective methods for the prevention and personalized treatment of cancer and CVD are the problems that can be solved only by joint efforts of cardiologists and oncologists.
Terapevticheskii arkhiv. 2015;87(9):4-10
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Impact of a cold wave on disease course, hemodynamics, carbohydrate metabolism, and blood rheological properties in cardiac patents

Ageev F.T., Smirnova M.D., Svirida O.N., Fofanova T.V., Vitsenya M.V., Blankova Z.N., Mikhailov G.V., Lankin V.Z., Konovalova G.G., Tikhaze A.K., Ageeva N.V.


Aim. To study the impact of cold waves on disease course, hemodynamics, lipid and carbohydrate metabolisms, oxidative stress, and blood rheological properties in patients with cardiovascular diseases (CVD). Subjects and methods. 24 men and 36 women (their mean age was 62.9±9.7 years) were examined; coronary heart disease (CHD) and hypertension were present in 40 and 95% of the patients, respectively; selected therapy remained unchanged throughout the entire period. The investigators measured blood pressure and pulse wave velocity (PWV), carried out biochemical blood tests, estimated plasma oxidized low-density lipoproteins (oxLDL) and malondialdehyde (MDA) and erythrocyte superoxide dismutase (SOD) activity, calculated a MDA/SOD ratio, determined blood viscosity, as well as assessed quality of life using a visual analogue scale (VAS) and a specially developed questionnaire. Results. Female sex, CHD, type 2 diabetes mellitus (DM-2) were independent predictors of cardiovascular events (CVEs) in the frost period. The persons who had experienced CVEs in frost had higher baseline PWV. CVEs, such as hypertensive crisis, emergency calls, cardiac arrhythmias, and the larger number of adverse reactions, were more commonly recorded in frost. There was an increase in blood glucose levels, a decrease in oxLDL, a rise in η2/η1, and a reduction in plasma viscosity during frost and elevated glycation end product levels at visit 2. Conclusion. The cold wave is associated with the larger number of CVEs in some patients with CVD during selected therapy. CHD, DM-2, female sex are independent predictors of CVE in patients with CVD during the winter period. In this period, there were increases in the levels of glucose, glycation end products, and erythrocyte aggregation, and a reduction in plasma viscosity.
Terapevticheskii arkhiv. 2015;87(9):11-16
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Cardiac involvement in thrombotic microangiopathies

Tuter D.S., Kopylov F.Y., Kozlovskaya N.L., Demyanova K.A., Shchekochikhin D.Y., Shilov E.M., Syrkin A.L.


Aim. To describe cardiac involvement in patients with acute thrombotic microangiopathy (TMA). Materials and methods. The case histories of 46 patients with proven TMA, including 17 patients diagnosed with atypical hemolytic uremic syndrome (aHUS) and 29 patients with catastrophic antiphospholipid syndrome (CAPS), were analyzed. Results. Different documentarily verified signs of cardiac involvement were revealed in 6 (13%) patients (5 and 1 patients diagnosed as having aHUS and CAPS, respectively). Five patients developed myocardial involvement at disease onset in the presence of multiple organ dysfunction. Conclusion. Cases of cardiac involvement in TMA of various genesis are presented. The exact incidence of myocardial involvement and its prognostic value are unknown so far.
Terapevticheskii arkhiv. 2015;87(9):17-25
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Alcohol anamnesis and a death place factor: Role in mortality rates due to leading cardiovascular diseases

Mordovsky E.A., Soloviev A.G., Sannikov A.L.


Aim. To reveal the specific features of marital status and educational level in people who have died of leading circulatory diseases (CDs) in Arkhangelsk in relation to the place of death, alcohol anamnesis, and demographic characteristics (gender, life span). Materials and methods. Data on the diagnosed underlying cause of death, marital status, educational level, and place of death were copied from 4137 medical death certificates (form 106/у-08) of all those who had died in Arkhangelsk in 1 July to 30 June 2012. Data on patients registered at a psychoneurology dispensary as having a diagnosis of alcohol-induced mental and behavioral disorders (F10) were copied. The data were statistically processed using the procedures of binary and multinomial logistic regression analysis. Results. A total of 2101 people (50.8% of the total number of deaths) died of CDs (ICD-10 Class IX) in the study period. Male sex and a compromised alcohol anamnesis were associated with untimely death (less than 60 years of age) from acute conditions in ICD-10 Class IX. Male sex, a compromised alcohol anamnesis, and negative characteristics of marital and educational statuses were related to untimely death from chronic conditions in ICD-10 Class IX. Single people having a lower educational level and a compromised alcohol anamnesis statistically more frequently died of CDs outside a health care facility. Conclusion. The results of the investigation suggest that there is inequality in the excess risk of death from leading CDs among the representatives of different social population groups in Arkhangelsk, as well as nonequivalence in their interaction with the public health system.
Terapevticheskii arkhiv. 2015;87(9):26-33
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Right ventricular dilatation in patients with coronary heart disease without myocardial infarction: According to the data of the Coronary Angiography Surgery Registry

Kuznetsov V.A., Yaroslavskaya E.I., Pushkarev G.S., Krinochkin D.V., Bessonov I.S., Gorbatenko E.A.


Aim. To identify factors associated with right ventricular (RV) dilatation in patients with coronary heart disease (CHD) without prior myocardial infarction (MI). Subjects and methods. Out of 16 839 patents from the Coronary Angiography Surgery Registry, the investigators selected patients with >75% stenosis in at least one coronary artery without acute or prior MI: 75 patients with echocardiographically detected RV dilatation and 1134 without RV dilatation. Results. Among the patients with RV dilatation, there were more men (92% versus 80.2%; p=0.012). In this group, the mean body mass index (BMI) was higher (31.7±5.2 kg/m2 versus 30.1±4.7 kg/m2; р=0.019); there was more commonly higher NYHA functional class (FC) (III) chronic heart failure (CHF) (22.2% versus 12.5%; p=0.002), clinically relevant mitral regurgitation (29.4% versus 4.0%; all рs<0.001), and cardiac rhythm and conduction disturbances (45.5% versus 17.8%; p<0.001) in rarer severe FC (III—IV) exertional angina (30.3% versus 52.8%; p=0.007). The groups were different as evidenced by coronarography and major blood biochemical indicators. Decreased myocardial contractility (odds ratio (OR), 4.22; p=0.002), male sex (OR, 4.03; p=0.007), cardiac rhythm and conduction disturbances (OR, 2.98; p<0.001), clinically relevant mitral regurgitation (OR, 2.34; p=0.001); higher FC CHF (OR, 1.87; p=0.034), BMI (OR, 1.08; p=0.010), and lower FC exertional angina (OR, 0.42; p=0.001) demonstrated an independent relationship to RV dilatation, as evidenced by a multivariate analysis. Conclusion. In the patients with CHD without MI, RV dilatation is independently related to male sex, left ventricular functional characteristics, and higher BMI.
Terapevticheskii arkhiv. 2015;87(9):34-38
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The levels of osteoprotegerin, transforming growth factor-β, and some cytokines in women with coronary heart disease concurrent with severe osteoporosis

Tsarenok S.Y., Gorbunov V.V.


Aim. To determine the serum level of cytokines in women with coronary heart disease (CHD) concurrent with osteoporosis (OP) and in those with isolated CHD; to assess a relationship of the levels of cytokines, osteoprotegerin (OPG), and transforming growth factor-β (TGF-β) to the ten-year absolute risk of osteoporotic fractures, the presence of fractures in the history, and that of CHD; and to establish the role of elevated cytokine levels in the development of future fractures. Subjects and methods. A cross-sectional cohort study included 98 women (mean age, 71.2±8.6 years) with CHD. Forty-eight patients had CHD concurrent with severe OP. The Fracture Risk Assessment Tool (FRAX) was applied to estimate a ten-year absolute risk for fractures in all the patients. The serum levels of OPG, TGF-β, interleukin (IL)-1β, IL-4, IL-6, IL-8, and IL-10, and tumor necrosis factor-α (TNF-α) were measured by enzyme immunoassay. Results. The women with comorbidity were found to have higher levels of OPG, TGF-β, IL-6, IL-8, IL-10, and TNF-α than those with isolated CHD. There was a direct correlation between fractures, CHD, and IL-10 and TNF-α levels and an inverse relationship between fractures, CHD, and IL-8; between CHD and OPG levels. Conclusion. The women with comorbidity were noted to have elevated levels of proinflammatory cytokines and OPG; a correlation was between cytokine levels and fractures and CHD. Increased OPG and IL-6 levels are independent predictors of fractures.
Terapevticheskii arkhiv. 2015;87(9):39-43
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Clinical effectiveness of pioglitazone in the combination treatment of patients with asthma concurrent with coronary heart disease

Byelan O.V., Borzykh O.A., Mamontova T.V., Kaidashev I.P.


Aim. To investigate the clinical effectiveness of pioglitazone in the combination treatment of patients with asthma concurrent with coronary heart disease (CHD). Subjects and methods. Fifty patients aged 40-75 years with asthma concurrent with CHD were examined. External respiratory function (ERF), electrocardiograms, blood pressure (BP), and anthropometric measurements were assessed in all the patients. Blood and urine laboratory values and high-sensitivity C-reactive protein (hs-CRP) concentrations were estimated; endothelial function was determined measuring endothelium-dependent and endothelium-independent vasodilation (EDVD and EIVD). The patients were randomized into a comparison group receiving only standard therapy and a study group taking pioglitazone as part of combination therapy for 3 months. Results. At the randomization stage prior to pioglitazone combination therapy, the patient groups did not statistically significantly differ in basic clinical and anamnestic data. Three-month standard therapy resulted in stabilization of ERF and endothelial function. During the treatment, there were increases in the frequency of asthma symptoms and the duration of angina attacks, however, there was a decline in hs-CRP levels (p<0.001). Incorporation of pioglitazone into the standard treatment regimen of patients with asthma concurrent with CHD improved clinical disease control, decreased the degree of bronchial obstruction and the frequency of angina pain and asthma attacks using nitroglycerin and salbutamol, lowered systolic and diastolic blood pressure, improved EDVD (increases in the maximum linear velocity of blood flow after a test for reactive hyperemia (RH), index of reactivity (IR), and Δ% brachial artery (BA) diameter) and EIVD (increases in IR and Δ% BA diameter), and reduced systemic inflammation from hs-CRP values (p<0.001) and hypercholesterolemia from total cholesterol levels (p<0.02). Conclusion. The incorporation of pioglitazone in the combination therapy of patients with asthma concurrent with CHD improves the clinical course of the diseases and increases their control, reduces systemic inflammation, and improves endothelial functional activity.
Terapevticheskii arkhiv. 2015;87(9):44-51
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Impact of chronic obstructive pulmonary disease on one-year prognosis in patients with ST-segment elevation myocardial infarction

Polikutina O.M., Slepynina Y.S., Bazdyrev E.D., Karetnikova V.N., Barbarach O.L.


Aim. To assess the role of chronic obstructive pulmonary disease (COPD) in the development of unfavorable outcomes of long-term (one-year) prognosis of ST-elevation myocardial infarction (STEMI). Subjects and methods. A total of 529 patients diagnosed with STEMI and no age limits were examined. Group 1 included 65 (12.3%) patients with previously diagnosed COPD; Group 2 consisted of 464 (87.7%) patients without COPD. One-year prognosis was studied in 384 (81.5%) patients. The investigators evaluated the following endpoints: evolving recurrent myocardial infarction (MI), progressive angina pectoris, decompensated chronic heart failure (CHF), repeat percutaneous coronary interventions, stroke, and death. Results. The prevalence of COPD was 12.3% in the patients with STEMI. Unfavorable one-year prognosis was significantly more often registered in the comorbidity group regardless of age, gender, and smoking status. COPD increased the risk of combined endpoints by 1.9 times within a year after MI and that of decompensated CHD by 2.6 times during a year after STEMI. Conclusion. COPD may be an independent risk factor for unfavorable outcomes during a year after MI.
Terapevticheskii arkhiv. 2015;87(9):52-57
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Cardiorenal prognosis in kidney dysfunction patients undergoing cardiac surgery

Iskenderov B.G., Sisina O.N.


Aim. To evaluate the impact of cardiac surgical procedures on cardiac and renal functions within 12 months after surgery in patients with a history of chronic kidney disease (CKD). Subjects and methods. A total of 875 patients (464 men and 411 women) aged 32 to 68 years (62.3±5.2 years), including 396 patients who had undergone heart valve replacement under extracorporeal circulation, 422 who had aortocoronary and/or mammary coronary artery bypass, and 57 who had a combination of these operations, were examined. According to the baseline glomerular filtration rate (GFR), the patients were divided into 2 groups: 1) 508 patients with preserved kidney function (GFR, higher than 90 ml/min/1.73 m2); 2) 367 with CKD (GFR, 89 to 60 ml/min/1.73 m2). Results. In Group 2, early postoperative cardiovascular events were noted significantly more frequently and mortality proved to be higher than in Group 1. By the end of the first year of a follow-up, CKD was diagnosed in 5.4% of the patients in Group 1. In Group 2, CKD regressed in 54.1% of the patients and, on the contrary, progressed in 9.5%. In Group 2, programmed hemodialysis was performed in 15 (4.4%) patients. Overall mortality was significantly higher in patients with a postoperative glomerular filtration fall in both Groups 1 and 2 (7.5 and 8.4%, respectively). Long-term cardiovascular events were significantly more common in patients with progressive CKD and postoperative kidney dysfunction. Conclusion. A slight decrease in glomerular filtration makes the immediate prognosis of cardiac surgery poorer. The late cardiorenal prognosis mainly depends on changes in kidney function; regression of CKD is noted in 50% of the cases.
Terapevticheskii arkhiv. 2015;87(9):58-63
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Approaches to therapy for pulmonary hypertension: Role of the endothelin receptor antagonist bosentan

Avdeev S.N.


Pulmonary hypertension (PH) is a specific clinical group of severe and rare diseases with similar morphological, hemodynamic, and therapeutic characteristics. Despite the fact that there have been international conciliative documents and advances in drug therapy for PH, the long-term prognosis of the disease in these patients remains rather poor. Clinical trials have demonstrated that bosentan therapy in patients with PH improves pulmonary hemodynamics and exercise endurance and delays the development of the disease. According to the data of long-term studies, as compared to the historical control, bosentan used as a first-line drug can improve survival in PH patients.
Terapevticheskii arkhiv. 2015;87(9):64-71
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Pleiotropic effects of atorvastatin in rheumatoid arthritis patients with no history of cardiovascular diseases

Smakotina S.A., Zelendinova A.R., Bondareva I.N., Berns S.A.


Aim. To evaluate the effect of atorvastatin (liprimar) on the laboratory values of inflammation and blood lipid composition in rheumatoid arthritis (RA) patients with no history of cardiovascular diseases (CVD). Subjects and methods. Fifty women with grade II RA activity according to DAS28 and radiologic (erosive) Stages I-III were examined; the patients were not former or current smokers; all were seropositive; their mean age was 50.2±9.9 years. All the patients with RA were divided into 2 groups: Group 1 took no atorvastatin and continued to receive standard previously prescribed therapy; Group 2 used atorvastatin in a dose of 20 mg. Lipidogram readings and the levels of Apo-A and Apo-B, neopterin, tumor necrosis factor-α, C-reactive protein, sP-selectin, sE-selectin, interleukin (IL)-6, IL-10, IL-12, and matrix metalloproteinases 3 and 9 were assessed. Results. The patients with RA show obvious blood lipid composition impairments. Incorporation of atorvastatin (liprimar) into combination therapy for RA not only causes a considerable reduction in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apo-B levels, but also positively affects the inflammatory activity of the disease, by lowering the level of proinflammatory cytokines and increasing that of the anti-inflammatory cytokine IL-10. Conclusion. The above changes may underlie the prevention of CVD complications in patients with RA.
Terapevticheskii arkhiv. 2015;87(9):72-76
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Mineralocorticoid receptor antagonists in the treatment of patients with chronic heart failure. Positions in 2015

Osmolovskaya Y.F., Zhirov I.V., Tereshchenko S.N.


Mineralocorticoid receptor antagonists (MCRA) are part of standard medical therapy for heart failure (HF). The clinical efficacy of MCRA in patients with systolic HF has been proven by randomized clinical trials. The efficacy of this drug group in patients with chronic HF with preserved left ventricular systolic function and the advent and practical introductions of safer new-generation MCRA remain to be answered.
Terapevticheskii arkhiv. 2015;87(9):77-83
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Heat and cardiovascular diseases: A review of epidemiological surveys

Kozlovskaya I.L., Bulkina O.S., Lopukhova V.V., Chernova N.A., Ivanova O.V., Kolmakova T.E., Karpov Y.A.


The review summarizes epidemiologic data on the effects of heat on cardiovascular morbidity and mortality. Patients with heart failure and cardiac arrhythmias are most susceptible to negative heat exposure. At the same time, measures aimed at preserving the health of the population lead to a considerable reduction in losses associated with an abnormal rise in air temperature.
Terapevticheskii arkhiv. 2015;87(9):84-90
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Acetylsalicylic acid for the prevention of primary myocardial infarction and ischemic stroke

Samorodskaya I.V., Bolotova E.V., Boytsov S.A.


There is evidence that acetylsalicylic acid (ASA) is effective in preventing events in a number of cardiovascular diseases. However, there is a number of unresolved problems concerning the efficiency and suitability of its use as an agent for the prevention of cardiovascular events (CVEs) (myocardial infarction (MI) and/or ischemic stroke (IS) and/or death) in subjects without any clinical manifestations and/or diagnosed coronary heart disease (primary prevention of CVEs). The aim of the review is to compare the current recommendations of professional communities for the use of ASA as an agent for the primary prevention of CVEs, to analyze cohort studies and meta-analyses that are not included in the above recommendations (2013-2014), and to consider particular issues on ASA administration (resistance to ASA; barriers to its preventive use). The analysis performed suggests that there is no convincing evidence that it is reasonable to use ASA as a population-wide prevention strategy. The studies and meta-analyses often show conflicting data, which is likely to be associated with the clinical features of population groups included in the studies, with the presence or absence of ASA resistance and motivation for therapy. According to the current clinical recommendations, the results of studies and meta-analysis, and expert’s opinions, deciding whether it is expedient to use ASA as an agent for the prevention of primary MI and/or IS and death from atherosclerostic vascular events should be based on the assessment of an individual’s risks for the above disorders, which are related to a risk for hemorrhages due to ASA intake.
Terapevticheskii arkhiv. 2015;87(9):91-96
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Silent myocardial ischemia in acute coronary syndrome

Oleinikov V.E., Shigotarova E.A., Kulyutsin A.V., Sergatskaya N.V.


The given review considers the pathogenesis, diagnosis, and clinical significance of silent myocardial ischemia (SMI) in individual patient groups. It discusses the problem of SMI in acute coronary syndrome (ACS), the possible causes of SMI and the specific features of its diagnosis. It also indicates that there is a need for 12-lead ECG telemonitoring in intensive care unit patients with ACS to intraoperatively correct patient management and treatment policy.
Terapevticheskii arkhiv. 2015;87(9):97-101
pages 97-101 views

Hereditary pheochromocytoma-associated syndromes. Part 1

Yukina M.Y., Troshina E.A., Beltsevich D.G.


Pheochromocytoma (PCC)/paraganglioma is a catecholamine-secreting tumor of the paraganglion. The hereditary variants of PCC have been previously considered to occur in 10% of cases. The latest researches have clearly demonstrated that the hereditary cause of chromaffin tumors is revealed in a much larger number of patients. There have been the most investigated NF, RET, VHL, SDHD, SDHC, and SDHB gene mutations. New EGLN1/PHD2, KIF1В, SDH5/SDHAF2, IDH1, TMEM127, SDHA, MAX, and HIF2А gene mutations have been recently discovered. This review describes new ideas of the genetic bases of PCC. The authors discuss criteria for patient referral for genetic examination on the basis of the phenotypic manifestations of mutations, such as a malignant course, bilateral adrenal lesion, and age at disease manifestations. Recommendations are determined for carriers to screen for the components of hereditary pathology.
Terapevticheskii arkhiv. 2015;87(9):102-105
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Role of measurement of fractional flow reserve in coronary artery atherosclerosis

Kopylov F.Y., Bykova A.A., Vasilevsky Y.V., Simakov S.S.


The paper considers coronary flow in health and coronary flow autoregulation in health and disease. It gives basic methods used to estimate coronary flow reserve in patients with coronary atherosclerosis. The physiological bases for determining fractional flow reserve are presented. Clinical trials investigating the use of fractional flow reserve in patients with coronary heart disease are analyzed.
Terapevticheskii arkhiv. 2015;87(9):106-113
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Magnesium deficiency and stress: Issues of their relationship, diagnostic tests, and approaches to therapy

Tarasov E.A., Blinov D.V., Zimovina U.V., Sandakova E.A.


Magnesium plays an important role in the functions of the central nervous system. It takes part in the regulation of the cell membrane, the transmembrane transport of calcium and sodium ions, and metabolic reactions that produce, accumulate, transfer, and utilize energy, free radicals, and their oxidation products. The magnesium-containing substances include many sequestered antigens, such as glial fibrillary acidic protein, S100, and neuron-specific enolase; magnesium may act as a neuroprotector that is able to modulate the regulation of blood-brain barrier permeability. Investigations have demonstrated a relationship between the manifestations of stress reactions (anxiety, autonomic dysfunction, and maladjustment) and magnesium deficiency (MD). Thus, mental and physical stresses cause an increase in magnesium elimination from the body. MD in turn enhances a response to stress, by paradoxically aggravating its sequels. Compensation for MD increases the ability of the nervous system to resist stress. The valid diagnosis of MD present difficulties; namely, a blood magnesium concentration decrease below 0.8 mmol/l is evidence of MD; but the constant blood level of magnesium may be long maintained due to its release from the bone tissue depot. So it is necessary to keep in mind the clinical manifestations of MD. The authors have developed and tested a simple rapid MD assessment test and a stress resistance self-rating test. The proposed tests will help to screen stress resistance and MD in outpatient settings.
Terapevticheskii arkhiv. 2015;87(9):114-122
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Consecutive formation of the functions of high-, low-density and very-low-density lipoproteins during phylogenesis. Unique algorithm of the effects of lipid-lowering drugs

Titov V.N., Rozhkova T.A., Aripovsky A.V.


During phylogenesis, all fatty acids (FA) were initially transported to cells by apoА-I high-density lipoproteins (HDL) in polar lipids. Later, active cellular uptake of saturated, monoenoic and unsaturated FA occurred via triglycerides (TG) in low-density lipoproteins (LDL). Active uptake of polyenoic FA (PUFA) required the following: а) PUFA re-esterified from polar phospholipids into nonpolar cholesteryl polyesters (poly-CLE), b) a novel protein, cholesteryl ester transfer protein (CETP), initiated poly-CLE transformation from HDL to LDL. CETP formed blood HDL-CETP-LDL complexes in which poly-CLE spontaneously came from polar lipids of TG in HDL to nonpolar TG in LDL. Then ligand LDLs formed and the cells actively absorbed PUFA via apoB-100 endocytosis. Some animal species (rats, mice, dogs) developed a spontaneous CETP-minus mutation followed by population death from atherosclerosis. However, there was another active CETP-independent uptake formed during phylogenesis; the cells internalized poly-CLE in HDL. Since apoА-I had no domain-ligand, another apoE/A-I ligand formed; the cells began synthesizing apoЕ/А-I receptors. In cells of rabbits and primates absorbed cells PUFA consecutively: HDL→LDL→apoВ-100 endocytosis; those of rats and dogs did HDL directly: HDL→апоЕ/А-I endocytosis. In the rabbits, CETP was high, apoE in HDL was low, and the animals were sensitive to exogenous hypercholesterolemia. In the rats, CETP was low and ApoE in HDL was high, and the animals were resistant to hypercholesterolemia. Reduced bioavailability of PUFA during their consecutive cellular uptake and development of intercellular PUFA deficiency are fundamental to the pathogenesis of atherosclerosis.
Terapevticheskii arkhiv. 2015;87(9):123-131
pages 123-131 views

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