Comorbidity as a problem of the 21st century: cardiovascular diseases and diabetes mellitus. Comorbidity in cardiology Definition and history

Among the main damaging factors of the cardiovascular system and kidneys are the following: activation of the renin-angiotensin-aldosterone system (RAAS), the sympathoadrenal system (SAS) and changes in renal sodium excretion. The action of these factors individually or in combination determines the development of many clinical pathologies of CVD (AMI, IHD, SCD, AF, hypertension, etc.), as well as the progression of CKD. When renal function changes, the above mechanisms appear, aggravating the course of renal pathology and CVD.

Another negative effect of CKD on the development and course of coronary artery disease is due to atherosclerotic lesions of the coronary arteries in patients. It turned out that in patients with CKD and in patients without this disease, there are significant differences not only in the degree of development of atherosclerosis of the coronary arteries, but also in the structure of the atherosclerotic plaque itself. The incidence and severity of stenotic lesions of the coronary arteries increase as the glomerular filtration rate decreases. Pathological changes in CKD are characterized by uneven thinning of the intima and media of the coronary arteries and their calcification. Chronic inflammation and hyperphosphatemia are the main causes of progression of coronary atherosclerosis in patients with CKD. Hyperphosphatemia and associated secondary hyperparathyroidism cause impaired elasticity of the vascular wall, deposition of Ca2+ ions in them and subsequent proliferation of smooth muscles.

Having considered all of the above, we can come to the conclusion that comorbid diseases worsen the patient’s condition, worsen the prognosis and increase treatment costs. Therefore, assessment of comorbidity in patients with CKD and CVD is an important component of the clinical examination. Early detection of this combined pathology will allow the doctor to take into account various features when choosing treatment tactics, prevent further development of both pathologies, and also help the patient eliminate many risk factors for the development of these diseases from his life. That is why the medical community needs to take a closer look at this problem from different angles in order to subsequently reduce the risk of developing both cardiovascular diseases and diseases of the genitourinary system.

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“We should not treat the disease itself, for which we cannot find a part or name, we should not treat the cause of the disease, which is often unknown to us, the patient, or those around him, but we should treat the patient himself, his composition, his organ, his strength "

Professor M. Ya. Mudrov(assembly speech “A speech on the way to teach and learn practical medicine or active medical art at the bedside of the sick,” 1820)

Part 2. read in No. 6, 2013.

As can be seen from recent works, in addition to therapists and general practitioners, narrow specialists also often encounter the problem of comorbidity. Unfortunately, they extremely rarely pay attention to the coexistence of a whole spectrum of diseases in one patient and primarily treat a specialized disease. In current practice, urologists, gynecologists, otorhinolaryngologists, ophthalmologists, surgeons and other specialists often include only “their” disease in the diagnosis, leaving the search for concomitant pathology to other specialists. The unspoken rule of any specialized department has become the advisory work of the therapist, who takes upon himself the syndromic analysis of the patient, as well as the formation of a diagnostic and treatment concept that takes into account the patient’s potential risks and his long-term prognosis.

Thus, the influence of comorbid pathology on clinical manifestations, diagnosis, prognosis and treatment of many diseases is multifaceted and individual. The interaction of diseases, age and drug pathomorphism significantly changes the clinical picture and course of the main nosology, the nature and severity of complications, worsens the patient’s quality of life, and limits or complicates the diagnostic and treatment process.

Comorbidity affects the prognosis for life and increases the likelihood of death. The presence of comorbid diseases contributes to an increase in bed days, disability, interferes with rehabilitation, increases the number of complications after surgical interventions, and increases the likelihood of falls in elderly patients.

However, in the majority of randomized clinical trials conducted, the authors included patients with a separate refined pathology, making comorbidity an exclusion criterion. That is why the listed studies, devoted to assessing the combination of certain individual diseases, are difficult to classify as works studying comorbidity in general. The lack of a unified, comprehensive scientific approach to assessing comorbidity leads to gaps in clinical practice. The absence of comorbidity in the taxonomy of diseases presented in the International Classification of Diseases, X Revision (ICD-10) cannot go unnoticed. This fact alone provides the basis for the further development of a general classification of diseases.

Despite the many unsolved patterns of comorbidity, the lack of its unified terminology and the ongoing search for new combinations of diseases, based on the available clinical and scientific data, we can conclude that comorbidity is characterized by a range of undoubted properties that characterize it as a heterogeneous, frequently occurring phenomenon that increases the severity of the condition and worsens the prognosis of patients. The heterogeneity of comorbidity is due to a wide range of causes that cause it.

There are a number of rules for formulating a clinical diagnosis for a comorbid patient that should be followed by a practicing physician. The basic rule is to distinguish in the structure of the diagnosis the main and background diseases, as well as their complications and concomitant pathologies.

If a patient suffers from many diseases, then one of them is the main one. This is the nosological form that itself or as a result of complications causes a priority need for treatment at a given time due to the greatest threat to life and ability to work. The underlying disease itself or through complications can cause death. The main disease is the reason for seeking medical help. As the examination progresses, the diagnosis of the least prognostically favorable disease becomes the main diagnosis, while other diseases become concomitant.

The underlying cause may be several competing serious diseases. Competing diseases are nosological forms present simultaneously in the patient, mutually independent in etiology and pathogenesis, but equally meeting the criteria of the underlying disease.

The background disease contributes to the occurrence or unfavorable course of the underlying disease, increases its danger, and contributes to the development of complications. This disease, like the main one, requires immediate treatment.

All complications are pathogenetically related to the underlying disease; they contribute to an unfavorable outcome of the disease, causing a sharp deterioration in the patient’s condition. They belong to the category of complicated comorbidity. In some cases, complications of the underlying disease, associated with it by a common etiological and pathogenetic factors, are designated as concomitant diseases. In this case, they must be classified as causal comorbidity. Complications are listed in descending order of prognostic or disabling significance.

The remaining diseases present in the patient are listed in order of importance. The concomitant disease is not etiologically or pathogenetically related to the main disease and is considered to not significantly affect its course.

The presence of comorbidity should be taken into account when choosing a diagnostic algorithm and treatment regimen for a particular disease. For this category of patients, it is necessary to clarify the degree of functional disorders and morphological status of all identified nosological forms. Whenever a new symptom, including a mild one, appears, a comprehensive examination should be carried out to determine its cause. It is also necessary to remember that comorbidity leads to polypharmacy, i.e. the simultaneous prescription of a large number of drugs, which makes it impossible to control the effectiveness of therapy, increases the material costs of patients, and therefore reduces their compliance (adherence to treatment). In addition, polypharmacy, especially in elderly and senile patients, contributes to a sharp increase in the likelihood of developing local and systemic unwanted side effects of drugs. These side effects are not always taken into account by doctors, since they are regarded as a manifestation of one of the comorbidity factors and entail the prescription of even more medications, closing a “vicious circle.”

Simultaneous treatment of several diseases requires strict consideration of the compatibility of drugs and thorough adherence to the rules of rational pharmacotherapy, based on the postulates of E. M. Tareev “Every non-indicated drug is contraindicated” and B. E. Votchal “If a drug has no side effects, you should think about whether it has any effects at all."

Thus, the significance of comorbidity is beyond doubt, but how can it be measured in a specific patient, for example, in patient S., 73 years old, who called an ambulance due to sudden pressing pain in the chest? From the anamnesis it is known that the patient has suffered from coronary artery disease for many years. She had experienced similar pain in the chest before, but always went away within a few minutes after taking sublingual organic nitrates. In this case, taking three nitroglycerin tablets did not produce an analgesic effect. From the anamnesis it is known that the patient suffered myocardial infarction twice over the past ten years, as well as acute cerebrovascular accident with left-sided hemiplegia more than 15 years ago. In addition, the patient suffers from hypertension, type 2 diabetes mellitus with diabetic nephropathy, uterine fibroids, cholelithiasis, osteoporosis and varicose veins of the legs. It was possible to find out that the patient regularly takes a number of antihypertensive drugs, diuretics and oral hypoglycemic agents, as well as statins, antiplatelet agents and nootropics. In the past, the patient underwent cholecystectomy for cholelithiasis more than 20 years ago, as well as lens extraction for cataracts in the right eye 4 years ago. The patient was hospitalized in the cardiac intensive care unit of a multidisciplinary hospital with a diagnosis of acute transmural myocardial infarction. The examination revealed moderate azotemia, mild hypochromic anemia, proteinuria and a decrease in left ventricular ejection fraction.

There are currently 12 generally accepted methods for measuring comorbidity. The first methods for assessing comorbidity were the CIRS (Cumulative Illness Rating Scale) system and the Kaplan-Feinstein index, developed in 1968 and 1974. respectively. The CIRS system, proposed by B. S. Linn, was a revolutionary discovery, as it enabled practitioners to assess the number and severity of chronic diseases in the structure of the comorbid status of their patients. However, it did not take into account the age of patients and the specifics of diseases of old age, and therefore 23 years later it was revised by M. D. Miller. A variation of the CIRS system in elderly patients is called CIRS-G (Cumulative Illness Rating Scale for Geriatrics).

Correct use of the CIRS system implies a separate summary assessment of the condition of each organ system: “0” corresponds to the absence of diseases of the selected system, “1” - mild deviations from the norm or previous diseases, “2” - a disease requiring drug therapy, “ 3" - a disease that has caused disability, and "4" - severe organ failure requiring emergency treatment. The CIRS system evaluates comorbidity by a score that can vary from 0 to 56. According to its developers, maximum results are not compatible with the life of patients. An example of comorbidity assessment is presented in Table. 1.

Thus, the comorbidity of patient S., 73 years old, can be regarded as moderate (23 points out of 56), however, it is not possible to assess the patient’s prognosis due to the lack of interpretation of the results obtained and their connection with a number of prognostic characteristics.

The Kaplan-Feinstein Index was created by examining the impact of comorbidities on 5-year survival in patients with type 2 diabetes. In this comorbidity assessment system, all existing diseases and their complications, depending on the severity of organ damage, are classified into mild, moderate and severe. In this case, the conclusion about total comorbidity is made on the basis of the most decompensated organ system. This index provides a summary, but less detailed than the CIRS system, assessment of the condition of each organ system: “0” - absence of disease, “1” - mild disease, “2” - moderate disease, “3” - severe disease. The Kaplan-Feinstein index evaluates comorbidity using a score that can vary from 0 to 36. An example of comorbidity assessment is presented in Table. 2.

Thus, the comorbidity of patient S., 73 years old, can be regarded as moderate (16 points out of 36), but its prognostic significance is again unclear due to the lack of interpretation of the total score obtained by summing up the diseases the patient has. In addition, the obvious disadvantage of this method of assessing comorbidity is the excessive generalization of nosologies and the absence of a large number of diseases on the scale, which should probably be noted in the “miscellaneous” column, which reduces the objectivity and effectiveness of this method. However, the undeniable advantage of the Kaplan-Feinstein index over the CIRS system is the possibility of independent analysis of malignant neoplasms and their severity.

Among the comorbidity assessment systems existing today, the most common are the ICED scale and the Charlson index, proposed to assess the long-term prognosis of patients in 1987 by Professor Mary Charlson.

This index is a scoring system (from 0 to 40) for the presence of certain concomitant diseases and is used to predict mortality. When calculating it, the points corresponding to concomitant diseases are summed up, and one point is added for every ten years of life when the patient exceeds forty years of age (i.e. 50 years - 1 point, 60 years - 2 points) (Table 3).

Thus, the comorbidity of patient S., 73 years old, according to this method corresponds to a mild degree (9 points out of 40). The main distinctive feature and unconditional advantage of the Charlson index is the ability to assess the patient’s age and determine the mortality of patients, which in the absence of comorbidity is 12%, with 1-2 points - 26%; with 3-4 points - 52%, and with a total of more than 5 points - 85%. Unfortunately, the presented method has some drawbacks: when calculating comorbidity, the severity of many diseases is not taken into account, and a number of prognostically important diseases are also missing. In addition, it is doubtful that the theoretically possible prognosis of a patient suffering from bronchial asthma and chronic leukemia is comparable to the prognosis of a patient with myocardial infarction and cerebral infarction. Some of the indicated shortcomings of the Charlson index were corrected by R. A. Deyo in 1992. Chronic forms of coronary heart disease and stages of chronic heart failure were added to the modified Charlson index.

The ICED (Index of Co-Existent Disease) index was originally developed by S. Greenfield to assess the comorbidity of patients with malignant neoplasms, and subsequently found application in other categories of patients. This method helps in calculating the length of hospital stay and the risk of readmission of a patient after surgery. To calculate comorbidity, the ICED scale proposes to evaluate the patient’s condition separately according to two components: physiological and functional characteristics. The first component includes 19 comorbidities, each of which is rated on a 4-point scale, where “0” is the absence of the disease and “3” is its severe form. The second component assesses the impact of comorbidities on the patient's physical condition. It rates 11 physical functions on a 3-point scale, where “0” is normal function and “2” is impossible to perform.

Having analyzed the comorbid status of patient S., 73 years old, using the most popular international scales for assessing comorbidity, we obtained fundamentally different results. Their ambiguity and inconsistency to a certain extent complicated our judgment about the true severity of the patient’s condition and complicated the prescription of rational pharmacotherapy for her diseases. Every clinician, regardless of clinical experience and knowledge of medical science, faces such challenges every day. Moreover, in addition to the comorbidity assessment systems discussed in this article, there are currently the GIC index (Geriatric Index of Comorbidity, 2002), the FCI index (Functional Comorbidity Index, 2005), the TIBI index (Total Illness Burden Index, 2009), as well as a number scales that allow patients to independently assess their comorbidity. Analysis of the patient's concomitant pathology in the same clinical case using these indices would undoubtedly give new results, but would also confuse the practitioner even more.

It seems to the authors that the main obstacles to the implementation of comorbidity assessment systems in the diverse treatment and diagnostic process are their fragmentation and narrow focus. Despite the variety of methods for assessing comorbidity, the lack of a single generally accepted way of measuring it, devoid of the shortcomings of existing methods, is of concern. The lack of a single tool created on the basis of enormous international experience, as well as the methodology for its use, does not allow comorbidity to “turn its face” to a practicing physician. At the same time, due to disparate approaches to the analysis of comorbid status and the absence of comorbidity components in the curricula of medical universities, its prognostic impact is not obvious to the clinician, which makes publicly available systems for assessing comorbidity unreasonable and therefore unclaimed.

“A specialist is like a gumboil - its completeness is one-sided,” a group of authors once wrote under the pseudonym Kozma Prutkov, and therefore today the question has arisen of conducting a generalizing fundamental study of comorbidity, its properties and patterns, as well as the phenomena and phenomena associated with it - bedside research the patient and at the section table. The result of this work should be the creation of a universal tool that allows a practicing doctor to easily and easily assess the structure, severity and possible consequences of comorbidity, conduct a targeted examination of patients and prescribe them adequate treatment.

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A. L. Vertkin,Doctor of Medical Sciences, Professor
A. S. Skotnikov 1,Candidate of Medical Sciences

B.K. Zholdin, Department of Therapy with Cardiology FPiDO, West Kazakhstan Medical University, Candidate of Medical Sciences, Prof., Chief Freelance Clinical Pharmacologist of the Health Department of the Aktobe Region, Head. Department of Therapy with Cardiology, Faculty of Postgraduate and Additional Education of West Kazakhstan State Medical University named after. M. Ospanova. The statement that cardiovascular diseases are the No. 1 cause of death in most countries is not entirely accurate. If we look at the main causes of death of the population of the Republic of Kazakhstan for 2008 (according to the RCHR data for 2014, diagram), we will see that the cause of 72.36% of all deaths of the population of the Republic of Kazakhstan are chronic non-infectious diseases (diseases of the circulatory system - 54, 8 %, malignant and benign neoplasms - 14.9%, accidents and injuries - 14.7%). Considering the causes of mortality in such European countries as Denmark, Belgium, France, Israel, the Netherlands, Portugal, Slovenia, Spain, Luxembourg, it should be noted that in these countries the mortality rate from malignant neoplasms is higher than from cardiovascular diseases, due to the effectiveness of primary and secondary prevention of CVD. As a result of the implementation of the state program “Salamatty Kazakhstan” since 2008, mortality from CVD in Kazakhstan is decreasing, and life expectancy is increasing, which leads to the expectation of an increase in older people and the problem of comorbidity is increasing. The primary definition of comorbidity is the presence of additional clinical a picture that already exists or can appear independently, in addition to the current disease, and is always different from it, was clarified by H.C. Kraemer and M. Vanden Akker, who defined comorbidity as a combination in one patient of two and/or more chronic diseases that are pathogenetically interrelated or coinciding in time in one patient, regardless of the activity of each of them. The main causes of comorbidity are: the anatomical proximity of the organs affected by the disease, a single pathogenetic mechanism of several diseases, a temporary cause-and-effect relationship between diseases, one disease is a complication of another. Factors influencing development of comorbidity, may be chronic infection, inflammation, involutive and systemic metabolic changes, iatrogeny, social status, ecology and genetic predisposition.
There are various forms of comorbidity: causal (parallel lesions of various organs and systems caused by a single pathological agent, process (diseases associated with smoking), complicated (the result of the underlying disease, appears sequentially some time after its destabilization and is manifested by damage to target organs (cerebral infarction) in hypertensive crisis) and iatrogenic (forced negative impact on the patient, despite the known danger of the medical procedure (glucocorticoid osteoparosis) forms. Currently, the problem of comorbidity is the most pressing problem in many highly developed countries, where the number of comorbid patients occupies a large proportion and increases with each year. If we turn to real clinical practice (according to A.L. Vertkin and E.A. Petrik for 2011), we will see that as a result of the analysis of autopsies of patients admitted to an emergency hospital (EMS) for emergency indications, comorbid pathology was diagnosed in 78.6% of cases, the vast majority in patients aged 65 years. Nosologies that make up comorbidity include cardiovascular diseases (CVD), incl. arterial hypertension (AH) and various forms of coronary heart disease (CHD), respectively, in 80 and 79% of cases, diseases of the urinary and respiratory systems, respectively, in 78 and 73%, vascular diseases of the brain and diseases of the liver and pancreas, respectively, in 69 and 49%. The increase in comorbidity with age is not only a medical, social, but also an economic problem for any state, since it leads to healthcare costs exponentially. Thus, in the USA, 80% of medical care costs are incurred by patients with 4 or more chronic diseases. Among the ways of forming comorbidity, the iatrogenic path is the least studied. Iatrogenic comorbidity is a consequence of long-term use of medications, leading to side complications that develop into independent nosological forms. In this regard, as a consequence, the problem of polypharmacy arises, which is observed in 56% of patients under the age of 65 years and in 73% of patients over 65 years of age. When taking 10 drugs, the risk of drug interaction reaches 100%, while in 96% of cases doctors do not know exactly which drugs their patients are taking. Recent studies have shown that the use of low-dose aspirin monotherapy increases the risk of urgent gastrointestinal bleeding, and in combination with clopidogrel further increases this risk. The American Society of Cardiovascular Angiography and Interventions (SCAI-2009) examined 16,690 patients treated with aspirin and PPIs after stent implantation. The results of the examination showed that the combination of clopidogrel and PPI increases the risk of coronary syndrome by 50%. The study of this problem led to the conclusion that the metabolic bioactivation of clopidogrel was impaired. Since clopidogrel is a prodrug, the bioactivation of which is mediated by cytochrome P450 isoenzymes, mainly CYP2C19, taking proton pump inhibitors metabolized by this cytochrome reduces the activation and antiplatelet effect of clopidogrel. In this regard, the European Medicines Agency (EMA) published information about that Omeprazole and Esomeprazole reduce the antiplatelet effect of clopidogrel. The EMA considers that there is no sufficient basis to extend these warnings to the use of other PPI drugs. Now other drugs have appeared, for example, rabeprazole, dexalansoprazole, which we can use for gastroprotection.
Speaking about the cardiotoxicity of drugs, it should be noted the drug Domperidone (Motilium), which is successfully used in gastroenterological practice. Domperidone is a highly selective blocker of peripheral dopamine receptors (DA2 receptors), increases the spontaneous activity of the stomach, increases the pressure of the lower esophageal sphincter and activates peristalsis of the esophagus and antrum stomach, increases the frequency, amplitude and duration of contractions of the duodenum. In 2010, the results of 2 new epidemiological studies were published, which showed that the use of domperidone in high doses (more than 30 mg / day) or in patients over 60 years of age may be associated with an increased risk of developing ventricular arrhythmia and sudden cardiac death. Why is this happening? The mechanism of action of Domperidone on the myocardium is reduced to prolongation of the QT interval - Domperidone blocks hERG K+ channels in the myocardium, which leads to rhythm disturbances in the ventricle. In this regard, in 2014, a decision was made by the Pharmacovigilance Risk Assessment Committee (PRAC), which had The following contents: - The benefits of Domperidone continue to outweigh the risks when used short-term at low doses for the treatment of nausea and vomiting - PRAC recommends that domperidone-containing medicinal products remain on the market and continue their use in the EU for the treatment of symptoms of nausea and vomiting, but reduce the recommended dose up to 10 mg up to three times daily orally in adults and adolescents weighing 35 kg or more. - The medicinal product should generally not be used for longer than one week. - Domperidone should no longer be registered as a drug for the treatment of other conditions such as bloating or heartburn. Another drug used in clinical practice is Itopride, which is also used in gastroenterological practice and differs from Domperidone in its mechanism of action. Itopride, in addition to blocking D2-dopamine receptors, has anticholinesterase activity and, accordingly, a cholinomimetic effect. Features of the pharmacokinetics of Itopride: rapid absorption, impermeability through the blood-brain barrier, metabolism in the liver by N-oxidation without the participation of cytochrome P450 isoenzymes, as well as the structural features of the Itopride molecule (obtained by modifying the metoclopromide molecule) led to the absence of the risk of cardiac effects. In a study of the effect of Itopride (dose 150 mg 3 times a day) and placebo on the duration of the QT interval, it was statistically proven that Itopride does not have a negative effect on the QT interval. In clinical practice, the drug Itopride is used at a dose of 50 mg 3 times a day. Experts are aware of the positive effects of statins in reducing the risk of cardiovascular diseases and complications, but their focus is on side effects, namely the effect of statins on the liver.
In connection with this problem, the effects and mechanisms of action of UDCA, which has hepatoprotective, choleretic, cholelitholytic, hypolipidemic, hypocholesterolemic and immunomodulatory effects, were studied. ANO "Research Center "National Society of Evidence-Based Medicine" conducted the RAKURS study "Study of the influence of ursodeoxycholic acid on the effectiveness and the safety of statin therapy in patients with diseases of the liver, gallbladder and/or biliary tract using the drug Ursosan.” A prospective, non-comparative, cohort study included 300 patients from various regions of the Russian Federation with various chronic liver diseases (with NAFLD - 61.8% of patients, uncomplicated cholelithiasis - 29.8%, biliary dyskinesia - 35.1%). - The RAKURS study demonstrated the possibility and safety of joint administration of statins and ursodeoxycholic acid in patients with a high risk of cardiovascular complications and concomitant liver diseases - High adherence of patients to the administration of ursodeoxycholic acid (Ursosan) has been demonstrated. - Reduction of cholesterol levels (both total and low-density lipoproteins) to at the end of 6-month therapy suggests that ursodeoxycholic acid either potentiates the lipid-lowering effect of statins or has its own lipid-lowering effect. - The absence of negative dynamics in the levels of transaminases and bilirubin at the end of 6-month therapy may indicate the presence of a hepatoprotective effect in ursodeoxycholic acid, reducing the likelihood side effects of statins on the liver. These results are practically reflected in Russian recommendations for dispensary observation of patients with non-infectious chronic diseases and patients at high risk of their development. Drug-induced liver damage accounts for about 10% of all adverse reactions associated with the use of pharmacological drugs. As shown research by American authors, 2-5% of all cases of jaundice and 50% of all cases of acute liver failure are caused by the action of drugs. In Russia, acute drug-induced liver damage is detected in 3-5% of hospitalized patients. New data on the toxicity of Amiodarone appear every year. The antiarrhythmic drug Amiodarone can cause toxic damage to the lungs, cornea, thyroid gland, peripheral nerves and liver. Violation of biochemical indicators of liver function is observed in 15-50% of patients. Toxic liver damage usually develops more than a year after the start of treatment, but can be observed during the first month. The range of clinical manifestations is wide: from an isolated asymptomatic increase in transaminase activity to fulminant hepatitis with a fatal outcome. Hepatotoxic effects are usually manifested by increased transaminase activity and rarely by jaundice. In the case of an asymptomatic course, liver damage is detected only during a routine biochemical blood test; The liver does not always enlarge. Severe cholestasis may develop. Amiodarone can cause liver cirrhosis, which can be fatal. Its toxic effect can also manifest itself in children. Amiodarone has a large volume of distribution and a long T1/2, so its elevated level in the blood after stopping use can persist for many months. Amiodarone and its main metabolite N-desethylamiodarone can be detected in liver tissue for several months after discontinuation of use. The likelihood and severity of side effects depend on the serum concentration of the drug. The daily dose of amiodarone should be maintained within 200-600 mg. Amiodarone is iodinated and this results in increased tissue density on CT scans. However, it does not correspond to the degree of liver damage. A comparison of the extracardiac side effects of allapinine and propafenone showed that propafenone was more favorable in terms of toxicity. In continuation of the research on antiarrhythmic drugs, a multicenter national study “Prostor” - “Propanorm - antiarrhythmic” was conducted from 2009 to 2012 effectiveness and safety of use for atrial fibrillation in patients with arterial hypertension, coronary heart disease and chronic heart failure with preserved systolic function of the left ventricle." The study proved that Propanorm, as a class 1C antiarrhythmic, can be used in patients with hypertension, stable forms of coronary artery disease and CHF with preserved left ventricular systolic function. The effectiveness of Propanorm (55.7%) is not inferior to the effectiveness of Cordarone (56.4%). Propanorm demonstrates a better safety profile - the frequency of adverse events with its use is 2% versus 33.7% in the Cordarone group. Thus, we should not refuse to use Cordarone, but must take into account its side effects. You should remember the words of Academician Boris Votchal that if the drug is devoid of any side effects, then you should find out whether it has any effects at all.

For quotation: Symposium “Myths and Reality. Risk of cardiovascular complications in a comorbid patient” // RMJ. 2017. No. 25. S. 1837-1840

The results of the symposium “Myths and Reality. Risk of cardiovascular complications in a comorbid patient" within the framework of the Russian National Congress of Cardiologists, where the problems of selecting effective treatment for patients with arterial hypertension and comorbid conditions were discussed.

On October 24, 2017, the symposium “Myths and Reality” was held in St. Petersburg as part of the Russian National Congress of Cardiologists. Risk of cardiovascular complications in a comorbid patient,” which discussed the problems of selecting effective treatment for patients with arterial hypertension and comorbid conditions.

The first speaker at the symposium was Doctor of Medical Sciences, Professor of the Department of Cardiology of the Federal Postgraduate Educational Institution “Russian National Research Medical University named after. N.I. Pirogov" E.E. Averin with a report on the topic “Myths and reality: a review of world experience in the treatment of hypertension.”


In his report, Professor E.E. Averin presented the latest statistical data on mortality from cardiovascular diseases (CVD) in the world and in the Russian Federation (RF), including those presented at the 27th annual congress of the European Society of Arterial Hypertension (ESH) in Milan . The analysis revealed that in the Russian Federation, mortality from CVD is not the highest in the world, however, continued work is necessary to further reduce this indicator, and special attention should be paid to patients with comorbid diseases.
In recent years, there has been a steady increase in the number of patients with comorbid conditions. Thus, according to forecasts, compared to the previous year, the number of obese patients will increase by 40%, which will lead to an increased risk of developing hypertension, diabetes mellitus (DM), coronary heart disease (CHD), kidney disease and other pathologies. Pediatricians were among the first to sound the alarm, expecting an increase in the number of adolescents (10–15 years old) with obesity in the coming years, which will lead to earlier development of CVD and associated comorbid conditions in adulthood.
Professor E.E. Averin indicated new target indicators to be achieved in this cohort of patients according to modern recommendations:
blood pressure (BP) in patients with diabetes is below 140/85 mmHg. Art., in patients with kidney diseases – 130/80 mm Hg. Art.;
low-density lipoprotein (LDL) value – up to 1.5 mmol/l (previous target level – 1.8 mmol/l);
heart rate (HR) for ischemic heart disease in the range of 55–60 beats/min;
maintaining glycemic levels in accordance with target values ​​for young, middle-aged and elderly patients.
It is known that antihypertensive therapy may increase the risk of developing type 2 diabetes. On February 23, 2017, a work was published that analyzed all 5 groups of antihypertensive drugs and their combinations in the treatment of hypertension, as well as their effect on the risk of developing diabetes. According to the results of the study, only 2 groups of drugs - sartans and angiotensin-converting enzyme inhibitors (ACEIs) have a preventive effect against the development of diabetes. At the same time, in the list of drugs recommended for prescription, ramipril took 4th place, and amlodipine – 12th place.
In published articles in 2013 and 2016. data are presented on the effectiveness of the combination of ramipril + amlodipine (Egipres ®, JSC Pharmaceutical Plant EGIS, Hungary) and the effect on metabolic parameters: improvement in fasting glycemia, reduction in the level of glycated hemoglobin (HbA1c), LDL, triglycerides and no worsening of diabetes were noted and other diseases.
Professor E.E. Averin also highlighted the results of the European prospective multicenter studies RAMONA and RAMSES involving more than 12 thousand patients.
The RAMSES study assessed the effectiveness and safety of the combination of ramipril + amlodipine in more than 6 thousand patients with metabolic syndrome (MS), 99% of whom had an increased risk of developing cardiovascular complications (CVD): 40% of patients suffered from tobacco addiction, a third patients were obese, a third had diabetes, more than 60% had dyslipidemia, and some patients had hyperuricemia. As a result of the use of the combination of ramipril + amlodipine, a decrease in daily systolic blood pressure was noted
(BPsyst.) by 17%, diastolic (BPdiast.) - by 19%. It was noted that the more accurately the patient followed the recommendations for the use of the drug, the better the results were in achieving target indicators. According to the results of daily blood pressure monitoring, for 6 months. There was a decrease in daytime and nighttime blood pressure: BPsist. –‒ by 12%, BPdiast. – by 10–11%. Thus, the use of the combination of ramipril + amlodipine led to a decrease in both systolic and diastolic blood pressure.
In each of these studies, separate subgroups of patients were identified – with diabetes and MS. 55–75% of patients achieved target blood pressure values ​​when using the combination of ramipril + amlodipine. In the subgroup of type 2 diabetes, a decrease in systolic and diastolic blood pressure was noted after 4 months. after the start of therapy: ADsyst. decreased by 26 mmHg. Art., ADdiast. – by 12 mm Hg. Art.
A special feature of the combination of ramipril + amlodipine (Egipres ®) is its ease of dosing. Today, there are 4 dosage options for the drug: 5/5, 5/10, 10/5, 10/10 mg of ramipril/amlodipine, respectively, which allows increasing adherence to therapy in patients.
Professor E.E. Averin cited the results of a study in Poland involving 45 thousand patients on antihypertensive therapy. Before inclusion in the study, the target blood pressure value was achieved in only 23% of patients; when patients were transferred to the fixed combination of ramipril + amlodipine, the frequency of achieving target values ​​in patients increased by 3.5 times (up to 80% of patients). To identify the reason for such a significant effect, a survey was conducted among European doctors, which showed that patients, as in all other countries of the world, could completely not comply with doctors’ prescriptions, skip doses of the drug, independently change the dosage, or even stop using the drug. In such cases, the half-life of amlodipine (approx.
45 hours): when skipping a dose of a fixed drug, a “reserve” was maintained to maintain target blood pressure. This property of a fixed combination is especially important in patients with cognitive impairment.
Adherence to therapy was also studied 1 year after the prescription of a free or fixed combination. The results revealed a difference in adherence to therapy of about 59%: adherence to the fixed combination was 1.5 times higher compared to that when taking the free combination. Assessment of adherence when switching from monotherapy (1 tablet) to fixed therapy (1 tablet) showed that adherence to the fixed combination was 80% greater than adherence to monotherapy. Patients followed the fixed combination regimen for 270 days of treatment, and monotherapy for 190 days. Thus, the use of fixed combinations not only allows one to achieve the target blood pressure level, but also increases adherence to therapy.
The RAMONA study focused on patients with hypertension and decreased glomerular filtration rate (GFR), who typically have difficulty achieving target values. According to the study results, the lower the GFR, the more difficult it is to achieve target BP. In the study
RAMIPROT, the dose-dependent nephroprotective effect of ramipril was proven, and when the maximum daily dose of 10 mg was divided into 2 doses (morning/evening), the nephroprotective effect increased.
A particularly severe group of patients was studied - patients with a significant decrease in GFR. results
A 6-year observation of 136 thousand patients showed that when using combination antihypertensive therapy based on ramipril, the risk of developing end-stage chronic renal failure is reduced by 8%, the number of hospitalizations by 25%, and mortality by 56%.
A study of the tolerability of the ramipril + amlodipine combination in Poland involving 24 thousand patients showed a very favorable profile: with monotherapy, edema syndrome was observed in 30% of patients; when using a fixed combination (due to the effect of ramipril on vascular tone), the frequency of this side effect decreased.
The speaker concluded that the combination of ramipril + amlodipine can reduce the risk of developing diabetes (including in patients with MS), achieve target values ​​of both systolic and diastolic blood pressure, increase patient adherence to therapy, and improve treatment tolerability. This combination can be used in complex patients with chronic kidney disease.
The work of the symposium was continued by Associate Professor of the Department of Psychiatry of the Vladimir Medical Academy. CM. Kirova, Doctor of Medical Sciences E.S. Kurasov with a report “Anxiety-depressive disorders and arterial hypertension: myth or reality.”


E.S. Kurasov noted the close relationship between somatic diseases and mental disorders. The prevalence of depression in the population averages about 18%, and in patients with cardiac diseases – up to 50%, while the combination of cardiac pathology and depression occurs in 20–50% of patients.
A modern view of the relationship between mental and somatic disorders was reflected in the 369th WHO bulletin, which separately emphasizes not only the significant contribution of depressive disorders to overall morbidity, but also the relationship between depression and CVD: CVD can lead to the development of depression and vice versa.
The prevalence of anxiety and depressive disorders prevails in patients with CVD, while depression undeniably increases mortality from myocardial infarction (MI) over a 5-year period.
Currently, the total number of patients with depression in the Russian Federation reaches 8 million people, 70% of them do not have an established diagnosis, while only 1.5 million people receive proper therapy. In patients with anxiety-depressive disorders, a vicious circle is observed: the level of anxiety reaches a panic level and turns into depression, which, in turn, further increases anxiety symptoms and reduces the results of treatment of somatic illness.
The relationship between mental and somatic illnesses is often encountered in the practice of a therapist, while depressive disorders have a negative impact on somatics:
provoke somatic diseases, increase the risk of occurrence and worsening of hypertension, coronary artery disease, etc.;
worsen treatment results;
reduce patient adherence (compliance) to therapy;
increase the length of hospital stay;
are the cause of the phenomenon of “revolving days” in cardiology, when the patient, after “going out into the outside world,” develops anxiety and deterioration of his condition and is followed by repeated hospitalization in the hospital.
The basis for the formation of mental disorders in cardiac patients are disorders of the hypothalamic-pituitary-adrenal axis: the hypothalamus, by stimulating the release of adrenocorticotropic hormones, triggers a chain of hormonal stress. With chronic stress, diseases can develop: hypertension, diabetes, cerebrovascular accidents, etc.
In this case, 4 types of relationships are most important:
1) psychosomatic diseases - when a mental disorder affects the development of somatic diseases;
2) personality reaction to illness (nosogenic disorders);
3) depression is a consequence of organic damage to the central nervous system;
4) somatized (masked) depression.
It is noted that the severity of neurological symptoms increases against the background of hypertension. This mechanism is implemented through the autonomic sympathetic division of the nervous system.
E.S. Kurasov notes that since the 1930s, psychotropic drugs (in particular, barbiturates) have been used in the treatment of anxious mental disorders; currently tranquilizers (anxiolytics) have taken first place. There are three generations of tranquilizers:
1st generation: meprobamate, benactizine, etc., when used, “behavioral” toxicity is noted (weakness, impaired coordination, etc.);
2nd generation - benzodiazepines, with long-term use addiction develops, when you stop taking the drug - withdrawal syndrome;
3rd generation – buspirone.
Grandaxin (JSC Pharmaceutical Plant EGIS, Hungary) does not impair cognitive and psychomotor functions, is well metabolized, and does not cause addiction. Prescribed for somatic diseases (including hypertension) in a dosage of 50 to 300 mg/day, and can be prescribed in the second and third trimesters of pregnancy.
Buspirone (Spitomin, JSC Pharmaceutical Plant EGIS, Hungary) from the norepinephrine-serotonin group has an anti-anxiety and mild antidepressant effect (including in cardiac patients), and is not inferior in effectiveness to diazepam. The manifestation of drowsiness is lower than that of other representatives of the group. Long-term use of the drug is possible (up to 1 year). A special feature is the cumulative effect: after the first dose of the drug, no significant effect is observed, after the 1st week of use the effect increases.
According to the speaker, psychotherapy, especially cognitive behavioral therapy, is of particular importance in the treatment of the disease. However, many patients
refuse this type of treatment due to prejudices and/or reluctance to admit the problem, and therefore pharmacotherapy comes to the fore, which is gradually joined by psychotherapy.
Thus, joint management of the patient by a cardiologist and a psychiatrist, the prescription of pharmacological and psychotherapeutic treatment methods lead to an improvement in the well-being and quality of life of these patients.


The final report “New opportunities for correcting the risk of cardiovascular complications” was made by the session chairman, MD, professor, head of the department of preventive pharmacology of the Federal State Budgetary Institution “National Medical Research Center for Pharmacology” S.Yu. Martsevich.
Hypertension is a risk factor for the development of CVD and mortality from CVD. Modern recommendations (2013) define the main goal of treatment - reducing the risk of developing CVD and mortality from these diseases, achieving target blood pressure values ​​(140/90 mm Hg). The treatment strategy depends not only on blood pressure numbers, but also on risk.
According to modern recommendations, there is the following algorithm for prescribing therapy:
monotherapy is indicated for patients with a low risk of developing cardiovascular complications and low blood pressure;
Combination therapy is indicated for patients with an average and high risk of developing cardiovascular complications, and is prescribed from the first days of treatment.
From the clinician's point of view, it is advisable to prescribe drugs separately, however, an increase in the number of drugs and the spread of the time of their administration reduces adherence to therapy. In this case, it is important to use fixed combinations, which increase compliance and reduce the risk of a doctor prescribing incorrect combinations.
To assess patient adherence to treatment, data from two outpatient registers were used: the 1st register included patients who came for an outpatient appointment in Ryazan, the 2nd register included patients who came for an appointment at a specialized research center (conducted in a medical organization speaker). The analysis showed that there are no reliably significant differences in the choice of treatment strategy for hypertension. However, achievement of target blood pressure was observed 2 times more often in the 2nd register. The analysis showed that the reason was not in the prescribed drugs, but in adherence to treatment. In the 1st register, it was difficult for the clinician to monitor compliance with the treatment regimen by patients. Doctors at the research center had a better understanding of the problem of adherence to therapy and were able to control it. Further analysis showed that 15% of patients in both registries were prescribed a fixed combination; in the remaining cases, doctors prescribed combination therapy with individual drugs.
Professor S.Yu. Martsevich reported on the combination ramipril + amlodipine (Egipres ®, JSC Pharmaceutical Plant EGIS, Hungary), new on the modern pharmaceutical market. According to the speaker, ramipril is not widely known in the Russian Federation, although in the West it is a frequently prescribed drug with a good evidence base. The addition of ramipril to standard therapy for hypertension can significantly reduce the risks of cardiovascular complications (mortality, MI, stroke, etc.).
The objectives of the observational study GRANATE with the participation of several treatment centers were to study the effectiveness and safety of prescribing combination drugs and adherence to therapy with these combination drugs.
The GRANATE-1 study also examined aspects of adherence to antihypertensive therapy in patients with hypertension and MS using the fixed combination ramipril + amlodipine as an example.
The study used an additional assessment method - the Morisky-Green compliance scale, which is a clinical-psychological technique designed for preliminary assessment of compliance and screening identification of insufficiently compliant patients in routine medical practice.
According to the results of the study, in patients with initially low adherence to treatment according to the Morisky-Green scale, due to the possibility of titration (convenient form of drug release, the presence of 4 variants of a fixed combination with different dosages of components), achievement of target blood pressure values ​​​​and regular visits to the doctor, adherence significantly increased in end of the study.
The GRANATE-2 study involved patients with hypertension and COPD who were contraindicated for beta-blocker therapy. In this group of patients, the selection of the drug dose began with minimal dosages with gradual titration. Based on the results of the work, compliance also increased. The importance of adherence to therapy is confirmed by the fact that low compliance leads to worse treatment results, including long-term ones.
In conclusion, Professor S.Yu. Martsevich, relying on the statement of the famous American cardiologist Norman Kaplan “when they talk about poor adherence to therapy, then we need to talk about three players - the doctor, the patient, the medicine,” emphasized that with the right choice of a drug (the doctor’s factor), the possibility of convenient use, good effectiveness, tolerability (drug factor), following the doctor’s recommendations (patient factor) it is possible to achieve good treatment results.