High risk patients

In recent years, the term “high risk patients” has become very popular. A number of publications are devoted to high-risk patients, and Russian and international CVD congresses often hold symposia on this topic. However, there is no common understanding of this term. The high-risk category includes patients of varying severity. For example, in the European guidelines for the prevention of CVD in clinical practice (2007), patients with high clinical risk include both patients with any clinical manifestations of atherosclerosis (coronary, cerebral, peripheral), and those without clinical signs of atherosclerosis. but there is a high risk of its development [91]. In the latest European and Russian recommendations on the diagnosis and treatment of hypertension, high-risk patients include those who have 3 risk factors,MS or sub-clinical lesions of target organs. If hypertensive patients have associated CVD, then they are classified as “very high risk”.

In order to objectively approach the definition of high-risk patients, it is necessary to recall the well-known concepts of the risk factors. There are three strategies for the prevention of CVDs that complement each other and are aimed at minimizing the risk of complications: a population strategy, a high risk strategy and secondary prevention.

The population strategy aims to influence those lifestyle and environmental factors that increase the risk of CVD development among the entire population. A high risk strategy involves identifying people at high risk of developing CVD among patients without clinical manifestations of atherosclerosis and implementing multifactorial prophylaxis. In essence, a high-risk strategy is the same as primary prevention. Thus, the key feature of high-risk patients is the absence of clinical manifestations of atherosclerosis. As for patients with clinical manifestations of atherosclerosis (coronary, cerebral, peripheral vessels), they are the object of secondary prevention, which is aimed at preventing the progression of CVD.

The relevance of a high-risk strategy is determined by the fact that high-risk patients in the total mass of cardiac patients are the overwhelming majority, therefore the main share of complications falls on this group. In this regard, timely identification of patients with high risk and the correct strategy for their management can significantly reduce the incidence of complications. If we talk about the strategy of managing high-risk patients, in recent years there have been major changes, and the importance of the drug component of managing such individuals has increased. Essentially, the principle of management of high-risk patients is the same as patients who already have CVD. For example, if you analyze the treatment strategy patients with stable angina pectoris, it can be noted that it consists of two aspects – the use of drugs to eliminate symptoms (nitrates) and the appointment of means to improve the prognosis (beta-blockers, statins, anti-aggregates).

For high-risk hypertensive patients, a modern management strategy will look similar: use of antihypertensive drugs (to lower blood pressure and improve patient well-being) and administer statins and antiplatelet agents to improve the prognosis. However, the problem of high-risk patients is that, unlike very high-risk patients, they are less motivated for treatment (risk factors do not “hurt”). Therefore, there is a gap between the need for intensive medical treatment and the weak motivation of these patients to treatment. However, this is another problem, and the physician should make every effort to guide these patients in terms of current requirements.

Let us dwell on the most important sections of the drug treatment of high-risk patients.

Antihypertensive therapy

The following chapter describes the main goals and objectives of antihypertensive therapy. Here we only note that high-risk patients, as well as very high-risk patients, need starting combination therapy, that is, quite intensive antihypertensive therapy at the initial stage of treatment.

Starting combination therapy is the key to the rapid achievement of target blood pressure in the majority of patients and significantly improves adherence to therapy. In actual clinical practice, patients with hypertension, most of whom are not motivated for treatment, need to quickly prove the effectiveness of the treatment chosen. Any delay in time associated with changing the dose, drug, or combination of drugs, undermines the patient’s confidence in the treatment and reduces adherence to it.

Lipid-lowering therapy

Recent studies have significantly expanded niches for the use of lipid-lowering therapy. If only recently the expediency of prescribing statins was justified by the presence of cardiovascular diseases, at present, lipid-lowering therapy is also indicated as a means of primary prophylaxis. A convincing evidence of this is the recently completed prematurely large randomized ASCOT – LL study [92]. The ASCOT – LL study on the efficacy of primary prevention of atorvastatin included 10305 patients, 40–79 years old, with moderate arterial hypertension, no history of IHD, but at least 3 risk factors for its development, in addition to arterial hypertension, with moderate hyperlipidemia (total plasma cholesterol <6.5 mmol / l, plasma triglycerides <4.5 mmol / l). In middle-aged patients with arterial hypertension, who, according to the existing recommendations, statin prescription is optional, atorvastatin for 3.5 years significantly reduced the combined risk of nonfatal heart attack and death from coronary heart disease (–36%), the total risk of cardiovascular complications and the need for revascularization ( –21%), risk of coronary complications (–29%), strokes (–27%) and the occurrence of stable coronary artery disease (–41%). In this way,According to the results of the ASCOT – LL study, there is an obvious need for the static use of statins in middle-aged patients with arterial hypertension and additional cardiovascular risk factors – even with normal or slightly elevated levels of atherogenic plasma lipid spectrum. However, in such patients, the positive effect of statins on the prognosis is not as impressive as in those with proven coronary artery disease and severe hyperlipidemia. A meta-analysis published in 2009, which compared statins with placebo, other active therapies or standard treatment of people without CVD, but with risk factors for their development, demonstrated the advisability of statin use in primary prevention. 10 recently completed randomized clinical trials, (70388 people, mean age 63 years,34% of women, 23% of patients with diabetes, the average duration of observation was 4.1 years, the initial LDL level was 3.63 mmol / l.) The primary end point of the meta-analysis was mortality from any cause. The secondary endpoints were: a) a combination of major coronary complications (death from coronary heart disease or nonfatal myocardial infarction), b) a combination of major cerebrovascular complications (fatal and nonfatal stroke). Lipid-lowering therapy significantly reduced overall mortality by 12%. The reduction in the risk of major coronary complications was 30%, of the main cerebrovascular complications – 19%. The risk of developing endpoints did not differ in the further analysis by subgroups depending on age (younger than 65 and over 65), gender, and the presence of diabetes. In this way,This meta-analysis demonstrated the effectiveness of statins in primary prevention of CVD, comparable to the use of statins in secondary prophylaxis in reducing the risk of death from all causes, as well as the main coronary and cerebrovascular complications.

Antiplatelet therapy

A joint analysis of studies, the Antiplatelet Trialist ‘Collaboration, devoted to evaluating the effectiveness of antiplatelet agents in various clinical manifestations of atherosclerosis, showed the possibility of reducing the risk from cardiovascular causes. Acetylsalicylic acid (ASA) was the most popular tool in studies subjected to meta-analysis. Despite convincing evidence of the feasibility of antiplatelet therapy obtained in evaluating many antiplatelet agents, only ASC is recommended as the gold standard. On the one hand, ASA drugs are recognized as the gold standard of antiplatelet therapy, but on the other hand, they cause side effects: gastropathy, gastrointestinal bleeding. Therefore, to ensure a balance between efficacy and safety, minimum doses of ASA (75–150 mg) are recommended.

In recent years, the niche for the use of Aspirin ® has significantly expanded . It has become possible to use this drug in high-risk patients, that is, as mentioned above, individuals without clinical manifestations of atherosclerosis [94]. This is evidenced by the results of a large-scale study, which included 4495 people with at least one of the traditional RF of coronary heart disease – age> 65 years, hypertension, hypercholesterolemia, diabetes, obesity, premature development of myocardial infarction in close relatives. Study participants were randomized to receive either Rowan 100 mg Aspirin ® Cardio or placebo. For 3.5 years of intervention among 2226 who took Aspirin ® 17 people died of cardio-vascular causes, and among 2269, in the control group, 31 patients died of these same causes – a 44% reduction in risk (p <0.05). Currently, in a number of recommendations, aspirin in small doses is recommended as an antiplatelet therapy not only for patients with clinical manifestations of atherosclerosis, but also for persons without clinical manifestations, but with a high risk (risk is more than 10% on the scale).

Nevertheless, according to the general opinion, the ratio of the effectiveness and safety of using aspirin in secondary prophylaxis exceeds a similar indicator when using this drug as a means of primary prophylaxis. In this regard, an individual approach and an assessment of the benefit / risk ratio is required when prescribing aspirin for primary prevention of SSO.

Objectives of antihypertensive therapy

According to current guidelines for the diagnosis and treatment of hypertension, five main classes of anti-hypertensive drugs are currently recommended for the treatment of hypertension: diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists. These classes of drugs are conventionally considered basic, since they have a solid evidence base not only in order to reduce blood pressure, but also to reduce the risk of cardiovascular complications.

Based on the results of international multicenter, randomized studies, we can see that none of these classes of antihypertensive drugs have a significant advantage in terms of reducing blood pressure and preventing the development of MTR. At the same time, the choice of the drug in hypertension is determined by many factors associated with this disease: lesion of target organs , associated clinical conditions, renal pathology, diabetes mellitus, and other diseases. In the new version of the recommendations, when choosing a drug, great importance is attached to pleiotropic (multiple) effects, which will be discussed below. In general, each of the main classes of drugs has its own niche of use.

As for the I1 agonists of the imidazoline receptor and α-adrenoblockers, they are recommended mainly as part of a combination therapy.

Regardless of the choice of drug, it is necessary to achieve the main objective of antihypertensive therapy – to achieve the target level of blood pressure, which is the basis for ensuring the strategic goal of treatment of hypertension – the maximum possible reduction in the risk of SSO.

In the new recommendations for the diagnosis and treatment of arterial hypertension, target blood pressure levels in the treatment of patients with hypertension should be a blood pressure of less than 140/90 mm Hg. In patients with high and very high risk of SSO, it is necessary to reduce blood pressure to 140/90 mm Hg. and less for 4 weeks. In the future, under the condition of good tolerability, a decrease in blood pressure to 130–139 / 80–89 mm is recommended.

In this work, I would like to dwell on the new possibilities of various classes of drugs, as well as the problematic issues of their use, taking into account the pleiotropic effects outlined in modern guidelines.

Beta-blockers and diuretics

Without BB, which have been used in clinical practice since the 60s, it is impossible to provide treatment for a wide range of cardiac diseases, such as hypertension, coronary heart disease, heart failure, tachyarrhythmias. However, in recent years, the issue of negative side effects of BB has been widely discussed. This enabled some researchers to raise the question of restricting their use.

Back in the early 90s, based on an analysis of large-scale studies, it was suggested that the positive side effects of antihypertensive drugs may affect the effectiveness of therapy in the long term [4]. The basis of this assumption is a meta-analysis of placebo-controlled studies on the efficacy of long-term treatment of BB and diuretics from the point of view of preventing SSO [5].

As it is known, BB and diuretics were the first of antihypertensive drugs, which proved to be effective not only in terms of adequate blood pressure control, but also in reducing the risk of MTR. On the other hand, this meta-analysis showed that the existing decrease in the risk of SSO was significantly lower than expected (calculated on the basis of a decrease in blood pressure). This was especially true for CHD. AT the risk of developing coronary artery disease was only 14–16% lower than in the placebo group. Considering that coronary artery disease is the main complication of hypertension, the efficacy of treatment of BB and diuretics was considered insufficient. Among the main causes of this phenomenon were considered and the negative side effects of these classes of drugs that could level the positive effect of reducing blood pressure. The negative effects of BB and diuretics include the worsening of insulin resistance, deterioration of the lipid profile and a decrease in glucose tolerance. Thus, if the positive effect of a decrease in blood pressure competes with the proatherogenic and prodiabetogenic effect of anti-hypertensive therapy, then the risk of developing diabetes increases, and in the long run, the SSO. Further studies have shownthat other classes of drugs – calcium antagonists, ACE inhibitors, ARA are, at least, metabolically neutral. Recently completed large-scale international multicenter studies have convincingly confirmed the validity of the metabolic theory. The frequency of development of type 2 diabetes with the use of calcium antagonist – verapamil SR in an INVEST (International Verapamil SR / Trandolapril Study) study [6], and an ACE inhibitor – lisinopril in a study of ALLHAT [ 7] and ARA-losartan in the LIFE (Losartan Intervention for Endpoint reduction) study [8] was significantly lower than in the group of patients who received BB and diuretics. Moreover, a meta-analysis of 22 studies published in 2007 that included more than 160,000 patients showedthat the use of BB and diuretics is associated with a higher risk of developing diabetes than placebo. In the same meta-analysis, it was revealed that the lowest risk of developing diabetes is observed when using ACE inhibitors and ARA [9].

The subject of negative side effects of some BB (mainly atenolol) and diuretics is currently being used by some scientists to limit their use in clinical practice. For example, a number of authors propose to completely remove BB from the arsenal of drugs used to treat patients with uncomplicated hypertension, leaving this class of drugs only for the purposes of secondary prevention of diseases [10]. Experts of the British recommendations for the treatment of hypertension, issued in 2006, went further than that in this regard. In them, they recommend using BB as a fourth-line treatment for treating hypertension [11]. How to be a practical doctor in this situation?

The recent criticism of the BB by individual researchers should not be misleading as a practical doctor. He should always ask himself what kind of BB are we talking about. Indeed, a number of BB, especially non-selective, have negative metabolic effects and in a number of clinical situations (metabolic disorders, COPD, peripheral atherosclerosis) cannot be used. At the same time, modern superselective BBs do not have these negative effects and can be widely used in clinical practice, including those with uncomplicated AH.

Thus, regarding the use of BB in clinical practice, it is necessary to take a flexible position. This is the opinion of experts from the European and Russian recommendations for the treatment of diagnosis and treatment of hypertension. These documents noted that modern BB have a less pronounced negative effect on metabolism. This number of BB includes, as is known, metoprolol, nebivolol, bisoprolol, carvedilol.

For example, bisoprolol has a solid evidence base regarding its metabolic neutrality: lack of influence on the lipid and carbohydrate profile. Moreover, in a recent randomized study in 92 patients with hypertension and compensated type 2 diabetes, bioprolol, like captopril, did not adversely affect glycated hemoglobin, fasting sugar and 2 hours after the glucose tolerance test.

Of particular interest is nebivolol with additional vasodilating effect by increasing the synthesis of NO. First of all, it should be noted good antihypertensive efficacy and tolerance of nebivolol. It has a prolonged effect and at the same time provides uniform control of blood pressure throughout the day, which is the most important requirement of modern antihypertensive therapy. This is evidenced by the 90% value of the ratio of the residual hypotensive effect to the maximum (T / P). The data of foreign and domestic studies convincingly demonstrate the improvement of endothelial function in the treatment of people with hypertension with nebivolol [95-97].

Moreover, in our own open-label study, in 25 patients with mild and moderate hypertension, positive microcirculatory effects of Nebivolol (Nebilet, Berlin-Chemie, Germany) were revealed. The study of microcirculation was carried out using laser Doppler flowmetry on a LAKK-01 apparatus by Lazma, Russia. Laser Doppler flowmetry (LDF) is a simple and safe method for studying microcirculation and indirect assessment of endothelial function. The method allows to investigate changes in blood flow in the microvasculature using laser radiation, using the Doppler effect. The LDF method is objective, accurate and gives reproducible results.

The most important parameters for assessing the state of microcirculation are the microcirculation index (PM) and the capillary blood flow reserve (RCM). PM is formed as a result of the reflection of a laser signal from erythrocytes moving at different speeds in the arterio- lar, capillary and venu- lar parts of the microvasculature. The decrease in PM occurs with spasm bringing reduction of the number of functioning capillaries and desolation of the arteriolar microcirculation link (MC), or with a decrease in the speed of red blood cells, i.e., with symptoms of stasis. An increase in PM occurs when the arterioles tone decreases and the blood supply in the microcirculation system increases. PM is calculated in perfusion units (perf. Units). RSC, expressed as a percentage, is calculated by the ratio of the maximum PM to the initial PM. RCC reflects the microvascular reactivity. A decrease in RSC is observed both with an increase in the inflow into arterioles and an increase in the number of functioning capillaries, as well as with stasis and stagnation. An increase in RSC is noted in spastic phenomena, when initially the majority of microvessels are in a non-functioning state,but retains the ability to expand in response to stress (in this case, clamping the cuff). The parameters of PM and RSC are determined by the hemodynamic type of microcirculation, which is an integral indicator for assessing the functional state of microcirculation. Normocirculatory, spastic, hyperemic, and congestive-stasis hemodynamic types of microcirculation are distinguished.

After Nebilet therapy in the group of patients with spastic type of MC (14 people), there was a marked increase in the microcirculation index. PM before treatment was 3.4 ± 0.3; after treatment – 7.2 ± 0.8 perf.ed, p <0.05. This indicates an improvement in blood flow in the microcirculation system. This is also evidenced by the dynamics of the RSC. As a result of treatment, the initially elevated RCC decreased by 30.6% (p <0.001). These changes indicate a decrease in spastic phenomena, an increase in the number of functioning capillaries and an improvement in tissue perfusion.

In patients with hyperemic type of MC (8 people) while receiving Nebivolol there was a decrease in PM from 7.2 ± 1.1 perf. units up to 4.0 ± 0.6 perf. units (p <0.05). In this case, a decrease in PM can be regarded as a positive moment since this indicates a decrease in the phenomena of hyperemia. In addition, in this group of patients, there was an increase in the initially reduced RCC by 36.8% (p <0.001). This may be due to a decrease in excess blood filling in the arteriolar circuit of the ICR. Thus, the use of Nebivolol led in general to an improvement in the microcirculation system in patients with AH. Of course, the positive microcirculatory effects of Nebilet are a consequence of the vasodilating properties of this drug.

Thus, the emergence of super-selective beta-blockers significantly expanded the boundaries of their use, and the practitioner should be more boldly prescribed in various clinical situations, including in the case of the metabolic syndrome and diabetes.

The same ambiguous approach is necessary when prescribing diuretics in clinical practice. Appointment of diuretics, of course, requires consideration of their negative metabolic effects, especially characteristic of high doses [17]. However, in some situations it is necessary to be guided by clinical expediency. Diuretics have been and remain indispensable means of treating hypertension complicated by CHF. In hypertension and concomitant renal failure, the appointment of loop diuretics is indicated. In these situations, diuretics can be given in high doses, since the clinical relevance outweighs the risk of exacerbating metabolic disorders. However, with uncomplicated hypertension, especially in the presence of concomitant metabolic disorders, it is better to avoid prescribing high doses of thiazide diuretics because of the increased risk of diabetes, as was shown in large-scale studies. The same applies to patients with hypertension and diabetes,since the use of high doses of diuretics may increase the risk of developing vascular complications. In these situations, it is better to use a metabolically neutral indapamide. In addition, thiazide diuretics in low doses do not adversely affect metabolism, but they enhance the effects of almost all classes of antihypertensive drugs.

The use of calcium antagonists in clinical practice

Calcium antagonists, currently widely used in cardiological practice, are one of five classes of antihypertensive drugs, whose effectiveness has been proven in both placebo-controlled and comparative studies with end-point studies. The first study where calcium antagonists showed comparable efficacy with diuretics and BB in reducing the incidence and mortality from CVD was the Swedish study STOP Hypertension-2 (Swedish Trial in Old Patients with Hypertension). In 6614 patients who received either a dihydropyridine calcium antagonist (felodipine or isradipine), or a diuretic and / or BB, or an ACE inhibitor (enalapril or lisinopril), the effectiveness of these antihypertensive drugs was comparable.In general, no differences were established between them in terms of their impact on mortality from CVD [18]. Similarly, in a large-scale randomized study INSIGHT (Intervention as a Goal in Hypertension Treatment), in which 6321 patients with moderate and high AH for 4 years studied the effectiveness of prolonged nifedipine and diuretics (25 mg of hydrochlorothiazide in combination with 2.5 mg of amiloride), there were no significant differences between the groups by the primary end points (MI + stroke + death from CVD) and total mortality. In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.in a large-scale randomized study INSIGHT (Intervention as a Goal in Hypertension Treatment), in which 6321 patients with moderate and high AH for 4 years studied the effectiveness of prolonged nifedipine and diuretics (25 mg of hydrochlorothiazide in combination with 2.5 mg of amiloride ), there were no significant differences between groups on the primary endpoints (MI + stroke + death from CVD) and total mortality. In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.in a large-scale randomized study INSIGHT (Intervention as a Goal in Hypertension Treatment), in which 6321 patients with moderate and high AH for 4 years studied the effectiveness of prolonged nifedipine and diuretics (25 mg of hydrochlorothiazide in combination with 2.5 mg of amiloride ), there were no significant differences between groups on the primary endpoints (MI + stroke + death from CVD) and total mortality. In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.in which 6321 patients with moderate and high AH over 4 years studied the effectiveness of prolonged nifedipine and diuretics (25 mg of hydrochlorothiazide in combination with 2.5 mg of amiloride), no significant differences were found between the groups on the primary end points (MI + stroke + death from CVD) and total mortality. In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.in which 6321 patients with moderate and high AH over 4 years studied the effectiveness of prolonged nifedipine and diuretics (25 mg of hydrochlorothiazide in combination with 2.5 mg of amiloride), no significant differences were found between the groups on the primary end points (MI + stroke + death from CVD) and total mortality. In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.In the same study, the most important data on the beneficial effects of nifedipine-GITS on metabolism were obtained. In the treatment group with this drug, the incidence of type 2 diabetes was significantly lower than in patients treated with diuretics.

Calcium antagonists are one of the most effective classes in terms of prevent the development of cerebral strokes. This is evidenced by a meta-analysis of large-scale studies. In this respect, the study of NORDIL stands out. This is the only study that demonstrated a statistically significant reduction in MI against the background of the use of a calcium antagonist compared with BB and diuretics. In the indicated randomized prospective study, which lasted 5 years and included 10881 previously untreated patients with hypertension aged 50- 74 years, compared the effectiveness of diltiazem (180-360 mg per day) and BB or diuretics. The frequency of the primary endpoints (total, including strokes, myocardial infarction, and death from other cardiovascular causes) was the same in both treatment groups. At the same time, the frequency of fatal and nonfatal MI was significantly lower in the diltiazem group (–20%, p = 0,04), despite the fact that the degree of blood pressure reduction in this group was slightly less than in the BB group or diuretics (–20.3 / 18.7 mm Hg vs. –23.3 / 18.7 mm Hg). Art.), which researchers explain is not sufficiently high dosage of diltiazem [21]. A possible explanation for the effectiveness of diltiazem in the prevention of stroke is the anti-atherogenic effect of the drug and the ability to reduce the activity of the SNA. Thus, in the VHAS study (Verapamil in Hypertension and Atherosclerosis Study), the same frequency of MTR was found in the treatment of Verapamil-SR and 1414 patients with hypertension with chlorthalidone. However, Verapamil-SR was superior to chlorthalidone in slowing the thickening of the carotid intima media (p <0.01) with a comparable decrease in blood pressure.3 / 18.7 mm Hg Art. against –23.3 / 18.7 mm Hg Art.), which researchers explain is not sufficiently high dosage of diltiazem [21]. A possible explanation for the effectiveness of diltiazem in the prevention of stroke is the anti-atherogenic effect of the drug and the ability to reduce the activity of the SNA. Thus, in the VHAS study (Verapamil in Hypertension and Atherosclerosis Study), the same frequency of MTR was found in the treatment of Verapamil-SR and 1414 patients with hypertension with chlorthalidone. However, Verapamil-SR was superior to chlorthalidone in slowing the thickening of the carotid intima media (p <0.01) with a comparable decrease in blood pressure.3 / 18.7 mm Hg Art. against –23.3 / 18.7 mm Hg Art.), which researchers explain is not sufficiently high dosage of diltiazem [21]. A possible explanation for the effectiveness of diltiazem in the prevention of stroke is the anti-atherogenic effect of the drug and the ability to reduce the activity of the SNA. Thus, in the VHAS study (Verapamil in Hypertension and Atherosclerosis Study), the same frequency of MTR was found in the treatment of Verapamil-SR and 1414 patients with hypertension with chlorthalidone. However, Verapamil-SR was superior to chlorthalidone in slowing the thickening of the carotid intima media (p <0.01) with a comparable decrease in blood pressure.A possible explanation for the effectiveness of diltiazem in the prevention of stroke is the anti-atherogenic effect of the drug and the ability to reduce the activity of the SNA. Thus, in the VHAS study (Verapamil in Hypertension and Atherosclerosis Study), the same frequency of MTR was found in the treatment of Verapamil-SR and 1414 patients with hypertension with chlorthalidone. However, Verapamil-SR was superior to chlorthalidone in slowing the thickening of the carotid intima media (p <0.01) with a comparable decrease in blood pressure.A possible explanation for the effectiveness of diltiazem in the prevention of stroke is the anti-atherogenic effect of the drug and the ability to reduce the activity of the SNA. Thus, in the VHAS study (Verapamil in Hypertension and Atherosclerosis Study), the same frequency of MTR was found in the treatment of Verapamil-SR and 1414 patients with hypertension with chlorthalidone. However, Verapamil-SR was superior to chlorthalidone in slowing the thickening of the carotid intima media (p <0.01) with a comparable decrease in blood pressure.01) with a comparable decrease in blood pressure.01) with a comparable decrease in blood pressure.

In the above-mentioned INSIGHT study among patients receiving nifedipine, there was a more pronounced slowing down of the intimal thickening of the carotid arteries than among patients treated with diuretics . In turn, the antiatherogenic effect attributable to calcium antagonists is associated with the ability of this class to correct endothelial dysfunction. This is evidenced by numerous clinical studies, including those performed at a high methodological level in the evaluation of the endothelial function .

The antiatherogenic effect of calcium antagonists is reflected in the new European guidelines for the diagnosis and treatment of hypertension: one of the most important niches for the use of calcium antagonists (both dihydropyridine and non-dihydropyridine) is associated with atherosclerosis of various localization vessels , including coronary . In addition, general indications for the use of all calcium antagonists are hypertension of various origins, arresting hypertensive crises, as well as prevention and relief of angina attacks of various nature (including vasopasmodic angina).

In conclusion, I would like to draw the attention of practitioners to one of the most important aspects of the use of calcium antagonists in clinical practice: the division of this class of drugs into two large subgroups based on their impact on the SNA, dysregulation of which plays an important role not only in raising and maintaining arterial levels – but also in the occurrence of a number of other negative effects , which significantly increase the risk of cardiovascular complications. . The first subgroup is the so-called pulse-reducing calcium antagonists (Verapamil and Diltiazem). These drugs reduce myocardial contractility, reduce the heart rate, and also have an anti-arrhythmic effect and slow down atrioventricular conductivity. Due to these properties, the drugs improve the function of the autonomic nervous system, restoring the balance between the sympathetic and parasympathetic nervous systems and reduce the myocardial oxygen demand . The second subgroup is pulse rate-increasing calcium antagonists, or dihydropyridines. In these drugs, the ability to cause dilatation of peripheral arteries prevails, as a result of which the SNS reflexively increases and the heart rate increases. . According to the results of numerous studies, on the basis of this, there are differences in the efficacy of dihydropyridine and non-dihydropyridine AK in different clinical situations. Pulse-reducing non-dihydropyridine calcium antagonists are effective and safe for treating various forms of coronary artery disease, whereas dihydropyridine calcium antagonists cause undesirable effects in acute conditions such as unstable angina and acute myocardial infarction, most likely due to SNA activation. . For example, in the HINT study (Holland Inter-University Nifedipine Trial), it was shown that intravenous administration of the short-range dihydropyridine calcium antagonist nifedipine resulted in a rate of adverse outcomes (recurrent ischemia and myocardial infarction) during the first 48 hours.(from the moment of hospitalization) was significantly higher than at using metoprolol . Another study demonstrated an increase in early mortality in these patients during therapy with nifedipine compared with nitrates and / or BB . In contrast, the diltiazem administered intravenously non-dihydropyridine calcium antagonist significantly reduced the incidence of some adverse outcomes (angina attacks, ischemic changes in the myocardium on the ECG) during the first two days and exceeded intravenous nitroglycerin in its efficacy . The use of dihydropyridine calcium antagonists (prolonged preparations) should be limited to cases of vasospastic angina pectoris and stable exertional angina pectoris.

It is no coincidence that the European recommendations for the control of hypertension emphasize the clinical significance of the division of calcium antagonists into two groups: dihydropyridine and non-dihydropyridine . In addition to the general indications for the use of these two subgroups of drugs, non-dihydropyridine calcium antagonists have an additional indication – treatment of tachyarrhythmias, as a fact indicating the sympatolytic effect of this subclass of calcium antagonists.

HOPE study results

The results of the HOPE and EUROPA study suggest a new clinical direction in the use of ACE inhibitors to slow the progression of atherosclerosis-related diseases. However, if we strictly rely on the principles of evidence-based medicine, we can talk about the protective effect of perindopril in treating patients with stable ischemic heart disease (CHD) and the universal protective effect of ramipril in treating all patients with clinical manifestations of atherosclerosis (CHD, strokes, peripheral atherosclerosis). Can the protective effect of ramipril and perindopril, associated with slowing the progression of atherosclerosis, be transferred to the entire class of ACE inhibitors? The answer must be negative, because in relation to other drugs in this regard there is no evidence base. Moreover,in the placebo-controlled PEACE study involving 8290 patients with stable angina without signs of heart failure, the addition of 4 mg of trandolapril during basic therapy did not lead to an additional reduction of complications [53]. Similarly, in the placebo-controlled study CAMELOT, which involved 1991 patients with stable coronary artery disease without signs of heart failure, the addition of 20 mg of enalapril to the main therapy did not lead to a more pronounced decrease in complicationswhich involved 1991 patients with stable coronary artery disease with no signs of heart failure, the addition of 20 mg of enalapril to the main therapy did not lead to a more pronounced decrease in complications compared with the patientwhich involved 1991 patients with stable coronary artery disease with no signs of heart failure, the addition of 20 mg of enalapril to the main therapy did not lead to a more pronounced decrease in complications compared with the patient placebo therapy . It is not by chance that only ramipril and perindopril are recommended in the European guidelines for the diagnosis and treatment of stable angina for these patients in terms of slowing the progression of the disease and improving the prognosis of this category of patients from an ACE inhibitor [55]. Similarly, in the second revision of the Russian recommendations on chronic heart failure for the prevention of this disease in patients with coronary artery disease, the prescription of either ramipril or perindopril is recommended as having an evidence base [35]. Moreover, ramipril has an evidence base in relation to the anti-atherogenic effect. The SECURE study, which was carried out within the framework of HOPE, studied the effect of ramipril and vitamin E on the condition of the carotid arteries, examined using the ultrasound method. Was shown,that long-term ramipril therapy delayed the progression of carotid atherosclerosis in patients with atherosclerosis or diabetes mellitus who did not have heart failure [56]. Largely due to this research, in the latest European guidelines for the treatment of AH 2007, a new niche for the use of ACE inhibitors has appeared – a concomitant terosclerosis of the carotid arteries . In another program MICRO-HOPE in the framework of the study NORE in 3577 patients with type 2 diabetes mellitus ramipril reduced the risk of microvascular complications of diabetes mellitus, such as chronic renal failure by 24% (p = 0.027) and retinopathy by 22% (p = 0.024) [57]. In a double-blind, randomized trial of AASK, a pronounced nephroprotective effect of ramipril was demonstrated. In the case of 1094 patients with hypertensive nephropathy (glomerular filtration rate (GFR) within 20–65 ml / min), ramipril at a dose of 2.5–10 mg is more effective than amlodipine and metoprolol slowed the decrease in GFR, the development of chronic renal failure and prolonged the life of patients [58]. Thus, the above studies indicate a powerful vazoprotective effect of ramipril, which has important clinical significance. In clinical practice, in addition to the traditional use of ramipril in hypertension and heart failure,It is necessary to provide patients with practically any manifestations of atherosclerosis – coronary, cerebral and great vessels, as well as patients with nephropathy. At present, an effective generic generic of ramipril – charter has appeared on the Russian pharmaceutical market. A preliminary analysis of a recently completed proprietary study indicates a high antihypertensive efficacy and safety of the charter. Summing up, the overview of international and Russian data presented above makes it possible to take a fresh look at the possibilities of an ACE inhibitor. Traditional niches for the use of ACE inhibitors (hypertension, cardiac insufficiency, diabetic nephropathy) have expanded in recent years thanks to the powerful vasoprotective effect of ACE inhibitors, which opens up new clinical possibilities for their use – in terms of slowing the progression of diseasesassociated with atherosclerosis. At the same time, it is necessary to understand that this effect is not inherent in the whole class of drugs, but is characteristic only of ramipril (charter) and perindopril. At least, based on evidence from evidence-based medicine, a protective effect on the progress of cardiovascular diseases can only be talked about these two drugs.

Atherosclerosis – the silent killer

Atherosclerosis, a chronic disease of the arteries that is accompanied by cholesterol deposition, is the gray cardinal of death, a silent killer that people, alas, underestimate. At the age of 30, 40% of Russians already have atherosclerotic lesions. At the age of 40, 50% already have pronounced atherosclerotic lesions. In 60 years, 70% of people have pronounced manifestations of atherosclerosis.

But in most cases, the course of atherosclerosis is asymptomatic. As long as the 70% plaque does not overlap the vessel, there will be no complaints. This is the case when “suddenly”, against the background of complete health, a person enters the hospital with an infocalct or stroke. But this is not “all of a sudden”, but because all people’s reserve capacities are very large and the vessels can carry the load for a long time.

“The main thing is the state of the vascular wall,” explains Alexey Chudinov. – From the outside, the vessel is smooth, like plastic. And if pure cholesterol is passed through this vessel, then cholesterol is not deposited there. Therefore, the discovery made was so important: even if the cholesterol is high, but the vascular wall is in a normal state – cholesterol plaques will not form there. But if microdamages appear on the vascular wall, then vascular plaques begin to form on these microcracks even with normal cholesterol.

What damages the vessels

The main aggravating factors that cause vascular damage are hypertension, diabetes, smoking, alcohol, obesity, a sedentary lifestyle, and taking various medications, often uncontrolled.

“Also, microdefects of blood vessels cause free radicals, saturated fatty acids, aggressive environmental factors, various additives and toxic components that are found in our food today,” Alexey Chudinov continues. – For example, in meat – in fat beef and pork – there are two main unhealthy fats – cholesterol and saturated fatty acids. When saturated fatty acids are subjected to heat treatment, they turn into aggressive factors that cause damage to the endothelium of the vessel. Not immediately, but the more meat there is, the higher the risk of damage to the blood vessels. With age, the vessel becomes rough and atherosclerotic plaques begin to deposit on it.

Headache – a sign of atherosclerosis?

“Atherosclerosis has been modified,” says Alexei Chudinov. – Even 25-30 years ago, we found plaques in large vessels – in the carotid artery, in the aorta, and so on. But now plaques affect even small capillaries, including the brain. Those people who suffer from headaches, dizziness, memory loss, should know that this is primarily a sign that the small vessels are no longer working, that is, they are amazed. After all, intracerebral vessels have a thinner endothelium.

All our organs and tissues, primarily the heart, liver, brain – have a phospholipid membrane, a membrane that protects our cells from damage. When a person constantly uses saturated fatty acids, this saturated fat has the same ability as a dishwashing detergent that destroys fat on a plate. It destroys the phospholipid membrane of brain cells, cardiac cells, liver cells. Two clinical studies of the Institute of Nutrition of the Russian Academy of Medical Sciences proved that excluding saturated fatty acids from food reduces the risk of death by 22%, and the incidence of heart attacks and strokes by 18%. The same studies proved that if a person had a heart attack or stroke, then most likely this condition will recur within 5 years. But if a person switches to a healthy lifestyle, the risk of their recurrence is reduced by 80%.

IMPORTANT

5 principles of a healthy lifestyle (according to the latest scientific data)

1. Proper nutrition – the elimination of cholesterol and saturated fatty acids.

That is, try to eat less or completely abandon the fried meat, especially red and fatty – lamb, marbled beef. Less baking with margarine. Do not fry anything in butter. Try to switch to lighter dairy products (for example, reject cream, hard varieties of cheese).

Try to prepare food in a good mood, do not sort things out in the kitchen, otherwise the kitchen will automatically be perceived as an unpleasant place, and the absorption of food will be worse.

2. Active lifestyle, which raises good cholesterol.

Good cholesterol rises only in one case – if the person is actively moving. Nothing else raises good cholesterol – neither drugs, nor food. After all, the body, in addition to external influence, synthesizes its own cholesterol.

Therefore, vegetarians are not always the right level of cholesterol in the blood. For example, in India, people practically do not eat meat, but still suffer from cardiovascular diseases, atherosclerosis. Our body produces its own endogenous cholesterol, and we have the so-called cholesterol metabolism receptors. As soon as cholesterol levels fall below normal, endogenous cholesterol synthesis increasya And even without eating meat, vegetarians can have quite high cholesterol due to endogenous internal cholesterol.

In order to compensate for this, there is one single way – an active lifestyle, that is, at least a person must move and walk a lot. But not to do grueling physical exertion – they also lead to an increase in cholesterol levels.

3. Freedom from stress and tension.

In addition to food containing saturated fatty acids, damage to the vascular endothelium causes stress. Stress is not what happens to us, but our reaction to situations. Only by remaining calm can we solve problems and difficulties. And only in this case our vessels will remain undamaged by stress.

4. Full sleep.

During a long (at least 8 hours) sleep, cholesterol levels are reduced. Vascular endothelium is restored. Alas, 45% of people today have trouble sleeping. The reason follows from the previous one – anxiety during the day.

5. Acceptance of omega-3 fatty acids.

These substances help the cells of the blood vessels to recover, stay elastic longer. They are contained in nuts, unrefined vegetable oils, wheat sprouts, oily fish.

TWO DIMENSIONAL ECHOCARDIOGRAPHY

Ultrasound is reflected from boundaries tissue deforms piezoelectric crystal and generates electric sky pulse which transformed at the point on the screen .

Brightness and position points depends on from of character and depths investigated structures .

For create two-dimensional Images ultrasonic Ray skipped through region interest . Ultrasound is transmitted along several (90-120) lines scanner of by wide ( about 90 ° ) arc up to20-30 times at second.

Summation reflected ultrasound waves form beats picture on the screen . Fast generation after respectable of images creates ” Living “ picture movable structures . Any frameliving Images can be “Frozen”, analyzed on the screen or printed out on thermal paper .

Two-dimensional Echocardiography allows to study anatomy hearts and relationship different structures .

With two-dimensional cardiography possibly revealing intracardiac formations and pathologies pericardium , visualized motion walls ventricles and leaflets valves .

Also spend measurement thickness walls wish daughters and sizes cameras, computed shock volume fraction emission and cordial overshoot .

Two-dimensional picture use at quality orientation shooting gallery at research at M – mode , and also at doppler – echocardiography for installations control volume .

Parasternal position along the long axis

2D echocardiography not It allows you to directly Rate Vat diastolic function of the left ventricle , however, may reveal associated with It LVH , violations of local by kratimosti , infiltrative diseases myocardium or thickening of the leaves of the pericardium . Alongside with diastolic dysfunction can be detected violation sistoliche tion function of the left ventricle . Special features Diastolic the blood flow ka of LP at LV can be studied with using pulse doppler – echocardiography . For of this control volume is set on level of the cusps of the mitral valve at apical four- position . This study allows to obtain a spectrum of good quality transmitral blood flow .

AT Normally transmitral bloodstream has the following characteristics ( Fig . 6.6, A).

.       Peak passive early diastolic Napoli nenie LV .

.       Peak BUT – active later diastolic Napoli nenie LV .

.       Ratio E / A— > 1.

With LV relaxation disorder at connections gipertro fiey or myocardial ischemia an increase in peak BUT and reduction peak E . With In this respect, the E / A ratio becomes less than 1 ( Fig . 6.6, B). Time deceleration of peak E is lengthened (> 220 ms ).

Have patients older than 50 years for confirmation dia stolicheskoy dysfunction required reduction ratio E / A of less than 0.5 in connections with normal increase am plitudy peakBUT with of this age . This type diastema netocrystalline dysfunction received the title of ” slow relaxation ” and reflects reduced LV compliance . With This is marked by an increase in the pre- rhythm systole contribution . at filling the ventricle .

With tackle extensibility infarction due infiltrative disorders or constrictive pericarditis peak E becomes very high , and the peak BUT low . Time deceleration peak E ukorachi INDICATES (<150 ms ). These violations diastole include to restrictive type and reflect an increase in diastolic pressure of course at LV . Filling of the ventricle occurs quickly. atearly diastole , when this contraction schenie atrial unable longer stretch of LV .