Layout 1 Thematic Section: Advances in Musculoskeletal and Neuromuscular Rehabilitation Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 Arterial Hypertension (AH) is a well-known predisposing factor for pathological changes in various organs and tissues that lead to atherothrombotic diseases, such as, ischemic heart disease (IHD), unstable angina, Acute Myocardial Infarction (AMI), and stroke.1 In AH patients, structural and functional disorders have been detected in all parts of the circulation, from microvessels to large vessels, including the aorta and Coronary Arteries (CA).2,3 Among the possible mechanisms of AH’s influence on atherogenesis are increased vascular permeability and adhesiveness of endotheliocytes, oxidative stress, and activation of inflammatory processes by angiotensin II (ATII). Results include endothelial dysfunction with weakening of endothelium-dependent vasorelaxation, accumulation of oxidized forms of Low Density Lipoproteins (LDL) in the subendothelial space, migration of smooth muscle cells and formation of atheroma that can be subjected to calcification and ulceration.4-6 AH is one of the factors that destabilize atherosclerotic plaque, and sudden rupture of atherosclerotic plaque in CA or carotid arteries likely results in AMI or stroke, respectively.7,8 Natali et al. reported that 41% AH and IHD patients had three-vessel CA disease according to coronary angiography data, and that their index of CA stenosis was 19% higher as compared to patients without AН.9 In AH patients, the average cardiovascular death rate was significantly higher after 96 months.9 In a follow-up study, the risk of developing non-fatal AMI in AH patients who underwent AMI was 21% higher than in patients without AH.9 The epidemiological study “ERSPECTIVE” (Perspective of antianginal therapy in Russian Federation, n=2768) car- ried out in 2012-2013 found that 91.3% of patients with angina pectoris had AH.10 Notably, AH had been dia- Abstract The clinical effectiveness of physical training in a Cardiac Rehabilitation Program (CRP) was assessed in hypertensive (Arterial Hypertension, AH), post-Myocardial Infarction (MI) patients. 206 patients were randomized into a physically trained group (PhTG, n=102) and an untrained, control group (CG, n=104). All patients received standard drug therapy. PhTG patients performed mild callisthenic exercises and moderately intensive bicycle exercise three times/week for one year. Compared to control patients, PhTG patients had significant changes in exercise capacity (duration +38%, p<0.001; total work +63.6%, p<0.001); rate-pressure product (-8.2%, p<0.01); left ventricular ejection fraction (+7.6%, p<0.001); left ventricular stroke volume (+5.1%, p<0.01). Resting BP decreased in PhTG patients (systolic BP, -3.1%, p<0.05; diastolic BP, -3.5%, p<0.001), but increased in CG patients (systolic BP, +3.1%, p<0.05; diastolic BP +3.4%, p<0.05). PhTG patients had fewer myocardial ischemic episodes, including painless ischemia during exercise, fewer angina attacks, less nitroglycerin consumption, improved quality of life, fewer cardiovascular events (-50%, p<0.05), and days of absence from work (-43.2%, p<0.05). Thus, supplementing a CRP with moderate exercise improved BP, work capacity, cardiac function, and quality of life in hypertensive, post-MI patients. Key Words: arterial hypertension, myocardial infarction, rehabilitation, cardiovascular bioindicators, physical exercise. Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 Effects of moderate physical training program in post-myocardial infarction patients with arterial hypertension David M. Aronov,1 Marina G. Bubnova,1 Nadezhda P. Lyamina,2 H. Fred Downey,3 Eugenia B. Manukhina,3,4 Svetlana V. Lyamina5 1National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russian Federation; 2Moscow Regional Research and Clinical Institute, Moscow, Russian Federation; 3Institute of General Pathology and Pathophysiology, Moscow, Russian Federation; 4University of North Texas Health Science Center, Fort Worth, Texas, USA; 5Russian University of Medicine, Moscow, Russian Federation. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (CC BY-NC 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. - 267 - Effects of moderate physical training program in post-myocardial infarction patients with arterial hypertension Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 gnosed 4.1 ± 0.2 years before the appearance of angina pectoris. In 61.6% of AH patients, the level of average Blood Pressure (BP) remained higher (146/88 mmHg) than the recommended target ranges, despite treatment with two or more antihypertensive drugs.10 According to the CLARIFY register (prospeCtive observational Lon- gitudinAl RegIstry of patients with stable coronary arterY disease), which included 33 000 patients with stable IHD in 45 countries, AH occurred in 71.1%.11 Clearly, the degree of AH control in post AMI patients would directly affect the clinical course of the disease and its prognosis. Prior studies have shown beneficial effects of Physical Training (PhT) in patients with cardiac dis- ease, including AH.12-17 However, these studies did not specifically evaluate the effects of PhT in AH patients fol- lowing AMI. Thus, the current study was designed to eval- uate in working patients with AH, the clinical efficacy of a one-year PhT rehabilitation program. Materials and Methods The study was carried out in accordance with Good Clin- ical Practice standards and with the Helsinki Declaration principles. Written informed consent was obtained from all participants of this study. Ethics Committee of the Na- tional Medical Research Center for Therapy and Preven- tive Medicine, Moscow, Russian Federation, approved the Study Protocol on March 19, 2015 (Protocol #3). 206 working patients, men<60 and women <55 years old, who had had ST-elevated AMI, and performed thrombol- ysis, between three and eight weeks previously were in- cluded in this randomized clinical study involving 10 medical centers from 10 Russian Federation cities. Pa- tients were randomized prospectively into two groups: a physically trained group (PhTG, n=102), who participated in a PhT rehabilitation program in addition to standard medical therapy, and a control group (CG, n=104), who received only standard medical therapy. Medical therapy included b-Adrenergic Blockers (bAB), antiplatelet drugs, Angiotensin-Converting Enzyme (ACE) inhibitors, statins, diuretics and nitrates. Patient records revealed no systematic difference in drug therapy between the groups. The study lasted for one year. Three times per week, PhTG patients performed mild cal- listhenic exercises and trained on a stationary bicycle at an intensity of 50-60% of their respective maximal power value (MxP, W), as determined pre-study by a cycle er- gometry test (CE-test). The CE-test was performed on a bicycle ergometer with an increase of 25 W every 3 min from the initial exercise power of 25 W until clinical or ECG criteria for stopping the exercise was observed, or until submaximal Heart Rate (HR)18 was reached, i.e., the maximal CT-test power value (MxP, W). Other CE-test values included i) exercise time (ET; min); ii) Threshold Power (ThP, W); iii) total work (ToW, kJ) computed by ThP × ET × 60/1000; iv) Rate-Pressure Product (RPP, units) computed by (HR× systolic BP)/100. The CE-test was performed on all subjects at the beginning of the study and at one year. Prior to the CE-test, BAB and nitro-drugs were withheld 48 and 24 hours, respectively. The potential therapeutic benefits of the physical rehabilitation program were assessed by comparing clinical, instrumental, and la- boratory data at 1 year with pre-study data and with re- spective CG patient data. Clinical data included medical history, physical examina- tion, measurements of BP and HR, and calculation of body mass index (BMI, kg/m2). Instrumental examination in- cluded standard ECG during and after the CE-test to de- termine rhythm disturbances and the number of ST-segment depressions (symptomatic or silent) ≥1 min. While clinical variables were monitored during the study, only values recorded before and at the conclusion are pre- sented in this report. Echocardiography (EchoCG) was performed to determine cardiac linear and volume parameters: maximum transverse Left Atrium (LA) dimension, LV End-Diastolic Volume (EDV) and End-Systolic Volume (ESV), Interventricular Septum Thickness (IST) at end-diastole, LV end-diastolic and systolic posterior wall thickness, LV ejection fraction (EF, Simpson method), LV ventricular ejection (VE), max- imal transmitral flow at beginning of P wave (E peak) and during atrial systole (A peak) and the E/A ratio. Stroke vol- ume was computed from the difference between LV EDV and LV ESV and then multiplied by heart rate to compute cardiac output. Total Peripheral Resistance (TPR) was cal- culated from mean arterial pressure divided by cardiac out- put. Cardiac index was computed by dividing cardiac output by estimated body surface area. Laboratory testing was performed after 12-14 hr fasting. These tests included determination of total cholesterol (TC, mmol/L) and triglycerides (TG, mmol/L) using a “Mars” autoanalyzer (Korea) with enzymatic diagnostic kits. High-density lipoprotein cholesterol (HDL-C, mmol/L) was detected by the same method as for TC measurement in the supernatant after LDL and very low- density lipoproteins (VLDL, mmol/L) precipitation with mix of sodium phosphotungstate and 0.5 M magnesium chloride. LDL content (LDL-C, mmol/L) was calculated according to Friedewald et al.19 Daily physical activity (PA) of patients was evaluated using the National Medical Research Center of Preventive Med- icine motion activity questionnaire QPHA23+20 Less than 62 questionnaire QPHA23+ points indicated a low level of PA, 62-84 points, a moderate level of PA, and more than 84 points, a high level of activity of PA. Patient Quality Of Life (QoL) was also analyzed.21 In addition, patient diaries were analyzed to determine of the number of angina attacks and use of Nitroglycerin (NTG) for their relief. Statistics. The SAS software package (Statistical Analysis Systems, SAS Institute, USA) was used to analyze the study results. For each quantitative scale indicator, the mean group value (M) and the standard error (SE) of the mean were determined. For nominal variables, the corre- sponding frequencies of different gradations were ex- pressed as percentages. Ratios were evaluated with a chi-square test. The significance of differences between variables, including percentages, was assessed by Stu- dent’s t-test for independent data or by a paired t-test for data from the same patients. The level of significance was set at p<0.05. - 268 - Effects of moderate physical training program in post-myocardial infarction patients with arterial hypertension Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 Results Table 1 shows that most characteristics of subjects in the two group were similar, including elevated systolic and diastolic BP. 42-44% of patients had symptoms of mild to moderate heart failure (HF). The percentage of patients with diabetes mellitus and with angina pectoris was greater in the PhTG. Men predominated in the study pop- ulations, but the proportion of men in the trained and con- trol groups did not differ significantly. Subjects were of working age, and about 50% had had at least one MI prior to a recent acute MI. The majority of study subjects (68%) had ST-Elevation Myocardial Infarction (STEMI); the re- mainder (32%) had Non-ST-Elevation Myocardial Infarc- tion (NSTEMI). During the one-year duration of the study, no patients with- drew for non-medical reasons. In the PhTG, two patients did not complete the study, one due to stroke and one due to cardiovascular death. In the CG, six patients did not com- plete the study, four due to stroke, one due to pulmonary embolism, and one due to cardiovascular cause (p=0.17). - 269 - Table 1. Pre-study characteristics of study patients with arterial hypertension and recent AMI. Variable PhTG (n=102) CG (n=104) p Men, % / Women, % 94.1 / 5.9 91.0 / 9.0 NS Age, years 52.7±0.7 53.2±0.7 NS Angina pectoris, % 85.7 64.0 <0.05 Angina, CCS class 1.4±1.0 1.2±1.1 NS Heart failure NYHA class I-II, % 41.9 44.2 NS Previous MI, % 51.9 48.5 NS Diabetes mellitus, % 7.0 3.4 <0.05 SBP, mmHg 134±2 133±2 NS DBP, mmHg 85±1 84±1 NS HR, beats/min 75±1 76±1 NS Ejection fraction of the left ventricle (LV EF), % 56.0±10.0 58.0±9.0 NS Body mass index (BMI) 27.7±3.3 27.8±3.6 NS Total cholesterol (TC), mmol/l 5.5±1.2 5.7±3.2 NS Low density lipoprotein cholesterol (LDL-C), mmol/l 3.7±1.2 3.8±1.3 NS Triglycerides, mmol/l 1.8±0.9 1.8±0.9 NS High density lipoprotein cholesterol (HDL-C), mmol/l 1.06±0.35 1.09±0.31 NS b-adrenergic blockers (bAB), % 92.8 92.7 NS i-ACE, % 77.1 80.5 NS Antiplatelet, % 95.1 98.8 NS Lipid lowering drugs, % 74.6 71.0 NS Values are percentages of the total (%) or means±SE; PhTG, patients in physical trained group; CG, patients in untrained, control group; CCS, Canadian Cardiovascular Society; NYHA, New York Heart Association; HF, heart failure; MI, myocardial infarction; Previous MI, MI prior to recent acute MI; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; p, probability of a statistically significant difference, PhTG vs CG; NS, p ≥0.05. Effects of moderate physical training program in post-myocardial infarction patients with arterial hypertension Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 Dynamics of office BP Initially, the patients of the two groups had similar systolic BP (SBP) and diastolic BP (DBP). After one year in the CRP, SBP of PhTG patients decreased by 3.0% from 134±2 mm Hg initially to 130±2 mm Hg (р<0.05), and DBP decreased by 3.5% from 85±1 mm Hg to 82±1 mm Hg (р<0.001). Over the same interval, SBP of CG patients increased by 3.1% from 133±2 mm Hg initially to 137±2 mm Hg (р<0.05), and DBP increased by 3.4% from 84±1 to 87±1 mm Hg (р<0.05). Dynamics of exercise capacity and BP Initially, the patients of the two groups did not differ in indicators of exercise capacity: ET, ThP, and ToW. After one year in the CRP, Figure 1 shows that ET of PhTG pa- tients increased by 38% (p<0.001), and ToW increased by 64% (p<0.001). These variables had not changed signifi- cantly in CG patients at one year. Thus, at the conclusion of the study, ET and ToW were sigificantly greater in the PhTG (p<0.001) compared to CG. At baseline, ThP was 80±2 W in PhTG patients and 87±2 W in CG patients. After one year, ThP had increased to 107±3 W (р<0.001), whereas ThP of CG patients had not changed significantly (89±2 W, р>0.05). Thus, following CRP, ThP was signif- icantly greater for PhTG patients than for CG patients (р<0.001). BP, HR and RPP of the two groups at MxP of the CE-test and at the 5th minute following its termination were similar before the CRP (Table 2). After one year, this was no longer the case. At MxP, patients SBP of PhTG patients had decreased by 4.6% (p<0.05), DBP by 4.4% (p<0.05), HR by 4.7% (p <0.05), and RPP by 8.2% (p <0.01) from initial, pre-CPR values. In contrast, these variables did not change significantly in CG patients. Between group com- parisons of these variables after one year showed that DBP, HR, and RPP, were significantly reduced in the PhTG (Table 2). At the 5th minute after termination of the CT-test, DBP of CG patients was significantly higher than recorded one year earlier, whereas in PhTG patients values of all C-test variables were similar to those recorded pre- CRP. Between group comparisons found DBP and HR to be significantly less in the PhTG at one year. Dynamics of EchoCG indicators of LV function At the beginning of the study, the values of LV EDV and ESV were significantly higher in PhTG patients than in CG patients: EDV, 142±3 ml vs 132±3 ml (p<0.05); ESV, 63±2 ml vs 56±2 ml (p<0.02). Other EchoCG parameters did not significantly between the groups. After one year of CRP, PhTG patients had improved LV function. Their LV ESV significantly decreased from 63±2 ml to 55±2 ml (7.8%, p<0.001); LV EF increased from 56±1% to 60±1% (7.6%, p<0.001); in control group there were no changes in LV EF, 58±8%; systolic volume increased from 79±2 ml to 81±2 ml (5.1%, p<0.01). These changes were accompanied by an increased cardiac index (5.9%, p <0.001) and decreased TPR (6.4%, p <0.05). LA size remained stable (3.8±0.1 cm at baseline and 3.8±0.1 at one year, р>0.05). After one year of observation, EchoCG parameters of CG patients either did not change or worsened: LA size in- creased (4.3%, p <0.05). Between group comparisons at one year found significantly favorable improvements in LV EDV, LV ESV, LV EF, size of LA and TPR of PhTG patients. The E/A ratio did not differ between the groups either at baseline (1.0±0.1 and 1.2±0.1, p>0.05) or at one year (0.9±0.1 and 1.1±0.1, p>0.05). - 270 - Figure 1. Exercise duration and total work performed during a cycle ergometry test performed prior to the study (Initial) and at conclusion of the study (After 1 year). CG, patients in the untreated control group; PhTG, patients in the physically trained group. *p<0.001vs Initial value #p<0.001 vs respective between group value. Effects of moderate physical training program in post-myocardial infarction patients with arterial hypertension Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 Dynamics of 24-h ECG monitoring and frequency of angina episodes Data of 24-hour ECG monitoring are presented in Table 3. After one year of CRP, the average number of episodes of ischemic ST depression during monitoring in PhTG patients decreased by 51.3% (p <0.01), the incidence of painless is- chemia decreased by 55.6% (p <0.05) and the episodes of silent myocardial ischemia by 46.8% (p <0.01). No positive changes were observed in the CG patients. Numbers of su- praventricular and ventricular extrasystoles were not af- fected by CRP. The diaries of the PhTG patients showed that during one year of CRP, the average frequency of angina pectoris attacks decreased by 47.6% (p <0.001), and the average number of NTG tablets taken by patients to treat attacks of angina pectoris decreased by 53.8% (p <0.01) (Figure 2). There were no changes in the number of angina at- tacks or the amount of NTG taken by CG patients. Also, among the PhTG patients, the number of taken long-acting nitrates significantly decreased by 25% (p <0.001). Dynamics of lipid transport indicators At one year of the CRP, an antiatherogenic response in the PhTG patients was evident with an increased serum HDL-C (13.1%, p <0.001). There was a significant de- crease in TC/HDL-C (-9.7%, p <0.01) and in LDL-C/ HDL-C (-11.2%, p <0.05). In contrast, atherogenicity in- dices of CG patients increased: TC/HDL-C (13.1%, p <0.05) and LDL-C/HDL-C (16.7%, p <0.05). In the CG group, HDL-C remained unchanged (1.07±0.03 mmol/l at baseline and 1.06±0.03 mmol/l in one year, p>0.05). Dynamics of PA. The daily PA of the CG patients scored 53 ± 1 points on the QPHA-23 + questionnaire, initially and 52 ± 3 points one year later. In contrast, PhTG patients in- creased their PA score by 13.1% (p <0.01) to 67.9 points. Thus, during the CRP, the PhTG patients transitioned from low to moderate daily PA.21 Clinical characteristics and disease outcome Positive changes of EchoCG indicators of LV function, the increase in exercise capacity, and daily PA in PhTG patients were reflected in their clinical improvement. The BMI in the main group decreased to 26.9±3.2 (decrease by 3.1%) and there were no changes in the control group -27.9±3.5. The number of revascularizations (PCI or CABG) in current year in the main group was 1 (1.6%) and 6 (5.3%), in the control group. Also, their quality of life significantly im- proved (30.8%, p <0.001) as compared with no change in the CG patients. The PhTG patients reported an average 1.9 days of temporary disability per person during the year compared to 4.9 days per person for CG patients (p <0.05). - 271 - Table 2. Initial and one-year, post-rehabilitation CE-test values of systemic arterial blood pressure, heart rate, and rate pressure product of PhTG and control patients recorded at maximum power of the CE test and at 5 min after cessation of the CE-test. Variable Groups PhTG vs CG PhTG (n=100) CG (n=98) Initial 1 year Initial 1 year p Before 1 year p p p At MxP of CE-test SBP, mmHg 173±3 166±3 <0.05 175±3 173±3 NS NS NS DBP, mm Hg 97±1 93±1 <0.05 96±1 97±1 NS NS <0.02 HR, beats/min 113±2 109±2 <0.05 116±2 116±2 NS NS <0.05 RPP, units 199±6 184±6 <0.01 206±6 203±6 NS NS <0.02 5 min after cessation of CE-test SBP, mm Hg 136±2 134±2 NS 138±2 137±2 NS NS NS DBP, mm Hg 87±1 84±1 NS 84±2 87±1 <0.01 NS <0.01 HR, beats/min 83±2 82±2 NS 86±2 88±1 NS NS <0.05 RPP, units 115±3 110±3 NS 120±3 120±3 NS NS <0.05 Values are means±SE; PhTG, patients in the physical trained group; CG, patients in the untrained, control group; CE-test, cycle ergometry test; MxP, maximal CT-test power; SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; RPP, rate pressure product; NS, p ≥0.05. Effects of moderate physical training program in post-myocardial infarction patients with arterial hypertension Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 - 272 - Table 3. Initial and one-year, post-rehabilitation results of 24-hour ECG monitoring. Variable Groups p PhTG vs CG PhTG CG Initial 1 year Initialn 1 year р Initial 1 year p =102 n=100 n=104 n=98 Duration of ECG 22.3±0.3 22.0±0.3 NS 23.0±0.1 22.6±0.2 NS NS NS monitoring, h Supraventricular 118±4 70±4 Eq 105±5 89±5 Eq Eq Eq extrasystoles, n Ventricular 256±7 231±6 Eq 272±7 205±7 Eq Eq Eq extrasystoles, n Ischemic ST depression, 4.4±0.6 2.1±0.3 <0.01 3.5±0.5 3.4±0.6 NS NS <0.05 n episodes Silent myocardial 3.5±0.5 1.9±0.3 <0.01 2.5±0.4 3.2±0.6 NS NS <0.02 ischemia, n episodes Painful myocardial 0.9±0.2 0.4±0.1 <0.05 0.9±0.1 0.5±0.1 NS NS NS ischemia, n episodes Values are means±SE; PhTG, patients in the physical trained group; CG, patients in the untrained, control group; NS = p ≥0.05. Figure 2. The number of angina attacks and nitroglycerin tablets taken by patients per week prior to the study (Initial) and at conclusion of the study (After 1 year). CG, patients in the untreated control group; PhTG, patients in the physi- cally trained group. *p<0.05 within group comparison. #p<0.001 between-group comparison. Effects of moderate physical training program in post-myocardial infarction patients with arterial hypertension Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 During the study, 12 of the PhTG and 29 of the CG had car- diovascular events that required medical evaluation (p <0.05). All of the patients in the PhTG with cardiovascular events were able to meet the criteria of at least 85% of scheduled exercise sessions and were also able to partici- pate in the post-study evaluations. Likewise, all CG patients who experienced cardiovascular events participated in the post-study evaluations. Discussion The study demonstrated positive, complex benefits of a one-year cardiac rehabilitation program that included sys- tematic exercise training and standard drug therapy for post-AMI patients with AH. Not only were cardiac vari- ables improved by this program, there were concurrent re- ductions in these patients’ arterial blood pressure compared to control patients treated with standard drug therapy alone. In addition, there was a positive influence of exercise training in restraining the pathological remod- eling of myocardium post-AMI.22 These new findings in patients with AH extend our earlier research that demon- strated benefits of a comprehensive rehabilitation program with systematic exercise training.23 As in our previously described “School for patients after AMI”,23 patients in the present study were highly motivated; no patients with- drew from the study for non-medical reasons. Further- more, safety of the present CRP was evident from the very low number of patients who withdrew from the study for medical reasons. Although these numbers were small for both PhTG and control group, significantly more patients withdrew from the control group than from the exercise trained group. Published meta-analyses data of randomized controlled clinical trials confirm the ability of moderate dynamic ex- ercise training to decrease BP levels, both systolic (-3.4 to -7.4 mm Hg) and diastolic (-2.4 to -5.8 mm Hg) pres- sures.24, 25 In the current study, the one-year exercise train- ing program decreased office SBP by 4 mmHg and DBP by 3 mmHg. BPs at MxP of the CE-test were also reduced. Meta-analysis of epidemiological and clinical data has shown that a decline in SBP or DBP as small as 2 mmHg is associated with a marked reduction in mortality due to ischemic heart disease (-7%) and to stroke (-10%).26 A decrease in TPR, which occurred the PhTG patients, is the primary mechanism that decreases BP after systematic exercise training.27 This is facilitated by positive neuro- humoral, vascular and structural adaptive changes in the background of exercise training. This decrease in systemic vasoconstriction reflects neutralization of excessive sym- pathetic stimulation of vascular smooth muscle.28 Also, systematic exercise training improved endothelium func- tional activity by increasing the release of the endothelial vasodilator, Nitric Oxide (NO), and reducing release of the vasoconstrictive agent, endothelin-1.28-30 This vascular remodeling induced by systematic exercise training in AH patients likely contributed to antihypertensive effect ob- served in this study. PhTG patients had fewer attacks of angina during the study and had more favorable findings on 24-hr ECG mo- toring post-test. These benefits may have accrued from recognized impacts of moderate, systematic exercise train- ing that include of decrease of HR and BP, improvement of the gas transport, and restoration of coronary endothe- lial function and the resulting expansion of the coronary reserve.31 Exercise training stimulates coronary angiogen- esis and increases collateralization.31-34 In this regard, ex- ercise training increases Vascular Endothelial Growth Factor (VEGF) and the expression of its receptors.35 Moderate dynamic exercise has previously been demon- strated to increase HDL-C and its apoprotein (apo) AI.36 The present study extends these antiatherogenic findings to hypertensive, exercising patients recovering from AMI. With aerobic exercise, the activity of peripheral lipopro- tein lipase increases, which leads to an increased rate of apo B-containing lipoproteins utilization and activation of the cholesterol reverse transport mechanism, so HDL-C and its apo AI are increased. HDL is a modulating factor for the activity of endothelial NO synthase, the main source of NO.37 Cardiac rehabilitation programs based on systematic ex- ercise training results have been shown to significantly re- duce risk of recurrent MI, cardiovascular mortality and total mortality.38 These findings are consistent with obser- vations that long-term exercise attenuates the progression of coronary artery disease and may even reduce athero- sclerosis lesions.39,40 The lower mortality of PhTG patients is consistent with these reports. The current study showed that the CRP reduced the number days of temporary disability. This benefits not only the patient, but the economy as well. The lesser inci- dence of cardiovascular events among the PhTG is con- sistent with previously described clinical benefits of CRP in non-AH subjects.41,42 Finally, it should be recognized that involving AMI pa- tients in a cardiac rehabilitation program is an important factor in increasing their adherence to other therapy.43 The continued contact with medical personnel motivates pa- tients to correct their lifestyle, to take prescribed medicat- ion, and to continue participation in the rehabilitation program. List of abbreviations CRP, cardiac rehabilitation program MI, myocardial infarction AMI, acute myocardial infarction AH, arterial hypertension PhT, physical training PhTG, physically trained group CG, control group MxP, maximal power CE-test, cycle ergometry test ET, exercise time ThP, threshold power ToW, total work RPP, rate-pressure product BAB, beta-adrenoblockers ATII, angiotensin II IHD, ischemic heart disease - 273 - Effects of moderate physical training program in post-myocardial infarction patients with arterial hypertension Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 CA, coronary artery BP, blood pressure LDL, low density lipoprotein HR, heart rate BMI, body mass index LA -left atrium EDV, end-diastolic volume ESV, end-systolic volume IST, interventricular septum thickness EF, ejection fraction VE, ventricular ejection TPR, total peripheral resistance TC, total cholesterol TG, triglycerides HDL-C, high-density lipoprotein cholesterol VLDL, very low-density lipoproteins PA, physical activity QoL, quality of life NTG, nitroglycerin SE, standard error HF, heart failure STEMI, ST-elevation myocardial infarction NSTEMI, non-ST-elevation myocardial infarction SBP, systolic blood pressure DBP, diastolic blood pressure EchoCG, echocardiogram CABG, coronary artery bypass grafting PCI, percutaneous coronary intervention NO, nitric oxide VEGF, vascular endothelial growth factor Contribution DMA conceived the study, designed the study and were in charge of overall direction and planning; MGB contributed to the design and implementation of the research, to the analysis of the results and to the writing of the manuscript, carried out the experiments; NPL carried out the experi- ments, contributed to the design and implementation of the research, to the analysis of the results and to the writing of the manuscript; HFD, EBM processed the experimental data, performed the analysis, the results and worked on the manuscript, authors contributed to the final version of the manuscript; SVL wrote the manuscript with input from all authors. All authors discussed the results and contributed to the final manuscript. Funding This study was performed as parts of State Assignment of the National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russian Federation #01201352203 and State Assignment of the Institute of General Pathology and Pathophysiology #FGFU-2025- 0007. Conflict of interest The authors declare no conflict of interest. Ethics approval and consent to participate The study was carried out in accordance with Good Clinical Practice standards and with the Helsinki Declaration prin- ciples. Written informed consent was obtained from all par- ticipants of this study. Ethics Committee of the National Medical Research Center for Therapy and Preventive Med- icine, Moscow, Russian Federation, approved the Study Protocol on March 19, 2015 (Protocol #3). Corresponding author Svetlana V. Lyamina, Russian University of Medicine, 1- 200 Milashenkova St., Moscow 127322, Russian Feder- ation. Tel.: +7.915.018-5006. ORCID ID: 0000-0001-8300-8988 E-mail: svlvs@mail.ru Co-authors David M. Aronov ORCID ID: 0000-0003-0484-9805 E-mail: aronovdm@mail.ru Marina G. Bubnova ORCID ID: 0000-0003-2250-5942 E-mail: mbubnova@gnicpm.ru Nadezhda P. Lyamina ORCID ID: 0000-0001-6939-3234 E-mail: lyana_n@mail.ru H. Fred Downey ORCID ID: 0000-0002-7280-1021 E-mail: freddowney@yahoo.com Eugenia B. Manukhina ORCID ID: 0000-0002-8102-173x E-mail: manukh@mail.ru Svetlana V. Lyamina ORCID ID: 0000-0001-8300-8988 E-mail: svlvs@mail.ru References 1. Mancia G, Kreutz R, Brunström M, et al. 2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hyper- tension of the European Society of Hypertension: En- dorsed by the International Society of Hypertension (ISH) and the European Renal Association (ERA). J Hypertens 2023;41:1874-2071. 2. Agabiti-Rosei E, Rizzoni D. Microvascular structure as a prognostically relevant endpoint. J Hypertens 2017; 35:914-21. 3. Zdravkovic M, Popadic V, Klasnja S, et al., Coronary microvascular dysfunction and hypertension: A bond more important than we think. Medicina (Kaunas). 2023;59:2149. - 274 - mailto:svlvs@mail.rum mailto:aronovdm@mail.ru mailto:mbubnova@gnicpm.ru mailto:lyana_n@mail.ru mailto:freddowney@yahoo.com mailto:manukh@mail.ru mailto: Effects of moderate physical training program in post-myocardial infarction patients with arterial hypertension Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 4. Briones AM, Hernanz R, García-Redondo AB, et al. Role of Inflammatory and Proresolving Mediators in Endothelial Dysfunction. Basic Clin Pharmacol Toxicol 2025;136:e70026. 5. Ellulu MS, Patimah I, Khaza’ai H, et al. Atherosclerotic cardiovascular disease: a review of initiators and pro- tective factors. Inflammopharmacology 2016;24:1-10. 6. Chlorogiannis DD, Pargaonkar S, Apostolos A, et al. The Predictive Value of Aortic Calcification on Com- puted Tomography for Major Cardiovascular Events. J Clin Med 2024;13:4019. 7. Sun Y, Yao J, Wang C, et al. Epigenetic modification of TWIST1 in macrophages promotes hypertension-in- duced atherosclerotic plaque instability. Int Immuno- pharmacol 2024;127:111313. 8. Saba L, Saam T, Jäger HR, et al. Imaging biomarkers of vulnerable carotid plaques for stroke risk prediction and their potential clinical implications. Lancet Neurol 2019;18:559-72. 9. Natali A, Vichi S, Landi P, Toschi E, Severi S, L’abbate A, Ferrannini E. Coronary artery disease and arterial hy- pertension: clinical, angiographic and follow-up data. Intern Med 2000;247:219-30. 10. Bubnova MG, Aronov DM, Oganov RG, et al. Clinical characteristics of stable angina patients and their treat- ment strategies in real-world clinical practice. A Russian Federation PERSPECTIVE Study (Part I). Cardiovasc Ther Prev 2010;9:47-56. 11. Steg PhG, Greenlaw N, Tardif J-C, et al. Women and men with stable coronary artery disease have similar clinical outcomes: insights from the international pro- spective CLARIFY registry. Eur Heart J 2012;33: 2831-40. 12. Dibben GO, Faulkner J, Oldridge N, et al. Exercise- based cardiac rehabilitation for coronary heart disease: a meta-analysis. Eur Heart J 2023;44:452-69. 13. Li C, Wu S, Lei B, et al. Effect of aerobic exercise on endothelial function in hypertensive and prehyperten- sive patients: a systematic review and meta-analysis of randomized controlled trials. J Hypertens 2025;43: 727-38. 14. Tozo JVA, Tadiotto MC, Tozo TAA, et al Effects of dif- ferent physical exercise programs on blood pressure in overweight children and adolescents: systematic review and meta-analysis. BMC Pediatr 2025;25:252. 15. Wang B, Gan L, Deng Y, et al. Cardiovascular disease and exercise: from molecular mechanisms to clinical applications. J Clin Med 2022;11:7511. 16. Schroeder EC, Franke WD, Sharp RL, D-c L. Com- parative effectiveness of aerobic, resistance, and com- bined training on cardiovascular disease risk factors: a randomized controlled trial. PLoS One 2019;14:e0210292. 17. Hanssen H, Boardman H, Deiseroth A, et al. Personal- ized exercise prescription in the prevention and treat- ment of arterial hypertension: a Consensus Document from the European Association of Preventive Cardiol- ogy (EAPC) and the ESC Council on Hypertension. Eur J Prev Cardiol 2022;29:205-15. 18. Leprêtre PM, Ghannem M, Bulvestre M, et al. Exer- cise-based cardiac rehabilitation in coronary disease: Training impulse or modalities? Int J Sports Med 2016;37:1144-9. 19. Friedewald WT, Levy RI and Fredrickson DS. Estima- tion of the concentration of low-density lipoprotein cho- lesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502. 20. Krasnitskyi VB, Aronov DM, Dzhanchotov SO. Study of physical activity in patients with ischemic heart dis- ease using a specialized questionnaire “QPHA-23+”. Cardiovasc Ther Prev 2011;10:90-7. Russian 21.Аronov DM, Zajtsev VP. Methods of assessing the qual- ity of life of patients with cardiovascular disease. Kar- diologiya 2002;42:92-5. Russian 22. Leon AS, Franklin BA, Costa F, et al. Cardiac rehabili- tation and secondary prevention of coronary heart dis- ease: an American Heart Association scientific statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Cardiac Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity), in collaboration with the American associa- tion of Cardiovascular and Pulmonary Rehabilitation. Circulation 2005;111:369-76. 23. Bubnova MG, Aronov DM, Krasnitskyi VB, Iosiliani DG, Novikova NK, Rodzinskaya EM. A home exercise training program after acute coronary syndrome and/or endovascular coronary intervention: efficiency and a pa- tient motivation problem. Теr Arkh 2014;86:23-32. Russian 24. Waclawovsky G, Pedralli ML, Eibel B, Schaun MI, Lehnen AM. Effects of Different types of exercise train- ing on endothelial function in prehypertensive and hy- pertensive individuals: A systematic review. Arq Bras Cardiol 2021;116:938-47. 25. Jabbarzadeh Ganjeh B, Zeraattalab-Motlagh S, Jayedi A, et al. Effects of aerobic exercise on blood pressure in patients with hypertension: a systematic review and dose-response meta-analysis of randomized trials. Hy- pertens Res 2024;47:385-98. 26. Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure-lowering treatment on cardiovascular out- comes and mortality: 13, benefits and adverse events in older and younger patients with hypertension: overview, meta-analyses and meta-regression analyses of random- ized trials. J Hypertens 2018;36:1622-36. 27. Sabbahi A, Arena R, Elokda A, Phillips SA. Exercise and hypertension: Uncovering the mechanisms of vas- cular control. Prog Cardiovasc Dis 2016;59:226-34. 28. Pastore MC, Cavigli L, Olivoni G, et al. Physical exer- cise in hypertensive heart disease: From the differential diagnosis to the complementary role of exercise. Int J Cardiol 2024;410:132232. 29. Liang C, Song Z, Yao X, et al. Exercise interventions for the effect of endothelial function in hypertensive pa- tients: A systematic review and meta-analysis. J Clin Hypertens (Greenwich) 2024;26:599-614. 30. Boeno FP, Ramis TR, Munhoz SV, et al. Effect of aero- bic and resistance exercise training on inflammation, endothelial function and ambulatory blood pressure in - 275 - Effects of moderate physical training program in post-myocardial infarction patients with arterial hypertension Eur J Transl Myol 35 (3) 13943, 2025 doi: 10.4081/ejtm.2025.13943 middle-aged hypertensive patients. J Hypertens 2020; 38:2501-9. 31. Heaps CL, Parker JL. Effects of exercise training on coronary collateralization and control of collateral re- sistance. J Appl Physiol 2011;111:587-98. 32. Schuler G, Adams V, Goto Y. Role of exercise in the prevention of cardiovascular disease: results, mech- anisms, and new perspectives. Eur Heart J 2013;34: 1790-9. 33. Möbius-Winkler S, Uhlemann M, Adams V, et al. Cor- onary collateral growth induced by physical exercise: Results of the impact of intensive exercise training on coronary collateral circulation in patients with stable coronary artery disease (EXCITE) trial. Circulation 2016;133:1438-48; discussion 1448. 34. Heutinck JM, de Koning IA, Vromen T, et al. Exer- cise-based cardiac rehabilitation in stable angina pec- toris: a narrative review on current evidence and underlying physiological mechanisms. Neth Heart J 2024;32:23-30. 35. Hoier B, Hellsten Y. Exercise-induced capillary growth in human skeletal muscle and the dynamics of VEGF. Microcirculation 2014;21:301-14. 36. Aronov DM, Bubnova MG, Perova NV, Orekhov AN, Bobryshev YuV. The effect of maximal versus submax- imal exertion on postprandial lipid levels in individuals with and without coronary heart disease. Clin Lipidol 2017;11:369-76. Russian 37. Robert J, Osto E, von Eckardstein A. The endothelium is both a target and a barrier of HDL’s protective func- tions. Cells 2021;10:1041. 38. Mahmood A, Ray R, Bin Salam SST, et al. The effec- tiveness of cardiac rehabilitation programs in improving cardiovascular outcomes: systematic review and meta- analysis. Cureus 2024;16:e72450. 39. Nishitani-Yokoyama M, Miyauchi K, Shimada K, et al. Impact of Physical Activity on coronary plaque volume and components in acute coronary syndrome patients after early phase II cardiac rehabilitation. Circ J 2018;83:101-9. 40. Wang C, Xing J, Zhao B, et al. The effects of high-in- tensity interval training on exercise capacity and prog- nosis in heart failure and coronary artery disease: A systematic review and meta-analysis. Cardiovasc Ther 2022;2022:4273809. 41. Martin BJ, Hauer T, Arena R, et al. Cardiac rehabili- tation attendance and outcomes in coronary artery dis- ease patients/clinical perspective. Circulation 2012; 126:677-87. 42. Zwisler ADO, Soja AMB, Rasmussen S, et al. Hospi- tal-based comprehensive cardiac rehabilitation versus usual care among patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease: 12-month results of a randomized clinical trial. Am Heart J 2008;155:1106-13. 43. Anderson L, Thompson DR, Oldridge N, et al. Exer- cise-based cardiac rehabilitation for coronary heart dis- ease. Cochrane Database of Systematic Review and Meta-Analysis. Am Coll Cardiol 2016;7:1-12. Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their af- filiated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Submitted: 2 May 2025. Accepted: 19 May 2025. Early access: 10 July 2025. - 276 -