Obstructive sleep apnea: a modern view of the problem

Introduction. In recent years, there has been evidence not only of the widespread prevalence of the obstructive sleep apnea (OSA) in the population, but also of the progression of the disease in the dynamic follow-up of patients. The purpose of this review article is to analyze the current state of etiopathogenesis, clinics of obstructive sleep apnea and to identify more promising treatment approaches and risk factors for its development. Materials and methods. The analysis of publications was performed for the period 2016-2021 on the basis of data from Elibrary, the Federal Electronic Medical Library of the Ministry of Health of the Russian Federation, the bibliographic database of medical publications MEDLINE, created by the US National Library of Medicine. Sixty-one sources were selected for the review. Results and discussion. Obstructive sleep apnea is widely represented in the group of sleep disorders and is correlated with a number of clinical conditions: cardiovascular diseases (acute cerebrovascular disease, resistant arterial hypertension, coronary heart disease, heart rhythm disorder), endocrine system (diabetes mellitus, hypothyroidism, metabolic syndrome, obesity), ophthalmological pathology (neurooptikopathies), sudden death, etc. Severe daytime sleepiness due to OSA is not only a medical but also a social problem due to increased injury rates, accidents at work and on the road, and decreased labor productivity. Conclusion. The introduction of a comprehensive interdisciplinary approach to diagnostic standards will improve the detection and treatment of obstructive sleep apnea and improve the quality of life of patients. Change of lifestyle and use of PAP-therapy in patients with OSA is currently the most adequate direction in the treatment of this pathology. High prevalence, serious consequences for the nation's health and economy dictate the need for further study of markers of this disease for early prediction and primary prevention of cardiovascular diseases and diseases associated with obstructive sleep apnea.

Renal artery denervation in patients with resistant arterial hypertension: clinical and organ-protective effect

Aim. To assess the clinical efficacy of renal artery denervation (RAD) in treatment of patients with resistant arterial hypertension (RAH) compared to patients taking drug therapy (DT) at long-term follow-up and the possibility of RAD impact on target organs (heart, kidneys). Materials and methods. 80 RAH patients were examined (mean age 54.3010.19 years). Patients were divided in two groups: the basic group was comprised of 40 RAH patients taking antihypertensive DT, who underwent RAD (gr. 1) and comparison group was composed of 40 RAH patients taking only antihypertensive DT (gr. 2). Gender and age differences between groups were statistically insignificant (p0.05). Mean duration of AH was 18.638.96 years. The follow-up was carried out during one year. Results. In RAD group there was confirmed decrease not only in the office, but also in the average day-time and night-time blood pressure (BP), changes were more significant in systolic BP (SBP) indicators: the overall daytime SBP was 17.369.31 mmHg (p0.001), the average day-time SBP was 17.1810.53 mmHg (p0.001), the average night-time SBP was 19.2210.76 mmHg (p0.001). At the same time, in DT group changes in values of overall, maximum, minimum, average day-time and average night-time SBP and diastolic BP were not statistically significant in 12 months. RAD in RAH was accompanied by decrease in left ventricular hypertrophy with initial hypertrophy (p0.05), decrease in microalbuminuria (p0.05), decrease in velocity in segmental (p0.05) and interlobar renal arteries (p0.01). Conclusion. RAD in patients with RAH had not only antihypertensive effect but also positive effect on target organs of AH (heart, kidneys).

Magnetic resonance imaging of the aortic wall as a risk index for acute ischemic stroke in patients with resistant arterial hypertension

Aim To value the possible relationship between the intensity of neoangiogenesis in the aortic wall in patients with resistant arterial hypertension and the subsequent development of ischemic cerebral disorders in them over a three-year follow-up. Materials and methods This study comprised 36 patients with resistant hypertension, in whom the renal denervation was carried out. MRI of the brain and also with contrast enhancement of the aorta and kidneys were examined. MRI studies included T2 and T1 spin-echo MRI, and also coronal slices, with suppression of the signal from adipose tissue (TR=150 ms, TE = 4 ms), before and in 12–15 minutes after contrast-enhanced. The diameter and thickness of the wall of the descending aorta were measured. Index of the enhancement of the aortic wall was calculated as the ratio of intensities of the wall after, and before contrast-enhanced. 9 according to MRI data - developed an acute ischemic stroke during this period, and 27 had no cerebral circulation disorders. The control group consisted of individuals without hypertension (n=12). Results After renal denervation, the systolic blood pressure significantly decreased in all patients for more than 15 mm Hg. In groups of patients with ischemic stroke, and without it, the diameter of the aortic lumen at the level above the renal arteries was 22,1±2,4 mm and 22,8±2,7 mm, respectively; the aortic wall thickness was 3,9±0,7 mm and 3,7±0,8 mm. In control subjects without hypertension, the wall thickness was less than 2,7 mm (on average 2,2±0,4 mm), with an aortic diameter of 21,3±0,9. As to the index of enhancement (as a marker of neoangiogenesis intensity) in the control group, in everybody, the IE was <1,12. In patients with stroke within 3 years after renal denervation, IE = 2,12±0,31, and in patients without stroke IE = 1,66±0,19. The value of IE = 1,82 was the best for separating groups with and without stroke in the three years endpoint, as from the ROC analysis. Conclusion Contrast enhancement of the aortic wall in MRI is associated with the risk of brain ischemic stroke in patients with resistant arterial hypertension, even when blood pressure control is achieved by renal denervation. This makes it possible to predict the risk of stroke in these patients more reliably and encourages the inclusion of agents that reduce the activity of inflammation and pathological neoangiogenesis in the aortic wall, to the spectrum of antihypertensive therapy. FUNDunding Acknowledgement Type of funding sources: None. Brain MRI T2WI MRI of the kidneys and aorta, T1WI

Correlation arterial stiffness and central blood pressure with obstructive sleep apnea in patients with resistant arterial hypertension

The aim assess correlation the arterial stiffness in patients with resistant arterial hypertension (AH) and obstructive sleep apnea (OSA) Design 185 patients with AH were enrolled into the study. They were divided on 2 groups: OSA group – 148 patients were found to have OSA, indicated by at mean AHI of 38.1±2.5 h–1, and control group – 37 patients without OSA, mean AHI 3.02±0.25 h–1 (P<0.001). Patients of both groups were comparable on age, growth, total cholesterol level and office systolic blood pressure (SBP) and diastolic blood pressure (DBP). Results Patients with RAH and OSA (mean apnea-hypopnea index (AHI) 36.5±2.7 event/h) in comparison with patients with RAH without OSA (mean AHI 3.4±0.2 event/h) had significantly higher body mass index (34.2±0.7 vs 31.6±0.7 kg/m2, P<0.05), uric acid level (6.7±0.1 vs 5.6±0.4 mg/dl, P<0,05), higher carotid-femoral pulse wave velocity (PWVcf) (12.1±0.5 vs 10.2 m/s, P<0,05) and central systolic blood pressure (CSBP) (143.8±2.7 vs 136.2±3.4 mm Hg, P<0,05). Patients of both groups had comparable office blood pressure (SBP 145.6±1.67 vs 138.4±3.66 mm Hg, P=0.057 and DBP 93.6+±1.18 vs 89.1±2.11 mm Hg, P=0.073), but significantly higher 24-h systolic and diastolic blood pressure. We suggest that in the study some patients with OSA had masked arterial hypertension. Daytime sleepiness in OSA patients was associated with structural remodeling of the left ventricle myocardium and more expressed arterial stiffness: ESS score was independently correlated with snoring duration (β=−0.008; P=0.021), interventricular septum thickness (β=0.023; P=0.026), LVMI (β=−0.037; P=0.039) and indexes of central pulse wave: ejection duration (ED) (β=−0.020; P<0.001) and subendocardial viability ratio (SEVR) (β=−0.224; P=0.012). Nocturnal hypoxemia in OSA patients was associated with increased aortic stiffness and higher central blood pressure: desaturation index was independently correlated with Aix (β=4.167; P=0.009), Aix75 (β=−3.929; P=0.006) and central DBP (β=0.151; P=0.004). Conclusion In patients with RH and OSA nocturnal hypoxemia correlation with increased aortic stiffness and higher central blood pressure. FUNDunding Acknowledgement Type of funding sources: None.

Russian Medical Society for Arterial Hypertension expert consensus. Resistant hypertension: detection and management

The diagnosis of resistant arterial hypertension allows us to single out a separate group of patients in whom it is necessary to use special diagnostic methods and approaches to treatment. Elimination of reversible factors leading to the development of resistant arterial hypertension, such as non-adherence to therapy, inappropriate therapy, secondary forms of arterial hypertension, leads to an improvement in the patient's prognosis. Most patients with resistant hypertension should be evaluated to rule out primary aldosteronism, renal artery stenosis, chronic kidney disease, and obstructive sleep apnea. The algorithm for examining patients, recommendations for lifestyle changes and a step-by-step therapy plan can improve blood pressure control. It is optative to use the most simplified treatment regimen and long-acting combined drugs. For a separate category of patients, it is advisable to perform radiofrequency denervation of the renal arteries.

Abstract P255: Resistance Hypertension And Achievement Of Target Blood Pressure Level By Continuous Positive Airway Pressure Long Therapy In Patients With Obstructive Sleep Apnea

The aim was to assess the arterial stiffness changes in patients with resistant arterial hypertension (AH) and obstructive sleep apnea (OSA) and possibilities of its correction by continuous positive airway pressure (CPAP)-therapy. Design: In 10 month follow-up study were included 46 patients with RAH, who were divided into groups: 1-st - patients with RAH and moderate to severe OSA on CPAP (n=21); 2-nd - patients with RAH and moderate to severe OSA without CPAP (n=25). They underwent somnography by dual-channel portable monitor device, office and ambulatory blood pressure monitoring, echocardiography and applanation tonometry. All patients received similar antihypertensive therapy according to 2013 ESH Guidelines for the management of arterial hypertension. Results: Patients with RAH and OSA (mean apnea-hypopnea index (AHI) 36.5±2.7 event h-1) in comparison with patients with RAH without OSA (mean AHI 3.4±0.2 event h-1) had significantly higher body mass index (34.2±0.7 vs 31.6±0.7 kg m-2, P<0.05), uric acid level (6.7±0.1 vs 5.6±0.4 mg dl-1, P<0,05)). Patients with RAH and OSA in comparison with patients with RAH without OSA had higher carotid-femoral pulse wave velocity (PWVcf) (12.1±0.5 vs 10.2 m s-1, P<0,05) and central systolic blood pressure (CSBP) (143.8±2.7 vs 136.2±3.4 mm Hg, P<0,05). During 10 months follow-up in patients with RAH and moderate and sever OSA on CPAP-therapy there were significantly decrease of PWVcf (from 12.1±0.5 to 10.5±0.5 m s-1, P<0,05), decrease office systolic blood pressure (from 147.8±3.7 to 136.7±2.8 mm Hg; P<0,05) and diastolic blood pressure (from 96.8±3.5 to 87.0±3.3 mm Hg; P<0,05) with achievement of target levels in 67,2% patients. Central systolic BP decreased (from 143.8±2.7 to 137.7±2.8 mm Hg; P<0,05). Conclusion: The combination of therapy continuous positive airway pressure with antihypertensive treatment in patients with resistant arterial hypertension and moderate to severe obstructive sleep apnea improved achievement of target blood pressure, decreased arterial stiffness and decreased central blood pressure.

Erythrocyte membranes beta-adrenoreactivity changes after renal denervation in patients with resistant hypertension, relationship with antihypertensive and cardioprotective intervention efficacy

Aim To study the functional condition of sympathoadrenal system as evaluated by beta-adrenoreactivity of erythrocyte membranes (beta-ARM) during two years following renal denervation (RD) in patients with resistant arterial hypertension (RAH) and to determine the relationship of this index with long-term antihypertensive and cardioprotective effectivity of this invasive treatment.Material and methods The study included 48 patients (mean age, 57.2±8.7 years, 18 men) with RAH on a stable antihypertensive therapy. Averaged daily systolic and diastolic blood pressure (SBP and DBP) and levels of beta-ARM were determined at baseline and in 7 days and 2 years following RD. Measurement of beta-ARM was based on beta-adrenoblocker inhibition of erythrocyte hemolysis induced by exposure to hypo-osmotic environment. The beta-adrenoblocker binds to erythrocyte membrane beta-adrenoceptors to prevent the erythrocyte destruction. Increased values of beta-ARM reflect a decrease in the number of functionally active erythrocyte membrane beta-adrenoceptors associated with long-term sympathetic hyperactivity.Results For two years of follow-up, values of average daily BP decreased from 160.4±16.0 / 88.1±14.6 to 145.3±19.3 / 79.4±13.6 mm Hg. At 7 days, the number of beta-ARM had decreased in the group of RD responders (р=0.028) who at two years had decreased their BP by 10 mm Hg or more, while in the group of non-responders, the number of beta-ARM remained unchanged. At one week, beta-ARM values correlated with changes in SBP and DBP (r= –0.54; р<0.05) and with left ventricular myocardial mass (LVMM) (r= –0.36; р<0.05) at two years of follow-up whereas beta-ARM delta at one week was interrelated with the renin concentration in the long-term (r= –0.44; р<0.05). At two years, the content of beta-ARM was increased in both groups.Conclusion The decrease in beta-ARM content at 7 days after RD shows the procedure efficacy and allows an expectation of clinically significant decreases in BP and LVMM in the long-term after the surgical treatment. At two years after the intervention, the content of beta-ARM increased, and the BP decrease was apparently due to some other mechanisms.

Resistant arterial hypertension: the search of new approaches to antihypertensive drug therapy

Improving the effectiveness of drug therapy and reducing the risk of adverse cardiovascular and renal outcomes in patients with resistant hypertension (HTN) remains an unsolved problem of cardiology. The results of the PATHWAY-2, PATHWAY-3 and ReHOT studies have shown the clinical efficacy of spironolactone, amiloride and, to a lesser extent, the antiadrenergic drugs clonidine, bisoprolol and doxazosin in improving blood pressure (BP) control in this patient population. However, the inclusion of spironolactone and other known drugs in antihypertensive therapy does not ensure the achievement of target BP level in a significant proportion of these patients. The review presents the results of clinical studies of new approaches aimed at increasing the effectiveness of drug therapy in resistant HTN including sodium-glucose cotransporter type 2 inhibitors, brain aminopeptidase A inhibitors, and new antagonists of endothelin receptors.

Relationship between metabolic syndrome components in patients with resistant arterial hypertension

Metabolic syndrome (MS) is a complex of interrelated pathological conditions based on insulin resistance, obesity, dyslipoproteinemia, arterial hypertension (AH). MS is a predictor of the cardiovascular disease, type 2 diabetes mellitus (DM), cancer and premature death. The incidence of type 2 diabetes increases with age and is 25.2% among the elderly. The prevalence of prediabetes or metabolic syndrome was approximately three times higher. Heart failure is another important cause of morbidity and mortality from the cardiovascular disease. Recent studies have shown that the incidence of hospitalizations for heart failure (adjusted for age and gender) was twice as high in patients with diabetes compared with patients without diabetes. Patients with hypertension and abdominal obesity (AO) have an increased risk of various complications: type 2 diabetes -5-9 times, stroke - 7 times, coronary heart disease - 4 times and mortality - 2 times. Objective: To analyze the relationship between the components of the metabolic syndrome in patients with resistant arterial hypertension (RAH). Materials and methods. A retrospective analysis of case histories of 120 patients, including 52 men (43.33%) and 68 women (56.67%) with a diagnosis of RAH and signs of MS. The presence of concomitant pathology, the level of office arterial pressure, pulse pressure (PP) were calculated; body weight, height with calculation of body mass index (BMI); waist circumference (WC), the levels of low-density lipoprotein (LDL) and high-density lipoprotein (HDL), triglycerides (TG), and plasma glucose were studied. Student's criterion was used to assess the degree of significance of the differences, p≤0.05 was taken as the critical level of significance. Pearson's correlation coefficient was used. Disorders of carbohydrate metabolism among patients with MS and RAH is 67.50%, of which type 2 diabetes makes 50.83%, impaired glucose tolerance - 16.67%. Patients with impaired carbohydrate metabolism are 2 times more likely to have complications of hypertension and lower HDL. Women with MS and RAH were significantly older than men and more often had concomitant pathology: morbid obesity (p <0.05), type 2 diabetes mellitus (p <0.05), chronic cerebral ischemia (p <0.05), higher body mass index (p <0.01). Strong correlation between WC and BMI (r = 0.707; p˂0.001), weak direct correlations between WC and PP (r = 0.231; p˂0.05) and WC and TG (r = 0.221; p˂0.05), weak feedback between WC and age (r = -0.188; p˂0.05), and for men direct correlations between WC and TG were confirmed (r = 0.454; p˂0.001), BMI and TG (r = 0.454, p˂0.002).

Renal Denervation Exacerbates LPS- and Antibody-Induced Acute Kidney Injury, but Protects from Pyelonephritis in Mice

• Background: Renal denervation (RDN) is an invasive intervention to treat drug-resistant arterial hypertension. Its therapeutic value is contentious. Here we examined the effects of RDN on inflammatory and infectious kidney disease models in mice. • Methods: Mice were unilaterally or bilaterally denervated, or sham operated, then three disease models were induced: nephrotoxic nephritis (NTN, a model for crescentic glomerulonephritis), pyelonephritis and acute endotoxemic kidney injury (as a model for septic kidney injury). Analytical methods included measurement of renal glomerular filtration, proteinuria, flow cytometry of renal immune cells, immunofluorescence microscopy and 3D imaging of optically cleared kidney tissue by light-sheet-fluorescence-microscopy followed by algorithmic analysis. • Results: Unilateral RDN increased glomerular filtration in denervated kidneys but decreased it in the contralateral kidneys. In the NTN model, more nephritogenic antibodies were deposited in glomeruli of denervated kidneys, resulting in stronger inflammation and injury in denervated compared to contralateral non-denervated kidneys. Also intravenously injected LPS increased neutrophil influx and inflammation in the denervated kidneys, both after unilateral and bilateral RDN. When we induced pyelonephritis in bilaterally denervated mice, both kidneys contained less bacteria and neutrophils. In unilaterally denervated mice, pyelonephritis was attenuated and intrarenal neutrophil numbers were lower in the denervated kidneys. The non-denervated contralateral kidneys harbored more bacteria, even compared to sham-operated mice, and showed the strongest influx of neutrophils. • Conclusions: Our data suggest that the increased perfusion and filtration in denervated kidneys can profoundly influence concomitant inflammatory diseases. Deposition of circulating nephritic material is higher, and hence antibody- and endotoxin-induced kidney injury was aggravated in mice. Pyelonephritis was attenuated in denervated murine kidneys, because the higher glomerular filtration facilitated better flushing of bacteria with the urine, at the expense of contralateral, non-denervated kidneys in case of unilateral denervation.