Обструктивное апноэ сна и сердечно-сосудистая коморбидность: современное разноголосье в оценке эффективности влияния СРАР-терапии на патогенетические механизмы и сердечно-сосудистые заболевания

Sleep-disordered breathing (and obstructive sleep apnea, OSA) is a common pathology in the general population in economically developed countries. In the last decades, CPAP therapy (continuous positive airway pressure) became the first-choice treatment option in clinically relevant OSA.Objective. The review summarized available evidence about the effects of CPAP-therapy on the main pathogenetic pathways of OSA (sleep-related sympathetic activity, vascular inflammation, endothelial dysfunction, oxidative stress, and blood coagulation) and cardiovascular diseases (CVDs - hypertension, cardiac arrhythmias, heart failure, pulmonary hypertension, coronary heart disease, and combined cardiovascular outcomes, including cardiovascular mortality).Methods. We analyzed the data of the randomized observational cohort clinical trials and metaanalyses, which assessed the effects of CPAP-therapy on the pathophysiological mechanisms of OSA and the associated CVDs. We also analyzed current guidelines on the management of patients with CVDs and OAS. We searched the following databases: Scopus, Pubmed, Google Scholar, Russian Scientific Citation Index.Results. Despite the rather recent implementation of this method, the accumulated evidence shows its favorable impact on OSA pathogenesis (on sympathetic activity and, to some extent, on vascular inflammation and endothelial dysfunction) and CVDs (hypertension, in particular, resistant hypertension, and paroxysmal atrial fibrillation). The observational studies also demonstrate favorable outcomes regarding other CVDs. However, the data of the randomized clinical trials are limited or controversial, the samples are rather small, which leads to inconsistent conclusions.Conclusion. Currently, most of the researchers emphasize that the required CPAP-adherence level (regular use for at least 4 h nightly) is the main barrier to getting the high-level evidence of CPAP efficiency with regard to the cardiovascular risk. This factor becomes the biggest limitation in patients who are characterized by the low compliance because they are not prone to daytime sleepiness.Нарушение дыхания во сне, в частности, обструктивное апноэ сна (ОАС), является широко распространенным заболеванием в общей популяции экономически развитых стран. В последние десятилетия ведущим методом лечения клинически значимых форм апноэ хорошо зарекомендовал себя метод неинвазивной вентиляции легких с созданием постоянного положительного давления в дыхательных путях (Continuous Positive Airway Pressure — СРАР) в качестве терапии первой линии.Целью работы явился обзор доказательной базы воздействия СРАР-терапии на различные звенья патогенеза ОАС (симпатическая активность во сне, процессы сосудистого воспаления, эндотелиальная функция, процессы оксидативного стресса и коагуляции крови) и сердечно-сосудистые заболевания (ССЗ) — артериальную гипертензию (АГ), сердечные аритмии, сердечную недостаточность (СН), легочную гипертензию, ишемическую болезнь сердца и комбинированные сердечно-сосудистые исходы, в т. ч. смертность.Методы. По данным когортных наблюдательных рандомизированных клинических исследований (РКИ) и метаанализов, в которых рассматривалось влияние CPAP-терапии на патофизиологические звенья ОАС и ассоциированные ССЗ, проанализированы существующие в настоящий момент рекомендации и регламентирующие документы, касающиеся ведения пациентов с ССЗ и ОАС. Поиск проводился по базам данных Scopus, Pubmed, Google Scholar, РИНЦ.Результаты. Несмотря на недолговременное использование CPAP-терапии в клинической практике, накоплено достаточно доказательств относительно положительного эффекта воздействия CPAP-терапии на некоторые звенья патогенеза (симпатическую активацию, в определенной мере — сосудистое воспаление и эндотелиальную дисфункцию) и ССЗ (АГ, в частности, ее резистентную форму, а также пароксизмальные формы фибрилляции предсердий). При изучении остальных форм ССЗ и патогенетических звеньев, связанных с ОАС, по данным, как правило, наблюдательных исследований продемонстрированы хорошие результаты лечения, однако данных РКИ либо недостаточно, либо они неоднозначны, часто при небольшом числе участников, поэтому на настоящий момент убедительных доказательств преимущества этого вида лечения не получено.Заключение. В настоящее время по результатам многих исследований подчеркивается, что при проведении РКИ основным барьером для получения приемлемых доказательств эффективности CPAP-терапии, связанных со снижением риска ряда ССЗ, особенно при плохой приверженности терапии из-за отсутствия дневной сонливости, является требуемый уровень приверженности CPAP-терапии — регулярное использование > 4 ч за ночь

Atorvastatin therapy modulates telomerase activity in patients free of atherosclerotic cardiovascular diseases

Background— Telomerase activity (TA) is considered as the biomarker for cardiovascular aging and cardiovascular diseases. Recent studies suggest a link between statins and telomere biology that may be explained by anti-inflammatory actions of statins and their positive effect on TA. Until now this effect has not been investigated in prospective randomized studies.We hypothesized that 12 months of atorvastatin therapy increased TA in peripheral blood mononuclear cells.Methods—In a randomized, placebo-controlled study 100 hypercholesterolemic patients, aged 35–75 years, free of known cardiovascular diseases and diabetes mellitus type 2 received 20 mg of atorvastatin daily or placebo for 12 months. TA was measured by quantitative polymerase chain reaction.Results—At study end 82 patients had sufficient peripheral blood mononuclear cells needed for longitudinal analysis. TA expressed as natural logarithms changed from 0.46±0.05 to 0.68±0.06 (p=0.004) in the atorvastatin group and from 0.67±0.06 to 0.60±0.07 (P=0.477) in the control group. In multiple regression analysis, atorvastatin therapy was the only independent predictor (p=0.05) of the changes in TA independently of markers of chronic inflammation and oxidative stress. Atorvastatin therapy was associated with increases in IL-6 within the normal range and a tendency towards reductionin blood urea.Conclusions—These initial observations suggest atorvastatin can act as telomerase activator and potentially as effective geroprotector

Age-Related Left Ventricular Changes and Their Association with Leukocyte Telomere Length in Healthy People

<div><p>Introduction</p><p>With advancing age the left ventricle (LV) undergoes structural and functional changes, thereby creating the substrate for the development of diseases. One possible mechanism of the ageing heart is a cellular senescence. Leukocyte telomere length (LTL) is a marker of replicative ageing. The purpose of this study was to evaluate the structure and function of the LV in people of different ages free of cardiovascular diseases (CVD) and regular drug medication and to assess their relationship with LTL. We hypothesized that age-related changes in LV myocardium are associated with telomere length.</p><p>Methods</p><p>The study population consisted of 150 healthy, non-obese volunteers aged 28 to 78 years without history of CVD, significant deviations by 12-lead electrocardiogram and negative exercise test (treadmill stress test). All the participants underwent standardized transthoracic echocardiography using an available system (iE33; Philips). The LTL was measured by real-time quantitative polymerase chain reaction. We determined the relative ratio of telomere repeat copy number (T) to single-copy gene copy number (S).</p><p>Results</p><p>In the older people there was a higher wall thickness than in the younger (1.03±0.09 vs. 0.88±0.10, p<0.01), whereas LV mass index was comparable between them (85.8±15.40 vs. 83.1±11.8, p = 0.20). There was a decrease in LV dimensions with advancing age (p<0.001). Older subjects had impairment in LV relaxation. LTL was associated with decreased E/A, Em/Am ratio (β = -0.323, p = 0.0001) after adjusting for age, sex and risk factors. There is no relation between the LTL and the structure of LV.</p><p>Conclusions</p><p>Our data suggest that the ageing process leads to changes in LV structure and diastolic function and is linked with a phenotype of concentric LV remodeling. Telomere attrition is associated with age-related LV diastolic dysfunction. Telomere length appears to be a biomarker of myocardial ageing.</p></div

Scatter plots showing the linear relationships between age and leukocyte telomere length, indices of LV diastolic function and leukocyte telomere length.

<p>(A) Linear regressions between E/A ratio and leukocyte telomere length. (B) Linear regressions between Em/Am ratio and leukocyte telomere length.</p

Comparison of the main clinical, echocardiographic characteristics and leukocyte telomere length between younger and older individuals.

<p>Measurements are shown as means ± SD. <i>LVDD</i>, LV diameter at the end of diastole; <i>LVDS</i>, LV diameter at the end of systole; <i>LVDV</i>, LV end-diastolic volume; <i>LVSV</i>, end-systolic volume; <i>LVMI</i>, LV mass index; <i>EF</i>, ejection fraction; <i>SWT</i>, septal wall thickness; <i>PWT</i>, posterior wall thickness; <i>E</i>, peak early phase filling velocity; <i>A</i>, peak atrial phase filling velocity; <i>DTE</i>, E wave deceleration time; <i>IVR</i>T, isovolumic relaxation time; <i>Em</i>, peak early diastolic mitral annular velocity; <i>Am</i>, peak diastolic mitral annular velocity; <i>S</i>, peak systolic velocity of pulmonary venous flow; <i>D</i>, peak anterograde diastolic velocity of pulmonary venous flow; <i>PV Ar</i>, peak retrograde velocity in late diastole of pulmonary venous flow.</p><p>Comparison of the main clinical, echocardiographic characteristics and leukocyte telomere length between younger and older individuals.</p