ОСОБЕННОСТИ ПОРАЖЕНИЯ ОРГАНОВ-МИШЕНЕЙ У БОЛЬНЫХ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ тема диссертации и автореферата по ВАК РФ 14.01.04, доктор наук Резник Елена Владимировна

• Резник Елена Владимировна
• доктор наук
• 2016

Оглавление диссертации доктор наук Резник Елена Владимировна

ОГЛАВЛЕНИЕ

СПИСОК СОКРАЩЕНИЙ

ВВЕДЕНИЕ

Актуальность темы

Цель исследования

Задачи исследования

Научная новизна работы

Практическая значимость работы

Внедрение

Публикации

Апробация диссертации

Объем и структура работы

ГЛАВА 1. ОБЗОР ЛИТЕРАТУРЫ

Почки как орган-мишень при ХСН, кардиоренальный синдром

Минеральные и костные нарушения при ХСН

Печень как орган-мишень при ХСН: кардиогепатический синдром

Бронхолегочный аппарат при ХСН: кардиореспираторный синдром

Метаболический синдром при ХСН: кардиометаболический синдром

Генетические предикторы СН и поражения органов-мишеней при этом заболевании

Эпигенетика СН

ГЛАВА 2. ХАРАКТЕРИСТИКА БОЛЬНЫХ И МЕТОДЫ ИССЛЕДОВАНИЯ

Характеристика больных, включенных в исследование

Методы исследования

Комплексное лабораторное обследование

Эхокардиографическое исследование

Холтеровское мониторирование ЭКГ

Суточное мониторирование АД

Ультразвуковое исследование почек

Оценка почечной гемодинамики

Оценкасубъективной выраженности клинической симптоматики ХСН

Оценка качества жизни

Оценка объективной выраженности клинической симптоматики

Исследование анамнестических данных

Тредмил-тест

6-минутный тест

Комплексное функциональное исследование внешнего дыхания

Двухэнергетическая рентгеновская денситометрия

Ультразвуковое исследование печени

Генетический анализ

Коррекция терапии, контроль за приверженностью к терапии, оценка ее влияния на

органы-мишени и лечение остеопороза у больных с ХСН

Статистическая обработка результатов

ГЛАВА 3. РЕЗУЛЬТАТЫ ИССЛЕДОВАНИЯ

Сравнительная характеристика структурно-функционального состояниясердечно-сосудистой системы у больных с ХСН со сниженной и сохраненной фракцией выброса

левого желудочка

Поражение почек как органа-мишени

Нарушения минерального и костного обмена при ХСН

Печень как орган-мишень при ХСН

Бронхолегочный аппарат у больных с ХСН

Предикторы и механизмы поражения органов-мишеней

Поражение органов-мишеней и лекарственная терапия ХСН

Влияние поражения органов-мишеней на прогноз у больных с ХСН

ГЛАВА 4. ОБСУЖДЕНИЕ ПОЛУЧЕННЫХ РЕЗУЛЬТАТОВ И ЗАКЛЮЧЕНИЕ328

Структурно-функциональное состояние сердечно-сосудистой системы у больных с ХСН

Поражение почек при ХСН

Минерально-костные нарушения

Печень как орган-мишень при ХСН

Бронхолегочный аппарат как орган-мишень при ХСН

Механизмыпораженияорганов-мишеней

Влияние поражения органов-мишеней на выживаемость больных с ХСН

Заключение:

ВЫВОДЫ

ПРАКТИЧЕСКИЕ РЕКОМЕНДАЦИИ

Клинические примеры

БЛАГОДАРНОСТЬ

СПИСОКЛИТЕРАТУРЫ

Введение диссертации (часть автореферата) на тему «ОСОБЕННОСТИ ПОРАЖЕНИЯ ОРГАНОВ-МИШЕНЕЙ У БОЛЬНЫХ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ»

ВВЕДЕНИЕ

Актуальность темы

Несмотря на значительные достижения в лечении различных сердечно-сосудистых заболеваний, распространенность хронической сердечной недостаточности (ХСН) продолжает расти [184].

В мире 23 миллиона человек страдают ХСН. В Европейских странах это заболевание диагностировано у1-2,6% населения[626], в США - у 5,7 млнвзрослых старше 20 лет, распространенность составляет 2,2% [383, 655]. В Российской Федерации ХСН выявлена у 7,9 миллионов человек, по другим данным - у 7% населения, и почти 70% у лиц старше 90 лет [38, 78], т.е. распространенность этого заболевания в нашей стране значительно превышает таковую в Европейских странах и США.

В Европе на долю ХСН приходится 5% всех госпитализаций [869]. В США ХСН приводит к 1,023 миллиону госпитализаций ежегодно (6,5 млн койко дней) [655]. В РФ среди госпитализированных больных с ССЗ ХСН является основной причиной госпитализации у 16,7%. Это заболевание является самой частой причиной стационарного лечения среди лиц старше 65 лет [78, 457]. Причем около 50% больных с ХСН повторно госпитализируется в течение 6 месяцев,20-25% больных - в течение 30 дней после выписки из стационара -[777]. 70% повторных госпитализаций связано с декомпенсацией СН[373].

В будущем в связи со старением популяции, увеличением распространенности кардиальных факторов риска и улучшением выживаемости больных с различной сердечно-сосудистой патологией ожидается дальнейший рост числа больных с ХСН [457].К 2030 году прогнозируется увеличение количества больных с ХСН на 46%[655].

Стоимость лечения ХСН в США в 2012 году составила 30,7 миллар-дов долларов [383]. К 2030 году ожидается ее увеличение на 127% - до 69,7 миллиардов долларов в год [383, 655].

Прогрессирование ХСН сопровождается резким снижением качества жизни, снижением/утратой трудоспособности больных и увеличением летальности. Причем потери трудоспособного населения, обусловленные сердечнососудистой заболеваемостью и смертностью, в Европейском Союзе составляют 45 миллионов евро в год [673].

Ведущей причиной сердечно-сосудистой летальностиявляется ХСН [101]. Смертность при ХСН в 4-10,3 раза выше, чем в общей популяции соответствующего возраста, и сравнима, или даже превосходит, смертность от ряда онкологических заболеваний [141, 596]. Пятилетняя летальность при ХСН момента постановки диагноза до 90-х годов составляла 6070% больных, в последние годы отметилось ее небольшое, но значимое снижение до 50%[383, 626, 655]. Ежегодная смертность при ХСН составляет 17,4-33%[591]: в США - 250 тысяч, вРФ - 612 тысяч человек в год[38]. Причем смертность у больных с ХСН со сниженной фракцией выброса левого желудочка (ФВ ЛЖ) выше, чем у больных с ХСН с сохраненной ФВ ЛЖ независимо от возраста, пола и этиологии ХСН [101]. Внутрибольнич-ная летальность при ХСН составляет 2-20%. Ранняя постгоспитальная (в течение 30 дней после выписки из стационара) - 11,3% [456].Смертность больных с ХСН остается высокой, даже несмотря на лечение ингибиторами АПФ, бета-блокаторами и антагонистами рецепторов альдостерона, показавших в многочисленных клдинических исследованиях значительное снижение относительного риска смертности по сравнению с плацебо[89, 93, 730].

В связи с этим задачами здравоохранения является значительное улучшение качества медицинской помощи больным с ХСН, профилактика прогрессирования заболевания и инвалидизации, улучшение качества и увеличение продолжительности жизни.

В настоящее время ХСН рассматривается как системная патология, при которой поражаются не только сердце и сосуды, но и многие системы органов [735].Однако комплексного изучения поражения различных органов-мишеней при этом заболевании не проводилось. Недостаточно изучены клинические, лабораторные, инструментальные, генетические и социальные факторы, влияющие на развитие поражения органов-мишеней, про-грессирование и декомпенсацию ХСН, взаимосвязь этих факторов друг с другом, а также их влияние на частоту госпитализаций и смертность боль-ных.Недостаточно изучено влияние поражения различных органов-мишеней на выраженность клинической симптоматики, переносимость физических нагрузок, качество жизни и прогноз при ХСН. Отсутствует сравнительная характеристика поражения органов-мишеней при ХСН с низкой и сохраненной систолической функцией левого желудочка.Не окончательно разработаны методы ранней диагностики и профилактики поражений органов-мишеней.Нет классификаций степени выраженности и клинических вариантов поражения органов-мишеней при ХСН. Сравнительные исследования влияния на органы мишени различных препаратов из групп, рекомендованных для лечения больных с ХСН, практически не проводились. Специфическая органопротективная терапия для данной категории больных в настоящее время не разработана. В Руководствах по ведению пациентов с СН конкретных рекомендаций по выявлению и лечению поражений органов-мишеней в настоящее время нет[130, 626]. При этом в Рекомендациях Европейского общества кардиологов по ведению больных с СН среди основных направлений, по которым необходимы дальнейшие исследования этой патологии, указано изучение особенностей ведения ХСН с кардиоренальным синдромом, сахарным диабетом, анемией, депрессией, апноэ во сне и другой сопутствующей патологией [626], в т.ч. с поражением различных органов-мишеней.

Учитывая все вышеперечисленное, изучение особенностей поражения органов-мишеней при ХСНявляется актуальной задачей.

Цель исследования

Изучить поражение органов-мишеней у больных с хронической сердечной недостаточностью и разработать методы ранней диагностики, профилактики и коррекции поражения органов-мишеней при этом заболевании.

Задачи исследования

Для достижения указанной цели были поставлены следующие задачи:

1. провести комплексную оценку структурно-функционального состояния сердечно-сосудистой системы, почек, печени, костной системы, бронхолегочного аппарата как основных органов-мишеней при ХСН,

2. изучить различные предикторы (клинико-анамнестические, инструментальные, лабораторные, генетические) и механизмы (гемодина-мические, нейрогормональные, метаболические, апоптоз, воспаление) поражения исследуемых органов-мишеней, разработать систему для оценки персонального риска развития поражения органов-мишеней при ХСН,

3. изучить возможности ранней диагностики поражения органов-мишеней у больных с ХСН и выявить их клинические варианты,

4. изучить взаимосвязьпоражения органов-мишеней свыраженно-стью клинической симптоматики, ограничением физической активности, поражениемдругих органов-мишеней, качеством жизни, течением, про-грессированием и прогнозом у больных с ХСН,

5. на основании полученных результатов, а также современных национальных и международных рекомендаций по лечению коморбидных состояний, результатов фармакологических исследований разработать комплексный подход к индивидуальный тактике ведения пациентов, направленный на профилактику и коррекцию поражения различных органов-мишеней, улучшение качества и увеличение продолжительности жизни больных с ХСН.

Научная новизна работы

Впервые произведена комплексная оценка характера, степени выраженности, распространенности, предикторов и механизмов поражения поражения различных органов-мишеней: структурно-функционального состояния сердечно-сосудистого аппарата, почек, печени, бронхолегочной и костной системы, метаболических изменений у больных с ХСН. Разработана научная концепция формирования поражения органов-мишеней при этом заболевании. Предложена гипотеза о наличии специфических факторов риска формирования и прогрессирования поражения органов-мишеней при ХСН. Выделены группы повышенного риска по развитию поражения органов-мишеней. Установлены общие закономерности и взаимосвязи поражения различных органов-мишеней. Выявлен влияние поражения различных органов-мишеней на выраженность клинической симптоматики, толерантность к физическим нагрузкам, качество жизни, течение и прогноз ХСН. Предложены методы ранней диагностики и подходы к коррекции поражения органов-мишеней при ХСН.

Выявлено частое развитие хронической болезни почек у больных ХСН без исходной внесердечной патологии. Установлены признаки поражения почек при ХСН различной этиологии и степени тяжести. Показана этапность и неблагоприятное прогностическое значение поражения почек при ХСН.

Впервые проведена комплексная оценка минерально-костных нарушений при ХСН. Показано частое развитие гипокальциемии, гиперфосфа-темии, вторичного гиперпаратиреоза, дефицита/недостаточности витамина D у больных с ХСН, их взаимосвязь с поражением сердца и почек. Выявлена роль гиперфосфатемии и вторичного гиперпаратиреоза как новых предикторов неблагоприятного прогноза при ХСН.

Впервые исследована костная система как орган-мишень у больных с ХСН. Показано частое поражение костной системы при ХСН в виде снижения минеральной плотности кости, развития остеопороза и остеопении,

ассоциированных с развитием переломов. Выявлена взаимосвязь поражения костной системы с переносимостью физических нагрузок, физической активностью, поражением почек, вторичным гиперпаратиреозом и дефицитом/недостаточностью витамина D. Выявлена тенденция к повышению смертности при развитии остеопороза и переломов при ХСН.

Впервые изучены маркеры костеообразования (интактный остео-кальцин - ОК) и костной резорбции (С-концевой телопептид коллагена I типа - СТП, остеопротегерин - остеопротегерин) и кальцитонин у больных с ХСН. Выявлена их взаимосвязь с нарушениями кальций-фосфорного го-меостаза, вторичным гиперпаратиреозом, поражением костной системы и почек, гипертензивным анамнезом и структурно-функциональными изменениями сердца.

Проведено обследование структурно-функционального состояния бронхолегочного аппарата (спирография, пневмотахография, исследование сопротивления дыхательных путей, газового состава крови с помощью бо-диплетизмографа) и оценка его влияния на выраженность клинической симптоматики, ограничение физической активности, прогрессирование заболевания, поражение других органов-мишеней, а также вклада в изменение качества жизни и прогноз у больных с ХСН.

Впервые проведен анализ полиморфных маркеров Рго72А^ и С(-594)СС гена ТР53, полиморфного маркера С825Т гена GNB3 и полиморфных маркеров генов, кодирующих бета2-адренорецептор (АДРБ2) как генетических факторов риска поражения органов-мишеней при ХСН.

Представлены результаты 10-летнего наблюдения за больными с ХСН, прослежены динамические изменения в органах-мишенях, взаимосвязь с проводимой терапией, осложнения, развившиеся в течение этого времени, их прогностическое значение и взаимосвязь с поражением органов-мишеней. Разработан подход для профилактики прогрессирования поражения органов-мишеней и развития осложнений.

Показана необходимость своевременной диагностики поражения ор-

ганов-мишеней и органопротективной терапии для улучшения качества и продолжительности жизни больных с ХСН и необходимость мультидис-циплинарного подхода к пациентам с этим заболеванием.

Практическая значимость работы

1. Показана необходимость скринингового обследования больных с ХСН для раннего и адекватного выявления поражения органов-мишеней и назначения органопротективных мероприятий с целью замедления его прогрессирования, предотвращения развития тяжелых осложнений и увеличения продолжительности и качества жизни пациентов.

2. Показано значение дуплексного сканирования почечных артерий для диагностики и определения степени тяжести дисфункции почек, динамического наблюдения и стратификации риска у больных с ХСН.

3. Показана важность выявления нарушений кальций-фосфорного обмена, недостаточности витамина D, гиперпартиреозаи гиперфосфатури-идля оценки прогноза у больных с ХСН.

4. Выявлены данные о предикторах и механизмах развития, прогрес-сирования и декомпенсации ХСН, распространенности, характере и степени тяжести поражения органов-мишеней, его влиянии на течение, выраженность клинической симптоматики, снижение функциональных возможностей пациентов, состояние центральной и периферической гемодинамики, поражение других органов и их систем, качество и продолжительность жизни больных с ХСН в российской популяции. Это может облегчить развитие выявляющих причины диагностических методов, патогенетических лечебных и профилактических мероприятий.

5. Предложены методы медикаментозной и немедикаментозной профилактики и терапии поражения органов-мишеней, способствующие улучшению качества жизни, сохранению работоспособности и уменьшению смертности больных, что может привести к снижению роста заболеваемости ХСН, частоты госпитализаций, уменьшению экономических затрат

на лечение, социальной реабилитации, увеличению количества трудоспособного населения страны и национального валового продукта, начато внедрение их в практическое здравоохранение.

6. На основе исследования взаимосвязи клинических и генетических маркеров развития ХСН и поражения органов-мишеней предложена модель для оценки персонального риска развития поражения органов-мишеней и неблагоприятного прогноза.

8. Внедрение результатов исследования позволит значительно повысить качество ранней диагностики, профилактики и лечения ХСН, снизив при этом расходы за счет индивидуального подбора профилактических и лечебных мероприятий, учитывая полученные результаты об имеющихся факторах риска.

Внедрение

Результаты исследования внедрены и используются в терапевтических и кардиологических отделениях, отделении функциональной и лабораторной диагностики ГБУЗ ГКБ №12 ДЗМ (с 09.2015 - ГБУЗ ГКБ им.В.М.Буянова ДЗМ) и в кардиологическом отделении ГБУЗ ГКБ №24 ДЗМ.

Публикации

По материалам диссертации опубликовано 86 печатных работ,17 - в рецензируемых журналах, 22 - в зарубежных изданиях.

Апробация диссертации

Основные положения диссертации представлены в виде докладов на:

• совместном заседании сотрудников кафедры госпитальной терапии №2 лечебного факультета ГБОУ ВПО РНИМУ им.Н.И.Пирогова Минздрава РФи ГКБ №12 ДЗМ,

• ХШи ХХПРоссийском Национальном Конгрессе «Человек и лекарство» (Москва, 2006 и 2015),

• Европейскихконгрессахкардиологов- ESCCongress(Munich, Germany, 2012; Barselona, Spain, 2014),

• XV-м Международном Конгрессе диетологов и нутрициологов «Питание и здоровье» (Москва, 2014),

• Конгрессе по сердечной недостаточности Европейского общества кардиологов 2010 - Heart Failure 2010 Congress (Berlin, Germany, 2010, Travel grant of the European Society of Cardiology (ESC),

• 20-й Конференции по артериальной гипертензии - 20th European Meeting on Hypertension (Oslo, Norway, 2010, Accomodation grant of the European Society of Hypertension (ESH),

• XLIII и LI Конгрессах Европейской Ассоциации Почек -Европейской Ассоциации Диализа и Трансплантации - Congress of the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) (Глазго, Великобритания, 2006; Амстердам, 2014),

• 11-й, 12-й и 15-й Конференциях Европейского Совета по сердечно-сосудистым исследованиям - Meeting of the European Council for Cardio-vascular Research (ECCR) (Ницца, Франция, 2006, 2007, 2010),

• VI, VII, Х Ежегодной Конференции (I и IV Конгрессах) Общества специалистов по сердечной недостаточности "Сердечная недостаточность' 2005, 2006, 2009" (Москва, 2005, 2006, 2009, диплом за лучшую работу в области патофизиологии и патогенеза кардиологической патологии конференции молодых ученых),

• 10-м Юбилейном Конгрессе Российского общества холтеров-ского мониторирования и неинвазивной электрофизиологии (РОХМиНЭ) и 3-й Всероссийский Конгресс "Клиническая электрокардиология" (Санкт-Петербург, 2009),

• 9-й Всероссийской медико-биологической конференции молодых ученых «Человек и его здоровье» (Санкт-Петербург, 2006, II место),

• Российском Национальном Конгрессе кардиологов 2006, 2015 (Москва, 2006, 2015),

• 14-м Европейском конгрессе по внутренним болезням -14thEuropeanCongressofInternalMedicine (ЕС1М) (Москва, 2015) и др.

Награды

• 2009 Национальная стипендия L'OREAL-Юнеско «Для женщин в науке»

• 2010 Избрание Действительным членом Европейского Совета по сердечно-сосудистым исследованиям (ECCR)

Гранты

• 2006-2007 Со-исполнитель гранта Президента РФ для поддержки ведущих научных школ «Хроническая сердечная недостаточность: изучение механизмов прогрессирования и путей повышения качества жизни» (грант НШ 2241.2006.7, грантополучатель -академик РАМН, д.м.н. Сторожаков Г.И.)

• 2008-2009 Со-исполнитель гранта Президента РФ для поддержки ведущих научных школ «Хроническая сердечная недостаточность: изучение механизмов прогрессирования и путей повышения качества жизни» (грант НШ-5839.2008.7, грантополучатель -академик РАМН, д.м.н. Сторожаков Г.И.)

• 2009-2010 Грантополучатель гранта Президента РФ для государственной поддержки молодых российских ученых «Нарушения кальций-фосфорного гомеостаза, обмена витамина D и вторичный гипер-паратиреоз при хронической сердечной недостаточности: взаимосвязь с клинической картиной, качеством жизни, выраженностью и прогрессиро-ванием кардиоренальной дисфункции, прогнозом» (МК-3133.2009.7)

• 2010-2011 Со-исполнитель гранта РГНФ по программе «Поддержка приоритетных фундаментальных гуманитарных исследований» 2010 г. «Исследование качества жизни и возможностей медицинской и социальной реабилитации у больных после жизнеспасающего лечения» (10-06-00112а)

• 2010 TravelgrantoftheEuropeanSocietyofCardiology (ESC) для участия и представления постерного доклада на Конгрессе по сердечной недостаточности, 29.05-1.06.2010 (HeartFailure 2010 Congress, Berlin, Germany)

• 2010 AccomodationgrantoftheEuropeanSocietyofHypertension (ESH) для участия и представления постерного доклада на 20-й Конференции по гипертензии, 18-22.06.2010 (20thEuropeanMeetingonHypertension, Oslo, Norway)

• 2011-2012 Грантополучатель гранта Президента РФ для государственной поддержки молодых российских ученых «Исследование поражения органов-мишеней у больных с хронической сердечной недостаточностью и возможностей органопротективной терапии для предотвращения прогрессирования заболевания, увеличения продолжительности и улучшения качества жизни пациентов» (МК-5070.2011.7)

• 2012 FreeregistrationfromtheEuropeanSocietyofCardiology (ESC) для участия и представления постерного доклада на Европейском Конгрессе кардиологов, 25.08-28.08.2012 (ESC 2012 Congress, Munich, Germany)

• 2014 Грант Российского кардиологического общества (РКО) для участия и представления постерного доклада на Европейском Конгрессе кардиологов, 30.08-3.09.2014 (ESC 2014 Congress, Barselona, Spain)

Объем и структура работы

Диссертация изложена на 500 страницах машинописного текста, иллюстрирована 64 таблицами и 56 рисунками, состоит из введения, обзора современной литературы, описания клинического материала и методов исследования, изложения результатов собственных исследований, обсуждения полученных результатов, заключения, выводов, практических рекомендаций. Список использованной литературы включает в себя 992 работы, из них 88 отечественных. В Приложении представлены использованные в работе опросники, клинические примеры.

Заключение диссертации по теме «Внутренние болезни», Резник Елена Владимировна

ВЫВОДЫ

1. Хроническая сердечная недостаточность (ХСН) является поли-органнойпатологией, при которой развиваются структурные и функциональные нарушения как сердечно-сосудистой системы, так и почек, пече-ни,бронхолегочного аппарата и костной системыс развитием кардиоре-нального, кардиогепатического, кардиореспираторного синдромов и комплекса костно-минеральных нарушений. В связи с этим целесообразен переход от миокардориентированной к многофункциональной как интра, так и экстракардиальной концепции сердечной недостаточности.

2. Развитию и прогрессированию поражения органов-мишеней при ХСН способствуют нарушение систолической и диастолической функции сердца, нейрогуморальная активация, фибрилляция предсердий, артериальная гипертензия и гипотензия, ожирение, нарушения пуринового, белкового и углеводного обмена, генетические факторы, пожилой возраст, мужской пол, злоупотребление алкоголем, курение и воспаление.Эти факторы необходимо учитывать при стратификации персонального риска развития поражения органов-мишеней при ХСН.

3. Кардиоренальный синдром при ХСН представляет собой хроническую болезнь почек со снижением скорости клубочковой фильтрации и развитием альбуминурии. Предикторами поражения почек при ХСН яв-ляляются большая выраженность клинической симптоматики ХСН, ише-мическая этиология ХСН, большая длительность и тяжесть АГ в анамнезе, наличие сахарного диабета, фибрилляции предсердий, большая выраженность поражения сердца (гипертрофия, диастолическая дисфункция миокарда левого желудочка, легочная гипертензия, кальциноз клапанов сердца), возраст, активация системы воспаления.

4. Кардиогепатический синдром при ХСН включает гепатомега-лию, развитие цитолитического, холестатического синдромов и реже пече-ночно-клеточной недостаточности. Факторами риска поражения печени

как органа-мишени при ХСН являются тяжесть СН, систолическая дисфункция миокарда левого желудочка и снижение функционального состояния почек.

5. Частым проявлением поражения бронхолегочного аппарата у пациентов с ХСН является рестриктивный тип вентиляционных нарушений. Факторами риска поражения поражения бронхолегочного аппаратаяв-ляется тяжесть СН, снижение толерантности к физической нагрузке, активация системы воспаления, снижение сердечного выброса и снижение почечного кровотока.

6. Костно-минеральные нарушения при ХСН представлены гипо-кальциемией, гиперфосфатемией, дефицитом/недостаточностью витамина D, вторичным гиперпаратиреозом, остеопенией и остеопорозом.Больные с ХСН являются группой повышенного риска возникновения минерально-костных нарушений, остеопороза и связанных с ним переломов.

7. Поражение органов-мишеней при ХСН связано с увеличением тяжести клинической симптоматики, снижением переносимости физических нагрузок, ухудшением качества жизни, ускорением прогрессирования ХСН, поражением других органов-мишеней и повышением смертно-сти.Неблагоприятными прогностическими факторами, связанными с поражением органов-мишеней при ХСН, являются снижение скорости клубоч-ковой фильтрации, наличие альбуминурии, вторичный гиперпаратиреоз, гиперфосфатемия, повышение значений индекса MELD-XI, с снижение общей емкости легких и альвеолярного объема. Это необходимо учитывать при разработке дальнейших направленийпо улучшению прогноза при ХСН.

8. В комплексный подход к индивидуальный тактике ведения пациентов с ХСН и поражением органов-мишеней необходимо включать мероприятия, направленныена профилактику и лечение поражения различных органов-мишеней, в том числе приверженность к диетическому ограничению потребления фосфатов, достаточное пребывание на солнце, дози-

рованные физические нагрузки.

ПРАКТИЧЕСКИЕ РЕКОМЕНДАЦИИ

1. При формулировке диагноза больным с хронической сердечной недостаточностью необходимо указывать наличие поражений органов-мишеней, их клинические варианты и стадии.

2. С целью своевременноговыявленияпоражения органов-мишенейв алгоритм обследования и медикоэкономические стандарты ведения всех больных с хронической сердечной недостаточностью следует включать оценку скорости клубочковой фильтрации по формуламCKD-EPI и МОЯО, количественное определение суточной экскреции альбумина с мочой, ультразвуковое исследование печени и почек, печеночные функциональные тесты, исследование функции внешнего дыхания и денситометрию.

3. При однократном выявлении снижения скорости клубочковой фильтрации у госпитализированных пациентов с хронической сердечной недостаточностью целесообразно повторить исследование и при повторном выявлении снижения скорости клубочковой фильтрации диагностировать хроническую болезнь почек.

4.С учетом неблагоприятного влияния на прогноз для профилактики и коррекции гиперфосфатемии у больных с хронической сердечной недостаточностью целесообразно ограничивать потребление фосфатов с пищей (путем замены белков животного на белки растительного происхождения, отказа от употребления полуфабрикатов, консервантов и фастфуда) и контролировать уровень неорганического фосфора в сыворотке крови (целевой уровень фосфора в сывороткекрови 2,7-4,6 мг/дл). Для возможного расчета потребления фосфатов с пищей необходимо обязать производителей продуктов питанияуказывать содержание фосфатов на этикетках производимых продуктов.

5. Определение минеральной плотности костной ткани и оценка вероятности перелома с помощью модели FRAXв динамике у больных с хронической сердечной недостаточностью необходимы для своевременной

диагностики остеопении, остеопороза и оценки риска развития переломов. При выявлении остеопороза и высоком риске переломов у пациентов с хронической сердечной недостаточностью необходимо рассмотрение вопроса об их медикаментозной терапии.

6. Поскольку использование нижней границы нормы (LLN) при анализе результатов спирометрии продемонстрировал наибольшую согласованность с клинико-анамнестическими данными, целесообразно в практической работе для оценки спирометрии использовать LLN наряду с системой должных значений (% от должного).

Список литературы диссертационного исследования доктор наук Резник Елена Владимировна, 2016 год

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