Влияние терапии розувастатином на факторы ангиогенеза у больных хронической ишемической болезнью сердца тема диссертации и автореферата по ВАК РФ 14.00.06, кандидат медицинских наук Семенова, Анна Евгеньевна

• Семенова, Анна Евгеньевна
• кандидат медицинских наук
• 2009

Оглавление диссертации кандидат медицинских наук Семенова, Анна Евгеньевна

СПИСОК СОКРАЩЕНИЙ.

ВВЕДЕНИЕ.

Глава 1. ОБЗОР ЛИТЕРАТУРЫ.

1.1. Ангиогенез как новый подход к ведению больных ИБС.

1.2. Механизмы неоваскуляризации при ИБС.

1.3. Роль факторов роста в неоваскуляризации зрелого миокарда.

1.4. Терапевтический ангиогенез.

1.5. Влияние статинов на неоваскуляризацию при ИБС.

Глава 2. МАТЕРИАЛЫ И МЕТОДЫ ИССЛЕДОВАНИЯ.

2.1. Клиническая характеристика больных.

2.2. Клинические и инструментальные методы исследования.

2.3. Лабораторные методы исследования.

2.4. Статистическая обработка результатов исследования.

Глава 3. РЕЗУЛЬТАТЫ ИССЛЕДОВАНИЯ.

3.1. Уровень факторов ангиогенеза - УЕвР, ТОБр, ЬГвГ, эндостатина - в крови у здоровых лиц и у больных ИБС.

3.2. Уровень факторов ангиогенеза и степень поражения коронарного русла по данным коронароангиографии.

3.3. Уровень факторов ангиогенеза и степень нарушения миокардиальной перфузии по данным радионуклидной перфузионной сцинтиграфии миокарда.

3.4. Влияние 3-х месячной терапии розувастатином в дозах 5 мг, 10 мг и 40 мг в сутки на динамику факторов ангиогенеза у больных ИБС.

3.5. Оценка переносимости больными ИБС 3-х месячной терапии розувастатином в дозах 5, 10 и 40 мг в сутки.

Глава 4. ОБСУЖДЕНИЕ РЕЗУЛЬТАТОВ.

ВЫВОДЫ.

Введение диссертации (часть автореферата) на тему «Влияние терапии розувастатином на факторы ангиогенеза у больных хронической ишемической болезнью сердца»

В связи с большой распространённостью ИБС среди населения, улучшение качества и продолжительности жизни этих больных является одной из приоритетных задач здравоохранения [1, 8, 9, 12, 16]. Поскольку, несмотря на постоянное совершенствование методов обследования и лечения, сохраняется высокий уровень смертности от данного заболевания, ведутся поиски и разработки новых подходов к ведению больных ИБС. Перспективным направлением является изучение ангиогенеза [21, 22]. Раскрытие механизмов этого процесса позволит экзогснно стимулировать, либо создавать благоприятные условия для формирования новых сосудов и тем самым улучшать кровоснабжение миокарда [65, 102, 269]. Однако вряд ли стоит рассчитывать существенно повлиять на сложный, многофакторный процесс ангиогенеза только путём введения одного потенциального стимулятора. Необходимо учитывать условия, благоприятные для формирования новых сосудов. Для этого важна оценка динамики уровней факторов ангиогенеза у больных ИБС. Существуют работы, в которых показано угнетение ангиогенеза на фоне гиперлипидемии, гипергликемии, при развитии эндотелиальной дисфункции [106, 337, 415]. Известно, что гиперлипидемия, являющаяся одним из основных факторов риска развития атеросклероза, подавляет стимулирующее действие факторов роста ангиогенеза УЕОР [415] и ЬБвР [98, 330] и замедляет артериогенез по данным ангиографии [404]. Также показано, что СРБ подавляет ангиогенез, индуцированный УЕСБ [411] и рост коронарных коллатералей по данным коронароангиографии [156]. Больным с ИБС необходима постоянная комбинированная терапия, которая влияет на липидный спектр крови, эпдотелиальную дисфункцию, активность факторов воспаления, симпатико-адрепаловой и ренин-ангиотензин-альдостероновой системы, показатели свёртываемости крови и многие другие факторы, возможно, играющие свою роль в процессе ангиогенеза [266]. Представляется интересным изучить влияние терапии статинами в различных дозах на динамику факторов ангиогенеза и маркёров воспаления, так как ранее было показано, что препараты этой группы могут изменять естественное течение ангиогенеза у больных ИБС [82, 145, 394]. Так же есть данные, что в зависимости от дозы статины могут по-разному влиять на процессы ангиогенеза [430, 401].

В настоящем исследовании были поставлены следующие цель и задачи:

Цель исследования:

Изучить влияние терапии низкими, средними и высокими дозами розувастатина на факторы ангиогенеза у больных ИБС.

Задачи исследования:

1. Сравнить уровень факторов ангиогенеза - сосудистого эндотелиального фактора роста (УЕвР), трансформирующего фактора роста (3 (ТвРр), основного фактора роста фибробластов (ЬРОР), эндостатина - в крови у больных ИБС и здоровых лиц.

2. Сопоставить уровень факторов ангиогенеза со степенью поражения коронарного русла по данным коронароангиографии.

3. Сопоставить уровень факторов ангиогенеза со степенью нарушения миокардиальной перфузии по данным радионуклидной перфузионной сцинтиграфии миокарда.

4. Изучить влияние 3-х месячной терапии розувастатином в дозах 5 мг, 10 мг и 40 мг в сутки на динамику факторов ангиогенеза у больных ИБС.

Научная новизна.

Впервые в рамках одного исследования проведена оценка связи между факторами риска сердечно-сосудистых осложнений, выраженностью стенокардии напряжения, медикаментозной терапией и уровнем факторов ангиогенеза в периферической крови больных ИБС. Показано, что уровень сосудистого эндотелиального фактора роста выше у больных ИБС по сравнению со здоровыми добровольцами. Выявлено отсутствие различий в уровне факторов ангиогенеза у мужчин и женщин в постменопаузе. Установлено, что уровень эндостатина достоверно ниже у курящих, чем у некурящих больных ИБС.

Впервые в мире изучено влияние терапии розувастатином в дозах 5, 10 и 40 мг/сут на уровень факторов аигиогеиеза (сосудистого эидотелиалыюго фактора роста, трансформирующего фактора роста (3 и эндостатина) у больных хронической ИБС. Показано, что терапия розувастатином приводит к достоверному снижению уровня сосудистого эндотелиального фактора роста, трансформирующего фактора роста р и не влияет на уровень эндостатина. Установлено, что влияние розувастатина на данные факторы ангиогенеза не связано с гиполипидемическим действием препарата-и его воздействием на уровень высокочувствительного С-реактивного белка.

Практическая значимость.

Результаты работы могут быть использованы при разработке новых методов лечения больных ИБС, в частности, терапевтического ангиогенеза, а также новых подходов к ведению этих больных с учётом процессов неоваскуляризации.

Заключение диссертации по теме «Кардиология», Семенова, Анна Евгеньевна

выводы

1. У больных ИБС уровень УЕОБ в периферической крови достоверно выше, уровень ТОБр ниже, а уровень эндостатина достоверно не отличается от уровня данных показателей у здоровых добровольцев.

2. Отсутствуют достоверные различия в уровне УЕОБ, ТОБр и эндостатина в периферической крови у мужчин и женщин в постменопаузе.

3. Отсутствует корреляция между уровнями ОХС, ХС ЛНП, ХС ЛВП, ТГ, в.ч.СРБ и уровнями УЕОБ, ТОБр и эндостатина в крови больных ИБС.

4. Выявлена прямая связь между суммарным коронарным индексом стенозов (модифицированный индекс Оеггени), площадью преходящего дефекта перфузии миокарда (ОЭКТ миокарда с 99т-Тс-МИБИ) и уровнем УЕОБ у больных ИБС.

5. Терапия розувастатином в независимости от гиполипидемического действия препарата и его влияния на в.ч.СРБ приводит к достоверному снижению уровня УЕОБ, ТОРр и не влияет на уровень эндостатина.

6. Приём розувастатина в дозе 5 и 10 мг/сут в течение трёх месяцев приводит к снижению уровня УЕОР на 19% и 22% соответственно. На фоне приёма розувастатина в дозах 5, 10 и 40 мг/сут в течение трёх месяцев отмечается снижение уровня ТОРр на 23%, 26% и 18% соответственно.

ПРАКТИЧЕСКИЕ РЕКОМЕНДАЦИИ

Результаты настоящего исследования рекомендуется использовать при проведении научно-исследовательских работ, направленных на разработку новых подходов к лечению больных ИБС путём воздействия на факторы ангиогенеза.

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