Предикторы дестабилизации атеросклеротической бляшки

[Igor73]

Plaque Rupture by Cholesterol Crystallization
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George S. Abela, MD, and Kusai Aziz, MD, hypothesized that soft plaque with large lipid deposits is supersaturated with cholesterol that can undergo transformation from liquid to a solid crystal state. During this transformation, the crystals expand within the confined space of atheromatous plaque, damaging the thin fibrous cap, and leading to rupture or erosion.

Фото 1. Elongated, needle-sharp crystals and flat, square or rhomboid-like crystals

[Igor73]

Plaque Rupture by Cholesterol Crystallization
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To evaluate the potential damage of cholesterol crystallization, clear liquid cholesterol was placed in four ml glass test tubes with the open end covered by rabbit pericardium, which is composed of collagen similar to the cap seen on vulnerable plaque. Once crystallization began, it proceeded rapidly and forcibly, perforating the overlying membrane in just three minutes

Фото 2. Cholesterol Crystals Emerging Through a Biological Membrane

[Igor73]

Plaque Rupture by Cholesterol Crystallization

In the human plaque, there were crystals protruding from both the arterial wall and plaque areas, with adjacent intimal sites showing crystals disrupting the endothelial lining of the artery.

Фото 3. Scanning Electron Micrographs of Necropsy Human Coronary Artery

[Igor73]

1. The presence of free cholesterol within a lipid-rich atheromatous plaque provides the ideal environment within a confined space that could lead to cap damage or rupture. They demonstrate two potentially injurious effects of cholesterol crystallization:
- One effect simulates plaque rupture by the force of crystal growth, leading to gross membrane damage with distortion and tearing.
- The second simulates plaque erosion by the extrusion of cholesterol crystals through overlying membrane causing local endothelial injury."

2. The findings are consistent, too, with the unpredictable and often seemingly random occurrence of plaque rupture and thrombosis seen clinically because the timing of crystallization depends on several local physical factors, including cholesterol concentration, pH, temperature, and pressure. There are a number of implications to this in terms of risk as well as treatment. For example, the elevated pressure of patients with hypertension might contribute to myocardial infarction in part due to the effects of pressure on crystallization.

[Igor73]

Хотелось бы привлечь внимание участников форума к проблеме поиска предикторов дестабилизации атеросклеротической бляшки. Ниже приведён отличный обзор на эту тему.
Sergio Waxman, Fumiyuki Ishibashi and James E. Muller. Detection and Treatment of Vulnerable Plaques and Vulnerable Patients: Novel Approaches to Prevention of Coronary Events. Circulation 2006;114;2390-2411.
Вкратце процесс представляется так: существует бляшка с тонкой покрышкой, в какой-то прекрасный момент в 70% случаев происходит кровоизлияние и разрыв бляшки, формируется тромб и развивается ИМ/НС.
Если бы мы умели прогнозировать дестабилизацию конкретной бляшки у конкретного пациента, то мы бы могли:
1. Ставить стенты только в vulnerable (угрожающие) plaques. При КАГ можно было бы определять угрожающие разрывом бляшки, не суживающие просвет сосуда и, возможно, стентировать их.
2. При наличии биохимического меркёра дестабилизации изменить стратификацию риска и подходы к лечению у пациентов со стабильной ИБС.
Фактически речь идёт о выделении неких предикторов возникновения ИМ/НС. Мне кажеться, это могло бы быть полезным.

[Igor73]

На глаза попалась информация о OCT (Optical Coherence Tomography), фотографии взяты с сайта [Ссылки доступны только зарегистрированным пользователям ] is OCT?

Optical Coherence Tomography (OCT) is a promising new class of diagnostic medical imaging technology that utilizes advanced photonics and fiber optics to obtain images and tissue characterization on a scale never before possible within the human body. When fully exploited, the technology has the potential to dramatically change the way physicians, researchers and scientists see and understand the human body in order to better diagnose and treat disease.

Simply put, OCT combines the principles of ultrasound with the imaging performance of a microscope and a form factor that is familiar to clinicians. Whereas ultrasound produces images from backscattered sound "echoes," OCT uses infrared light waves that reflect off the internal microstructure within the biological tissues. The frequencies and bandwidths of infrared light are orders of magnitude higher than medical ultrasound signals -- resulting in greatly increased image resolution - 8-25 times greater than any existing modality.

Infrared light is delivered to the imaging site through a single optical fiber only .006" diameter (about the size of the period in this sentence). The imaging guidewire contains a complete lens assembly to perform a variety of imaging functions. The guidewire can be deployed independently or integrated into existing therapeutic or imaging catheters.

OCT imaging can be performed over approximately the same distance of a biopsy at high resolution and in real time making the most attractive applications for OCT those where conventional biopsies cannot be performed or are ineffective. (Huang, Science 254:1178, 1991)

While standard electronic techniques are adequate for processing ultrasonic echoes that travel at the speed of sound, interferometric techniques are required to extract the reflected optical signals from the infrared light used in OCT. The output, measured by an interferometer, is computer processed to produce high-resolution, real time, cross sectional or 3-dimensional images of the tissue. This powerful technology provides in situ images of tissues at near histological resolution without the need for excision or processing of the specimen.

[Abugov]

Идея прогнозирования поведения атеросклеротической бляшки очень востребована. Несколько лет назад, были модны и.к. термография и пальпография (подробности можно поискать на TCTMD). Сейчас – это OCT. Это один из самых дорогих девайсов, который можно засунуть в коронарную артерию. По цене сравнимы только интракоронарные рентгеновские трубки, которые, некоторое время назад, применялись для брахиотерапии. Кстати, брахиотерапию убили стенты с лекарственным покрытием. На территории бывшего СССР купить OCT смогла позволить себе только богатая Республика Белоруссия (да будет мне позволено написание в дореформенной транскрипции). Смущает, что оценка «температуры» бляшки превышает стоимость последующего лечения.
А вообще, прибор, совмещающий в себе OCT, IVUS,FFR – мечта……….(может быть немного воспаленная).

[Igor73]

Сообщение от Abugov

Сейчас – это OCT. Это один из самых дорогих девайсов, который можно засунуть в коронарную артерию

Ну вот, такая идея была похоронена. Легко, по касательной. Мимоходоми и заживо.

[Abugov]

Сообщение от Igor73

Ну вот, такая идея была похоронена. Легко, по касательной. Мимоходоми и заживо.

Не-не-не!!! За ценой не постоим. IVUS тоже был, когда-то, уделом богатых. Просто рука сама по себе начала про бабло писать, а не про клиническую пользу. Дело хорошее и, может оказаться, действительно полезным.
Я же, лично, надеюсь, что МСКТ (или МР, что менее вероятно) будет давать нам структуру бляшки, определяя ее "температуру".

[Igor73]

Возможный (неожиданный) предиктор дестабилизации бляшки у мужчин. Вот она где, собака-то порылась..
B W V Schouten et al. International Journal of Impotence Research (2008) 20, 92–99; doi:10.1038/sj.ijir.3901604; published online 30 August 2007
Erectile dysfunction prospectively associated with cardiovascular disease in the Dutch general population: results from the Krimpen Study

The possible relationship between erectile dysfunction and the later occurrence of cardiovascular disease while biologically plausible has been evaluated in only a few studies. Our objective is to determine the relation between ED as defined by a single question on erectile rigidity and the later occurrence of myocardial infarction, stroke and sudden death in a population-based cohort study. In Krimpen aan den IJssel, a municipality near Rotterdam, all men aged 50–75 years, without cancer of the prostate or the bladder, without a history of radical prostectomy, neurogenic bladder disease, were invited to participate for a response rate of 50%. The answer to a single question on erectile rigidity included in the International Continence Society male sex questionnaire was used to define the severity of erectile dysfunction at baseline. Data on cardiovascular risk factors at baseline (age smoking, blood pressure, total- and high-density lipoprotein cholesterol, diabetes) were used to calculate Framingham risk scores. During an average of 6.3 years of follow-up, cardiovascular end points including acute myocardial infarction, stroke and sudden death were determined. Of the 1248 men free of CVD at baseline, 258 (22.8%) had reduced erectile rigidity and 108 (8.7%) had severely reduced erectile rigidity. In 7945 person-years of follow-up, 58 cardiovascular events occurred. In multiple variable Cox proportional hazards model adjusting for age and CVD risk score, hazard ratio was 1.6 (95% confidence interval (CI): 1.2–2.3) for reduced erectile rigidity and 2.6 (95% CI: 1.3–5.2) for severely reduced erectile rigidity. The population attributable risk fraction for reduced and severely reduced erectile rigidity was 11.7%. In this population-based study, a single question on erectile rigidity proved to be a predictor for the combined outcome of acute myocardial infarction, stroke and sudden death, independent of the risk factors used in the Framingham risk profile.
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[Igor73]

In Search of the "Vulnerable Plaque"

Can it Be Localized and Will Focal Regional Therapy Ever Be an Option for Cardiac Prevention?

John A. Ambrose, MD, FACC* University of California, San Francisco, Fresno, California.
Manuscript received September 25, 2007; revised manuscript received December 7, 2007, accepted December 17, 2007.


The search to find the location of future plaque ruptures or plaque erosions leading to myocardial infarction (so-called "vulnerable plaques") is an important area of cardiovascular research. Systemic therapy, including use of statins, targets the vulnerable patient. However, adverse events cannot be completely eliminated with the appropriate application of systemic therapies and thus has given rise to the possibility of local or regional therapy of "vulnerable plaques" to prevent future events. Until now, no criteria have been developed for consideration of this therapy. For such a strategy to work, there should be several prerequisites. These involve the identification of susceptible lesions, the number of lesions, their natural history, and proof that an interventional technique is preferable to medical therapy alone. The greatest deficiency relates to the fact that until the natural history of presumed "vulnerable plaques" is known one can never truly identify what constitutes a "vulnerable plaque." Much work needs to be done in this area, but ongoing and new trials should provide important information that could potentially change drastically how coronary artery disease is diagnosed and treated.
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