Genetic Polymorphisms and the Risk of Stroke After Cardiac Surgery

Grocott, Hilary P.; White, William D.; Morris, Richard W; Podgoreanu, Mihai V.; Mathew, Joseph P.; Nielsen, Dahlia M.; Schwinn, Debra A.; Newman, Mark F.

doi:10.1161/01.str.0000177482.23478.dc

Cited by 79 publications

(58 citation statements)

References 30 publications

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“…продемонстрировали, что по-вышение плазменного уровня СРБ позволяет достоверно прогнозировать риск инсульта и транзиторных ишемиче-ских атак у пожилых пациентов [16]. В ряде исследований доказано, что структурные особенности гена СРБ ассо-циированы с развитием одного из грозных осложнений КШ -ишемического инсульта, а также имеют значение при развитии когнитивного дефицита после проведения операции на сердце.…”

Section: P%'>% обзор посвящен проблеме развития послеоперационных оunclassified

“…В ряде исследований доказано, что структурные особенности гена СРБ ассо-циированы с развитием одного из грозных осложнений КШ -ишемического инсульта, а также имеют значение при развитии когнитивного дефицита после проведения операции на сердце. Одним из примеров является ми-норный аллель 3'UTR 1846 C>T СРБ, который был связан с увеличением базальных плазменных уровней СРБ и представляет собой часть гаплотипа, ассоциирующегося с повышенными пиковыми уровнями СРБ после КШ [16]. Хотя точный механизм действия СРБ в патогенезе инсульта при операции на сердце до конца не изучен, высокий уро-вень СРБ ассоциируется с повышением риска развития инсульта [16].…”

Section: P%'>% обзор посвящен проблеме развития послеоперационных оunclassified

“…Одним из примеров является ми-норный аллель 3'UTR 1846 C>T СРБ, который был связан с увеличением базальных плазменных уровней СРБ и представляет собой часть гаплотипа, ассоциирующегося с повышенными пиковыми уровнями СРБ после КШ [16]. Хотя точный механизм действия СРБ в патогенезе инсульта при операции на сердце до конца не изучен, высокий уро-вень СРБ ассоциируется с повышением риска развития инсульта [16]. Так, присутствие аллеля СРБ 3'UTR 1846Т у пациентов, подвергшихся операции на сердце увеличивает риск развития инсульта более чем в 3 раза.…”

Section: P%'>% обзор посвящен проблеме развития послеоперационных оunclassified

“…Выявление специфических механизмов, при помощи которых реализуются эффекты СРБ 3'UTR1846 C>T, может быть полезным для определения мишеней, воздействуя на которые позволит модулировать периоперационный воспалительный ответ и улучшить, та-ким образом, прогноз после операции на сердце [16].…”

Section: P%'>% обзор посвящен проблеме развития послеоперационных оunclassified

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Prognostic Role of C-Reactive Protein, Apolipoprotein E and Polymorphisms of Their Coding Genes in the Development of Complications After Myocardial Revascularization

Bayrakova¹,

Понасенко²,

Kazachek³

2013

SMR

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Section: P%'>% обзор посвящен проблеме развития послеоперационных оunclassified

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Prognostic Role of C-Reactive Protein, Apolipoprotein E and Polymorphisms of Their Coding Genes in the Development of Complications After Myocardial Revascularization

Bayrakova¹,

Понасенко²,

Kazachek³

2013

SMR

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“…Perioperative complications, including acute kidney injury [6], postoperative bleeding [7], myocardial injury [8], and stroke [9], have been correlated with a variety of proinflammatory genotypes. The fact that a number of these genes (and/or gene products) identified in these association studies, such as the inflammatory mediators IL-6 and CRP as well as the endothelial adhesion molecules E-selectin and ICAM, have been previously implicated in the natural history of chronic inflammatory diseases provides proof of principle that this model is robust and can be extrapolated beyond the perioperative context.…”

Section: How Do We Study Patients In the Perioperative Period?mentioning

confidence: 99%

Understanding the Transition to Acute Illness: The Promise of Perioperative Genomics

Turer

Schwinn

2008

J. of Cardiovasc. Trans. Res.

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Over the last decades, tremendous advances have been made in understanding the genomic basis of a large number of chronic human diseases. Such advances were made possible by studying large numbers of patients over relatively long periods of time. It is increasingly recognized that acute robust stress stimulates pathways activated in chronic disease, facilitating mechanistic studies in much shorter time frames. A new field of molecular medicine, called perioperative genomics, uses robust surgical stress as a perturbation designed to explore such mechanisms. This new field is described briefly below. KeywordsPerioperative Care; Genomics; Risk Assessment; Postoperative Complications; Acute Disease Importance of the Perioperative PeriodMore than 40 million patients undergo surgery in the United States each year, and that number is expected to rise by 25% by 2020 [1]. In terms of monetary costs, the numbers are staggering with current estimates of $450 billion spent annually in the perioperative period [2]. Adverse events such as perioperative myocardial injury, renal failure, cognitive dysfunction, and stroke are devastating. Cardiovascular complications can occur after procedures even in patients without known heart disease. This problem is increasing as the population ages and cardiac risk factors, such as hypertension and diabetes mellitus, become more prevalent.Outside of its overall economic impact, the perioperative period provides an ideal model of acute illness. Although a dynamic and complicated environment, the operating room offers unique advantages for studying patients. In this environment, physiologic changes from baseline with robust stress can be prospectively quantified (e.g., hemo-dynamic parameters or plasma biomarkers). Even perturbations such as drug administration and organ ischemic time can be studied. Exposure to extremes of physiology offers the advantage of revealing (uncovering) phenotypes which might otherwise be dormant or take years to be expressed. Indeed, for patients at risk for proinflammatory activation, the operating room may transition an otherwise healthy individual into one who is acutely ill and at risk for postoperative complications and organ dysfunction.Coronary thrombosis is one example of how perioperative genomics can aid our understanding of illness beyond the operating room. There are more than one million spontaneous myocardial infarctions annually in the United States, but despite this incidence, molecular events triggering

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The effect of NQO1 polymorphism on the inflammatory response in cardiopulmonary bypass

Isbir

Ergen

Tekeli

et al. 2007

Cell Biochemistry & Function

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Cardiopulmonary bypass (CPB) has been associated with systemic inflammatory response syndrome (SIRS). Endothelial dysfunction related to non-laminar flow during CPB is known to play a key role in this complex pathology. Antioxidant response element (ARE) dependent NAD(P)H:quinone oxidoreductase 1 (NQO1) promoter is a regulatory element involved in the anti-inflammatory mechanism in vasculature exposed to non-laminar flow. Mutation of the NQO1 could represent a novel anti-inflammatory effect in CPB. The goal of this study was to demonstrate whether genetic variants of NQO1 affect cytokine release after CPB. Eighteen patients who underwent standard coronary artery bypass grafting (CABG) operation were included in the study. Genotyping for NQO1 was performed. Serum Interleukin-6 (IL-6) levels were measured before induction, during CPB after declamping the aorta, and 24 h after operation. Clinical data were collected respectively. Seven patients were NQO1 T carriers and 11 patients were NQO1 T non-carriers. During CPB, IL-6 concentrations were increased in NQO1 T carriers compared to T non-carriers (p = 0.038). Although ventilation times and blood loss were higher in T carriers these were not statistically significant. Patients with NQO1 T carriers showed significantly higher IL-6 levels during CPB. Non-laminar flow during CPB may diminish the transcriptional activation of the NQO1 in T carriers. Preoperative determination of this novel anti-inflammatory mechanism could be useful to improve operative outcome in CPB.

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Genetic Polymorphisms and the Risk of Stroke After Cardiac Surgery

Cited by 79 publications

References 30 publications

Prognostic Role of C-Reactive Protein, Apolipoprotein E and Polymorphisms of Their Coding Genes in the Development of Complications After Myocardial Revascularization

Prognostic Role of C-Reactive Protein, Apolipoprotein E and Polymorphisms of Their Coding Genes in the Development of Complications After Myocardial Revascularization

Understanding the Transition to Acute Illness: The Promise of Perioperative Genomics

The effect of NQO1 polymorphism on the inflammatory response in cardiopulmonary bypass

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