Inducible Nitric Oxide Synthase Promoter Polymorphism Affords Protection Against Cognitive Dysfunction After Carotid Endarterectomy

Yocum, Gene T.; Gaudet, John G.; Lee, Susie S.; Stern, Yaakov; Teverbaugh, Lauren A.; Sciacca, Robert R.; Emala, Charles W.; Quest, Donald O.; McCormick, Paul C.; McKinsey, James F.; Morrissey, Nicholas J.; Solomon, Robert A.; Connolly, E. Sander; Heyer, Éric

doi:10.1161/strokeaha.108.541177

Cited by 22 publications

(23 citation statements)

References 38 publications

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“…Age was dichotomized at 75 years and treated as a categorical variable (> 75 or ≤ 75 years). 3,21,31,32 All other factors were also treated categorically, and the results are presented as percentages of patients who satisfy the criteria for that variable. For univariate analyses, Student t-test, Wilcoxon rank-sum test, Fisher exact test, Pearson chi-square test, and simple logistic regression were used where appropriate.…”

Section: Neuropsychometric Evaluation and Statistical Analysismentioning

confidence: 99%

“…8,9,11,12,21,27 The underlying pathophysiology of this early cognitive dysfunction (eCD) is not completely understood, but data from a number of studies suggest that ischemic injury is a contributing factor, 3,21,31,32 related to hypoperfusion during intraoperative CA cross-clamping and/or to dislodgment of atheroemboli during vessel dissection and plaque removal.…”

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confidence: 99%

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Radiographic absence of the posterior communicating arteries and the prediction of cognitive dysfunction after carotid endarterectomy

Sussman¹,

Kellner

Mergeche³

et al. 2014

JNS

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Object Approximately 25% of patients exhibit cognitive dysfunction 24 hours after carotid endarterectomy (CEA). One of the purported mechanisms of early cognitive dysfunction (eCD) is hypoperfusion due to inadequate collateral circulation during cross-clamping of the carotid artery. The authors assessed whether poor collateral circulation within the circle of Willis, as determined by preoperative CT angiography (CTA) or MR angiography (MRA), could predict eCD. Methods Patients who underwent CEA after preoperative MRA or CTA imaging and full neuropsychometric evaluation were included in this study (n = 42); 4 patients were excluded due to intraoperative electroencephalographic changes and subsequent shunt placement. Thirty-eight patients were included in the statistical analyses. Patients were stratified according to posterior communicating artery (PCoA) status (radiographic visualization of at least 1 PCoA vs of no PCoAs). Variables with p < 0.20 in univariate analyses were included in a stepwise multivariate logistic regression model to identify predictors of eCD after CEA. Results Overall, 23.7% of patients exhibited eCD. In the final multivariate logistic regression model, radiographic absence of both PCoAs was the only independent predictor of eCD (OR 9.64, 95% CI 1.43–64.92, p = 0.02). Conclusions The absence of both PCoAs on preoperative radiographic imaging is predictive of eCD after CEA. This finding supports the evidence for an underlying ischemic etiology of eCD. Larger studies are justified to verify the findings of this study. Clinical trial registration no.: NCT00597883 (http://www.clinicaltrials.gov).

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Section: Neuropsychometric Evaluation and Statistical Analysismentioning

confidence: 99%

mentioning

confidence: 99%

Radiographic absence of the posterior communicating arteries and the prediction of cognitive dysfunction after carotid endarterectomy

Sussman¹,

Kellner

Mergeche³

et al. 2014

JNS

Self Cite

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“…Recent studies implicate a genetic basis for post-CEA cognitive dysfunction 5 6. The presence of at least one apolipoprotein E (APOE)-ε4 allele, which is associated with plasma lipoproteins and is involved in the metabolism and transport of CNS lipids, has been associated with increased risk of cognitive dysfunction 1 month after CEA 5.…”

Section: Introductionmentioning

confidence: 99%

“…The presence of at least one apolipoprotein E (APOE)-ε4 allele, which is associated with plasma lipoproteins and is involved in the metabolism and transport of CNS lipids, has been associated with increased risk of cognitive dysfunction 1 month after CEA 5. A more recent study demonstrated that an inducible nitric oxide synthase (iNOS) promoter polymorphism afforded protection against moderate/severe cognitive dysfunction 1 month after CEA 6. Based on our current understanding of these genes, the APOE-ε4 polymorphism may be related to neuronal membrane repair and remodelling after injury, while the iNOS promoter polymorphism may be related to global cerebroprotective ‘baseline preconditioning.’…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in complement component 3 (C3F) and complement factor H (Y402H) increase the risk of postoperative neurocognitive dysfunction following carotid endarterectomy

Gigante

Kotchetkov

Kellner

et al. 2010

Journal of Neurology, Neurosurgery & Psychiatry

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Background Up to 28% of patients undergoing carotid endarterectomy (CEA) are estimated to experience neurocognitive dysfunction following surgery. The complement cascade plays a central role in ischaemia-reperfusion injury. The authors investigated the effect of common polymorphisms in the complement component 3 (C3F) and complement factor H (CFH Y402H) genes on incidence of neurocognitive dysfunction post-CEA. Methods This study examined a nested cohort of prospectively recruited patients receiving elective CEA, who were genotyped for the C3F or Y402H polymorphisms. Each patient underwent a standard battery of eight neuropsychometric tests before, and 1 day and 30 days after, surgery. Results 57 of 142 (40%) CEA patients had at least one copy of the C3F allele (C3F+), and 17 of 137 (12%) patients had two copies of the CFH Y402H allele (Y402H++). At postoperative day 1, patients were three times (OR 3.05, p=0.045) or six times (OR 6.41, p=0.006) more likely to experience moderate-to-severe neurocognitive dysfunction if they carried the C3F+ or Y402H++ genotype, respectively. Patients with both risk genotypes had an almost eightfold risk of dysfunction (OR 7.67, p=0.046). Right-hand-dominant C3F+ subjects undergoing right-side CEA performed significantly worse on tests of visuospatial function than C3F− subjects. At day 30, C3F+ and Y402H++ genotypes trended towards significance as predictors of dysfunction (p=0.07 and p=0.22, respectively). Conclusion The C3F and Y402H polymorphisms are strong independent predictors of moderate-to-severe neurocognitive dysfunction at 1 day following CEA. Furthermore, patients undergoing right-sided CEA are predisposed to deficits associated with cortex ipsilateral to the operative carotid artery.

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“…Whether or not aged, hypertensive, or diabetic animals should be included in future preconditioning experiments was also discussed. In addition, data showing that inducible nitrous oxide synthase promoter polymorphism affords protection against cognitive dysfunction after carotid endarterectomy was reported by Dr. Raqeeb Haque (Columbia University) [9], and the results suggest that cognitive dysfunction could be an endpoint to measure success in future potential preconditioning trials.…”

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confidence: 80%

Clinical Translation of Cerebral Preconditioning

2010

Transl. Stroke Res.

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Inducible Nitric Oxide Synthase Promoter Polymorphism Affords Protection Against Cognitive Dysfunction After Carotid Endarterectomy

Cited by 22 publications

References 38 publications

Radiographic absence of the posterior communicating arteries and the prediction of cognitive dysfunction after carotid endarterectomy

Radiographic absence of the posterior communicating arteries and the prediction of cognitive dysfunction after carotid endarterectomy

Polymorphisms in complement component 3 (C3F) and complement factor H (Y402H) increase the risk of postoperative neurocognitive dysfunction following carotid endarterectomy

Clinical Translation of Cerebral Preconditioning

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