RESUMO
Approximately 25% of patients undergoing carotid endarterectomy (CEA) exhibit cognitive dysfunction (CD) 1 day and 1 month after CEA. The apolipoprotein E (apoE)-ε4 polymorphism has been previously identified as a robust independent risk factor for CD 1 month after CEA. We aimed to determine whether the apoE-ε4 polymorphism is also an independent risk factor for CD as early as 1 day after CEA and to confirm the previous findings at 1 month. Patients undergoing elective CEA (n=411) were enrolled with written informed consent in this follow-up observational study. CD was evaluated via an extensive neuropsychometric battery. apoE-ε4 carriers exhibited significantly more CD 1 day (30.1% versus 17.9%, p=0.01) and 1 month (25.7% versus 9.8%, p=0.001) after CEA compared to non-carriers. Multivariate regression models were generated to determine independent predictors of CD. At 1 day, apoE-ε4 was significantly associated with higher risk of CD (odds ratio [OR]: 2.24 [95% confidence interval 1.29-3.84], p=0.004), while statin use was significantly associated with lower risk (OR: 0.40 [0.24-0.67], p<0.001). At 1 month, apoE-ε4 was significantly associated with higher risk of CD (OR: 3.14 [1.53-6.38], p=0.002), while symptomatic status was significantly associated with lower risk (OR: 0.45 [0.20-0.94], p=0.03). The apoE-ε4 polymorphism is an independent risk factor for CD as early as 1 day after CEA and is confirmed to be an independent risk factor for CD at 1 month as well.
Assuntos
Apolipoproteína E4/genética , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/genética , Endarterectomia das Carótidas/efeitos adversos , Predisposição Genética para Doença , Polimorfismo Genético , Idoso , Estenose das Carótidas/cirurgia , Feminino , Seguimentos , Heterozigoto , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Testes Neuropsicológicos , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Phosphodiesterase 4D (PDE4D), through the regulation of cyclic AMP, modulates inflammation and other processes that affect atherosclerosis and stroke. A PDE4D polymorphism, single-nucleotide polymorphism (SNP) 83 (rs966221), is associated with ischemic stroke. The association of SNP 83 with postoperative cognitive dysfunction has never been investigated. OBJECTIVE: To determine whether SNP 83 is associated with cognitive dysfunction 1 day and 1 month following carotid endarterectomy (CEA). METHODS: Three hundred fourteen patients with high-grade carotid stenosis scheduled for CEA consented to participate in this single-center cohort study of cognitive dysfunction. RESULTS: Patients with the C/C genotype of SNP 83 exhibited significantly more cognitive dysfunction at 1 day (29.7%) than the C/T (15.8%, P = .008) and T/T (12.7%, P = .01) genotypes. In a multivariate logistic regression model, C/T and T/T genotypes were both associated with significantly decreased odds of cognitive dysfunction compared with the C/C genotype (odds ratio, 0.45 [0.24-0.83], P = .01 and odds ratio, 0.33 [0.12-0.77], P = .02). There were no significant associations at 1 month. CONCLUSION: The C/C genotype of SNP 83 is significantly associated with the highest incidence of cognitive dysfunction 1 day following CEA in comparison with the C/T and T/T genotypes. This PDE4D genotype may lead to accelerated cyclic AMP degradation and subsequently elevated inflammation 1 day after CEA. These observations, in conjunction with previous studies, suggest that elevated inflammatory states may be partially responsible for the development of cognitive dysfunction after CEA, but more investigation is required.
Assuntos
Transtornos Cognitivos/etiologia , Transtornos Cognitivos/genética , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Endarterectomia das Carótidas , Polimorfismo de Nucleotídeo Único/genética , Complicações Pós-Operatórias/genética , Idoso , Idoso de 80 Anos ou mais , Estenose das Carótidas/genética , Estenose das Carótidas/cirurgia , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Testes Neuropsicológicos , Análise de Regressão , Estatísticas não ParamétricasRESUMO
OBJECT: The role of genetic polymorphisms in the neurological outcome of patients after carotid endarterectomy (CEA) remains unclear. There are single nucleotide polymorphisms (SNPs) that predispose patients to postoperative cognitive dysfunction (CD). We aim to assess the predictability of three complement cascade-related SNPs for CD in patients having CEAs. METHODS: In 252 patients undergoing CEA, genotyping was performed for the following polymorphisms: complement component 5 (C5) rs17611, mannose-binding lectin 2 (MBL2) rs7096206, and complement factor H (CFH) rs1061170. Differences among genotypes were analyzed via the chi-square test. Patients were evaluated with a neuropsychometric battery for CD 1 day and 1 month after CEA. A multiple logistic regression model was created. All variables with univariate p < 0.20 were included in the final model. RESULTS: The C5 genotypes A/G (OR 0.26, 95% CI 0.11-0.60, p = 0.002) and G/G (OR 0.22, 95% CI 0.09-0.52, p < 0.001) were significantly associated with lower odds of exhibiting CD at 1 day after CEA compared with A/A. The CFH genotypes C/T (OR 3.37, 95% CI 1.69-6.92, p < 0.001) and C/C (OR 3.67, 95% CI 1.30-10.06, p = 0.012) were significantly associated with higher odds of exhibiting CD at 1 day after CEA compared with T/T. Statin use was also significantly associated with lower odds of exhibiting CD at 1 day after CEA (OR 0.43, 95% CI 0.22-0.84, p = 0.01). No SNPs were significantly associated with CD at 1 month after CEA. CONCLUSIONS: The presence of a deleterious allele in the C5 and CFH SNPs may predispose patients to exhibit CD after CEA. This finding supports previous data demonstrating that the complement cascade system may play an important role in the development of CD. These findings warrant further investigation.
Assuntos
Transtornos Cognitivos/genética , Complemento C5/genética , Fator H do Complemento/genética , Endarterectomia das Carótidas/efeitos adversos , Lectina de Ligação a Manose/genética , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/etiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Lectina de Ligação a Manose/biossíntese , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/genética , Regiões Promotoras Genéticas/genética , Estudos ProspectivosRESUMO
BACKGROUND AND PURPOSE: Statins are neuroprotective in a variety of experimental models of cerebral injury. We sought to determine whether patients taking statins before asymptomatic carotid endarterectomy exhibit a lower incidence of neurological injury (clinical stroke and cognitive dysfunction). METHODS: A total of 328 patients with asymptomatic carotid stenosis scheduled for elective carotid endarterectomy consented to participate in this observational study of perioperative neurological injury. RESULTS: Patients taking statins had a lower incidence of clinical stroke (0.0% vs 3.1%; P=0.02) and cognitive dysfunction (11.0% vs 20.2%; P=0.03). In a multivariate regression model, statin use was significantly associated with decreased odds of cognitive dysfunction (odds ratio, 0.51 [95% CI, 0.27-0.96]; P=0.04). CONCLUSIONS: Preoperative statin use was associated with less neurological injury after asymptomatic carotid endarterectomy. These observations suggest that it may be possible to further reduce the perioperative morbidity of carotid endarterectomy. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00597883.
