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

Background Up to 28% of patients undergoing endarterectomy (CEA) are estimated to experience neurocognitive dysfunction following surgery. The complement cascade plays a central role in reperfusion injury. The authors investigated the effect common polymorphisms in the complement 3 (C3F) and complement factor H (CFH Y402H) genes incidence of neurocognitive dysfunction post- CEA. Methods This study examined a nested cohort of prospectively recruited patients receiving elective 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 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 times (OR 3.05, p=0.045) or six times (OR 6.41, p=0.006) more likely to experience moderate- toneurocognitive dysfunction if they carried the C3F(+) or Y402H(++) genotype, respectively. Patients with both 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 C3F e subjects. At day 30, C3F(+) and Y402H(++) genotypes trended towards significance as predictors 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 to the operative carotid artery.