Association between 4G/5G polymorphism of the plasminogen activator inhibitor 1 gene with stroke or encephalopathy after cardiac surgery

Abstract

Objective: To evaluate whether the 4G/5G polymorphism of the plasminogen activator inhibitor 1 gene increases the risk of thromboembolic neurological complications, and, if so, whether these complications lengthen the period of mechanical ventilation and hospital stay.

Design: Prospective, case-control study in a 14 bed surgical intensive care unit of a university hospital.

Patients: 260 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass and 111 controls.

Interventions: DNA was isolated and 4G/5G polymorphism was typed using RFLP methodology.

Measurements and results: Genetic analysis revealed 4G/5G in 131 patients (50.4%), 5G/5G genotype in 82 (31.5%), and 4G/4G in only 47 (18.1%). Prevalence of neurological complications was 20.8% (n=54) (stroke 5.4%, n=14; encephalopathy 15.4%, n=40]. A trend towards higher risk of developing stroke (8.5% vs. 4.7%, RR 1.9) and a significant twofold increase in encephalopathy (27.7% vs. 12.7%; RR 2.6) was documented in 4G/4G carriers. Multivariate analysis showed that development of stroke or encephalopathy was independently associated with prolonged mechanical ventilation (OR 20), and that neurological complication (OR 2.4) and 4G/4G genotype (OR 2.6) were independently associated with hospital stay of 2 weeks or longer.

Conclusions: The 4G/4G genotype can increase the risk of thromboembolic neurological complications after cardiac surgery with cardiopulmonary by-pass. The neurological complications result in longer time on ventilator and longer hospital stay.