Role of plasminogen activator inhibitor-1 polymorphism on the development of vasoplegic syndrome associated with cardiopulmonary bypass

Introduction

Vasoplegic syndrome (VS) after cardiac surgery with cardiopulmonary bypass (CPB) can vary from mild to severe complication and it appears with an incidence ranging between 5% and 15%. The etiology is not completely elucidated but risk factors such as temperature and duration of cardiopulmonary bypass and preoperative treatment with angiotensin-converting enzyme (ACE) inhibitors have been associated [1]. We wanted to investigate the possible role of several genetic polymorphisms in patients with VS after elective CPB.

Methods

We performed a nested case–control study of 50 patients undergoing CPB, 27 (54%) men and 23 (46) women, mean age 66.5 (SD 9.6) years. VS was defined as systemic vascular resistance index lower than 1,600 dyn∙seg/cm⁵/m² and a cardiac index greater than 2.5 l/min/m² within the first 4 hours after surgery. We recorded data related to hemodynamic parameters at different postoperative time points, at ICU admission (0 hours), 4 and 24 hours after surgery, and the polymorphism of the following genes: plasminogen activator inhibitor-1 (PAI-1) and β-TNF + 250. In addition, 23 neutral markers were genotyped to follow genomic control strategies that would detect spurious associations due to population substructure. We used the Pearson chi-squared test and binary logistic regression. SPSS version 12.1 was used.

Results

We observed 17 (34%) patients with vasoplegia criteria, 11 (65%) men and six (35%) women, age 67 (61–72) years. The only one associated with VS was the PAI-1 polymorphism, and its distribution in the study population was: 4G/G genotype in 10 (20%) patients, 4G/5G in 26 (52%) patients, and 5G/G in 14 (28%) patients. According to the PAI-1 polymorphism, vasoplegia criteria were found in one (5.5%) 4G/G carrier, in seven (39%) 4G/5G carriers and in 10 (55.5%) 5G/G carriers (P = 0.012) (Figure 1). The post-hoc power for PAI-1 polymorphism and vasoplegia was 0.85. After controlling for temperature, clamping time, antifibrinolytics, body mass index and ACE inhibitors, the 5G/G genotype was independently associated with vasoplegia (P = 0.017); OR: 24.6 (95% CI: 1.8–342).

Figure 1

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Conclusion

The PAI-1 polymorphism (homozygous 5G/G) was independently associated with the onset of VS.