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Anemia and Sex Disparity in Operative Mortality After CABG
Quick Takes
- In patients undergoing CABG, women had higher operative mortality than men (2.8% vs. 1.7%, p < 0.001) and it was largely mediated by the risk of intraoperative anemia between the two groups.
- The association of gender with increased CABG operative mortality is mediated to a large extent by intraoperative anemia with worse outcomes in women. Avoiding nadir intraoperative hematocrit values below 22.0% may reduce sex differences in CABG operative mortality.
Study Questions:
Women undergoing coronary artery bypass grafting (CABG) have higher operative mortality than men. What is the relationship between intraoperative anemia (nadir intraoperative hematocrit), CABG operative mortality, and sex?
Methods:
A cohort study of 1,434,225 isolated primary CABG patients (344,357 women) from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS-ACSD) (2011–2022) was used for analysis. Patients were included if they underwent primary isolated CABG during the study period. Patients were excluded if they required resuscitation prior to surgery, if they underwent emergent or salvage surgery, or if they underwent re-operative CABG. Baseline demographics were stratified both by sex and intraoperative anemia, with hematocrit values stratified based on the World Health Organization anemia classification as follows: none to mild (nadir intraoperative hematocrit ≥33.0%), moderate (intraoperative hematocrit 24.0%-<19.5%), to severe (nadir intraoperative hematocrit 19.5%-<19.5%).
The primary outcome was operative mortality. The attributable risk (AR) (the risk-adjusted strength of the association of female sex with CABG outcomes) for the primary outcome was calculated. Causal mediation analysis derived the total effect of female sex on operative mortality risk and the proportion of that effect mediated by intraoperative anemia.
Results:
Women had lower median nadir intraoperative hematocrit (22.0%, interquartile range [IQR] 20.0-25.0% vs. 27.0% [IQR 24.0-30.0], standardized mean difference 97.0%) than men. Women had higher operative mortality than men (2.8% vs. 1.7%, p < 0.001). The AR of women for operative mortality was 1.21 (95% confidence interval [CI], 1.17-1.24). After adjusting for nadir intraoperative hematocrit, AR was reduced by 43% (1.12; 95% CI, 1.09-1.16). Intraoperative anemia mediated 38.5% of the increased mortality risk associated with female sex (95% CI, 32.3-44.7%). Spline regression showed a stronger association between operative mortality and nadir intraoperative hematocrit at hematocrits below 22.0% (p < 0.001).
Conclusions:
In this analysis of 1,434,225 patients (344,357 women) from the STS-ACSD, the investigators found that women had a higher risk of operative mortality after CABG compared with men, and that the association of gender with mortality was mediated to a large extent by intraoperative anemia with worse outcomes in women. The association between operative mortality in women and anemia was strongest at intraoperative nadir hematocrit below 22.0%. Those results were solid in all the sensitivity analyses.
Perspective:
Prior studies have shown more severe intraoperative anemia, and higher operative mortality in CABG patients with small body size, a category in which women are disproportionately represented. Preoperative hematocrit is strongly correlated with nadir intraoperative hematocrit and is significantly lower in women compared to men even when accounting for the body size differences between sexes and is associated with elevated major adverse cardiac events in women with ischemic heart disease. Due to the combination of lower starting hematocrit and smaller body size, women are more susceptible to severe intraoperative anemia than men. These results indicate that the sex and gender difference in severe intraoperative anemia largely explains the increased CABG operative mortality in women. As such, avoiding severe intraoperative anemia and hematocrit below 22.0% may help close the gap between men and women in CABG outcomes.
Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention
Keywords: Anemia, Coronary Artery Bypass
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