Sex-Specific Associations Between Preoperative Anemia and Postoperative Clinical Outcomes in Patients Undergoing Cardiac Surgery

Abstract

BACKGROUND: Preoperative anemia is common in cardiac surgery, yet there were limited data describing the role of sex in the associations between anemia and clinical outcomes. Understanding these relationships may guide preoperative optimization efforts. METHODS: This is an observational cohort study of adults undergoing isolated coronary artery bypass grafting or single- or double-valve surgery from 2008 to 2018 at a large tertiary medical center. Multivariable regression assessed the associations between preoperative hemoglobin concentrations and a primary outcome of postoperative acute kidney injury (AKI) and secondary outcomes of perioperative red blood cell (RBC) transfusion, reoperation, vascular complications (ie, stroke, pulmonary embolism, and myocardial infarction), and hospital length of stay (LOS). Each outcome was a single regression model, using interaction terms to assess sex-specific associations between hemoglobin and outcome. RESULTS: A total of 4117 patients were included (57% men). Linear splines with sex-specific knots (13 g/dL in women and 14 g/dL in men) provided the best overall fit for preoperative hemoglobin and outcome relationships. In women, each 1 g/dL decrease in hemoglobin <13 g/dL was associated with increased odds of AKI (odds ratio = 1.49; 95% confidence interval [CI], [1.23-1.81]; P < .001), and there was no significant association between hemoglobin per 1 g/dL >13 g/dL and AKI (0.90 [0.56-1.45]; P = .67). The association between hemoglobin and AKI in men did not meet statistical significance (1.10 [0.99-1.22]; P = .076, per 1 g/dL decrease <14 g/dL; 1.00 [0.79-1.26]; P = .98 for hemoglobin per 1 g/dL >14 g/dL). In women, lower preoperative hemoglobin (per 1 g/dL decrease <13 g/dL) was associated with increased odds of RBC transfusion (2.90 [2.33-3.60]; P < .001), reoperation (1.27 [1.11-1.45]; P < .001) and a longer hospital LOS (multiplicative increase in geometric mean 1.05 [1.03-1.07]; P < .001). In men, preoperative hemoglobin (per 1 g/dL decrease <14 g/dL) was associated with increased odds of perioperative RBCs (2.56 [2.27-2.88]; P < .001) and longer hospital LOS (multiplicative increase in geometric mean 1.02 [1.01-1.04] days; P < .001) but not reoperation (0.94 [0.85-1.04]; P = .256). Preoperative hemoglobin per 1 g/dL >13 g/dL in women and 14 g/dL in men were associated with lower odds of RBCs transfusion (0.57 [0.47-0.69]; P < .001 and 0.74 [0.60-0.91]; P = .005, respectively). CONCLUSIONS: Preoperative anemia was associated with inferior clinical outcomes after cardiac surgery. The associations between hemoglobin and outcomes were distinct for women and men, with different spline knot points identified (13 and 14 g/dL, respectively). Clinicians should consider data-driven approaches to determine preoperative hemoglobin values associated with increasing risk for adverse perioperative outcomes across sexes.

Mortality across the spectrum of hemoglobin level in patients undergoing surgical coronary revascularization

“…In 2021, Ripoll et al concluded that associations between Hb levels and outcomes were distinct for females and males, with different spline knot points (13 and 14 g/dL, respectively). As reported, in females, each 1 g/dL decrease in Hb below 13 was associated with increased odds of acute kidney injury (AKI) 11 . Mechanistically, there is an increased risk of insufficient delivery of tissue oxygenation through lower Hb levels preoperatively which can independently be correlated with mortality, cerebral accident, and AKI, as mentioned 36–38 .…”

“…Mid‐ and long‐term outcomes are associated with much more parameters and cannot be justified merely with preoperative baseline characteristics. Unfortunately, we could not capture changes in risk factor profile after CABG; hence postdischarge results should be assessed with caution 11,22,26 . Finally, the single‐center nature of our study is another limitation that should be taken into consideration.…”

“…Anemia can cause postoperative complications such as arrhythmia, hypoxemia, and heart failure; if left untreated 10 . The major adverse cardiac and cerebrovascular events rate in patients undergoing coronary artery bypass grafting with preoperative anemia is higher than in patients with normal Hb concentration 11–15 . Hemoglobin (Hb) level variation may affect in‐hospital and midterm mortality in anemic or even nonanemic patients undergoing CABG 12 .…”

Preoperative anemia and long-term survival in patients undergoing colorectal cancer surgery: a retrospective cohort study

“…As the confounders for outcomes in anemic patients, these missing data may weaken the strength of our conclusions. Second, Hb levels remain the most widely accepted laboratory parameter for the diagnosis of anemia, even though they are not true markers of RBC mass or tissue oxygen delivery [ 38 ] and are influenced by physiological changes associated with aging, such as declining production and shortening the lifespan of RBCs [ 39 ]. The WHO definition of anemia (< 13 g/dL in men and < 12 g/dL in women), which is different with that in China (< 12 g/dL in men and < 11 g/dL in women) adopted in this study, is derived from the distribution of Hb values in epidemiologic investigations and not by the clinical and physiological impact of those values [ 40 , 41 ], thereby it may influence the results of a long-term survival following CRC surgery.…”

Coagulation and Transfusion Updates From 2021

“…[43][44][45] Recent evidence, however, has shown that hemoglobin thresholds for increased risk may vary between men and women and between younger and older patients. [45][46][47][48][49] Combined with evidence suggesting RBC transfusion may not eliminate the risk of organ dysfunction and is associated with impaired outcomes, transfusion best practices remain elusive. 2,43,50,51 Contributing to uncertainty, 2 large randomized controlled trials in cardiac surgery did not show an impaired outcome with a more liberal transfusion strategy compared to a restrictive regimen.…”