Abstract
This cohort study examines the association between blood transfusion and major adverse cardiovascular events and mortality among people undergoing elective open vascular operations.
There is substantial variation in transfusion practices across institutions, and the optimal transfusion threshold in vascular surgery is undefined.1,2 It is unclear whether absolute hemoglobin number, the underlying cause of anemia, or other related factors play a role in adverse outcomes. We evaluated the association between blood transfusion and major adverse cardiovascular events (MACE) at different anemic thresholds in patients undergoing open vascular surgery.
Methods
This retrospective cohort study obtained data on patients undergoing elective open vascular operations from Society for Vascular Surgeons Vascular Quality Initiative (VQI) registries between January 1, 2003, and December 31, 2020. Cohorts were grouped by operation type (open abdominal aortic aneurysm [AAA] repair, suprainguinal bypass [SIB], or infrainguinal bypass [IIB]), preoperative hemoglobin level (severe: 7-10 g/dL, moderate: >10-12 g/dL, normal: >12 g/dL; to convert to grams per liter, multiply by 10.0), and transfusion status (with vs without perioperative transfusion). Patients with a hemoglobin level under 7 g/dL and urgent or emergent cases were excluded. In accordance with the Common Rule, this study was exempt from ethics review and informed consent requirement because deidentified data were used. We followed the STROBE reporting guideline.
Primary outcomes were MACE, defined as myocardial infarction, new congestive heart failure, stroke, or arrhythmia during index hospitalization, and 30-day mortality. Multivariable logistic regression was performed for each operation type, adjusting for preoperative hemoglobin level, transfusion status, surgical blood loss, and comorbidity profile (defined by Vascular Surgery Group of New England Cardiac Risk Index) and variables significant (P < .05) on univariate analysis. Two-sided P < .05 indicated statistical significance. Data analysis was performed between July and December 2023 using SAS 9.4 (SAS Institute Inc).
Results
Of 95 475 patients evaluated in the VQI registries, 11 033 were excluded, leaving 84 442 patients (57 144 males [67.7%], 27 293 females [32.3%]; mean [SD] age, 67.9 [9.9] years) for analysis. Among these patients, 12.3% underwent open AAA repair; 21.6%, SIB; and 66.2%, IIB. Additionally, 14.0% of patients had severe anemia; 23.0%, moderate anemia, and 63.0%, normal hemoglobin level.
On univariate analysis, transfusion (vs without) was associated with higher rates of MACE at all hemoglobin levels in each operation (eg, IIB: 7-10 g/dL; 12.2% vs 4.8%; P < .001). Similarly, transfusion (vs without) was associated with increased rates of 30-day mortality in each operation (eg, IIB: 7-10 g/dL; 3.6% vs 2.5%; P = .004) (Table 1).
Table 1. Association of Perioperative Blood Transfusion With Major Adverse Cardiovascular Events and 30-Day Mortality at All Anemic Thresholds for Patients With Hemoglobin Level Over 7 g/dL.
| Hemoglobin level, g/dL | Without perioperative transfusion, No. (%) | With perioperative transfusion, No. (%) | P value |
|---|---|---|---|
| Outcome: MACE | |||
| Open AAA repair | |||
| >12 | 609 (11.9) | 773 (24.2) | <.001 |
| 10-12 | 55 (11.8) | 231 (22.4) | <.001 |
| 7-10 | 13 (12.6) | 88 (23.2) | .02 |
| Suprainguinal bypass | |||
| >12 | 550 (5.7) | 571 (19.3) | <.001 |
| 10-12 | 96 (5.0) | 290 (16.7) | <.001 |
| 7-10 | 26 (5.0) | 178 (13.3) | <.001 |
| Infrainguinal bypass | |||
| >12 | 955 (3.4) | 716 (16.1) | <.001 |
| 10-12 | 430 (4.8) | 769 (14.0) | <.001 |
| 7-10 | 141 (4.8) | 752 (12.2) | <.001 |
| Outcome: 30-d mortality | |||
| Open AAA repair | |||
| >12 | 42 (0.8) | 196 (6.1) | <.001 |
| 10-12 | 9 (1.9) | 95 (9.1) | <.001 |
| 7-10 | 3 (2.9) | 45 (11.6) | .008 |
| Suprainguinal bypass | |||
| >12 | 77 (0.8) | 158 (5.4) | <.001 |
| 10-12 | 29 (1.5) | 105 (6.0) | <.001 |
| 7-10 | 12 (2.3) | 90 (6.4) | <.001 |
| Infrainguinal bypass | |||
| >12 | 184 (0.7) | 150 (3.4) | <.001 |
| 10-12 | 134 (1.5) | 199 (3.6) | <.001 |
| 7-10 | 73 (2.5) | 222 (3.6) | .004 |
Abbreviations: AAA, abdominal aortic aneurysm; MACE, Major Adverse Cardiovascular Events.
SI conversion factor: To convert hemoglobin to grams per liter, multiply by 10.0.
Multivariable analyses found that transfusion was independently associated with MACE in each operation (odds ratio [OR]: open AAA repair, 2.0 [95% CI, 1.8-2.3]; SIB, 3.0 [95% CI, 2.7-3.4]; IIB, 3.5 [95% CI, 3.2-3.8]) (Table 2). Transfusion was also independently associated with 30-day mortality in each operation (OR: open AAA repair, 5.5 [95% CI, 4.0-7.5]; SIB, 4.7 [95% CI, 3.7-5.9]; IIB, 2.6 [95% CI, 2.2-3.0]) (Table 2).
Table 2. Multivariable Logistic Regression for Major Adverse Cardiovascular Events and 30-Day Mortality.
| OR (95% CI) | |||
|---|---|---|---|
| Open AAA repair | Suprainguinal bypass | Infrainguinal bypass | |
| Outcome: MACE | |||
| Transfusion | 2.0 (1.8-2.3) | 3.0 (2.7-3.4) | 3.5 (3.2-3.8) |
| Hemoglobin level, g/dL | |||
| >12 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| >10-12 | 0.9 (0.7-1.0) | 0.8 (0.7-0.9) | 1.0 (0.9-1.1) |
| 7-10 | 0.9 (0.7-1.2) | 0.7 (0.6-0.8) | 0.9 (0.8-0.9) |
| Blood loss, mL | |||
| <800 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| 800-1300 | 1.0 (0.9-1.2) | 1.5 (1.2-1.7) | 1.1 (1.0-1.3) |
| 1301-2250 | 1.2 (1.0-1.3) | 1.7 (1.4-2.0) | 1.3 (1.2-1.5) |
| >2250 | 1.3 (1.1-1.5) | 2.1 (1.7-2.4) | 1.4 (1.3-1.5) |
| Hypertension | |||
| Yes | 1.2 (1.0-1.4) | 1.1 (0.9-1.3) | 1.2 (1.1-1.4) |
| VSG-CRI | |||
| 0-3 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| 4 | 1.4 (1.2-1.7) | 1.8 (1.0-1.4) | 1.4 (1.3-1.6) |
| 5 | 1.6 (1.4-1.9) | 1.6 (1.3-1.8) | 1.6 (1.4-1.8) |
| 6 | 1.9 (1.6-2.3) | 1.6 (1.3-1.9) | 1.7 (1.5-2.0) |
| 7 | 2.1 (1.7-2.6) | 2.0 (1.6-2.4) | 2.2 (1.9-2.5) |
| ≥8 | 2.8 (2.3-3.4) | 2.6 (2.2-3.1) | 2.7 (2.5-3.1) |
| Outcome: 30-d mortality | |||
| Transfusion | 5.5 (4.0-7.5) | 4.7 (3.7-5.9) | 2.6 (2.2-3.0) |
| Hemoglobin level, g/dL | |||
| >12 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| >10-12 | 1.4 (1.1-1.7) | 1.1 (0.9-1.4) | 1.4 (1.2-1.6) |
| 7-10 | 1.9 (1.4-2.6) | 1.2 (1.0-1.6) | 1.5 (1.2-1.7) |
| Blood loss, mL | |||
| <800 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| 800-1300 | 0.8 (0.6-1.2) | 0.9 (0.6-1.2) | 0.9 (0.8-1.1) |
| 1301-2250 | 1.2 (0.8-1.6) | 0.8 (0.6-1.1) | 1.0 (0.8-1.2) |
| >2250 | 1.5 (1.1-2.0) | 1.2 (0.9-1.6) | 1.1 (1.0-1.4) |
| Hypertension | |||
| Yes | 1.0 (0.7-1.4) | 1.4 (1.0-2.0) | 0.92 (0.7-1.2) |
| VSG-CRI | |||
| 0-3 | 1 [Reference] | 1 [Reference] | 1 [Reference] |
| 4 | 2.0 (1.2-3.2) | 1.0 (0.7-1.5) | 1.5 (1.1-2.0) |
| 5 | 2.7 (1.7-4.2) | 1.7 (1.2-2.4) | 2.2 (1.7-2.9) |
| 6 | 2.6 (1.6-4.0) | 2.4 (1.8-3.3) | 2.3 (1.7-2.9) |
| 7 | 3.9 (2.5-6.1) | 2.9 (2.1-4.0) | 3.7 (2.8-4.7) |
| ≥8 | 5.8 (3.8-8.8) | 4.0 (3.0-5.4) | 4.7 (3.8-6.0) |
Abbreviations: AAA, abdominal aortic aneurysm; MACE, Major Adverse Cardiovascular Events; OR, odds ratio; VSG-CRI, Vascular Surgery Group of New England Cardiac Risk Index.
SI conversion factor: To convert hemoglobin to grams per liter, multiply by 10.0.
Discussion
Rather than mitigating adverse outcomes of anemia, transfusion was independently associated with MACE and 30-day mortality. These findings build on prior reports of an increased risk for cardiac morbidity and mortality in patients who received transfusion after various operations.3,4 Furthermore, the effect size of transfusion was significantly larger than the effect size of anemia or surgical blood loss. While transfusion can be a lifesaving treatment for hemorrhagic shock, these results suggest transfusion should be used sparingly in stable patients with hemoglobin level over 7 g/dL.
Transfusion can cause fluid overload, hormonal changes, and a complex inflammatory and immunological cascade associated with hospital-acquired infections, lung injury, cardiac stress, and reduced survival.5 Our data corroborated these proposed mechanisms: regardless of anemia severity, baseline cardiovascular risk, and surgical blood loss, transfusion was independently and consistently associated with MACE and 30-day mortality.
Study limitations are the retrospective design, which cannot prove causation, and lack of granular detail. In particular, data on timing (preoperative, postoperative, intraoperative), indication, and clinical context for the patients’ transfusion were not available for review. Such missing information is an important consideration since prior research found that postoperative transfusion was associated with cardiac events whereas intraoperative transfusion was not.6
Data Sharing Statement
References
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Supplementary Materials
Data Sharing Statement
