Association Between Postoperative Day 7 Hypoalbuminemia and Mortality After Surgery: A Single-Center Retrospective Landmark Cohort Study

Background/Objectives: We evaluated postoperative day 7 serum albumin for its association with mortality after surgery and whether it varied by frailty or surgical urgency. Methods: This single-center landmark cohort study was conducted at an 817-bed tertiary hospital (April 2018–March 2025). Follow-up began on day 7 to reduce immortal-time bias. Of 41,506 surgical episodes, 18,296 met the landmark and 14,992 (82%) had day 7 albumin measured. Hypoalbuminemia was <3.0 g/dL. We assessed 365-day mortality by landmark Cox regression. We compared discrimination with the preoperative Surgical Outcome Risk Tool (SORT) and American Society of Anesthesiologists (ASA) physical status, added day 7 albumin to each, and tested effect modification by frailty and urgency. Results: Adding day 7 albumin improved discrimination of post-landmark in-hospital mortality (area under the curve 0.638 to 0.769). When added to SORT, discrimination rose from 0.662 to 0.803, and when added to ASA physical status, from 0.700 to 0.837. Temporal internal validation yielded similar AUCs (33 deaths). Day 7 hypoalbuminemia was associated with higher 365-day mortality (adjusted hazard ratio 3.43; 95% CI, 2.95–3.98), attenuating to 1.89 (95% CI, 1.60–2.23) after adjustment for preoperative albumin. No clear interaction with frailty emerged; an exploratory inverse interaction with emergency surgery was observed (odds ratio, 0.30; 95% CI, 0.13–0.68). Conclusions: Day 7 hypoalbuminemia, possibly reflecting the overall postoperative course, was associated with short- and long-term mortality and improved discrimination beyond routine and preoperative models. Effect modification was limited and exploratory. These hypothesis-generating findings require external validation and prospective assessment of clinical utility.