Albumin-corrected anion gap and risk of mortality among US adults

Elevated albumin-corrected anion gap (ACAG) has been linked to increased mortality across various patient populations, but its prognostic value in the general population remains unclear. This study examined the association between ACAG and all-cause, cardiovascular disease (CVD), and cancer mortality among US adults.

Data from 40,702 adults aged ≥ 20 years were analyzed from the National Health and Nutrition Examination Survey 1999-2018. ACAG was calculated as: anion gap + (4.4 - serum albumin [g/dL]) × 2.5. Cox proportional hazards models, restricted cubic splines, and Kaplan-Meier curves were used to assess associations. Subgroup and sensitivity analyses were conducted.

Over a median 113 month follow-up, 6,087 deaths occurred, including 1,601 from CVD and 1,372 from cancer. Each 1-unit increase in ACAG was associated with higher risk of all-cause (HR = 1.08, 95% CI: 1.06-1.10), CVD (HR = 1.08, 95% CI: 1.05-1.12), and cancer mortality (HR = 1.06, 95% CI: 1.03-1.09). Participants in the highest ACAG quartile had significantly higher mortality risks compared to the lowest quartile. No evident nonlinear associations were observed for all-cause, CVD, and cancer mortality. The positive association with all-cause mortality was more pronounced among participants aged < 60 years, males, current smokers, and those with hyperlipidemia or diabetes. Sensitivity analyses confirmed robustness.

Elevated ACAG is independently associated with increased risks of all-cause, CVD, and cancer mortality in US adults. ACAG has potential value in stratifying mortality risk in public health contexts.