Serum albumin and gamma gap levels, and combined effect for risk of mortality in a Japanese population from the J-MICC study

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Abstract

Although the clinical importance of serum albumin and gamma gap levels is well established, it is unclear how these levels are associated with health risks in the general population. This cohort study aimed to clarify the association between serum albumin and gamma gap levels, and their combined effect, and mortality risk in a Japanese population. The participants totaled 35,746 (17,160 men and 18,586 women) aged 35–69 years from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. The mean follow-up period was 11.8 years, with 1,529 deaths and 1,907 censoring. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals after adjusting for related factors. Increased HRs of low albumin and high gamma gap levels were respectively observed for deaths from all-causes, cancer, cardiovascular diseases, respiratory system diseases without pneumonia, and other-causes; and the HR was the highest on respiratory system diseases without pneumonia (HR=7.31, 4.15–12.9). Low albumin and low gamma gap levels were strongly associated for pneumonia death (HR=12.4, 3.98–38.5). The interaction between albumin and gamma gap levels was significant for deaths from all-causes, pneumonia and other-causes. The dose relationship for each association was dose-dependent in albumin and threshold-type in gamma gap, except for other-causes. This study suggests that albumin and gamma gap levels are independent indicators of an increased risk of mortality in a Japanese population. Combined effect was apparent for mortality from all-causes, pneumonia, and other-causes.

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Shibuya, K., Ibusuki, R., Nishimoto, D., Tanoue, S., Koriyama, C., Niiyama, S., … Kakihana, Y. (2025). Serum albumin and gamma gap levels, and combined effect for risk of mortality in a Japanese population from the J-MICC study. PLOS ONE, 20(11 November). https://doi.org/10.1371/journal.pone.0336926

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