The gamma gap and all-cause mortality risk: considerations of physical activity

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Only one study has examined the association between the ‘gamma gap’ (total serum protein minus albumin) and all-cause mortality risk. No study has evaluated this relationship while considering patient physical activity behaviour.


To examine the effects of gamma gap on all-cause mortality, with considerations by physical activity behaviour.


Data from the 1999–2006 National Health and Nutrition Examination Survey were employed, with follow-up occurring through 2011 via the National Death Index. Gamma gap was evaluated from a comprehensive medical panel, with physical activity assessed via self-report. Various potential confounders were evaluated via self-report, examination and laboratory assessment.


Among the evaluated 14,936 participants, 1,564,112 person-months occurred with an incidence rate of 0.63 deaths per 1000 person-months. The unweighted median follow-up period was 105 months, with 989 deaths occurring during the follow-up period. After adjusting for all covariates with the exception of physical activity, gamma gap was significantly associated with all-cause mortality risk (HR=1.33; 95% CI: 1.07-1.64). The inclusion of physical activity as a covariate did not appreciably alter the relationship between the gamma gap and all-cause mortality (HR = 1.30; 95% CI: 1.05–1.60; p = 0.02). Participants with an elevated gamma gap (≥ 3.1 g/dl; ≥ 31.0 g/l) and who met moderate-to-vigorous physical activity guidelines had a 44% reduced all-cause mortality risk (HR = 0.56; 95% CI: 0.40–0.78; p = 0.001).


This study lends further credence to the effect of the gamma gap on all-cause mortality risk independent of other mortality risk factors and physical activity status, as well as provides evidence for a beneficial effect of physical activity on mortality among individuals with an elevated gamma gap. Thus, it may be possible that serial monitoring of total protein and albumin may be beneficial in the clinical setting and we highlight a potential beneficial role of physical activity in patients with elevated gamma gap.

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