title: The Gamma Gap and All-Cause Mortality.
abstract: BACKGROUND
  The difference between total serum protein and albumin, i.e. the gamma gap, is a frequently used clinical screening measure for both latent infection and malignancy. However, there are no studies defining a positive gamma gap. Further, whether it is an independent risk factor of mortality is unknown.
  
  
  RESULTS
  This study examined the association between gamma gap, all-cause mortality, and specific causes of death (cardiovascular, cancer, pulmonary, or other) in 12,260 participants of the National Health and Nutrition Examination Survey (NHANES) from 1999-2004. Participants had a comprehensive metabolic panel measured, which was linked with vital status data from the National Death Index. Cause of death was based on ICD10 codes from death certificates. Analyses were performed with Cox proportional hazards models adjusted for mortality risk factors. The mean (SE) age was 46 (0.3) years and the mean gamma gap was 3.0 (0.01) g/dl. The population was 52% women and 10% black. During a median follow-up period of 4.8 years (IQR: 3.3 to 6.2 years), there were 723 deaths. The unadjusted 5-year cumulative incidences across quartiles of the gamma gap (1.7-2.7, 2.8-3.0, 3.1-3.2, and 3.3-7.9 g/dl) were 5.7%, 4.2%, 5.5%, and 7.8%. After adjustment for risk factors, participants with a gamma gap of ≥3.1 g/dl had a 30% higher risk of death compared to participants with a gamma gap <3.1 g/dl (HR: 1.30; 95%CI: 1.08, 1.55; P = 0.006). Gamma gap (per 1.0 g/dl) was most strongly associated with death from pulmonary causes (HR 2.22; 95%CI: 1.19, 4.17; P = 0.01).
  
  
  CONCLUSIONS
  The gamma gap is an independent risk factor for all-cause mortality at values as low as 3.1 g/dl (in contrast to the traditional definition of 4.0 g/dl), and is strongly associated with death from pulmonary causes. Future studies should examine the biologic pathways underlying these associations.
authors.affiliation: Department of Epidemioloy, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.|The Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, United States of America.|Division of General Internal Medicine, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, United States of America.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Juraschek
authors.affiliation: Division of Hematology, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States of America.
authors.forename: Alison R
authors.initials: AR
authors.lastname: Moliterno
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, United States of America.|Department of Biostatistics, Johns Hopkins Bloomberg, School of Public Health, Baltimore MD, United States of America.
authors.forename: William
authors.initials: W
authors.lastname: Checkley
authors.affiliation: Department of Epidemioloy, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.|The Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, United States of America.|Division of General Internal Medicine, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, United States of America.
authors.forename: Edgar R
authors.initials: ER
authors.lastname: Miller
mesh_terms: D000418:Albumins / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000378:metabolism / Q000401:mortality*; D002423:Cause of Death; D005260:Female; D006801:Humans; D015994:Incidence; D008171:Lung Diseases / Q000453:epidemiology / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009026:Mortality / Q000639:trends*; D009369:Neoplasms / Q000453:epidemiology / Q000378:metabolism / Q000401:mortality*; D009749:Nutrition Surveys; D012307:Risk Factors; D014481:United States
chemical_list: D000418:Albumins; D001798:Blood Proteins