The Association between Serum Albumin and Globulin and All-Cause Mortality of Adults
Serum albumins have been used as biomarkers in chronic kidney disease  and heart disease . Using data from National Health and Nutrition Examination Survey (NHANES), Serum albumin was associated with coronary heart disease and heart disease related mortality . Serum albumin and creatinine ratio was found to predict mortality using NAHNES III data . Serum albumin level was associated with serum acidosis and inflammation in chronic renal disease patients . Albuminuria was also found to be associated with cancer mortality . The relationship between serum albumin levels and all-cause mortality in adults has not been well defined. This study used NHAENS III and NHANES III mortality linked data files to study the association between serum albumin and globulin concentrations and all cause mortality. There is little information on the relationship between serum globulins [6,7] and all-cause mortality. The effect of serum globulin levels on all cause mortality was further studied here. This study was a part of a larger effort to identify potential chemicals with harmful and beneficial health effects. It took advantage of the vastness of the public use NHANES III (National Health and Nutrition Examination Survey) data to adjust for socio-demographic, health status factors may be confound the effects of serum albumin and globulin concentrations
and the mortality of US adults.
Materials and Methods
NHANES and NHANES III
NHANES III participants were followed passively until December 31, 2006 for their mortality data. Detailed information about the data and analysis guidelines are available at their website . In brief, probability matching was used to link NHANES III with National Death Index for vital status and mortality, age 90 years old was censored because they contribute little in person years. NHANES used multiple sources including the use of death certificates and with the National Death Index to ascertain vital status and cause of death.Statistical analysis
ResultsThe general characteristics of the NHANES III linked mortality data were as follows. There were 20024 cases in NHANES III linked mortality data file included in this study. 13944 cases were not available in the public use file to protect the privacy of youth subjects. 26 cases in the NHANES III linked dataset did not have mortality data. All cause mortality (5291 deaths out of 33994 subjects, uod_113 codes were used to determine the cause of death) was used as the binary outcomes for this analysis. The NHANES III adult data file and the NHANES III linked mortality file were merged according to the SEQN number provided by NHANES III to uniquely identify the cases. All the results were obtained by using survey command taking into account the primary sampling unit and stratification variables and the weights assigned to the sample persons examined in the MEC. Thus these results were representative of the US population.
There were 2512 sample persons (Table 1) had complete data and were used in this analysis. The univariables (S.E.) were: the risk of death (S.E.) (IndicatorDeath), 0.147, (0.129-0.165); body mass index (BMI), 25.231 (24.940- 25.522); age (MXPAXTMR), 474.180 (464.512-483.847); sex (HSSEX), 1.446 (1.425-1.467); urbanicity (DMPMETRO), 1.563 (1.433-1.692); race (DMARETHN), 1.374 (1.278-1.469); poverty income ratio (DMPPIR), 2.737 (2.551-2.923); smoking (cigarettes per day) (HAR4S), 19.584 (18.479-20.689); drinking hard liquors (drinks per month) (HAN6JS), 2.802 (2.089-3.514); follow up in months (permth_exm) 163.387 (158.824-167.949); serum albumin level (umol/L) (AMPSI) 41.582 (41.141 -42.023); serum globulin concentration (umol/L) (GBPSI), 31.040 (30.536-31.544).
For univariate analysis, the significant univariates (Fig. 2), odds ratios (95% confidence intervals) were: age 1.00821 (1.00712-1.00931); serum albumin concentration 0.852 (0.809-0.898); serum globulin concentration 1.089 (1.0465 -1.1322). For multivariate analysis, the significant variables (Fig. 3), odds ratios (95% confidence intervals) were: age 1.00809 (1.00694-1.00925); female relative to male 0.613 (0.384-0.978); poverty income ratio 0.869 (0.789- 0.956); drinking hard liquors 1.0126 (1.00061-1.02471); serum albumin concentration 0.914 (0.846-0.988); serum globulin concentration 1.0503 (1.00612-1.09649).
The relationship between serum albumin and globulin levels and all cause mortality has not been well defined. Although albumin serum level has been associated with mortality related to heart disease  and cancer . Serum globin is a large family of globular functional serum proteins . There is little information on the relationship between serum globulin and mortality [6,7]. This study investigated the association between serum globulin and albumin levels with mortality in adults. The NHANES III data and HNAHES III linked mortality data were taken to represent US non-institutionalized population as designed by NHANES. There were 2512 sample persons (Table 1) had complete data and were used in this analysis. This study had a long follow up time of 163 months (Table 1). From the univariate analysis (Table 2), this study found significant association between age of the subject, serum albumin and globulin concentrations and all cause mortality in adults.
Table 1 Baseline characteristics of serum albumin and globulin and covariables of adult all-cause mortality. Indicator Death: 0=alive, 1=dead. Linearized Taylor Standard Error estimation was used. The NHANES III codes used were: body mass index, MXPAXTMR (age at the MEC final examination), HSSEX (sex), AMPSI (serum albumin concentration in S.I. units), GBPSI (serum albumin concentration in S.I. units),DMPMETRO (urban rural residence status), HAM6S (weight in lbs without clothes), DMARETHN (race and ethnicity), DMPPIR (poverty index ratio), HAN6JS (alcohol consumption), HAR4S (smoking), and permth_exm (months of follow up from MEC examination). n = 2512 samples.
Table 2. Univariate analysis of socio-economic and serum albumin and globulin factors of all cause mortality. Indicator Death: 0=alive, 1=dead. Linearized Taylor Standard Error estimation was used. The NHANES III codes used were: body mass index, MXPAXTMR (age at the MEC final examination), HSSEX (sex), AMPSI (serum albumin concentration in S.I. units), GBPSI (serum globulin concentration in S.I. units), DMPMETRO (urban rural residence status), HAM6S (weight in lbs without clothes), DMARETHN (race and ethnicity), DMPPIR (poverty index ratio), HAN6JS (alcohol consumption), HAR4S (smoking), and permth_exm (months of follow up from MEC examination). n = 2512 samples.All of the univariables were used in the final multivariate analysis so as not to miss the potentially important predictors. For multivariate analysis (Table 3), this study found that the significant predictors of all cause mortality in adults were age, female sex (relative to males), poverty income ratio, drinking hard liquors, serum albumin and globulin concentration. Previous studies have found racial disparities [17,18] and the adverse effects of smoking and drinking . This study found an increased risk of mortality with drinking and lower poverty income ration. After adjusting for all the covariates, serum globulin and albumin levels remained an independent risk factor of adult all cause mortality.
clothes), DMPMETRO (urban rural residence status, _IDMPMETRO_2=rural residence, urban residence used as the reference group), DMARETHN (race and ethnicity, _IDMARETHN_2=non-Hispanic black, _IDMARETHN_3 =Mexicans, _IDMARETHN_4=others, non-Hispanic white used as the reference group), DMPPIR (poverty index ratio), HAN6JS (alcohol consumption), and HAR4S (smoking) ). n=2512 samples.
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