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Association of Lymphopenia With Risk of Mortality Among Adults in the US General Population.

Publication ,  Journal Article
Zidar, DA; Al-Kindi, SG; Liu, Y; Krieger, NI; Perzynski, AT; Osnard, M; Nmai, C; Anthony, DD; Lederman, MM; Freeman, ML; Bonomo, RA; Simon, DI ...
Published in: JAMA Netw Open
December 2, 2019

IMPORTANCE: Immune dysregulation can increase the risk of infection, malignant neoplasms, and cardiovascular disease, but improved methods are needed to identify and quantify immunologic hazard in the general population. OBJECTIVE: To determine whether lymphopenia is associated with reduced survival in outpatients. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of the National Health and Nutrition Examination Survey (NHANES) included participants enrolled from January 1, 1999, to December 31, 2010, a large outpatient sample representative of the US adult population. Associations were evaluated between lymphopenia and other immunohematologic (IH) markers, clinical features, and survival during 12 years of follow-up, completed on December 31, 2011. Spearman correlations, Cox proportional hazards regression models, and Kaplan-Meier curves were used in univariable and multivariable models, allowing for nonlinear associations with bivariate cubic polynomials. Data were analyzed from September 1, 2018, through July 24, 2019. EXPOSURES: Absolute lymphocyte counts (ALC), red blood cell distribution width (RDW), and C-reactive protein (CRP) level. MAIN OUTCOMES AND MEASURES: All-cause survival. RESULTS: Among the 31 178 participants, the median (interquartile range) age at baseline was 45 (30-63) years, 16 093 (51.6%) were women, 16 260 (52.2%) were nonwhite, and overall 12-year rate of survival was 82.8%. Relative lymphopenia (≤1500/μL) and severe lymphopenia (≤1000/μL) were observed in 20.1% and 3.0%, respectively, of this general population and were associated with increased risk of mortality (age- and sex-adjusted hazard ratios [HRs], 1.3 [95% CI, 1.2-1.4] and 1.8 [95% CI, 1.6-2.1], respectively) due to cardiovascular and noncardiovascular causes. Lymphopenia was also associated with worse survival in multivariable models, including traditional clinical risk factors, and this risk intensified when accompanied by bone marrow dysregulation (elevated RDW) and/or inflammation (elevated CRP level). Ten-year mortality ranged from 3.8% to 62.1% based on lymphopenia status, tertile of CRP level, and tertile of RDW. A high-risk IH profile was nearly twice as common as type 2 diabetes (19.3% and 10.0% of participants, respectively) and associated with a 3-fold risk of mortality (HR, 3.2; 95% CI, 2.6-4.0). Individuals aged 70 to 79 years with low IH risk had a better 10-year survival (74.1%) than those who were a decade younger with a high-risk IH profile (68.9%). CONCLUSIONS AND RELEVANCE: These findings suggest that lymphopenia is associated with reduced survival independently of and additive to traditional risk factors, especially when accompanied by altered erythropoiesis and/or heightened inflammation. Immune risk may be analyzed as a multidimensional entity derived from routine tests, facilitating precision medicine and population health interventions.

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Published In

JAMA Netw Open

DOI

EISSN

2574-3805

Publication Date

December 2, 2019

Volume

2

Issue

12

Start / End Page

e1916526

Location

United States

Related Subject Headings

  • United States
  • Survival Rate
  • Risk Factors
  • Retrospective Studies
  • Proportional Hazards Models
  • Nutrition Surveys
  • Middle Aged
  • Male
  • Lymphopenia
  • Humans
 

Citation

APA
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ICMJE
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Zidar, D. A., Al-Kindi, S. G., Liu, Y., Krieger, N. I., Perzynski, A. T., Osnard, M., … Dalton, J. E. (2019). Association of Lymphopenia With Risk of Mortality Among Adults in the US General Population. JAMA Netw Open, 2(12), e1916526. https://doi.org/10.1001/jamanetworkopen.2019.16526
Zidar, David A., Sadeer G. Al-Kindi, Yongmei Liu, Nikolas I. Krieger, Adam T. Perzynski, Michael Osnard, Christopher Nmai, et al. “Association of Lymphopenia With Risk of Mortality Among Adults in the US General Population.JAMA Netw Open 2, no. 12 (December 2, 2019): e1916526. https://doi.org/10.1001/jamanetworkopen.2019.16526.
Zidar DA, Al-Kindi SG, Liu Y, Krieger NI, Perzynski AT, Osnard M, et al. Association of Lymphopenia With Risk of Mortality Among Adults in the US General Population. JAMA Netw Open. 2019 Dec 2;2(12):e1916526.
Zidar, David A., et al. “Association of Lymphopenia With Risk of Mortality Among Adults in the US General Population.JAMA Netw Open, vol. 2, no. 12, Dec. 2019, p. e1916526. Pubmed, doi:10.1001/jamanetworkopen.2019.16526.
Zidar DA, Al-Kindi SG, Liu Y, Krieger NI, Perzynski AT, Osnard M, Nmai C, Anthony DD, Lederman MM, Freeman ML, Bonomo RA, Simon DI, Dalton JE. Association of Lymphopenia With Risk of Mortality Among Adults in the US General Population. JAMA Netw Open. 2019 Dec 2;2(12):e1916526.

Published In

JAMA Netw Open

DOI

EISSN

2574-3805

Publication Date

December 2, 2019

Volume

2

Issue

12

Start / End Page

e1916526

Location

United States

Related Subject Headings

  • United States
  • Survival Rate
  • Risk Factors
  • Retrospective Studies
  • Proportional Hazards Models
  • Nutrition Surveys
  • Middle Aged
  • Male
  • Lymphopenia
  • Humans