Year-end Sale % OFF 
Abstract
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. To determine whether lymphopenia is associated with reduced survival in outpatients. 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. Absolute lymphocyte counts (ALC), red blood cell distribution width (RDW), and C-reactive protein (CRP) level. All-cause survival. 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%). 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.
Highlights
Lymphopenia was associated with worse survival in multivariable models, including traditional clinical risk factors, and this risk intensified when accompanied by bone marrow dysregulation and/or inflammation
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%). 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
The increased mortality was due to cardiovascular disease, malignant neoplasm, and influenza or pneumonia but not deaths due to unintentional injuries (Figure 2)
Summary
Dysregulation of immunologic function is associated with autoimmune disease, infection,[1,2,3] malignant neoplasms,[4,5,6] and cardiovascular disease.[7,8,9,10,11] Inflammation worsens cardiovascular disease outcomes[9,12] and may promote malignant disease,[13] whereas immune exhaustion or failure is associated with the pathogenesis of some cancers,[14,15] sepsis,[16] and infectious diseases.[17,18] Drugs to reduce or promote immune activation are increasingly available to treat established disease, but improved methods are needed to test and deploy optimally novel strategies to prevent immuneassociated diseases in the general population.Depending on the clinical context, immune status is typically viewed through the lens of individual measures of immune status. C- reactive protein (CRP) is a marker of generalized inflammation and improves risk stratification in healthy adults.[19,20] immune pathways often affect multiple variables, some of which are measured routinely as part of primary care. Inflammation can impair erythropoiesis,[21,22] and an elevated red blood cell distribution width (RDW) is associated with cardiovascular and noncardiovascular illness and death.[23,24,25] Immune activation can alter T-cell homeostasis through various mechanisms,[26,27,28,29,30,31] and lymphopenia is among the strongest risk factors for decreased longevity in those with aortic stenosis.[32] to our knowledge, the extent to which lymphopenia is associated with survival in the general population and whether lymphopenia is associated with additive risk beyond previously established risk markers have not been previously studied
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
