L 300 incident sepsis events; the associations were largely similar. Compared with incident sepsis individuals included in the analysis, the excluded individuals were older, more likely to be male, and had a higher number of chronic medical conditions. There were no racial differences between individuals included and excluded from the analysis.Discussion 25033180 Sensitivity AnalysisDue to the time lag in observations and medical record retrieval, we could not review medical records for 1,157 participants with a reported hospitalization for serious infection. Furthermore, these unexamined hospitalizations occurred across the observation period (2003?011) and were not limited to select time periods. Therefore, in a sensitivity analysis we repeated the analysis excluding participants with reported hospitalizations for serious infection that had not yet been adjudicated. This study confirms the association of baseline chronic medical conditions with the risk of future sepsis events. While prior studies have linked medical comorbidities with severity 
of sepsis or degree of organ dysfunction, there have been no efforts connecting these conditions at stable baseline with risk of future sepsis events. [11,15,16,17,18] The findings of this study may prove useful in sepsis care, pointing to risk detection, stratification and reduction as potential sepsis management strategies. Risk prevention and reduction strategies have proven effective for common medical conditions such as cardiovascular disease and stroke. [6]. We emphasize that this study identifies associations between baseline chronic medical conditions and sepsis but does not indicate a causal relationship. However, there are possible pathophysiologic connections between chronic medical conditions and the future risk of sepsis. Numerous common conditions have been associated with chronic inflammation, including obesity, diabetes, heart disease and smoking, among others. [19,20,21,22,23,24] Inflammation plays a central role in sepsis pathophysiology, and chronic inflammation could raise the risk of progression to sepsis when subjected to a bacterial pathogen. [25] Chronic inflammation may also indicate individuals prone to developing a dysfunctional or exaggerated response to microbial infection. Associations between vascular disease and sepsis haveResultsAmong the 30,239 REGARDS participants, from 94-09-7 February 5, 2003 through October 14, 2011 we identified 2,157 hospitalizations for serious infection, encompassing 1,297 sepsis and 975 incident sepsis events. The most common infection types associated with incident sepsis cases were pneumonia, kidney and urinary tract infections, and abdominal infections. (Table 1) Pneumonia and other lung infections comprised over half of incident sepsis cases. The risk of incident sepsis was higher among older individuals. (Table 2) Whites were at higher risk of incident sepsis than blacks. Sepsis risk was also increased among those in the lowest 16574785 education and income categories. While both current and past tobacco useTable 1. Infection types associated with hospitalizations for sepsis.Infection Type Pneumonia Kidney and Urinary Tract Infections Abdominal 548-04-9 chemical information Bronchitis, Influenza and other Lung Infections Skin and Soft Tissue Sepsis Fever of Unknown Origin Unknown/Other Surgical Wound Catheter (IV/Central/Dialysis) Meningitis doi:10.1371/journal.pone.0048307.tPercentage of Incident Sepsis Hospitalizations (n = 975); n ( ) 427 (43.4) 155 (15.9) 133 (13.6) 84 (8.6) 71 (7.L 300 incident sepsis events; the associations were largely similar. Compared with incident sepsis individuals included in the analysis, the excluded individuals were older, more likely to be male, and had a higher number of chronic medical conditions. There were no racial differences between individuals included and excluded from the analysis.Discussion 25033180 Sensitivity AnalysisDue to the time lag in observations and medical record retrieval, we could not review medical records for 1,157 participants with a reported hospitalization for serious infection. Furthermore, these unexamined hospitalizations occurred across the observation period (2003?011) and were not limited to select time periods. Therefore, in a sensitivity analysis we repeated the analysis excluding participants with reported hospitalizations for serious infection that had not yet been adjudicated. This study confirms the association of baseline chronic medical conditions with the risk of future sepsis events. While prior studies have linked 
medical comorbidities with severity of sepsis or degree of organ dysfunction, there have been no efforts connecting these conditions at stable baseline with risk of future sepsis events. [11,15,16,17,18] The findings of this study may prove useful in sepsis care, pointing to risk detection, stratification and reduction as potential sepsis management strategies. Risk prevention and reduction strategies have proven effective for common medical conditions such as cardiovascular disease and stroke. [6]. We emphasize that this study identifies associations between baseline chronic medical conditions and sepsis but does not indicate a causal relationship. However, there are possible pathophysiologic connections between chronic medical conditions and the future risk of sepsis. Numerous common conditions have been associated with chronic inflammation, including obesity, diabetes, heart disease and smoking, among others. [19,20,21,22,23,24] Inflammation plays a central role in sepsis pathophysiology, and chronic inflammation could raise the risk of progression to sepsis when subjected to a bacterial pathogen. [25] Chronic inflammation may also indicate individuals prone to developing a dysfunctional or exaggerated response to microbial infection. Associations between vascular disease and sepsis haveResultsAmong the 30,239 REGARDS participants, from February 5, 2003 through October 14, 2011 we identified 2,157 hospitalizations for serious infection, encompassing 1,297 sepsis and 975 incident sepsis events. The most common infection types associated with incident sepsis cases were pneumonia, kidney and urinary tract infections, and abdominal infections. (Table 1) Pneumonia and other lung infections comprised over half of incident sepsis cases. The risk of incident sepsis was higher among older individuals. (Table 2) Whites were at higher risk of incident sepsis than blacks. Sepsis risk was also increased among those in the lowest 16574785 education and income categories. While both current and past tobacco useTable 1. Infection types associated with hospitalizations for sepsis.Infection Type Pneumonia Kidney and Urinary Tract Infections Abdominal Bronchitis, Influenza and other Lung Infections Skin and Soft Tissue Sepsis Fever of Unknown Origin Unknown/Other Surgical Wound Catheter (IV/Central/Dialysis) Meningitis doi:10.1371/journal.pone.0048307.tPercentage of Incident Sepsis Hospitalizations (n = 975); n ( ) 427 (43.4) 155 (15.9) 133 (13.6) 84 (8.6) 71 (7.