Sepsis/InfectionDecreased high-density lipoprotein cholesterol level is an early prognostic marker for organ dysfunction and death in patients with suspected sepsis
Introduction
Sepsis is a serious complication of a microbial infection characterized by a dysregulated inflammatory response and altered metabolic state, leading to tissue injury, organ failure, and sometimes death. During sepsis, lipopolysaccharide (LPS) and other pathogen lipids are sequestered within high- (HDL-C), low- (LDL) and very low-density lipoproteins [1] and are then cleared from circulation via the liver through receptors such as the LDL receptor [2] and the HDL-C receptor SR-BI [3]. High-density lipoprotein in particular has the highest affinity for both LPS [4] and the gram-positive toxin lipoteichoic acid [5], making it especially beneficial in reducing their ability to trigger an innate immune response. High-density lipoprotein is also important in healthy endothelial function and repair [6]. Thus, HDL-C plays an important role in modulating the septic inflammatory response.
High-density lipoprotein cholesterol levels are known to be low in established septic shock [7], [8], [9], [10]. In patients admitted to a critical care unit for organ failure(s), an HDL-C level lower than 20 mg/dL is associated with increased 30-day mortality, prolonged (>7 days) intensive care unit (ICU) stay, and greater hospital-acquired infection rate [11]; pediatric nonsurvivors of severe meningococcal sepsis have lower HDL-C than do survivors [12]; and low HDL-C during septic shock is generally associated with increased hospital mortality [13], [14], [15], [16].
Despite this extensive literature, lipid profiles are rarely measured or interpreted in clinical management of sepsis [17] and are not even mentioned in the Surviving Sepsis Campaign guidelines [18]. However, previous studies of lipoproteins during sepsis focus exclusively on patients already receiving critical care for established septic shock and therefore may have missed the opportunity to assess the prognostic value of an early HDL-C measurement at triage. To date (to our knowledge), no studies have measured HDL-C level in a suspected sepsis cohort at the time of emergency department (ED) presentation and assessed its association with outcomes of sepsis.
Accordingly, we sought to determine whether low HDL-C levels precede the development of organ dysfunction and could therefore be of utility as an early prognostic biomarker in the ED setting. To do this, we recruited patients with clinically suspected sepsis at the time of presentation to the ED and measured a full lipid panel on plasma collected at the time of first blood draw for routine testing. We tested the association of early plasma HDL-C levels with the subsequent development of single or multiple-organ dysfunction and mortality. The prognostic value of HDL-C level was compared with other lipid panel components (LDL-C, non-HDL-C, and triglycerides) as well as several other routinely measured biomarkers, namely, lactate, platelets, white blood cell (WBC) count, creatinine, and hemoglobin.
Section snippets
Design, setting, and patient eligibility
In this blinded, observational cohort study, we recruited 200 adult patients with suspected sepsis at the time of admission to the ED of St Paul's Hospital (SPH), a tertiary care teaching hospital in Vancouver, Canada. Patients were identified when the attending physician activated our Institutional “Suspected Sepsis Protocol”; this requires a clinically suspected infection and at least 2 of the following: (i) temperature > 38 °C or <36 °C, (ii) heart rate >90 beats/min, (iii) WBC count >12 000
Baseline characteristics
Of the 200 enrolled patients, 96 required ICU admission, 112 had at least 1 organ dysfunction over the course of their hospital stay, 74 developed MODS, 14 patients died within 28 days (7%), and 28 died within 90 days (14%). There were no significant differences in baseline demographics or underlying conditions, with the exception of conditions affecting the liver (hepatitis and cirrhosis) between patients who did or did not develop MODS (Table 1). As expected, patients who developed MODS had
Discussion
We make the novel observation that the decrease in HDL-C precedes the onset of single- and multiple-organ failure by measuring plasma lipoprotein levels at the time of ED admission in a suspected sepsis population. Low HDL-C was independently and uniquely associated with development of MODS and 28-day mortality, and in ROC analysis, the predictive value of HDL-C level surpassed that of all other measured variables for both events. An HDL-C level lower than 25.1 mg/dL at admission was highly
Conclusion
The results of our study suggest that a low plasma HDL-C level at the time of ED admission for suspected sepsis is strongly and independently prognostic of subsequent multiple-organ dysfunction and death, with a predictive value surpassing that of all other clinical variables routinely measured at triage in this patient population. High-density lipoprotein cholesterol level may therefore provide valuable and easily accessible prognostic information for clinicians when encountering patients with
Acknowledgments
The authors would like to thank the Centre for Heart Lung Innovation's clinical research team for facilitating patient recruitment and data collection. This research was supported by Grant No. 1368896 from the Canadian Institutes of Health Research.
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