A fascinating cohort study published in JAMA Network Open conducted by QiPing Feng, Ph.D., and colleagues from Vanderbilt University Medical Center in Nashville, Tennessee, refuted previous studies that showed a significant relationship between low levels of Low-density lipoprotein cholesterol (LDL-C) level and sepsis.
“New therapies to prevent or treat sepsis are an important but elusive goal. Thus, LDL-C levels represent an interesting candidate for prevention and treatment of sepsis.”- Dr. Wei-Qi Wei, M.D., Ph.D.
The correlation between LDL-C levels and sepsis was of clinical importance as pointed out by the investigators. According to them, the use of new lipid-lowering medications could potentially lead to sepsis and they also proposed the use of lipoproteins as a therapeutic strategy to evade and treat sepsis. There had been similar studies in the past that proved a significant association between low-level LDL-C and increased risk of sepsis; however, Feng and her colleagues tested the hypothesis by using a de-identified electronic health record (EHR) repository attached with a DNA biobank to establish baseline LDL-C levels and an LDL-C genetic risk score (GRS) to prevent confounding. The findings of the study portrayed that, lower measured LDL-C levels were significantly associated with an increased risk of sepsis (P = .001) and ICU admission (P = .008), but not in-hospital mortality ( P = .06); however, there was no statistical significance in these associations after modifying of confounding variables ( 95% CI, P > .05 for all). The LDL-C GRS correlated with measured LDL-C levels (r = 0.24; P < 2.2 × 10−16) but was not significantly associated with any of the outcomes.
“We used epidemiological and genetic approaches to define the association between LDL-C levels and sepsis and found that lower LDL-C levels measured in patients at least 1 year before they were admitted to the hospital with infection were associated with increased risk of sepsis, ICU admission, and in-hospital mortality. However, when comorbidities were considered, no association between LDL-C levels and sepsis or its outcomes occurred.“-Dr. QiPing Feng, Ph.D.
Feng and her team acknowledged that the study was not a randomized controlled trial and patients could have received treatment in centers other than the VUMC in Nashville. Also, the genetic variations of overall LDL-C calculated by GRS were a small percentage of the population. Other limitations of the diet, environmental factors, and other lipids were not taken into account. Therefore, the study showed that the cause of this discrepancy was due to the presence of comorbidities as when both clinical models and genetic models were adjusted for confounders, they showed no increased risk of sepsis and admissions to the ICU in patients admitted with infections.
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