No Association Between LDL Cholesterol Levels and Risk for Sepsis

A low level of LDL cholesterol was initially associated with increased risk for sepsis and admission to the ICU.

A low level of low-density lipoprotein (LDL) cholesterol was initially associated with increased risk for sepsis and admission to the intensive care unit (ICU) in patients admitted to the hospital with infections. After adjusting the model for confounders, however, it was found that the association was caused by comorbidities. Therefore, the study, published in JAMA Network Open, concluded that levels of LDL cholesterol do not alter the risk for sepsis or poor outcomes directly.

This cohort study used deidentified electronic health records to define a cohort of patients with infection admitted to Vanderbilt University Medical Center from January 1, 1993, to December 31, 2017. The cohort contained white adults and clinically measured LDL cholesterol levels where obtained from 3961 patients. A genetic risk score for LDL cholesterol was determined for 7804 patients.

Lower measured LDL cholesterol levels in both groups of patients were associated significantly with increased risk for sepsis (odds ratio [OR] 0.86; 95% CI, 0.79-0.94; P =.001) and ICU admission (OR 0.85; 95% CI, 0.76-0.96, P =.008) but not in-hospital mortality (OR 0.80; 95% CI, 0.63-1.00, P =.06). However, after adjustment for age, sex, and comorbidity variables (OR for risk for sepsis, 0.96; 95% CI, 0.88-1.06; OR for ICU admission, 0.94; 95% CI, 0.83-1.06; OR for in-hospital death, 0.97; 95% CI, 0.76-1.22; P >.05 for all), none of these associations remained significant. Further, no significant associations were found between any outcome and the LDL cholesterol genetic risk score, which was correlated only with measured LDL cholesterol levels (r = 0.24; P <2.2 × 10−16).

The confounders included accounted for many of the association between LDL cholesterol and sepsis, and the investigators noted that although it is unlikely, the results might be influenced by unmeasured confounders. It is also possible that covariates were incomplete as patients may have received treatment outside of the Vanderbilt University Medical Center. Generalizability of the results from a single center study including only white adults who had LDL cholesterol levels measured or had undergone genotyping is also limited. Investigators commented that LDL cholesterol genetic risk score did not capture LDL changes caused by environmental factors and they could not exclude the possibility of unrelated competing effects of LDL cholesterol levels and comorbidities on sepsis risk, despite little evidence for this. In addition, they noted that only the relatively common variants reported to be associated with LDL cholesterol levels were studied and that concentrations of other lipids might also affect the outcomes of sepsis.

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Sepsis is a costly and life-threatening condition that is difficult to anticipate and treat. According to investigators, “strategies to determine which patients with infection are likely to develop sepsis are important because these patients can be targeted for early intensive monitoring.” However, no new therapies to treat or prevent sepsis currently exist. Results from this study reveal that LDL cholesterol levels “do not appear to alter the risk of sepsis or poor outcomes directly in patients hospitalized with infection.”


Feng Q, Wei WQ, Chaugai S, et al. Association between low-density lipoprotein cholesterol levels and risk for sepsis among patients admitted to the hospital with infection. JAMA Netw Open. 2019;2:e187223.