Low-density lipoprotein (LDL) cholesterol level was not significantly associated with sepsis and poor sepsis outcomes after controlling for comorbidities associated with the life-threatening infection complication in a cohort study.
Lower LDL cholesterol levels were associated with an increased risk of sepsis and admission to the ICU in patients hospitalized for infection, but after adjusting for confounders in several clinical models, the association was no longer seen, according to QiPing Feng, PhD, and colleagues from Vanderbilt University Medical Center in Nashville.
Genetic risk factors for higher LDL cholesterol (LDL-C) were also not associated with sepsis or its outcomes, as they reported in JAMA Network Open.
Studies in animals, and to a lesser extent in humans, suggest a link between low LDL-C levels and an increased sepsis risk and worse outcomes in some, but not all, studies.
“Understanding the link between LDL-C levels and sepsis is important because newer medications to lower lipid levels can reduce LDL-C concentrations to very low levels,” wrote Feng’s group. “Also, administering lipoproteins to patients at risk for sepsis is a therapeutic strategy that could potentially prevent or ameliorate the disease.”
The researchers explained that given these considerations, they decided to test the hypothesis that low LDL-C are directly associated with increased risk of sepsis and poor outcomes.
The team used a de-identified electronic health record repository linked to a DNA biobank to define baseline measured LDL-C levels and an LDL-C genetic risk score. To define the association between LDL-C and sepsis, the researchers examined the association between measured LDL-C levels and LDL-C genetic risk score and the outcomes of sepsis, admission to the ICU, and in-hospital mortality.
Among 3,961 patients with clinically measured LDL-C levels (57.8% women, mean age 64.1 years) and the 7,804 with a genetic risk score for LDL-C (54.0% men, mean age 59.8 years), lower measured LDL-C levels were significantly associated with increased risk of sepsis (OR 0.86, 95% CI 0.79-0.94, P=0.001) and ICU admission (OR 0.85, 95% CI 0.76-0.96, P=0.008), but not in-hospital mortality (OR 0.80, 95% CI 0.63-1.00, P=0.06).
None of these associations, however, were statistically significant after adjustment for age, sex, and comorbidity variables (P>0.05 for all):
- Risk of sepsis: OR 0.96, 95% CI 0.88-1.06
- ICU admission: OR 0.94, 95% CI 0.83-1.06
- In-hospital death: OR 0.97, 95% CI 0.76-1.22
The LDL-C genetic risk score correlated with measured LDL-C levels (r=0.24; P<2.2 × 10−16), but was not significantly associated with any of the outcomes.
“Newer agents to lower LDL-C levels, such as PCSK9 inhibitors, can reduce LDL-C levels to extremely low levels,” Feng and co-authors wrote. “Although lowering of LDL-C levels with PCSK9 inhibitors has been shown to reduce cardiovascular events in statin-treated patients with coronary artery disease and acute coronary syndrome, little information is available about other effects of long-term low LDL-C levels.”
“Traditional postmarketing drug safety approaches to determine these long-term effects will require years of study,” the team continued. “By applying a clinical and genetic approach, we observed no association between low LDL-C levels and sepsis. Therefore, therapy to lower LDL-C levels is unlikely to increase sepsis risk for patients with serious infection.”
Funding for the research was provided by the Rheumatology Research Foundation, the American Heart Association, the Vanderbilt Faculty Research Scholar Fund, and others.
Feng reported having no conflicts of interest; other co-authors reported financial relationships with Amgen and Regenxbio, unrelated to this study.