Association Between Low-Density Lipoprotein Cholesterol Levels and Risk for Sepsis Among Patients Admitted to the Hospital With Infection

Abstract

Importance: Whether low levels of low-density lipoprotein cholesterol (LDL-C) are associated with increased risk of sepsis and poorer outcomes is unknown.

Objective: To examine the association between LDL-C levels and risk of sepsis among patients admitted to the hospital with infection.

Design, setting, and participants: Cohort study in which deidentified electronic health records were used to define a cohort of patients admitted to Vanderbilt University Medical Center, Nashville, Tennessee, with infection. Patients were white adults, had a code indicating infection from the International Classification of Diseases, Ninth Revision, Clinical Modification, and received an antibiotic within 1 day of hospital admission (N = 61 502). Data were collected from January 1, 1993, through December 31, 2017, and analyzed from January 24 through October 31, 2018.

Interventions: Clinically measured LDL-C levels (excluding measurements <1 year before hospital admission and those associated with acute illness) and a genetic risk score (GRS).

Main outcomes and measures: The primary outcome was sepsis; secondary outcomes included admission to an intensive care unit (ICU) and in-hospital death.

Results: Among the 3961 patients with clinically measured LDL-C levels (57.8% women; mean [SD] age, 64.1 [15.9] years) and the 7804 with a GRS for LDL-C (54.0% men; mean [SD] age, 59.8 [15.2] years), lower measured LDL-C levels were significantly associated with increased risk of 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, none of these associations were statistically significant after adjustment for age, sex, and comorbidity variables (OR for risk of 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). 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.

Conclusions and relevance: Results of this study suggest that lower measured LDL-C levels were significantly associated with increased risk of sepsis and admission to ICU in patients admitted to the hospital with infection; however, this association was due to comorbidities because both clinical models adjusted for confounders, and the genetic model showed no increased risk. Levels of LDL-C do not appear to directly alter the risk of sepsis or poor outcomes in patients hospitalized with infection.

Figure 1.. Overview of Clinical and Genetic Approaches

LDL-C indicates low-density lipoprotein cholesterol.

Figure 2.. Algorithm to Identify Sepsis Within the Infection Cohort

ICD-9-CM indicates International Classification of Diseases, Ninth Revision, Clinical Modification; ICD-10, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision; and ICU, intensive care unit. To convert bilirubin to micromoles per liter, multiply by 17.104.

Figure 3.. Association Between Low-Density Lipoprotein Cholesterol (LDL-C) Quartiles and Sepsis, Intensive Care Unit (ICU) Admission, and Death

The associations between sepsis and its adverse outcomes and measured LDL-C quartiles (top) and genetic risk score (GRS) quartiles (bottom) are shown. Analyses of measured LDL-C quartiles were adjusted for age, sex, and comorbidity variables; analyses of GRS quartiles, for age and sex. GLCG indicates Global Lipids Genetics Consortium; OR, odds ratio.