Serum Low-Density Lipoprotein Cholesterol Levels are Associated with Relapse in Neuromyelitis Optica Spectrum Disorder

Abstract

Background: The relationship between serum low-density lipoprotein cholesterol (LDL-C) and the risk of relapse in neuromyelitis optica spectrum disorder (NMOSD) remains uncertain. We aimed to examine the association between serum LDL-C level and relapse in NMOSD patients.

Methods: We conducted an analysis of the prospective observational NMOSD cohort study with consecutive 184 hospitalized NMOSD patients from department of neurology. Blood samples were collected to measure LDL-C level upon admission. Primary and relapse were evaluated during hospitalization. The relationship between serum LDL-C level and relapse were analyzed by linear curve fitting analyses. Crude and adjusted odds ratios (OR) of LDL-C for relapse with 95% confidence intervals were analyzed using multiple logistic regression models. ROC curve analysis was used to identify the target lipid-lowering value of LDL-C and the probability of relapse was evaluated by the Kaplan-Meier Plot.

Results: Over a mean disease course of 100±87 days, 59.24% (n=109) participants developed relapse with higher LDL-C than the primary group (n=75) (p<0.001). Adjusted smoothed plots suggested that there were linear relationships between serum LDL-C level and relapse (p< 0.001). The OR (95% CI) between serum LDL-C level and relapse were 2.67 (1.76-4.04, p<0.001), and 2.38 (1.48-3.83, p<0.001) respectively in NMOSD patients before and after adjusting for potential confounders. The target LDL-C lowering values were 2.795 mmol/L with potential benefits to prevent relapse in NMOSD.

Conclusion: In this sample of NMOSD patients, we found that the elevated serum LDL-C was independently and positively associated with the relapse, and serum LDL-C should be well-controlled to prevent the relapse of NMOSD.

Keywords: NMOSD; low-density lipoprotein cholesterol; multivariate analysis; neuromyelitis optica spectrum disorder; relapse.

Figure 1

A flowchart of the study.

Figure 2

Association between serum LDL-C level and risk of relapse. (A) The LDL-C level was significantly higher in relapse group than that in primary group in all patients (p<0.001). (B) Similar results were observed in both female and male (p<0.001 and p=0.003). (C) The prevalence of relapse showed grade increase according to the increased LDL-C tertile’s levels in all patients (p<0.001). (D) The prevalence of relapse in the high LDL-C group was significantly higher than that in the normal LDL-C group in all patients (p<0.001). (E) Linear relationships between the LDL-C level and relapse after adjusted for confounder factors. Solid lines represent the fitting curve and dotted lines represent the corresponding 95% CI. (F) Hierarchical analysis by sex also showed there are linear relationships between LDL-C level and relapse in women and men.

Figure 3

Hierarchical analysis on relationship of LDL-C and relapse. Each stratification adjusted for all the factors (sex, age, onset season, gastrointestinal infection, vision impaired, HDL-C, ALT, UA, SCR, AQP4-IgG, and IVIG) except the stratification factor itself.

Figure 4

ROC curve of LDL-C level to identify target value of lowering LDL-C. The target value of lipid lowering in NMOSD patients was determined by the optimal cut-off value of LDL-C using ROC curves. These results suggest that the target LDL-C value of 2.795 mmol/L, 2.790 mmol/L, and 2.695 mmol/L have good performance in discriminating relapse from primary patients in whole, female and male patients, respectively. An AUC value <0.7 indicates low diagnostic accuracy, 0.7–0.9 indicates moderate accuracy, and >0.9 indicates high accuracy.

Figure 5

Kaplan-Meier Plot of relapse grouped by target value of lowering LDL-C. Patients with high level of LDL-C exhibited significantly shorter time for relapse (median survival = 98 days) than those with low LDL-C level (median survival = 180 days) (HR= 1.51, 95% CI=1.03–2.19, p= 0.027, Kaplan-Meier plot and Log rank test).