Abstract
Objectives:
This study aimed to determine the effect of low-density lipoprotein (LDL) cholesterol blood levels on synovial fluid biomarker concentrations in the knee joint. This understanding may help elucidate the possible mechanism of LDL as an inflammatory mediator of osteoarthritis.
Methods:
Patients undergoing arthroscopic knee surgery were prospectively enrolled. Synovial fluid was aspirated from the operative knee before surgical incision and the concentrations of 10 biomarkers of interest (RANTES, IL-6, MCP-1, MIP-B, VEGF, TIMP-1, TIMP-2,IL-1RA, MMP-3, and bFGF) were measured by immunoassay. Patients with LDL cholesterol levels available by chart review were retrospectively identified and included for subsequent analysis. The LDL value nearest in date to the time of surgery was used. LDL and biomarker concentrations were log-normalized. A multivariable linear regression analysis was performed for each biomarker variable, with LDL as the primary predictor, and age at surgery, sex, and body mass index included as covariates.
Results:
A total of 119 patients (mean age 45.3 years ± 14.3) were included in the study with median absolute duration of 253.5 days [IQR: 125 - 751] between date of surgery and date of LDL. Demographic attributes of cohort are listed in Table 1. Multivariable linear regression analysis demonstrated a significant negative association of TIMP-1 (p = 0.014, beta = -0.232) and TIMP-2 (p = 0.018, beta = -0.224) with LDL when controlling for age at surgery, sex, and BMI. No other biomarkers were found to have significant associations with blood LDL level. (Table 2).
Conclusions:
Increased blood LDL levels near the time of surgery are negatively associated with TIMP-1 and TIMP-2 levels in operative knee synovial fluid at the time of arthroscopic knee surgery. Given that TIMP-1 and TIMP-2 are established anti-inflammatory cytokines with chondroprotective effects, their relative decrease in the setting of elevated LDL offers a mechanism by which LDL cholesterol may act as a mediator of knee inflammation and osteoarthritis.
