Greater Remnant Cholesterol Levels Associated with Increased Risk of Rheumatoid Arthritis

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Findings from a recent study are calling attention to the association between remnant cholesterol and rheumatoid arthritis (RA), suggesting elevated remnant cholesterol may be linked to a greater risk of RA.¹

The analysis of data from the National Health and Nutrition Examination Survey (NHANES) 1999–2008 database found a strong positive correlation between remnant cholesterol and RA, further alluding to the potential for early intervention strategies for susceptible populations at risk of developing RA based on these findings.¹

“[Remnant cholesterol] has emerged as a critical parameter in lipidology and is subject to ongoing research to uncover its broader clinical applications,” wrote Qian Qu, MD, of the department of orthopedic surgery at Soochow University in China, and colleagues.¹ “However, no study has reported whether [remnant cholesterol] is associated with RA or how.”

An autoimmune disorder in which the immune system attacks healthy joint tissue, the underlying causes of RA are not well understood. Although lipid metabolism is a known contributor to inflammation, its role in RA requires further analysis as most studies have focused on low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C).^1,2

To assess whether remnant cholesterol is associated with RA disease events, investigators extracted relevant data from the NHANES 1999–2008 database. Sanctioned by the National Center for Health Statistics, the NHANES database is an all-encompassing study conducted in the United States that collects information on the overall health and nutritional well-being of the general population.¹

Participants were excluded if they were missing data on total cholesterol, LDL-C, and HDL-C, had incomplete data related to arthritis, had osteoarthritis or other non-applicable conditions, or were pregnant. After applying these exclusion criteria, investigators excluded 41,060 participants due to insufficient arthritis and lipid data, 2278 due to osteoarthritis or other irrelevant conditions, and 508 pregnant participants. The final study population comprised 7777 participants.¹

Investigators derived patients’ remnant cholesterol values by subtracting the combined amount of LDL-C and HDL-C from the total cholesterol. Arthritis was diagnosed based on a self-report questionnaire and patients’ responses to the following question: “Have you ever been informed by a healthcare professional that you have arthritis?”

Among the cohort, 71.9% of participants were < 60 years of age, 52.72% were male, and 7.47% were diagnosed with RA. The overall mean value was 0.44 mg/dL for CRP, 5.09 mmol/L for total cholesterol, 1.37 mmol/L for HDL-C, 3.06 mmol/L for LDL-C, and 0.66 mmol/L for remnant cholesterol. Investigators categorized participants into tertiles based on their remnant cholesterol values, defining T1 as < 0.46 mmol/L, T2 as 0.46–0.72 mmol/L, and T3 as ≥ 0.72 mmol/L.¹

Upon analysis, an increase in the remnant cholesterol level was accompanied by significantly increased RA occurrence in T1 (5.16%), T2 (7.88%), and T3 (9.35%) (all P <.001). Both the crude (Odds ratio [OR], 1.91; 95% CI, 1.54–2.37; P <.0001) and adjusted models (OR, 1.91; 95% CI, 1.53–2.45; P <.0001) consistently demonstrated a strong positive correlation between remnant cholesterol and RA.¹

Of note, this relationship remained significant and positive even after investigators adjusted for gender, age, ethnicity, marital status, education level, BMI, vigorous activity, moderate activity, hypertension, diabetes, smoking status, alcohol use, steroid use, statin use, PIR, and CRP in the multivariate logistic regression analysis (OR, 1.54; 95% CI, 1.11–2.13; P = .0092).¹

“The findings significantly contribute to the growing evidence supporting the clinical utility of [remnant cholesterol] as a predictive index for RA, offering valuable insights for the development of early intervention strategies in populations susceptible to RA,” investigators concluded.¹

References:

1. ^{Yan Y, La R, Jiang M, et al. The association between remnant cholesterol and rheumatoid arthritis: insights from a large population study. Lipids Health Dis. https://doi.org/10.1186/s12944-024-02033-z}
2. ^{Mayo Clinic. Rheumatoid Arthritis. Diseases & Conditions. January 25, 2023. Accessed February 13, 2024. https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648}