The Association Between Serum Leptin Levels and Cardiovascular Events in Patients With Rheumatoid Arthritis

Jiliang Chen, MD; Zhiping Xie, PhD; Zou Bin, MD


Lab Med. 2021;52(1):86-92. 

In This Article

Abstract and Introduction


Objective: Cardiovascular diseases (CVDs) are important complications for patients with rheumatoid arthritis (RA). The study aimed to explore whether serum leptin is associated with a increased risk of cardiovascular (CV) events in patients with RA.

Methods: Two hundred twenty-three patients with RA were followed for a mean of 40 (range = 8–42) months. Serum leptin levels were measured at baseline. Cox regression analysis was performed to assess the association between leptin levels and the risk of CV events.

Results: The univariate analysis showed that patients with RA with higher serum leptin levels had higher rates of CV events and CV mortality, respectively (P <.001). The logistic regression model showed that leptin was independently related to CVD history (odds ratio = 1.603, 95% confidence interval [CI], 1.329–2.195; P =.005) after adjusting for confounding factors in patients with RA at baseline. The multivariate Cox proportional hazard model suggested that leptin was an independent prognostic factor for CV events in patients with RA after adjustments were made for clinical confounding factors (hazard ratio = 2.467, 95% CI, 2.019–4.495; P <.001). The Kaplan-Meier analysis showed that compared with patients with RA with leptin levels below the median value (≤15.4 mg/L), patients with leptin above the median value (>15.4 μg/L) had a higher rate of CV events (P <.001).

Conclusion: Leptin was significantly associated with CV events in patients with RA. Elevated serum leptin levels may be a reliable prognostic factor for predicting CV complications in patients with RA.


Rheumatoid arthritis (RA) has become an important public health problem because of its high disability rate and huge social burden in the world.[1,2] The rate of cardiovascular diseases (CVDs) in patients with RA is significantly higher than that in the general population without RA, and CVDs have become the leading cause of death in patients with RA.[3,4] Although the exact underlying mechanisms are still unclear, increasing inflammation and oxidative stress in RA are regarded as the primary mechanisms causing a high risk for cardiovascular (CV) complications.[5,6]

Leptin is a kind of hormone secreted by adipose tissue.[7] It is generally believed that leptin participates in the regulation of sugar, fat, and energy metabolism after entering the blood circulation.[8,9] Increased leptin levels will lead to less appetite and more energy expenditure by the hypothalamus in the general population.[8–11] However, many studies have also indicated that leptin is involved in the regulation of immune responses. It can promote the secretion of many proinflammatory cytokines in vivo and in vitro and plays an important role in inflammatory responses.[12–16] As a chronic inflammatory disease, RA promotes the development of various CVD-related pathological mechanisms.[17–19] Given the close association between leptin and inflammation, we hypothesized that leptin may be associated with CV outcomes in patients with RA.

There have been no relevant studies to assess the association between serum leptin and CV events in patients with RA. The aim of this study was to investigate whether elevated leptin levels contribute to the increased risk for CV events during a follow-up period (3 years).