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

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

Disclosures

Lab Med. 2021;52(1):86-92. 

In This Article

Results

Clinical Characteristics

Clinical data for all study participants are presented in Table 1. The median serum leptin level in this cohort study was 15.4 (6.4–25.3) μg/L. We stratified the study cohort into 2 groups according to median leptin level. For clinical features, there were no significant differences in age, sex, admission blood pressure (BP; systolic BP and diastolic BP) between the 2 groups. Patients with RA with leptin levels above the median (>15.4 μg/L) had a higher BMI, a history of smoking and drinking, and significantly higher percentages of CVD history, CV events, and CV mortality. For laboratory measurements, the levels of TC, TG, LDL, FBG, HOMA-IR and hs-CRP were higher and ALB levels were lower in patients with higher leptin levels. There were no significant differences in Hb, SCr, BUN, and HDL between the 2 groups.

Serum Leptin Showed an Independent Association With CVD History

To determine the association of serum leptin levels in patients with RA with a history of CVD, multivariate logistic regression analyses were performed (Table 2). The Crude Model indicated that higher serum leptin levels were associated with a higher risk of CVD history after adjusting for age and sex. After adjustments were made for age, sex, BMI, smoking history, drinking history, and admission systolic BP and diastolic BP, the results in Model 1 were similar to those of the Crude Model. This association remained statistically significant and changed little when we continued to add laboratory measurements to Model 1 (to formulate Model 2). The fully adjusted odds ratio (OR) of CVD history in Model 2 was 1.603 (1.329–2.195) in serum levels in quartile 4 (the highest) vs in quartile 1 (the lowest).

Serum Leptin Levels Showed an Independent Value for Predicting CV Events in Patients With RA by Cox Proportional Hazard Regression Analysis

We determined CV events from patient inclusion onward with a mean follow-up period of 40 (range = 8–42) months (Table 3). Fifteen patients died, and 12 of those deaths were related to CV causes including myocardial infarction (n = 5), HF (n = 3), stroke (n = 2), complicated peripheral vascular disease (n = 1), and sudden cardiac death (n = 1). Three patients died of non-CV causes. In addition, a total of 31 nonfatal CV events took place during the follow-up period. These nonfatal CV events included myocardial infarction (n = 11), HF (n = 8), stroke (n = 10), and peripheral vascular disease (n = 2).

The predictors for CV events (fatal and nonfatal CV events = 43) were analyzed by univariate and multivariate Cox regression. The univariate Cox analysis showed that age, BMI, smoking history, drinking history, CVD history, TC, TG, LDL, ALB, hs-CRP, HOMA-IR, and leptin were each significantly associated with an increased risk of CV events (Table 3). After adjustments were made for age, BMI, smoking history, drinking history, CVD history, systolic BP, HOMA-IR, TC, TG, LDL, ALB, hs-CRP, and SCr, the multivariate Cox analysis showed that higher leptin levels were still significantly associated with an increased risk of CV events (OR = 2.467, 95% confidence interval, 2.019–4.495; P <.001). In addition, Kaplan-Meier survival curves showed that patients with leptin levels above the median value (>15.4 μg/L) had a higher rate of CV events than did patients with leptin levels below the median value (≤15.4 μg/L; log-rank test, P <.001; Figure 1).

Figure 1.

Kaplan-Meier analysis of CV events-free rate stratified into 2 groups by median levels of serum leptin. CV, cardiovascular.

We performed a sensitivity analysis to assess the association of serum leptin levels with CV events in patients with RA who did not have a previous CVD history (n = 204). The number of CV events was 36. The multivariate Cox analysis showed that higher leptin levels were still independently associated with an increased risk of CV events (data not shown). Similarly, compared with patients with leptin levels below the median value, Kaplan-Meier survival curves still showed that patients with leptin levels above the median value had a higher rate of CV events (log-rank test, P <.001; data not shown).

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