Rheumatoid arthritis (RA) is a chronic, inflammatory, and disabling disease that affects about 18 million people worldwide [1]. The major consequence of RA is work disability [2], with a rate being relatively high at 20% to 35% after 5 years of the disease course [3, 4, 5]. Furthermore, RA patients have a 1.5-fold higher mortality rate than the general population [6]. The most frequently reported cause of death in RA patients is cardiovascular disease (CVD) [7, 8]. Indeed, RA is closely associated with a substantially increased risk of CVD, largely due to the presence of atherosclerosis (AS) [9], which is the thickening or hardening of the arteries due to the plaque accumulation in the inner arterial lining. In addition to traditional cardiovascular risk factors, chronic inflammation may also be regarded as an independent risk factor for AS in RA patients [10].

Recently, a large body of evidence supports the notion that insulin resistance (IR) is critical in both RA and CVD [11, 12]. Indeed, the triglyceride glucose (TyG) index may be considered a surrogate marker for IR [13]. The systemic inflammation associated with RA contributes to the development of abnormal lipid and glucose metabolisms [14, 15]. Recent studies have also shown that the TyG index is a strong and useful predictor of cardiovascular outcomes in various disease settings [16, 17]. However, investigations into potential associations between the TyG index and cardiovascular outcomes in RA patients are still lacking, especially in males. Hence, the current study aimed to investigate whether the TyG index could be used to predict major adverse cardiovascular events (MACEs) in a predominantly male cohort of RA patients.

Numerous studies have shown that RA patients are at greater risk of CVD compared with the general population [18, 19]. The excess risk is due to RA-specific risk-factor profiles, such as systemic inflammation, rather than traditional CVD risk factors [20]. Furthermore, RA can be regarded as an independent risk factor for CVD [21]. Together with risk-based CVD management, the use of anti-rheumatic medication is fundamental procedure for reducing the incidence of CVD [22]. Still, it has been found that RA is associated with an increased risk of CVD [23]. Solomon et al. [24] reported that female RA patients had a significantly higher risk of MI compared to those without RA. Specifically, for women with a medical history of RA of at least 10 years, the adjusted relative risk (RR) was 3.10, and for those with a medical history of RA less than 10 years, the RR was 1.16 [24]. Fischer et al. [25] also reported an increased risk of acute MI in patients with RA, with an adjusted odds ratio (OR) of 1.47. Södergren et al. [26] found that RA patients had higher morbidities from acute MI than the general population, with all-cause mortality showing an HR of 1.67. Holmqvist et al. [27] reported a rapid increase in the risk of MI within 1–4 years after RA diagnosis.

Similarly, both the morbidity and mortality from stroke were found to be higher in RA patients than in the general population [28]. Trömmer et al. [29] reported that RA was associated with both stroke (HR = 1.42) and transient ischemic attack (TIA) (HR = 1.69). Furthermore, patients aged 18–40 years showed the highest risk group for stroke (HR = 3.45) [29]. However, Holmqvist et al. [27, 30] reported that the progress of ischemic stroke in RA patients was slower than for ischemic heart disease. Moreover, Tiosano et al. [31] reported that RA was independently associated with stroke (OR = 1.18), particularly among young adults aged less than 65 years (OR = 1.79). Meissner et al. [32] reported that adverse events, particularly serious infections, and inadequate CVD treatment increased the risk of stroke in RA patients.

Insulin resistance can be defined as a pathological condition in which normal insulin concentrations induce subnormal biological effects [33]. Thus, the TyG index is more cost-effective and readily available for the direct measurement of IR compared to the gold standard, which is the hyperinsulinemic-euglycemic clamp. Therefore, the TyG index can be considered a surrogate marker for IR [34]. Furthermore, an increasing body of evidence suggests that the TyG index can be used to predict MACEs in different disease settings [35, 36, 37, 38].

As far as we are aware, this is the first study to investigate the TyG index in relation to MACEs in a predominantly male cohort of RA patients. We found that a higher TyG quartile (quartile 2: 8.28 $\le$ TyG 8.73) was associated with an increased risk of MACEs. However, a cut-off value for TyG could not be confirmed because the quartile 3 and quartile 4 groups did not show statistically significant associations with MACEs.

Since the Kailuan group is a company in the coal industry, considerably more males than females were employed, meaning that over 80% of the RA patients in this study were males. Our results are in contrast with the 3-fold higher incidence of RA found in women in the general population compared to men. Therefore, it is unclear whether the current findings are applicable to a more general RA population. On the one hand, CVD has long been regarded as a “male” disease [39], since males have an inherently greater risk for MACEs occurring than females. Research on gender differences in CVD indicates that males may not cope with stress as well as females, either physiologically, behaviorally, or emotionally, thereby increasing their risk of MACEs occurring. Stress-related factors can cause direct effects by influencing physiological parameters associated with the risk of CVD, as well as asserting indirect effects by increasing unhealthy behavioral and emotional responses associated with CVD (e.g., smoking, alcohol consumption, and depression) [40]. Alternatively, RA is known to affect about two to three times more women than men. Sex hormones play a critical role in regulating the immune response and are therefore strongly associated with the etiology of RA [41]. Presently, there has been a lack of research regarding cardiovascular risk factors for RA in men. Indeed, as far as we are aware, this is the first study to investigate the TyG index in relation to MACEs in a predominantly male cohort of RA patients. However, further research is needed to confirm whether the TyG index is a predictor of MACEs in RA patients.

In summary, our study found that the TyG index was associated with an increased risk of MACEs in a predominantly male cohort of RA patients. These results suggest that the TyG index is a potentially useful predictor of MACEs in predominantly male patients with RA. The pathological mechanism of IR and its effect on cardiovascular outcomes in RA patients warrants further investigation.

The data that support the findings of this study are available from the corresponding author upon reasonable request.

QLH, SLW, and KBL designed the research study. JWZ, QQH, QLH, XP, HXC, SLW, and KBL participated in the acquisition, analysis, and interpretation of data for the work. JWZ, QQH, QLH, XP, HXC, SLW, and KBL contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

All procedures performed in the Kailuan study involving human participants were in accordance with the standards of the ethics committee of Kailuan Hospital (Approval number: [2006] yilunzi 5). A written informed consent was obtained from each patient.

Not applicable.

This work was supported by the Key Scientific Research Project (No. 20231775), Health Commission of Hebei Province, P.R. China.

The authors declare no conflict of interest.