Limited evidence exists on the combined and mediating effects of systemic inflammation on the association between insulin resistance and cardiovascular events in patients with diabetes and chronic coronary syndrome (CCS). This secondary analysis of a multicenter prospective cohort included 4419 diabetic CCS patients. Triglyceride–glucose index (TyG) and high-sensitivity C-reactive protein (hsCRP) were applied to evaluate insulin resistance and systemic inflammation, respectively. The primary endpoint was major adverse cardiac event (MACE). Associations of TyG and hsCRP with cardiovascular events were estimated using Cox regression. A mediation analysis was performed to assess whether hsCRP mediates the relationship between TyG and cardiovascular events. Within a median 2.1-year follow-up period, 405 MACEs occurred. Patients with high levels of TyG and hsCRP experienced the highest MACE risk (hazard ratio = 1.82, 95% confidence interval: 1.24–2.70, p = 0.002) compared to individuals with low levels of both markers. HsCRP significantly mediated 14.37% of the relationship between TyG and MACE (p < 0.001). In diabetic CCS patients, insulin resistance and systemic inflammation synergically increased the risk of cardiovascular events, and systemic inflammation partially mediated the association between insulin resistance and clinical outcomes. Combining TyG and hsCRP can help identify high-risk patients. Controlling inflammation in patients with insulin resistance may bring added benefits.

Background: Inflammation plays a crucial role in coronary atherosclerosis progression, and growing evidence has demonstrated that the fibrinogen-to-albumin ratio (FAR), as a novel inflammation biomarker, is associated with the severity of coronary artery disease (CAD). However, the long-term risk of cardiovascular events remains indistinct in patients with different level of FAR and different glycemic metabolism status. This study was to assess 5-year clinical outcomes of diabetic and non-diabetic patients who underwent percutaneous coronary intervention (PCI) with different level of FAR. Methods: We consecutively enrolled 10,724 patients with CAD hospitalized for PCI and followed up for the major adverse cardiac and cerebrovascular events (MACCE) covering all-cause mortality, cardiac mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, and unplanned coronary revascularization. FAR was computed using the following formula: Fibrinogen (g/L)/Albumin (g/L). According to the optimal cut-off value of FAR for MACCE prediction, patients were divided into higher level of FAR (FAR-H) and lower level of FAR (FAR-L) subgroups, and were further categorized into four groups as FAR-H with DM and non-DM, and FAR-L with DM and non-DM. Results: 5298 patients (58.36 ± 10.36 years, 77.7% male) were ultimately enrolled in the present study. A total of 1099 (20.7%) MACCEs were documented during the 5-year follow-up. The optimal cut-off value of FAR was 0.0783 by the surv_cutpoint function. Compared to ones with FAR-H and DM, patients with FAR-L and non-DM, FAR-H and non-DM, FAR-L and DM had decreased risk of MACCEs [adjusted hazard ratio (HR): 0.75, 95% confidence interval (CI) 0.64–0.89, P = 0.001; HR: 0.78, 95% CI 0.66–0.93, P = 0.006; HR: 0.81, 95% CI 0.68–0.97, P = 0.019; respectively]. Notably, non-diabetic patients with lower level of FAR also had lower all-cause mortality and cardiac mortality risk than those in the FAR-H/DM group (HR: 0.41, 95% CI 0.27–0.63, P < 0.001; HR: 0.30, 95% CI 0.17–0.53, P < 0.001; respectively). Multivariate Cox proportional hazards regression analysis also indicated the highest risk of MACCEs in patients with FAR-H and DM than others (P for trend = 0.005). In addition, post-hoc analysis revealed consistent effects on 5-year MACCE across various subgroups. Conclusion: In this real-world cohort study, higher level of FAR combined with DM was associated with worse 5-year outcomes among patients with CAD undergoing PCI. The level of FAR may help to identify high-risk individuals in this specific population, where more precise risk assessment should be performed.

Background: Fibrinogen (FIB) is an independent risk factor for mortality and cardiovascular events in the general population. However, the relationship between FIB and long-term mortality among CAD patients undergoing PCI remains unclear, especially in individuals complicated with diabetes mellitus (DM) or prediabetes (Pre-DM). Methods: 6,140 patients with CAD undergoing PCI were included in the study and subsequently divided into three groups according to FIB levels (FIB-L, FIB-M, FIB-H). These patients were further grouped by glycemic status [normoglycemia (NG), Pre-DM, DM]. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. Results: FIB was positively associated with hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) in CAD patients with and without DM (P < 0.001). During a median follow-up of 5.1 years (interquartile range 5.0–5.2 years), elevated FIB was significantly associated with long-term all-cause mortality (adjusted HR: 1.86; 95% CI 1.28–2.69; P = 0.001) and cardiac mortality (adjusted HR: 1.82; 95% CI 1.15–2.89; P = 0.011). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause and cardiac mortality compared with NG group (all P < 0.05). When grouped by both FIB levels and glycemic status, diabetic patients with medium and high FIB levels had higher risk of mortality [(adjusted HR: 2.57; 95% CI 1.12–5.89), (adjusted HR: 3.04; 95% CI 1.35–6.82), all P < 0.05]. Notably, prediabetic patients with high FIB also had higher mortality risk (adjusted HR: 2.27; 95% CI 1.01–5.12). Conclusions: FIB was independently associated with long-term all-cause and cardiac mortality among CAD patients undergoing PCI, especially in those with DM and Pre-DM. FIB test may help to identify high-risk individuals in this specific population.

Low-density lipoprotein cholesterol (LDL-C) is a well-recognized risk factor for cardiovascular diseases. However, several clinical studies demonstrated an inverse association between LDL-C and mortality risk in patients with acute myocardial infarction (AMI), known as the lipid paradox. This study aims to investigate the potential impact of inflammation on the association between LDL-C levels and mortality risks. A total of 5244 patients with AMI from a large nationwide prospective cohort were included in our analysis. Patients were stratified according to LDL-C quartiles. The primary outcome was all-cause mortality, and the secondary endpoint was cardiac mortality. High-sensitive C-reactive protein (hsCRP) > 3 mg/L was defined as high inflammatory risk. During a median follow-up of 2.07 years, 297 mortality events (5.5%) and 227 cardiac mortality events (4.2%) occurred. Patients in the lowest LDL-C quartile had the highest incidence of all-cause mortality (7.3%) and cardiac mortality (5.8%). A U-shaped association between LDL-C levels and mortality risk was observed after multivariable adjustment, which persisted only in patients with high hsCRP levels. In contrast, a linear association between LDL-C and mortality risk was shown in patients with low hsCRP levels. AMI patients with lower LDL-C levels had a higher risk of mortality. However, this association was only observed in those with high inflammatory risk. In contrast, the relationship between LDL-C and mortality risk was linear in patients with low inflammatory risk. This suggests the importance of considering inflammation when managing LDL-C levels in AMI patients.