Relationship between Fibrinogen Levels and Cardiovascular Events in Patients Receiving Percutaneous Coronary Intervention: A Large Single-Center Study
Introduction
Fibrinogen, a key protein in the coagulation cascade, has long been implicated in the pathogenesis of coronary artery disease (CAD). Elevated fibrinogen levels are associated with increased plasma viscosity, platelet aggregation, and fibrin formation, all of which contribute to atherothrombosis. Despite extensive research, the role of fibrinogen as an independent risk factor for adverse cardiovascular events remains controversial. Some studies suggest that fibrinogen is a causal factor in CAD, while others argue that it merely serves as a biomarker of underlying comorbidities and other risk factors. This study aims to investigate the association between fibrinogen levels and 2-year all-cause mortality in patients undergoing percutaneous coronary intervention (PCI) and to assess whether fibrinogen provides additional prognostic value beyond traditional risk factors.
Methods
The study population consisted of 6,293 consecutive patients who underwent PCI at Fuwai Hospital, Beijing, China, from January to December 2013. Patients were diagnosed with either acute coronary syndrome (ACS) or stable CAD and were included regardless of their clinical presentation. Baseline fibrinogen levels were measured using the Clauss method, and patients were stratified into three groups based on tertiles of fibrinogen levels: low (<2.98 g/L), medium (2.98 to 3.58 g/L), and high (≥3.58 g/L). The primary endpoint was 2-year all-cause mortality, with secondary endpoints including cardiac mortality, myocardial infarction (MI), stroke, revascularization, stent thrombosis (ST), major adverse cardiovascular and cerebrovascular events (MACCE), and bleeding.
Baseline Characteristics
The baseline characteristics of the study population revealed significant differences among the three fibrinogen groups. Patients in the high fibrinogen group were older and had a higher prevalence of traditional risk factors such as hypertension, diabetes mellitus, previous MI, previous PCI, and worse left ventricular ejection fraction (LVEF). Laboratory data showed higher levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, high-sensitivity C-reactive protein (hs-CRP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the high fibrinogen group. Angiographic and procedural characteristics also indicated a higher SYNTAX score and more left main and/or three-vessel disease in the high fibrinogen group.
Clinical Outcomes
The 2-year all-cause mortality rate in the overall study population was 1.2%. Kaplan-Meier analysis demonstrated that the high fibrinogen group had a significantly higher mortality rate (1.7%) compared to the low (0.9%) and medium (1.0%) fibrinogen groups (log-rank P=0.022). Univariate Cox regression analysis showed that fibrinogen was significantly associated with all-cause mortality (HR 1.496, 95% CI: 1.221–1.833, P<0.001) and cardiac mortality (HR 1.439, 95% CI: 1.112–1.864, P=0.006). Multivariate Cox regression analysis, after adjusting for traditional risk factors, confirmed that fibrinogen remained independently associated with all-cause mortality (HR 1.339, 95% CI: 1.109–1.763, P=0.005).
Traditional Risk Factors
Traditional risk factors such as age, sex, diabetes mellitus, LVEF, creatinine clearance (CCr), and LDL-C were the strongest predictors of 2-year all-cause mortality. Age (HR 1.062, 95% CI: 1.024–1.101, P<0.001), diabetes mellitus (HR 2.108, 95% CI: 1.107–4.016, P=0.023), and LVEF (HR 4.701, 95% CI: 1.408–15.702, P=0.012) were particularly significant. These findings underscore the importance of traditional risk factors in predicting long-term outcomes in PCI patients.
Subgroup Analysis
Subgroup analysis revealed that fibrinogen was associated with all-cause mortality across various subgroups, including patients aged >65 years, males, those with a body mass index (BMI) ≥30 kg/m², and patients with or without previous MI, PCI, hypertension, diabetes mellitus, ACS, or stable CAD. The association was consistent regardless of renal function (CCr >60 mL/min), LVEF (>40%), or SYNTAX score (0.05, indicating no significant heterogeneity.
Incremental Value of Fibrinogen
To assess the incremental predictive value of fibrinogen, the area under the receiver operating characteristic curve (AUC) was calculated for models with and without fibrinogen. The basic model, which included traditional risk factors, had an AUC of 0.776 (95% CI: 0.725–0.827). The addition of fibrinogen only marginally improved the AUC to 0.787 (95% CI: 0.736–0.838; IDI=0.003, z=0.140, P=0.889). This suggests that while fibrinogen is associated with all-cause mortality, it provides little additional prognostic information beyond traditional risk factors.
Discussion
The findings of this study indicate that fibrinogen levels are independently associated with 2-year all-cause mortality in patients undergoing PCI. However, the incremental predictive value of fibrinogen over traditional risk factors is minimal. These results are consistent with previous studies, such as the AtheroGene study and the PRIME study, which also found that fibrinogen was associated with adverse cardiovascular outcomes but did not significantly improve risk prediction models.
The role of fibrinogen in CAD is complex. As an acute-phase reactant, fibrinogen levels increase in response to inflammation, which is a key driver of plaque rupture and thrombosis. Elevated fibrinogen levels have been observed in patients with unstable angina, further supporting its role in acute coronary events. However, fibrinogen is also influenced by traditional risk factors such as age, smoking, obesity, and diabetes mellitus, which may explain its limited independent prognostic value.
The study has several limitations. First, fibrinogen levels were measured only at baseline, and any changes during the follow-up period were not accounted for. Second, the study population consisted of patients who underwent PCI, limiting the generalizability of the findings to the broader population. Finally, the study was conducted at a single center, and multicenter studies are needed to confirm these results.
Conclusion
In conclusion, this study demonstrates that fibrinogen levels are associated with 2-year all-cause mortality in patients undergoing PCI. However, fibrinogen provides little additional prognostic information beyond traditional risk factors. These findings suggest that while fibrinogen may serve as a biomarker of poor long-term outcomes in PCI patients, it is not a strong independent predictor of adverse events. Future research should focus on understanding the causal relationship between fibrinogen and CAD and exploring whether interventions to lower fibrinogen levels can improve cardiovascular outcomes.
doi.org/10.1097/CM9.0000000000000181
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