Fibrinogen is associated with glucose metabolism and cardiovascular outcomes in patients with coronary artery disease

Abstract

Background: The present cohort study aims to examine the relationship between fibrinogen (Fib) levels and glucose metabolism [fasting blood glucose (FBG) and hemoglobin A1c (HbA1c)] and investigate the impact of high Fib on cardiovascular outcomes in patients with stable CAD and pre-diabetes mellitus (pre-DM) or diabetes mellitus (DM).

Methods: This study included 5237 patients from March 2011 to December 2015. Patients were distributed into three groups according to Fib levels (low Fib, median Fib, high Fib) and further categorized by glucose metabolism status [normal glucose regulation (NGR), Pre-DM, DM]. All patients were followed up for the occurrences of major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal MI, stroke, and unplanned coronary revascularization.

Results: Linear regression analyses showed that FBG and HbA1c levels were positively associated with Fib in overall CAD participants, either with or without DM (all P < 0.001). During an average of 18,820 patient-years of follow-up, 476 MACEs occurred. High Fib was independently associated with MACEs after adjusting for confounding factors [Hazard Ratio (HR): 1.57, 95% confidence interval (CI) 1.26-1.97, P < 0.001]. Furthermore, DM but not pre-DM was a significant predictor of MACEs (P < 0.001 and P > 0.05, respectively). When patients were stratified by both glucose metabolism status and Fib levels, high Fib was associated with a higher risk of MACEs in pre-DM (HR 1.66, 95% CI 1.02-2.71, P < 0.05). Medium and high Fib levels were associated with an even higher risk of MACEs in DM (HR 1.86, 95% CI 1.14-3.05 and HR 2.28, 95% CI 1.42-3.66, all P < 0.05). After adding the combination of Fib and glucose status to the Cox model, the C-statistic was increased by 0.015 (0.001-0.026).

Conclusions: The present study suggested that Fib levels were associated with FBG and HbA1c in stable CAD patients. Moreover, elevated Fib was independently associated with MACEs in CAD patients, especially among those with pre-DM and DM, suggesting that Fib may provide incremental value in the cardiovascular risk stratification of pre-DM and DM patients.

Keywords: Coronary artery disease; Diabetes mellitus; Fasting blood glucose; Fibrinogen; HbA1c; Prognosis.

Fig. 1

Flowchart of the study population. ACS acute coronary syndrome, CAD coronary artery disease, PCI percutaneous coronary intervention, CABG coronary artery bypass grafting

Fig. 2

Linear regression analysis of the relationship between glucose metabolism and FIB. a Linear regression analysis of the relationship between glucose metabolism [HbA1c (a1), FBG (a2)] and FIB in overall participants with CAD. b Linear regression analysis of the relationship between glucose metabolism [HbA1c (b1), FBG (b2)] and FIB in CAD patients with DM. c Linear regression analysis of the relationship between glucose metabolism [HbA1c (c1), FBG (c2)] and FIB in CAD patients without DM. FIB fibrinogen, DM diabetes mellitus, HbA1c HaemoglobinA1c, FBG fasting blood glucose

Fig. 3

Relation of the different glucose metabolism status and cardiovascular outcomes in univariate and multivariate survival analysis. Univariate and multivariate Cox proportional hazards regression analysis was performed to test statistical significance. Model adjusted for age, sex, body mass index, smoking, hypertension, family history of coronary artery disease, left ventricular ejection fraction, low density lipoprotein cholesterol, high lipoprotein cholesterol, Ln-transformed triglyceride, Ln-transformed high-sensitivity C-reactive protein, and creatinine. NGR normal glucose regulation, Pre-DM pre-diabetes mellitus, DM diabetes mellitus

Fig. 4

Kaplan-Meier analysis according to different fibrinogen levels (a), glucose metabolism status (b), and status of both fibrinogen levels and glucose metabolism (c)