Elevated Coagulation Factor Linked to Higher Risk for CV Events in Type 2 Diabetes

Plasma coagulation factor X1 (FXI) is an independent risk factor for adverse cardiovascular (CV) events in type 2 diabetes (T2DM), according to a study published in Cardiovascular Diabetology.

Individuals with T2DM are at an increased risk of adverse CV events, accounting for more than 50% of mortality. Recent studies have indicated the utility of coagulation FX1 as a prognostic factor in atherosclerotic vascular disease and thrombosis. As studies on their utility in diabetic patients is lacking, researchers investigated the relationship of FX1 levels and thromboembolic events in T2DM patients.

Individuals with T2DM were enrolled in a long-term (median 72 months) observational study to assess plasma clotting factors in relation to adverse CV events. Venous blood samples were collected and analyzed for clotting proteins (plasminogen, a2-antiplasmin, tissue plasminogen activator, circulating plasminogen activator inhibitor antigen, thrombin-activatable fibrinolysis inhibitor antigen, FXI). Those with acute infection, chronic inflammatory disease, recent thromboembolic events, active malignancy, or chronic kidney disease were excluded from the study.

The primary endpoint of the study was a composite of myocardial infarction (MI), ischemic stroke, and CV death.

The analysis included 133 patients aged 66±8.0 years. Baseline median time since T2DM diagnosis was 5 (2-10) years, and mean glycated hemoglobin was 6.5% (6.1–7.1%).

In 18.8% of patients, plasma FX1 was above 120% of the upper limit, however no differences in clinical and laboratory characteristics were found when compared to those with normal FX1 levels, except for total and LDL cholesterol (R, 0.40; P <.001; and R, 0.35; P <.001; respectively).

The composite endpoint was observed in 15.8% of patients, including 1 fatal MI, 16 CV deaths, and 4 nonfatal strokes. Patients who met the composite endpoint had a higher mean FX1 level, when compared to those who did not (16.8% vs. 10.7%, P <.001).

Patients who died of CV causes had a higher mean FX1 (17.4%vs. 11.9%, P =.002), and FX1 was elevated in a higher proportion in CV death cases (46.7% vs. 15.3%, P =.003). Univariable analysis found FX1 to increase the risk of CV death (HR, 7.11; 95 CI%, 2.61–19.31; P <.001).

Subgroup analysis found that patients with concomitant coronary artery disease (CAD) who met the composite endpoint had a higher baseline FX1 (13.8% vs. 10.8% , P < .001) than those who did not meet any endpoint.

Limitations of the study include lack of recommended T2DM therapy in the cohort, which may have influenced the risk of long-term adverse CV events. As baseline, screening for CAD in asymptomatic patients was not completed and there may have been some undiagnosed cases.

“This is the first study to show that in long-term follow-up elevated FXI is a strong, independent predictor of arterial thromboembolic events, including CV death, in patients with T2DM, regardless of concomitant CAD,” the study authors wrote.