In patients with coronary artery disease, having >4% tissue factor-positive platelets was associated with significantly higher all-cause mortality compared to <4% (HR 1.91; p=0.018) over 5 years.
Cohort (n=527)
Does elevated platelet-associated tissue factor predict 5-year mortality in patients with coronary artery disease?
Platelet-associated tissue factor is an independent predictor of 5-year all-cause and cardiovascular mortality in patients with coronary artery disease, potentially improving thrombotic risk stratification.
Hazard Ratio: 1.91
Absolute Event Rate: 30.6% vs 16.1%
p-value: p=0.018
Abstract Background Improving thrombotic risk stratification in coronary artery disease (CAD) patients is an unmet need. Increased platelet activation has been extensively reported in CAD, but its prognostic relevance remains unexplored. The challenge with using platelet activation biomarkers in CAD lies in the absence of a gold standard. Furthermore, common soluble biomarkers lack absolute specificity for platelets since they can also be released by other cells. Purpose To assess the prognostic value of platelet-associated activation biomarkers on mortality in CAD patients. Methods Surface expression of platelet-associated P-selectin, activated GPIIbIIIa, tissue factor (TF) and formation of platelet-leukocyte aggregates were evaluated in 527 CAD patients by whole blood flow cytometry. All cause (AC)- and cardiovascular (CV)-mortality was evaluated. 5-year survival analysis was performed with COX regression model. Euclidean distance method with cross-validation analysis was used to calculate the best cut-off value of the percentage of circulating TF+ platelets. Kaplan-Meier survival analysis was performed. To assess the ability of TF+ platelets to implement the thrombotic risk stratification, the net reclassification improvement (NRI) was calculated. Results 5-year AC- and CV-mortality rates were 9.7% and 6.5%, respectively. Among the biomarkers evaluated, only platelet-associated TF independently predicted AC-mortality (HR=2.66 for 4-unit increase of TF+ platelet value; p=0.042) also after adjustment for CAD clinical presentation (ACS or CCS, n=149 and 378, respectively). ROC curve analysis identified 4% TF+ platelets as a cut-off value for AC-mortality prediction. AC- and CV-mortality in patients with a score and 4% were 30.6 and 16.1 (p=0.019) and 23.3 and 9.3 (p=0.006) per 1000 person-years, respectively. Kaplan-Meier survival analysis showed that CAD patients with TF+ platelets 4% had a worse prognosis than those with 4% TF+ platelets for AC- and CV-mortality (HR=1.91; p=0.018 and HR=2.51; p=0.005; respectively), even when adjusted for age, eGFR, angiotensin II receptor blocker, antiarrhythmics, dual antiplatelet therapy (DAPT) use and ACS vs CCS. TF+ platelet levels 4% predicted CV-mortality in both ACS and CCS patients (Figure). Interestingly, a subgroup analysis according to antiplatelet drug treatment showed that patients on DAPT (n=246) with TF+ platelets 4%, despite responders to P2Y12 inhibitors, had the highest risk for AC- (HR=4.11; p=0.021) and CV-mortality (HR=6.88; p=0.041). In these patients, TF+ platelet levels outperformed a clinical model in CV-mortality prediction (NRI=0.436, p0.001). Platelet-associated TF predicted AC (HR=3.03; p=0.012) and CV-mortality (HR=3.56; p=0.008) also in aspirin-only treated patients (n=239). Conclusions Our findings highlight that platelet-associated TF is an independent predictor of AC- and CV-mortality in CAD patients on antiplatelet therapy and it enhances the thrombotic risk stratification.
Camera et al. (Sat,) conducted a cohort in Coronary artery disease (n=527). Tissue factor-positive (TF+) platelets >4% vs. Tissue factor-positive (TF+) platelets <4% was evaluated on All-cause mortality (HR 1.91, p=0.018). In patients with coronary artery disease, having >4% tissue factor-positive platelets was associated with significantly higher all-cause mortality compared to <4% (HR 1.91; p=0.018) over 5 years.