This study focused on the association between D-dimer and in-hospital mortality in ACS patients undergoing PCI. It found that: (1) D-dimer could independently predict in-hospital mortality; (2) GRACE score + D-dimer got a better prognostic performance than GRACE score, and D-dimer could significantly improve the prognostic performance of GRACE score.
As a kind of soluble degradation product of cross-linked fibrin, D-dimer increased when coagulation was active, thrombin was generated, or fibrin was formed [5]. Pathophysiological factors associated with plasma D-dimer levels in coronary artery disease patients were studied. In stable coronary artery disease subjects, high D-dimer had a significant association with plaque necrosis, lipoprotein (a) and plaque calcium [6]. D-dimer level also independently predicted no-reflow in STEMI patients with primary PCI [7, 8]. A CMR imaging study also found that high D-dimer on admission predicted larger myocardial infarct size, larger area at risk, and smaller myocardial salvage index in STEMI patients undergoing PCI [9]. Moreover, D-dimer might be associated with advanced myocardial injury [9]. Furthermore, the association between higher D-dimer and the clinical long-term adverse outcome other studies was also confirmed. Two studies focused on the role of D-dimer for predicting the prognosis in patients with STEMI receiving PCI [13, 14]. They confirmed that D-dimer could independently predict the long-term mortality in those patients [13, 14]. Other studies also verified and extended this observation. High D-dimer was associated with long-term adverse outcome in stable coronary artery disease [10, 11], and ACS [12]. Our study also found that D-dimer was independently associated with in-hospital mortality in patients with ACS receiving PCI.
Taken together, these findings had clinical value. It may be worth to monitor D-dimer in patients with ACS, which would identify the ACS patients at high risk. Moreover, the LIPID study presented evidence that D-dimer reflected an inflammatory state [11]. The studies also showed that anticoagulant and anti-inflammatory treatments could reduce ischemic events and venous thromboembolism [20,21,22,23]. So, high D-dimer patients may benefit from the anticoagulant and anti-inflammatory treatments. Such a strategy was tested in the Attenuation of D-dimer Using Vorapaxar to Target Inflammatory and Coagulation Endpoints (ADVICE) (NCT02394730) in patients with HIV. In the future, adequately powered randomized studies, targeting on attenuation of high D-dimer in ACS patients, should be performed to obtain the conclusions.
The GRACE score is a widely recommended and important prognostic tool in patients with ACS [1,2,3,4]. It contains the main traditional risk factors. However, recently, more and more new risk factors, which were not contained by GRACE score, were studied. D-dimer was an important member of them [5]. This study found that GRACE score combining D-dimer showed good discrimination, calibration and precision. The prognostic performance of GRACE score combining D-dimer was also better than GRACE score. The prognostic performance of the GRACE score could be significantly improved by D-dimer. With the help of the new model (GRACE score combining D-dimer), more accurate assessment of the in-hospital mortality risk and better clinical decisions in patients with ACS will be made.
There were some limitations in this study. Firstly, it was a single-center, prospective and observational study. It was hard to completely adjust potential confounders and selection bias. Secondly, high-sensitivity C-reactive protein, other proinflammatory cytokines, or markers of oxidative stress were not included in this study. However, the LIPID study confirmed that, even after adjustment for high-sensitivity C-reactive protein, D-dimer was still a significant predictor [11]. Thirdly, the use of unfractionated heparin or low molecular weight heparin might affect D-dimer levels. Fourthly, some high-risk patients might be excluded because of the use of unfractionated heparin or LMWH, which might cause the potential selection bias. At last, data about the history of medication treatment that influenced coagulation and inflammatory, such as statin, was not complete. Patients with the high coagulation and inflammatory status could benefit from the statin use [24].