Association Of D-dimer Research Articles

Inflammation and hemostasis in atrial fibrillation and coronary heart disease: The REasons for Geographic And Racial Differences in Stroke study

BackgroundRecent studies suggest atrial fibrillation (AF) is an independent risk factor for coronary heart disease (CHD). AimsTo determine if alterations in hemostasis or inflammation explain the association between AF and CHD. MethodsC-reactive protein (CRP), D-dimer, factor VIII, and fibrinogen were measured in incident CHD cases (n = 647) and a stratified cohort random sample (CRS, n = 1104) between 2003 and 2007 from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Using a case-cohort approach, Cox models examined whether inflammation or hemostasis biomarkers explained the association between AF and CHD. ResultsIn participants free of CHD at baseline, 12.2% of CHD cases and 7.1% of the CRS had AF. Over a median follow-up of 4.4 years, all biomarkers were associated with an increased risk of CHD in those with and those without AF after adjusting for CHD risk factors. The association of D-dimer with CHD was greater in those with AF (HR 2.52, 95% CI = 1.49, 4.26) than those without AF (HR 1.34, 95% CI = 1.12, 1.61) (p-interaction = 0.02). Similar interactions were not observed for the other biomarkers. ConclusionsOur results suggest that alterations in D-dimer, a marker of hemostasis, explain the association between AF and CHD. Potentially, D-dimer is a useful biomarker to assess CHD risk in persons with AF.

D-dimer as a Prognostic Biomarker for Mortality in Chronic Obstructive Pulmonary Disease Exacerbation

BackgroundA major barrier to chronic obstructive pulmonary disease (COPD) research and management is lack of easily obtained biomarkers that are predictive of clinically important outcome measures. ObjectivesWe sought to investigate in patients admitted for acute exacerbation of COPD (AECOPD) the association of d-dimer (fibrin degradation product) obtained upon admission with in-hospital mortality and postdischarge prognosis. MethodsClinical and laboratory data were evaluated in 61 patients admitted for AECOPD in whom d-dimer levels were obtained and in whom venous thromboembolism/ pulmonary embolism was excluded. Receiver operating characteristics curve was used to determine the optimal cutoff level for d-dimer that discriminated survivors versus nonsurvivors during index hospitalization, and during follow-up that extended to a median observation period of 62.6months. ResultsMean (±SD) age of the study cohort was 71.2 ± 10.5years. Mean d-dimer level in nonsurvivors (n = 12) was significantly higher than in survivors (n = 49): 3.18 ± 0.97mg/L versus 1.45 ± 1.18mg/L, respectively, P = 0.0006. d-dimer level >1.52mg/L predicted in-hospital mortality with a sensitivity and specificity of 100% and 63.6%, respectively. After discharge, median survival of patients with d-dimer above and below 1.52mg/L were 9.6 and 62.6months, respectively (hazard ratio = 2.636; 95% confidence interval = 1.2716.426, P = 0.0111). ConclusionsElevated d-dimer is a reliable prognostic marker for both short-term and long-term survival in patients admitted for AECOPD. Prospective studies are required to further establish the appropriate role of d-dimer as a prognostic biomarker in patients with COPD.

Abstract P276: Differential Association of D-dimer with Stroke and Coronary Heart Disease: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Introduction: D-dimer, a marker of coagulation activation, has higher levels in blacks than whites and has been variably associated with stroke and coronary heart disease (CHD). Methods: REGARDS recruited 30,239 participants in their homes across the continental US between 2003-07; by design 55% were female, 41% black, and 56% lived in the southeast. In a case-cohort study, D-dimer was measured in 646 participants with incident stroke, 515 with incident CHD, and 1104 in a cohort random sample. D-dimer was log transformed and modeled per 1-unit increase. Cox models were used to determine the HR for vascular disease for D-dimer and the difference in HR (95% CI) by race and vascular disease calculated by bootstrapping with 1000 replicate samples and using the 2.5 and 97.5 percentiles of the distribution (see Table for model variables). Results: Median D-dimer was higher in blacks (0.45 mcg/mL; IQR 0.26, 0.85) than whites (0.38 mcg/mL; IQR 0.23, 0.69); p <0.001. D-dimer was higher with increasing age, female gender, diabetes, hypertension and prebaseline cardiovascular disease (all p <0.05). The table shows the HR of stroke and CHD by baseline D-dimer. In minimally-adjusted models, D-dimer was associated with both stroke and CHD. Accounting for Framingham stroke and CHD risk factors, D-dimer remained associated with CHD (HR 1.45; 95% CI 1.18, 1.79), but was marginally associated with stroke (HR 1.20; 95% CI 0.99, 1.45). The difference in the HR of D-dimer between CHD and stroke was 0.22 in the basic model and 0.25 in the Framingham model, but this difference was of marginal statistical significance (Table). There was no difference in the HRs for stroke or CHD for D-dimer in blacks compared to whites (Table). Discussion: The association of D-dimer with stroke appeared smaller than for CHD with similar associations by race. Findings suggest that hemostasis activation may play a greater role in pathogenesis of CHD than stroke. Further study is needed to confirm these findings and evaluate the association of D-dimer with different stroke subtypes.

Abstract MP069: A Genetic Association Study of D-dimer Levels with 50K SNPs from a Candidate Gene Chip in Four Ethnic Groups: the Candidate Gene Association Resource (CARe) consortium

Introduction: D-dimer, a marker of blood coagulation and fibrinolysis, is a widely-used biomarker of venous thromboembolism. While the coagulation factors V, III, II and fibrinogen alpha chain genes contain known genetic determinants of D-dimer, other determinants are not well characterized, especially in populations other than European Americans (EAs); no data have been reported for Asian American populations. Hypothesis: Large-scale candidate gene association analysis will identify D-dimer related gene variants in EA, African-American (AA), Chinese, and Hispanic populations. Methods: Four cohorts, comprised of 6,848 EA, 2,192 AAs, 670 Chinese, and 1,286 Hispanics from Cleveland Family Study, Cardiovascular Health Study, Framingham Heart Study, and Multi-Ethnic Study of Atherosclerosis in the Candidate Gene Association Resource (CARe) consortium, were included. The inverse normal transformed residual of D-dimer was used in genetic analysis. About 50,000 SNPs located in 2,100 inflammation and atherosclerosis-related genes were genotyped using the custom ITMAT-Broad-CARe (IBC) chip and analyzed by linear regression adjusted for age, sex, study site, and principal components to account for potential population stratification in each cohort and race group. Significance was set at p<2x10-6 after accounting for multiple testing. Results: Twelve SNPs in the coagulation factor V gene and 3 SNPs in the fibrinogen alpha chain genes exceeded the significant p-value threshold in EA. The top SNPs in these two regions were rs6025 (p-value=7.41x10-16) and rs13109457 (p-value=7.52x10-7), respectively. The signals for the remaining significant SNPs in these two regions were no longer statistically significant after adjusting for the known functional SNPs in each region (rs6025 and rs6050, respectively). The top signal at the coagulation factor V gene was replicated in Hispanics but not other race groups. Neither AA nor the other race groups replicated the signals for fibrinogen alpha chain gene. No additional variants in AA, Chinese, or Hispanics showed significant associations with D-dimer, but several SNPs in neuregulin 1 and Bruton agammaglobulinemia tyrosine kinase for AA and vanin 1 for Chinese were suggestively associated with D-dimer levels (p-value<5x10-5). Conclusion: Our study replicated previously reported associations of D-dimer with coagulation factor V and fibrinogen alpha chain variants in EAs and identified coagulation factor V variation in Hispanics. Additional studies are required to confirm the suggestive findings in AAs, Chinese, and Hispanic populations.

Association of Coagulation Activation with Clinical Complications in Sickle Cell Disease

BackgroundThe contribution of hypercoagulability to the pathophysiology of sickle cell disease (SCD) remains poorly defined. We sought to evaluate the association of markers of coagulation and platelet activation with specific clinical complications and laboratory variables in patients with SCD.Design and MethodsPlasma markers of coagulation activation (D-dimer and TAT), platelet activation (soluble CD40 ligand), microparticle-associated tissue factor (MPTF) procoagulant activity and other laboratory variables were obtained in a cohort of patients with SCD. Tricuspid regurgitant jet velocity was determined by Doppler echocardiography and the presence/history of clinical complications was ascertained at the time of evaluation, combined with a detailed review of the medical records.ResultsNo significant differences in the levels of D-dimer, TAT, soluble CD40 ligand, and MPTF procoagulant activity were observed between patients in the SS/SD/Sβ0 thalassemia and SC/Sβ+ thalassemia groups. Both TAT and D-dimer were significantly correlated with measures of hemolysis (lactate dehydrogenase, indirect bilirubin and hemoglobin) and soluble vascular cell adhesion molecule-1. In patients in the SS/SD/Sβ0 thalassemia group, D-dimer was associated with a history of stroke (p = 0.049), TAT was associated with a history of retinopathy (p = 0.0176), and CD40 ligand was associated with the frequency of pain episodes (p = 0.039). In multivariate analyses, D-dimer was associated with reticulocyte count, lactate dehydrogenase, NT-proBNP and history of stroke; soluble CD40 ligand was associated with WBC count and platelet count; and MPTF procoagulant activity was associated with hemoglobin and history of acute chest syndrome.ConclusionsThis study supports the association of coagulation activation with hemolysis in SCD. The association of D-dimer with a history of stroke suggests that coagulation activation may contribute to the pathophysiology of stroke in clinically severe forms of SCD. More research is needed to evaluate the contribution of coagulation and platelet activation to clinical complications in SCD.

Associations of D-dimer and von Willebrand factor with atherosclerosis in Japanese and white men

Objective — D-dimer and von Willebrand factor (vWF) are associated with atherosclerosis. We recently reported that in a post-World War II birth cohort, Japanese men in Japan had lower levels of atherosclerosis than white men in the United States (US).We examined whether the differences in D-dimer and vWF levels are associated with differences in atherosclerosis between the two populations.Methods and results — Population-based samples of 99 Japanese and 100 white American men aged 40-49 years were examined for coronary artery calcification (CAC), carotid intima-media thickness (IMT), D-dimer, vWF, and other factors using a standardized protocol.When compared to white American men, Japanese had similar levels of D-dimer (0.22 ± 0.28 vs. 0.19 ± 0.24 mg/L, respectively, P= 0.39) but significantly higher levels of vWF (124.1 ± 36.6 vs. 91.3 ± 48.8%, respectively, P < 0.01). Japanese as compared to white American men had significantly lower prevalence of CAC (13.1 vs. 28.0%, P < 0.01, respectively) and significantly lower IMT (0.61 ± 0.07 vs. 0.66 ± 0.08 mm, P < 0.01, respectively). Japanese men had a significant positive association of D-dimer with the prevalence of CAC and a negative association of vWF with IMT, whereas white American men did not have any significant associations.Conclusions — In men aged 40-49 years, Japanese as compared to white Americans had similar levels of D-dimer and higher levels of vWF although Japanese had a significantly lower prevalence of CAC and IMT. These haemostatic factors are unlikely to explain the difference in atherosclerosis in these populations.

Evaluation of d-Dimer for the exclusion of myocardial infarction in conjunction with troponin I in an emergency department

Study objectives: Chest pain is a frequent symptom in the emergency department (ED) and often presents a diagnostic challenge. Some published studies have shown that hemostatic markers had a diagnostic value in patients presenting to the ED with chest pain or shortness of breath. This study, performed in our military hospital, was aimed to demonstrate that d-dimer associated with troponin (bioMérieux SA, France) could be used as an exclusion test for patients suspected of having myocardial infarction in the ED, thus enabling a reduction of the patient hospital stay and cost savings. Methods: One hundred nineteen consecutive patients presenting with chest pain selected within the hospital ED were included in this prospective study during 6 months. T₀ corresponds to the onset of chest pain. Fresh plasma samples collected from those patients were tested with the VIDAS d-Dimer New and VIDAS Troponin assays at different times. T₁ corresponds to the time of the first sample collection at patient arrival, T₂ corresponds to T₁+6 hours. Troponin I cutoff was fixed at 0.8 μg/L as described previously; d-dimer cutoff was fixed at 250 ng/mL. An ECG was performed for all patients. Patients were classified into 4 categories: normal, stable angina, unstable angina, and myocardial infarction. Results: The results obtained are consolidated in the Table. For the diagnosis of myocardial infarction at T₁, troponin I alone gave a sensitivity of 46.2% and a specificity of 96.8%, whereas at T₂, the sensitivity was 96.2% and the specificity was 96.8%. At T₁, d-dimer showed a sensitivity of 88.5% and a specificity of 25.8%. When we associated both troponin I and d-dimer assays, the sensitivity was 96.2% and the specificity was 25.8%. The combination of the 2 parameters allowed us to exclude 24 patients (20% of the total population) at T₁, 1 patient remaining false negative. Conclusion: The association of d-dimer and troponin can safely enable the exclusion of myocardial infarction in an ED population and may be incorporated into clinical decision models in EDs.Table, abstract 46T₁No. of Patientsd-Dimer Value at T₁, ng/mLd-Dimer Value at T₂, ng/mLNormal29971.25±1765822±1312Stable angina14532.78±386718±1208Unstable angina50757.9±1064796±1108Myocardial infarction26958.46±11431148±1322