Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

25 November 2022: Database Analysis  

Correlation Between Serum Albumin and D-Dimer Levels in 909 Patients with Non-Valvular Atrial Fibrillation: A Retrospective Study from a Single Center in China

Hua-jing Yuan1ABCDEF, Xia Zhong2DEF, Yan Li3EFG, Yi-tao Xue3ADEG*, Hua-chen Jiao3ACDEG

DOI: 10.12659/MSM.938511

Med Sci Monit 2022; 28:e938511

0 Comments

Abstract

BACKGROUND: D-dimer level can reflect the hypercoagulable state of atrial fibrillation (AF) and predict thromboembolic events. However, no effective indicator associated with D-dimer of AF patients has been found to prevent thromboembolic events in AF. This retrospective study from a single center aimed to investigate the correlation between serum albumin and D-dimer levels in 909 patients with non-valvular AF (NVAF) and 653 subjects in sinus rhythm.

MATERIAL AND METHODS: A total of 909 NVAF patients and 653 sex- and age-matched sinus rhythm participants were used to compare serum albumin and D-dimer levels. Serum albumin was determined by colorimetry, and D-dimer level was determined by latex-enhanced photoimmunoassay. We analyzed the correlation of serum albumin and D-dimer with NVAF by correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve.

RESULTS: Albumin (P<0.001) and D-dimer (P<0.001) were significantly associated with NVAF. Among NVAF patients, D-dimer level was negatively correlated with albumin levels (P<0.001), and albumin level was an independent risk factor of abnormal D-dimer level (>0.5 ug/mL), which was also an effective predictor of abnormal D-dimer level (the area under the ROC curve was 0.77, P<0.001), and the optimal cutoff value was 36.95 g/L.

CONCLUSIONS: Serum albumin and D-dimer levels were significantly associated with NVAF. In NVAF patients, D-dimer level was inversely correlated with albumin levels, and albumin level was an independent risk factor and effective predictor of abnormal D-dimer level. Close examination and supplementation of serum albumin can prevent thromboembolic events, but further clinical research and confirmation are needed.

Keywords: Atrial Fibrillation, fibrin fragment D, Retrospective Studies, Serum Albumin

Background

Atrial fibrillation (AF) is a common clinical arrhythmia [1]. With the advancement of medical care, the medical burden and complications caused by AF have gradually attracted increased attention, and the importance of treating AF has become self-evident [2]. Epidemiology data show that the incidence of AF has been increasing globally in the past 20 years, and will continue to increase over the next 30 years [2]. The number of adults with atrial fibrillation in the EU is projected to grow to 17.9 million by 2060 (95% CI: 13.6–23.7 million) [3]. It is widely accepted that AF is closely associated with hypercoagulability [4], which can lead to atrial thrombosis and further embolisms such as ischemic stroke. Therefore, AF is an important risk factor for ischemic stroke [5]. The presence of AF increases the risk of a cerebrovascular accident by 2.6-fold to 4.5-fold [6], and given the asymptomatic nature of AF, this risk may be underestimated [7]. Assessing the risk of stroke and preventing thromboembolic events in AF patients is accepted practice [1]. Although the risks and benefits of anticoagulation in AF patients are controversial [1,8], it is important to detect thromboembolic risk in patients with AF.

D-dimer level is commonly used for stratification of venous thromboembolism risk and is the criterion standard used to reflect coagulation activation or fibrinolysis [9]. Several studies have shown that hypercoagulability and thromboembolic risk in patients with AF can be reflected by D-dimer level [10–13]. Even with warfarin anticoagulation, D-dimer level predicts thromboembolic events in patients with non-valvular AF (NVAF) [13]. D-dimer level is also significantly correlated with the infarct size and functional prognosis after cardioembolic stroke in patients with NVAF [14]. Therefore, looking for influencing factors related to D-dimer level may help to reduce the risk of thromboembolism in patients with NVAF.

Serum albumin is widely involved in many physiological functions such as transport of substances within the human body and regulates inflammation and oxidative stress [15]. Albumin has anti-inflammatory activity [16,17], and chronically low albumin levels are often accompanied by a systemic inflammatory response [18,19]. There is increasing evidence that low serum albumin levels are closely related to cardiovascular diseases, including ischemic heart disease, AF, and heart failure [15,20]. The correlation between low serum albumin levels and the occurrence of AF has been increasingly demonstrated [21–23]. In addition, the development of thromboembolism, a complication of AF, is also associated with inflammatory activity and oxidative stress [24,25]. D-dimer, a degradation product of fibrin, which reflects the risk of thromboembolism, also influences the inflammatory response [26,27]. Serum albumin and D-dimer seem to participate in the same pathophysiological process in AF, and a study has found that normal serum albumin can inhibit platelet aggregation [28].

Therefore, we reasonably hypothesized that: (1) serum albumin and D-dimer and their associations might be associated with NVAF; and (2) serum albumin might be associated with risk factors for the hypercoagulable state in NVAF patients, possibly due to inflammatory response and oxidative stress affecting coagulation status and thromboembolism [24–26]. This retrospective, single-center aimed to investigate the correlation between serum albumin and D-dimer levels in 909 patients with non-valvular AF (NVAF) and 653 subjects in sinus rhythm at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan City, Shandong Province, China.

Material and Methods

PATIENTS AND METHODS:

This case-control, retrospective study was conducted according to the principles of the Declaration of Helsinki and was approved by the Medical Research Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine. The data were anonymized and the Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (NO.2021-022-LY) waived the need for informed consent.

The study group consisted of 909 patients with NVAF who were treated in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 2005 to January 2022, and the control group consisted of 653 sex- and age-matched participants with sinus rhythm and no history of AF. The inclusion criteria of patients were: (a) admitted to the hospital meeting the diagnostic criteria for AF [29] or with a history of AF; and (b) aged 18–80 years. Exclusion criteria were: (a) valvular AF/prosthetic heart valve; (b) concomitant diseases: hematological disease, malignancy, surgery or other trauma; and (c) taking drugs that affect D-dimer or albumin levels, except anticoagulants.

DATA COLLECTION:

All data were based on hospital medical records. Demographic data (age and sex), medical history (coronary heart disease [CHD], diabetes, hypertension, and ischemic stroke), medication use, CHA2DS2-VASc scores, and laboratory blood parameters were retrospectively collected for this study.

Blood samples were collected from fasting patients upon admission, and sent to the Laboratory Department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine for laboratory blood index determination. D-dimer level was determined using a latex-enhanced photometric immunoassay (Stago automated coagulation instrument), and the upper limit of normal was 0.5 ug/mL. Albumin, globulin, serum uric acid (SUA), triglycerides (TG), and glucose (GLU) levels were determined by colorimetry (OLYMPUS-AU2700, Automatic Biochemical Analyzer). Fibrinogen (FIB) and international normalized ratio (INR) were measured by an instrumental method (Stago automated coagulation instrument). White blood cell (WBC), neutrophil, lymphocyte, packed cell volume (PCV), and mean platelet volume (MPV) were determined using SYSMEX BC-5000, a hematology analyzer. B-type natriuretic peptide level (BNP) was determined using electrochemiluminescence (Elecsys 2010 system, Roche Diagnostic).

STATISTICAL ANALYSIS:

IBM SPSS Statistics version 21.0 (SPSS, Inc., Chicago, Illinois, USA) was used for statistical analysis. For continuous variables, normally distributed or approximately normally distributed data were presented as mean±standard deviation (SD), and non-normally distributed data were presented as the median and interquartile range (IQR). Categorical variables were presented as numerical values and percentages. Continuous variables between 2 groups were compared by t test or Mann-Whitney U test. Pearson and spearman correlation analysis was used to explore interrelationships. We divided AF patients into 2 groups according to the D-dimer level (0.5 ug/mL). Categorical variables were compared by chi-square distribution. Univariate and multivariate logistic regression were used to correct for potential confounding factors, explore the correlation of serum albumin, D-dimer, and NVAF, and determine whether serum albumin affects D-dimer levels in NVAF patients. The receiver operating characteristic (ROC) curve of GraphPad Prism version 9.0.0 (GraphPad Software Inc., La Jolla, CA, USA) was used to analyze the predictive ability of research indicators. Two-tailed P values <0.05 were considered statistically significant and these results were further analyzed.

Results

BASELINE CHARACTERISTICS OF THE STUDY POPULATION:

The baseline characteristics of the AF group and the control group are shown in Table 1. A total of 909 patients were included in the AF group, including 491 males, with an average age of 69.54±8.56 years; 653 subjects in sinus rhythm with no history of AF were included in the control group, including 353 males, with an average age of 69.51±8.08 years. Compared with controls, AF patients were more likely to have a history of CHD (P<0.001), hypertension (P<0.001), diabetes (P<0.001), and ischemic stroke (P<0.001). In addition, AF patients showed higher levels of WBC, neutrophil-to-lymphocyte ratio (NLR), MPV, INR, FIB, D-dimer, SUA, and lower levels of PCV and albumin. These factors were statistically significant between AF and controls. There were no significant differences in sex, age distribution, and levels of globulin, TG, and GLU between the 2 groups.

ASSOCIATION BETWEEN D-DIMER, ALBUMIN, AND AF:

Univariate logistic regression was used to determine the association between D-dimer, albumin, and AF, and multiple logistic regression was used to adjust for confounding factors to improve the accuracy of analysis of the association between D-dimer, albumin, and AF. The results showed that both D-dimer and albumin were independent risk factors for AF (Table 2). After adjusting for CHD, diabetes, hypertension, and ischemic stroke, D-dimer and albumin levels were significantly associated with AF. After adjusting for WBC, NLR, PCV, MPV, INR, FIB, and SUA levels, D-dimer and albumin levels were significantly associated with AF. Then, after adjusting for all the above confounding factors, D-dimer (OR=2.52, 95% CI 1.60–3.98, P<0.001) and albumin (OR=0.85, 95% CI 0.81–0.89, P<0.001) levels remained significantly associated with AF (Figure 1).

In AF patients, we explored the correlation between D-dimer and various variables. After correcting for outliers, we observed that D-dimer was negatively correlated with albumin (r=−0.504, P<0.001) and PCV (r=−0.299, P<0.001), and was positively correlated with NLR (r=0.185, P<0.001) and BNP (r=0.289, P<0.001) (Figure 2). In addition, WBC showed a very weak correlation with D-dimer (r=0.101, P=0.002). Although several variables were associated with D-dimer, only albumin showed a strong correlation with D-dimer, while PCV, BNP, NLR, and WBC all had a weak correlation with D-dimer.

CORRELATION OF ALBUMIN WITH D-DIMER IN AF:

To further explore the effect of various levels of D-dimer in AF patients and the connection between D-dimer and albumin, we divided AF patients into 2 groups according to the D-dimer cutoff level of 0.5 ug/mL. There were 379 patients in the D-dimer >0.5 ug/mL group and 530 patients in the D-dimer ≤0.5 ug/mL group. The baseline characteristics of the D-dimer group are shown in Table 3. Among AF patients, people with high D-dimer levels were more likely to be older (P<0.001) and not using anticoagulants (P<0.001), and they were more likely to be patients with ischemic stroke (P=0.002). Elevations in CHA2DS2-VASc (P<0.001), WBC (P=0.004), NLR (P<0.001), INR (P=0.044), FIB (P<0.001), BNP (P<0.001), and decreases in PCV (P<0.001), albumin (P<0.001), TG (P<0.001) and GLU (P=0.045) were more likely to affect D-dimer. Sex (P=0.685), CHD (P=0.509), diabetes (P=0.374), hypertension (P=0.827), MPV (P=0.614), globulin (P=0.134), and SUA (P=0.324) had no statistically significant effect on D-dimer.

Variables that were statistically significant in the univariate logistic regression analysis were used for multivariate logistic regression analysis (Table 4). Albumin was significantly correlated with D-dimer levels (OR= 0.77, 95% CI 0.73–0.80, P<0.001). After adjustment, the correlation between albumin and D-dimer is shown in Figure 3. After adjustment for age, ischemic stroke, anticoagulants, and CHA2DS2-VASc, albumin was significantly associated with D-dimer levels (OR=0.77, 95% CI 0.74–0.81, P<0.001). After adjustment for WBC, NLR, PCV, INR, FIB, BNP, TG, and GLU, albumin was significantly associated with D-dimer levels (OR=0.80, 95% CI 0.76–0.83, P<0.001). After adjusting for the above confounding factors, albumin was significantly associated with D-dimer level (OR=0.81, 95% CI 0.77–0.85, P<0.001), and it can be seen that albumin is an independent risk factor for D-dimer level in AF patients.

The ROC curves were used to analyze the predictive ability of albumin for D-dimer in AF patients. Figure 4 shows the analysis results of the ROC curve. Albumin can be used as an effective predictor of abnormal D-dimer levels in AF. The area under the ROC curve was 0.77 (95% CI 0.74–0.80, P<0.001), indicating that albumin had good accuracy in predicting D-dimer levels in AF. The optimal cutoff point was 36.95 g/L.

Discussion

This case-control study showed that serum albumin and D-dimer were significantly associated with AF. In AF patients, there is an association between serum albumin and D-dimer, and serum albumin was inversely correlated with D-dimer. Albumin is an independent risk factor for D-dimer in AF patients. These associations remained significant whether or not confounding factors were adjusted. This association supports our hypothesis. Serum albumin can be used as an effective predictor of D-dimer levels in AF patients. According to ROC curve analysis, the optimal cutoff point for albumin to predict abnormal D-dimer (>0.5 ug/mL) in AF is 36.95g/L. To the best of our knowledge, this is the first study to investigate the association of serum albumin with D-dimer in patients with AF.

D-dimer is a specific degradation product of fibrin, which can reflect coagulation activation or fibrinolysis [30]. D-dimer has been used as a common evaluation index for the evaluation of venous thromboembolism and pulmonary embolism [31,32]. However, more and more studies have confirmed that AF patients have higher D-dimer levels, and D-dimer is closely related to the occurrence of AF and its thromboembolic complications [13,33,34]. Hypercoagulability is common in AF patients [30], which is also an important cause of thromboembolic complications and poor prognosis. The D-dimer level can reflect the degree of hypercoagulable state accompanying AF [30]. Several studies have found that D-dimer is an effective indicator for excluding NVAF thromboembolic events[35,36] and assessing the risk of ischemic stroke [34,37–39]. Moreover, D-dimer can predict the prognosis of cardiovascular events and thromboembolic events [40–42]. Although use of anticoagulation in patients with AF has become widely accepted, it also increases the risk of bleeding [43], and in many hospitals the use of anticoagulants is under-therapeutic, and inappropriate anticoagulation can lead to higher mortality [44–46]. For AF patients with higher D-dimer levels, even on anticoagulants, subsequent thromboembolic and cardiovascular events can be effectively predicted [37,40]. Therefore, it is necessary to explore the influencing factors related to the level of D-dimer in patients with AF.

Serum albumin is involved in regulating systemic inflammatory response through pro-inflammatory substances. According to previous reports, low serum albumin levels are often accompanied by a systemic inflammatory response [19], and inflammation is associated with the pathophysiology of AF [24] and can predict the occurrence or recurrence of AF, which has also been verified in the literature [22,23]. In particular, a study with a sample size of 12 833 showed that serum albumin was inversely associated with the incidence of AF, but MR analysis did not support a causal relationship [23]. AF prevention with the goal of serum albumin supplementation is unlikely to be effective. However, the inflammatory response of AF increases thrombus formation [47]. Pro-inflammatory factors can induce platelet activation [48], leukocyte-platelet interactions may also mediate thrombosis [24], and normal serum albumin can inhibit platelet aggregation [28], which reminds us that albumin may interact with thrombosis and hypercoagulability in AF.

Clinical studies have found that D-dimer is an effective predictor of acute ischemic stroke [10]. Even with anticoagulants, D-dimer is also an effective predictor of thromboembolic events in AF patients [13]. A meta-analysis based on 71 studies also showed that D-dimer was significantly associated with AF patients [33]. Our study found that D-dimer levels were significantly associated with AF (OR=2.52, 95% CI 1.60–3.98, P<0.001), and abnormal D-dimer is closely related to ischemic stroke in patients with AF (P=0.002), which is consistent with previously reported results. Another prospective study, based on 12 833 participants, showed that serum albumin levels were linearly associated with AF [23]. A clinical study based on 32 130 participants also showed that low serum albumin levels were significantly associated with an increased risk of AF [49]. Our study found similar results, with low serum albumin levels significantly associated with AF (OR=0.85, 95% CI 0.81–0.89, P<0.001). In exploring the risk factors associated with D-dimer in AF patients, our analysis showed that serum albumin was significantly associated with D-dimer of AF patients (OR=0.81, 95% CI 0.77–0.85, P<0.001) and could serve as an effective predictor of D-dimer levels in AF patients. Albumin is a commonly used clinical indicator, and clinicians should pay more attention to serum albumin levels to improve D-dimer levels and prognosis in patients with AF. Furthermore, we observed that in NVAF patients, D-dimer was negatively correlated with albumin and PCV, and was positively correlated with WBC, NLR, and BNP. Although several variables were significantly correlated with D-dimer, only albumin showed a strong correlation with D-dimer. Among the different D-dimer levels in NVAF patients, albumin also showed significant differences.

Interestingly, after adjusting for multiple confounders, including medical history and laboratory blood parameters, by multivariate logistic regression analysis, the ORs for D-dimer were significantly reduced, and studies also showed that age-adjusted D-dimer significantly improves the specificity of diagnosing venous thromboembolic events, but the ORs of the adjusted albumin did not change significantly. It can be seen that albumin is less affected by confounding factors and has higher specificity. Serum albumin can predict the hypercoagulable state of AF patients, and this suggests that serum albumin supplementation might prevent the development of thromboembolic complications in AF, but this needs further verification.

This study has some shortcomings. First, the sample size of this study was relatively small and was from a single-center institution, so our analysis has the potential to be biased, and we used a retrospective analysis and were unable to explore causality. Second, oxidative stress status of AF patients was not included, and inflammatory markers such as IL-6 and hs-CRP were not adjusted as confounding factors. Albumin can decline with frailty; we only performed age matching, and BMI and other indicators were not included. This is because they were either not measured or were missing at the time of patient admission. Finally, we did not classify AF and were unable to analyze the association of serum albumin and D-dimer between different AF types. It is hoped that there will be large-sample, multi-center studies and prospective cohort studies to further confirm the results of this study.

Conclusions

The results of this study revealed that serum albumin and D-dimer were significantly associated with AF. In AF patients, serum albumin was inversely correlated with D-dimer. We also found that serum albumin is an independent risk factor and effective predictor of abnormal D-dimer (>0.5 ug/mL). This may affect the hypercoagulable state and thromboembolic events of AF due to inflammatory responses. Close examination and supplementation of serum albumin may prevent thromboembolic events, but further clinical research and confirmation are needed.

References

1. Cheung CC, Nattel S, Macle L, Andrade JG, Management of atrial fibrillation in 2021: An updated comparison of the current ccs/chrs, esc, and aha/acc/hrs guidelines: Can J Cardiol, 2021; 37; 1607-18

2. Lippi G, Sanchis-Gomar F, Cervellin G, Global epidemiology of atrial fibrillation: An increasing epidemic and public health challenge: Int J Stroke, 2021; 16; 217-21

3. Krijthe BP, Kunst A, Benjamin EJ, Projections on the number of individuals with atrial fibrillation in the european union, from 2000 to 2060: Eur Heart J, 2013; 34; 2746-51

4. Ding WY, Gupta D, Lip G, Atrial fibrillation and the prothrombotic state: Revisiting Virchow’s triad in 2020: Heart, 2020; 106; 1463-68

5. Mukherjee K, Kamal KM, Impact of atrial fibrillation on inpatient cost for ischemic stroke in the usa: Int J Stroke, 2019; 14; 159-66

6. Go AS, Mozaffarian D, Roger VL, Heart disease and stroke statistics – 2013 update: A report from the american heart association: Circulation, 2013; 127; e6-e245

7. Dilaveris PE, Kennedy HL, Silent atrial fibrillation: Epidemiology, diagnosis, and clinical impact: Clin Cardiol, 2017; 40; 413-18

8. January CT, Wann LS, Calkins H, 2019 aha/acc/hrs focused update of the 2014 aha/acc/hrs guideline for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and The Heart Rhythm Society in Collaboration with The Society of Thoracic Surgeons: Circulation, 2019; 140; e125-e51

9. Weitz JI, Fredenburgh JC, Eikelboom JW, A test in context: D-dimer: J Am Coll Cardiol, 2017; 70; 2411-20

10. Ramos-Pachon A, Lopez-Cancio E, Bustamante A, D-dimer as predictor of large vessel occlusion in acute ischemic stroke: Stroke, 2021; 52; 852-58

11. Diaz-Arocutipa C, Gonzales-Luna AC, Branez-Condorena A, Hernandez AV, Diagnostic accuracy of d-dimer to detect left atrial thrombus in patients with atrial fibrillation: A systematic review and meta-analysis: Heart Rhythm, 2021; 18; 2128-36

12. Berg DD, Ruff CT, Morrow DA, Biomarkers for risk assessment in atrial fibrillation: Clin Chem, 2021; 67; 87-95

13. Nozawa T, Inoue H, Hirai T, D-dimer level influences thromboembolic events in patients with atrial fibrillation: Int J Cardiol, 2006; 109; 59-65

14. Matsumoto M, Sakaguchi M, Okazaki S, Relationship between plasma (d)-dimer level and cerebral infarction volume in patients with nonvalvular atrial fibrillation: Cerebrovasc Dis, 2013; 35; 64-72

15. Arques S, Human serum albumin in cardiovascular diseases: Eur J Intern Med, 2018; 52; 8-12

16. Wiedermann CJ, Anti-inflammatory activity of albumin: Crit Care Med, 2007; 35; 981-82

17. Sheinenzon A, Shehadeh M, Michelis R, Serum albumin levels and inflammation: Int J Biol Macromol, 2021; 184; 857-62

18. Alves FC, Sun J, Qureshi AR, The higher mortality associated with low serum albumin is dependent on systemic inflammation in end-stage kidney disease: PLoS One, 2018; 13; e190410

19. Eckart A, Struja T, Kutz A, Relationship of nutritional status, inflammation, and serum albumin levels during acute illness: A prospective study: Am J Med, 2020; 133; 713-22

20. Shaper AG, Wannamethee SG, Whincup PH, Serum albumin and risk of stroke, coronary heart disease, and mortality: The role of cigarette smoking: J Clin Epidemiol, 2004; 57; 195-202

21. Mukamal KJ, Tolstrup JS, Friberg J, Fibrinogen and albumin levels and risk of atrial fibrillation in men and women (the Copenhagen city heart study): Am J Cardiol, 2006; 98; 75-81

22. van Beek D, Kuijpers Y, Konigs M, Low serum albumin levels and new-onset atrial fibrillation in the ICU: A prospective cohort study: J Crit Care, 2020; 56; 26-30

23. Liao LZ, Zhang SZ, Li WD, Serum albumin and atrial fibrillation: Insights from epidemiological and mendelian randomization studies: Eur J Epidemiol, 2020; 35; 113-22

24. Hu YF, Chen YJ, Lin YJ, Chen SA, Inflammation and the pathogenesis of atrial fibrillation: Nat Rev Cardiol, 2015; 12; 230-43

25. Martin-Ventura JL, Rodrigues-Diez R, Martinez-Lopez D, Oxidative stress in human atherothrombosis: Sources, markers and therapeutic targets: Int J Mol Sci, 2017; 18; 2315

26. Robson SC, Shephard EG, Kirsch RE, Fibrin degradation product d-dimer induces the synthesis and release of biologically active il-1 beta, il-6 and plasminogen activator inhibitors from monocytes in vitro: Br J Haematol, 1994; 86; 322-26

27. Zhou D, Yang PY, Zhou B, Rui YC, Fibrin D-dimer fragments enhance inflammatory responses in macrophages: Role in advancing atherosclerosis: Clin Exp Pharmacol Physiol, 2007; 34; 185-90

28. Lam FW, Cruz MA, Leung HC, Histone induced platelet aggregation is inhibited by normal albumin: Thromb Res, 2013; 132; 69-76

29. Fuster V, Ryden LE, Cannom DS, ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation – executive summary: E report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The European Society of Cardiology Committee for Practice Guidelines (writing committee to revise the 2001 guidelines for the management of patients with atrial fibrillation): J Am Coll Cardiol, 2006; 48; 854-906

30. Danese E, Montagnana M, Cervellin G, Lippi G, Hypercoagulability, D-dimer and atrial fibrillation: an overview of biological and clinical evidence: Ann Med, 2014; 46; 364-71

31. Schouten HJ, Geersing GJ, Koek HL, Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: Systematic review and meta-analysis: BMJ, 2013; 346; f2492

32. Halaby R, Popma CJ, Cohen AC, D-dimer elevation and adverse outcomes: J Thromb Thrombolysis, 2015; 39; 55-59

33. Weymann A, Sabashnikov A, Ali-Hasan-Al-Saegh S, Predictive role of coagulation, fibrinolytic, and endothelial markers in patients with atrial fibrillation, stroke, and thromboembolism: A meta-analysis, meta-regression, and systematic review: Med Sci Monit Basic Res, 2017; 23; 97-140

34. Christersson C, Wallentin L, Andersson U, D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation – observations from the aristotle trial: J Thromb Haemost, 2014; 12; 1401-12

35. Almorad A, Ohanyan A, Pintea BG, D-dimer blood concentrations to exclude left atrial thrombus in patients with atrial fibrillation: Heart, 2021; 107; 195-200

36. Du X, Wang Y, The diagnostic efficacy of cardiac CTA combined with D-dimer assay for the detection of left atrial thrombus in patients with atrial fibrillation: Am J Emerg Med, 2019; 37; 1922-26

37. You LR, Tang M, The association of high D-dimer level with high risk of ischemic stroke in nonvalvular atrial fibrillation patients: A retrospective study: Medicine (Baltimore), 2018; 97; e12622

38. Ohara T, Farhoudi M, Bang OY, The emerging value of serum D-dimer measurement in the work-up and management of ischemic stroke: Int J Stroke, 2020; 15; 122-31

39. Siegbahn A, Oldgren J, Andersson U, D-dimer and factor viia in atrial fibrillation – prognostic values for cardiovascular events and effects of anticoagulation therapy. A re-ly substudy: Thromb Haemost, 2016; 115; 921-30

40. Mahe I, Bergmann JF, Chassany O, A multicentric prospective study in usual care: D-dimer and cardiovascular events in patients with atrial fibrillation: Thromb Res, 2012; 129; 693-99

41. Mahe I, Drouet L, Simoneau G, Minh-Muzeaux S, D-dimer can predict survival in patients with chronic atrial fibrillation: Blood Coagul Fibrinolysis, 2004; 15; 413-17

42. Sadanaga T, Sadanaga M, Ogawa S, Evidence that D-dimer levels predict subsequent thromboembolic and cardiovascular events in patients with atrial fibrillation during oral anticoagulant therapy: J Am Coll Cardiol, 2010; 55; 2225-31

43. Rusin G, Konieczynska M, Bijak P, Bleeding tolerance among patients with atrial fibrillation on oral anticoagulation: Can J Cardiol, 2020; 36; 500-8

44. Camm AJ, Cools F, Virdone S, Mortality in patients with atrial fibrillation receiving nonrecommended doses of direct oral anticoagulants: J Am Coll Cardiol, 2020; 76; 1425-36

45. Yu HT, Yang PS, Jang E, Label adherence of direct oral anticoagulants dosing and clinical outcomes in patients with atrial fibrillation: J Am Heart Assoc, 2020; 9; e14177

46. Liu X, Huang M, Ye C, Effect of non-recommended doses versus recommended doses of direct oral anticoagulants in atrial fibrillation patients: A meta-analysis: Clin Cardiol, 2021; 44; 472-80

47. Harada M, Nattel S, Implications of inflammation and fibrosis in atrial fibrillation pathophysiology: Card Electrophysiol Clin, 2021; 13; 25-35

48. Marino M, Scuderi F, Ponte E, Novel path to il-6 trans-signaling through thrombin-induced soluble il-6 receptor release by platelets: J Biol Regul Homeost Agents, 2013; 27; 841-52

49. Wang Y, Du P, Xiao Q, Relationship between serum albumin and risk of atrial fibrillation: A dose-response meta-analysis: Front Nutr, 2021; 8; 728353

SARS-CoV-2/COVID-19

26 January 2023 : Editorial  

Editorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread

Med Sci Monit In Press; DOI: 10.12659/MSM.939580  

19 January 2023 : Clinical Research  

Evaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...

Med Sci Monit In Press; DOI: 10.12659/MSM.938892  

27 December 2022 : Clinical Research  

Effect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...

Med Sci Monit 2022; 28:e938926

In Press

27 Jan 2023 : Database Analysis  

Association Between Neutrophil-Lymphocyte Ratio and All-Cause Mortality in Critically Ill Patients with Chr...

Med Sci Monit In Press; DOI: 10.12659/MSM.938554  

27 Jan 2023 : Clinical Research  

Proposal for a Simple Equation for Limb Muscle Weight Calculation

Med Sci Monit In Press; DOI: 10.12659/MSM.938606  

26 Jan 2023 : Editorial  

Editorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread

Med Sci Monit In Press; DOI: 10.12659/MSM.939580  

20 Jan 2023 : Clinical Research  

A Study of 42 Partially Edentulous Patients with Single-Crown Restorations and Implants to Compare Bone Los...

Med Sci Monit In Press; DOI: 10.12659/MSM.939225  

Most Viewed Current Articles

13 Nov 2021 : Clinical Research  

Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...

DOI :10.12659/MSM.932788

Med Sci Monit 2021; 27:e932788

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

08 Mar 2022 : Review article  

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...

DOI :10.12659/MSM.936292

Med Sci Monit 2022; 28:e936292

01 Jan 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...

DOI :10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750