Heparin versus aspirin thromboprophylaxis adds independent value to IMPEDE-VTE score for venous thrombosis prediction in multiple myeloma.

Multiple myeloma (MM) is associated to an increased incidence of venous thromboembolism (VTE). IMPEDE-VTE score constitutes a valuable risk assessment tool for VTE prediction in first-line MM patients. Nevertheless, refinement of the primary thromboprophylaxis category of this score (which pools aspirin and heparin) seems desirable. To investigate the role of the type of thromboprophylaxis, within IMPEDE-VTE score, for VTE prediction in MM patients. Retrospective analysis of a single-center cohort of 438 MM patients receiving first-line antimyeloma treatment (1991-2020). IMPEDE-VTE score was calculated. Primary thromboprophylaxis was additionally stratified into aspirin- and heparin-based regimen subgroups. VTE risk was analyzed by Cox regression. Median follow-up during first-line antimyeloma treatment was 6.0 months (IQR 4.1-9.0 months). Twenty-three patients developed VTE (5.3%, 95%CI 3.4-7.8%). IMPEDE-VTE score showed a notable predictive value (area under the ROC curve: 0.70, 95%CI 0.60-0.80). Cox analysis confirmed that 1-point increase in the score resulted in a 1.3-fold increase in VTE risk (HR 1.30, 95%CI 1.13-1.53, p < 0.001). In the multivariable analysis, the type of primary thromboprophylaxis (heparin versus aspirin) was an independent predictive factor (HR 0.15, 95% CI 0.05-0.47, p = 0.001). The combined model showed a higher goodness-of-fit (Akaike Information Criterion [AIC]: 99) than IMPEDE-VTE separately (AIC:235). Our analysis contributes to the external validation of IMPEDE-VTE score for the prediction of VTE in MM. But more interestingly, our results demonstrate that among those patients receiving thromboprophylaxis, the type of regimen (heparin versus aspirin) adds independent predictive value and should be explored for a more accurate risk assessment.

Quality and effectiveness of osteoporosis treatment decision aids: a systematic review and environmental scan.

Decision aids (DAs) are evidence-based tools that support shared decision-making (SDM) implementation in practice; this study aimed to identify existing osteoporosis DAs and assess their quality and efficacy; and to gain feedback from a patient advisory group on findings and implications for further research. We searched multiple bibliographic databases to identify research studies from 2000 to 2019 and undertook an environmental scan (search conducted February 2019, repeated in March 2020). A pair of reviewers, working independently selected studies for inclusion, extracted data, evaluated each trial's risk of bias, and conducted DA quality assessment using the International Patient Decision Aid Standards (IPDAS). Public contributors (patients and caregivers with experience of osteoporosis and fragility fractures) participated in discussion groups to review a sample of DAs, express preferences for a new DA, and discuss plans for development of a new DA. We identified 6 studies, with high or unclear risk of bias. Across included studies, use of an osteoporosis DA was reported to result in reduced decisional conflict compared with baseline, increased SDM, and increased accuracy of patients' perceived fracture risk compared with controls. Eleven DAs were identified, of which none met the full set of IPDAS criteria for certification for minimization of bias. Public contributors expressed preferences for encounter DAs that are individualized to patients' own needs and risk. Using a systematic review and environmental scan, we identified 11 decision aids to inform patient decisions about osteoporosis treatment and 6 studies evaluating their effectiveness. Use of decision aids increased accuracy of risk perception and shared decision-making but the decision aids themselves fail to comprehensively meet international quality standards and patient needs, underpinning the need for new DA development.

Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE-LY trial.

BACKGROUND: Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF. OBJECTIVES: To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE-LY trial. METHODS: HAS-BLED, ORBIT, ATRIA and HEMORR2 HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated. RESULTS: There were 1182 (6.5%) major bleeding events during a median follow-up of 2.0 years. For all the four schemes, high-risk subgroups had higher risk of major bleeding (all P < 0.001). The ORBIT score showed the best discrimination with c-indices of 0.66, 0.66 and 0.62, respectively, for major, life-threatening and intracranial bleeding, which were significantly better than for the HAS-BLED score (difference in c-indices: 0.050, 0.053 and 0.048, respectively, all P < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P = 0.0019), ATRIA (P < 0.001) and HEMORR2 HAGES (P < 0.001) scores. HAS-BLED score showed a nonsignificant trend for interaction (P = 0.0607). CONCLUSIONS: Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

High incidence of FXI deficiency in a Spanish town caused by 11 different mutations and the first duplication of F11: Results from the Yecla study.

INTRODUCTION: Factor XI (FXI) deficiency is a rare disorder with molecular heterogeneity in Caucasians but relatively frequent and molecularly homogeneous in certain populations. AIM: To characterize FXI deficiency in a Spanish town of 60 000 inhabitants. METHODS: A total of 324 764 APTT tests were screened during 20 years. FXI was evaluated by FXI:C and by Western blot. Genetic analysis of F11 was performed by sequencing, multiplex ligation-dependent probe amplification and genotyping. RESULTS: Our study identified 46 unrelated cases and 170 relatives with FXI deficiency carrying 12 different genetic defects. p.Cys56Arg, described as founder mutation in the French-Basque population, was identified in 109 subjects from 24 unrelated families. This mutation was also identified in 2% of the general population. p.Cys416Tyr, c.1693G>A and p.Pro538Leu were identified in 7, 6 and 2 unrelated families, respectively. NGS analysis of the whole F11 gene revealed a common haplotype for each of the four recurrent mutations, suggesting a founder effect. The analysis of plasma FXI of four p.Pro538Leu homozygous carriers revealed that this variant was not activated by FXIIa. We identified four mutations previously described in other Caucasian subjects with FXI deficiency (p.Lys536Asn; p.Thr322Ile, p.Arg268Cys and c.325G>A) and four new gene defects: p.(Cys599Tyr) potentially causing a functional deficiency, p.(Ile426Thr), p.(Ile592Thr) and the first worldwide duplication of 1653 bp involving exons 8 and 9. Bleeding was rare and mild. CONCLUSIONS: Our population-cohort study supplies new evidences that FXI deficiency in Caucasians is more common than previously thought and confirmed the wide underlying genetic heterogeneity, caused by both recurrent and sporadic mutations.

Biomarkers in atrial fibrillation: an overview.

Atrial fibrillation (AF) confers a raised risk of stroke and death, and this risk of adverse events is increased by the coexistence of other cardiovascular risk factors. The pathophysiology of AF is complex, involving the role of inflammation, structural remodelling with apoptosis, inflammation or fibrosis. These changes confer a prothrombotic or hypercoagulable state in this arrhythmia. Despite being easy to use for decision-making concerning oral anticoagulant therapy in AF, clinical risk scores used for stratification have shown modest capability in predicting thromboembolic events, and biomarkers may improve our identification of 'high risk' patients. Biomarkers, whether measured in the peripheral blood, urine or imaging-based may improve our knowledge of the pathophysiology of AF. Importantly these biomarkers could help in the assessment of AF prognosis. The aim of this review was to summarise the published data about biomarkers studied in AF, with focus on data from randomised prospective clinical trials and large community-based cohorts. We will also review the application of these biomarkers to prognosis on the main schemes used to help stratify risk in AF.

Testing spatial working memory in pigs using an automated T-maze.

Pigs are an important large animal model for translational clinical research but underutilized in behavioral neuroscience. This is due, in part, to a lack of rigorous neurocognitive assessments for pigs. Here, we developed a new automated T-maze for pigs that takes advantage of their natural tendency to alternate. The T-maze has obvious cross-species value having served as a foundation for cognitive theories across species. The maze (17' × 13') was constructed typically and automated with flanking corridors, guillotine doors, cameras, and reward dispensers. We ran nine pigs in (1) a simple alternation task and (2) a delayed spatial alternation task. Our assessment focused on the delayed spatial alternation task which forced pigs to wait for random delays (5, 60, 120, and 240 s) and burdened spatial working memory. We also looked at self-paced trial latencies, error types, and coordinate-based video tracking. We found pigs naturally alternated but performance declined steeply across delays (R2 = 0.84). Self-paced delays had no effect on performance suggestive of an active interference model of working memory. Positional and head direction data could differentiate subsequent turns on short but not long delays. Performance levels were stable over weeks in diverse strains and sexes, and thus provide a benchmark for future neurocognitive assessments in pigs.

Peri-operative management of ophthalmic patients taking antithrombotic therapy.

Increasing number of patients presenting for ophthalmic surgery are using oral anti-coagulant and anti-platelet therapy. The current practice of discontinuing these drugs preoperatively because of a presumed increased risk of bleeding may not be evidence-based and could pose a significant risk to the patient's health. To provide an evidence-based review on the peri-operative management of ophthalmic patients who are taking anti-thrombotic therapy. In addition, we briefly discuss the underlying conditions that necessitate the use of these drugs as well as management of the operative field in anti-coagulated patients. A semi-systematic review of literature was performed. The databases searched included MEDLINE, EMBASE, database of abstracts of reviews of effects (DARE), Cochrane controlled trial register and Cochrane systematic reviews. In addition, the bibliographies of the included papers were also scanned for evidence. The published data suggests that aspirin did not appear to increase the risk of serious postoperative bleeding in any type of ophthalmic surgery. Topical, sub-tenon, peri-bulbar and retrobulbar anaesthesia appear to be safe in patients on anti-thrombotic (warfarin and aspirin) therapy. Warfarin does not increase the risk of significant bleeding in most types of ophthalmic surgery when the INR was within the therapeutic range. Current evidence supports the continued use of aspirin and with some exceptions, warfarin in the peri-operative period. The risk of thrombosis-related complications on disruption of anticoagulation may be higher than the risk of significant bleeding by continuing its use for most types of ophthalmic surgery.

May captive populations of Greater Rhea (Rhea americana) act as genetic reservoirs in Argentina?

The Greater Rhea (Rhea americana) is a characteristic bird of the Argentine Pampas. Despite the increasing farming interest of this ratite, their natural populations are progressively decreasing in size and range. The object of this study was to evaluate the status of captive populations as potential genetic reservoirs. Using Inter-Simple Sequence Repeats as molecular markers, levels of genetic variability of F1 individuals from two captive populations were estimated and compared with those of wild populations in the same region. The captive populations were polymorphic for 12.22 and 13.33% of the loci, with a genetic diversity of 0.050. Differences with wild populations were not significant (z=1.79; P>0.05). Therefore, captive populations of rheas in Argentina should not be overlooked as genetic reservoir and source of individuals for reinforcement of natural populations, through reintroduction and translocation.

Left atrial remodelling in hypertrophic cardiomyopathy: relation with exercise capacity and biochemical markers of tissue strain and remodelling.

BACKGROUND: Left atrial remodelling, assessed as left atrial volume (LAV), has been proposed as a good marker of left ventricular diastolic dysfunction. The aim of this study was to analyse the influence of LAV on exercise performance in hypertrophic cardiomyopathy (HCM), and in a subset of subjects, assess the relation of LAV and exercise performance to four biomarkers of disease pathophysiology: matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) (as indices of tissue remodelling), N-terminal portion of pro B-type natriuretic peptide (NT-pro-BNP) (associated with ventricular dysfunction) and C-reactive protein (CRP, an index of inflammation). METHODS: We studied 75 consecutive HCM patients (aged 46 +/- 14 years, 56 men) where LAV was calculated assuming the ellipsoid model with two orthogonal planes. LAV was indexed to body surface area. Exercise capacity was evaluated by treadmill exercise test (symptom limited) and assessed with metabolic equivalent units (MET). Basal NT-pro-BNP and CRP levels were measured in 70 patients, whereas MMP-2 and TIMP-1 in 43 patients. RESULTS: Enlarged LAV was observed in those patients with previous atrial fibrillation (p = 0.016). Mean LAV was greater in patients with impaired functional New York Heart Association (NYHA) class (p < 0.001). LAV correlated with age (Spearman, r: 0.28), higher maximal left ventricular wall thickness (r: 0.32) and raised E/A ratio (r: 0.37) (all p < 0.01). LAV was significantly correlated with NT-pro-BNP values (r: 0.34; p = 0.04), MMP-2 (r: 0.32; p = 0.034), CRP (r: 0.33; p = 0.005) and correlated inversely with MET units (r: -0.39; p < 0.01). In multivariate analysis, MET units were only associated with NT-pro-BNP (p = 0.002) and LAV (p = 0.010). CONCLUSIONS: Enlarged LAV is associated with impaired functional NYHA class and inversely with treadmill exercise capacity. Enlarged LAV is also associated with NT-pro-BNP, MMP-2 and CRP, perhaps as markers of disease severity and tissue remodelling. Age, LAV and NT-pro-BNP are independent predictors of exercise performance.

Efficacy and safety of peri-procedural bridging therapy with low molecular weight heparin in atrial fibrillation patients under vitamin K antagonists.

BACKGROUND: The clinical effect of peri-operative bridging therapy in atrial fibrillation (AF) patients remains unclear given that it may increase bleeding risk without providing significant benefits. We aimed to investigate peri-procedural events in relation to peri-operative use of bridging therapy in AF patients under Vitamin K Antagonists (VKAs). METHODS: We included AF patients stable the previous 6 months on VKAs. During a median follow-up of 6.5 years (IQR 4.3-7.9), we recorded all invasive procedures and the peri-operative clinical management. All peri-procedural events (ischaemic stroke/transient ischaemic attack/systemic embolism, clinically relevant non-major bleeding and major bleeding) and severe peri-procedural events (ischaemic stroke/transient ischaemic attack/systemic embolism and major bleeding) suffered until the 30-days post-intervention period were recorded. RESULTS: We included 1361 patients (48.7% male, median age 76 [IQR 71-81] years). There were 1100 (70.9%) procedures performed using bridging therapy. The rate of any (4.5% vs. 0.7%, P < 0.001) and severe (2.3% vs. 0.0%, P = 0.002) peri-procedural events were higher in patients receiving bridging therapy. Adjusted logistic regressions demonstrated that the bleeding risk of the procedure was related with higher risk of severe peri-procedural events (OR 3.51, 95% CI 1.54-8.01) and peri-procedural events (OR 2.77, 95% CI 1.56-4.91). Importantly, the use of bridging therapy was also independently associated with higher risk of any peri-procedural events (OR 4.32, 95% CI 1.28-14.51). CONCLUSIONS: In this study including AF patients under VKA therapy, the use of bridging therapy as part of the clinical management during an invasive procedure was independently associated with higher risk of any peri-procedural event.

The genetic interaction between VKORC1 c1173t and calumenin a29809g modulates the anticoagulant response of acenocoumarol.

BACKGROUND: The efficacy of oral anticoagulant therapy is largely conditioned by both environmental and genetic factors. OBJECTIVES: To attempt to define the genetic profile involved in the response to this treatment. PATIENTS AND METHODS: We selected 100 men younger than 75 years, with non-valvular atrial fibrillation, who started anticoagulation with acenocoumarol following the same protocol: 3 mg for three consecutive days. Then, doses were individually adjusted to achieve a steady International Normalized Ratio (INR). The basal plasma level and the level after 3 days were obtained, and the INR was determined. We studied five functional polymorphisms: FVII -323 Del/Ins, CYP2C*9, VKORC1 c1173t, calumenin (CALU) R4Q and CALU a29809g. The dose required for a steady INR was also recorded. RESULTS: Only the VKORC1 genotype had significant impact on the efficacy of therapy. Carriers of the 1173t allele were significantly more sensitive to therapy for 3 days [INR 2.07 (1.59-2.87) vs. 1.74 (1.30-2.09); P = 0.015] and they needed lower acenocoumarol doses to stabilize their INR (15.8 +/- 5.6 vs. 19.5 +/- 6.0 mg week(-1); P = 0.004). Its effect was exacerbated by combination with the CALU a29809g polymorphism. Carriers of both variants (27% of the sample) achieved the highest INR [2.26 (1.70-3.32)] and required the lowest dose (14.1 +/- 5.1 mg week(-1)). This genetic profile was particularly relevant in patients with INR >or= 3.5 at the start of therapy (P = 0.005; odds ratio = 6.67, 95% confidence interval = 1.32-37.43). CONCLUSIONS: Our results suggest that CALU a29809g might be a new genetic factor involved in the pharmacogenetics of anticoagulant therapy, and confirm that specific genetic profiles defined by different polymorphisms will determine the initial response and dose required to achieve a stable and safe INR.

A multimarker risk stratification approach to non-ST elevation acute coronary syndrome: implications of troponin T, CRP, NT pro-BNP and fibrin D-dimer levels.

INTRODUCTION: Biomarkers have emerged as interesting predictors of risk in non-ST elevation acute coronary syndromes (non-ST ACS). The aim of this study was to define the utility of the combined measurement of troponin T (TnT), C-reactive protein (CRP), NT pro-brain natriuretic peptide (NT pro-BNP) and D-dimer as biomarkers to predict adverse events. METHODS: We included 358 consecutive patients admitted in two hospitals for non-ST ACS. Baseline measurements of TnT (associated with myocardial injury, positive, if > or =0.1 ng mL(-1)), CRP (a marker of inflammation), NT-proBNP (associated with left ventricular (dys)function) and fibrin D-dimer (and index of thrombogenesis) were performed. A positive CRP, NT-proBNP and D-dimer test was considered upper than the 75th percentile of our population. The risk for major events (death, new ACS, revascularization and heart failure) at 6 months' follow-up was analysed. RESULTS: Troponin T, NT pro-BNP and CRP were predictors of adverse events in the multivariate analysis [hazards ratio (HR): 2.00 (1.30-3.07), P = 0.0016; HR: 2.27 (1.47-3.50), P = 0.0002; HR: 1.90 (1.24-2.92), P = 0.0034 respectively], but not D-dimer levels [HR: 1.26 (0.79-2.02), P = 0.337). After adjusting for baseline characteristics and electrocardiographic changes, multimarker risk approach was associated with adverse events at 6 months, especially with the presence of three positive biomarkers [HR 2.80 (95%CI 1.68-4.68), P < 0.001]. When we divided patients by risk groups [Thrombolysis in Myocardial Infarction (TIMI) risk score], patients with two or three elevated biomarkers had higher event rates [HR 2.59 (95% CI 1.37-4.91), P = 0.004]. CONCLUSION: A multimarker approach based on TnT, CRP and NT-proBNP provides added information to the TIMI risk score in terms of ACS prognosis at 6 months, with a worse outcome for those with two or three elevated biomarkers.

Hypoglycosylation is a common finding in antithrombin deficiency in the absence of a SERPINC1 gene defect.

UNLABELLED: Essentials We investigated the molecular base of antithrombin deficiency in cases without SERPINC1 defects. 27% of cases presented hypoglycosylation, transient in 62% and not restricted to antithrombin. Variations in genes involved in N-glycosylation underline this phenotype. These results support a new form of thrombophilia. Click here to listen to Dr Huntington's perspective on thrombin inhibition by the serpins SUMMARY: Background Since the discovery of antithrombin deficiency, 50 years ago, few new thrombophilic defects have been identified, all with weaker risk of thrombosis than antithrombin deficiency. Objective To identify new thrombophilic mechanisms. Patients/methods We studied 30 patients with antithrombin deficiency but no defects in the gene encoding this key anticoagulant (SERPINC1). Results A high proportion of these patients (8/30: 27%) had increased hypoglycosylated forms of antithrombin. All N-glycoproteins tested in these patients (α1-antitrypsin, FXI and transferrin) had electrophoretic, HPLC and Q-TOF patterns indistinguishable from those of the congenital disorders of glycosylation (rare recessive multisystem disorders). However, all except one had no mental disability. Moreover, intermittent antithrombin deficiency and hypoglycosylation was recorded in five out of these eight patients, all associated with moderate alcohol intake. Genetic analysis, including whole exome sequencing, revealed mutations in different genes involved in the N-glycosylation pathway. Conclusions Our study provides substantial and novel mechanistic insights into two disease processes, with potential implications for diagnosis and clinical care. An aberrant N-glycosylation causing a recessive or transient antithrombin deficiency is a new form of thrombophilia. Our data suggest that congenital disorders of glycosylation are probably underestimated, especially in cases with thrombosis as the main or only clinical manifestation.

A new method to quantify ß-antithrombin glycoform in plasma reveals increased levels during the acute stroke event.

INTRODUCTION: ß-antithrombin, the minor antithrombin glycoform in plasma, is probably the major thrombin inhibitor in vivo because of its high heparin affinity. The levels and variability of this glycoform in general population and its relevance in thromboembolic diseases is unknown since there is no specific method to measure this glycoform in clinical samples. METHODS: Plasma and recombinant α- and ß-antithrombins were purified by heparin affinity chromatography. An anti-FXa chromogenic method in presence of pentassacharide was used with two NaCl concentrations (15mM and 1.1M). This method was applied to plasma samples from 97 healthy subjects and 117 consecutive patients with ischemic cerebrovascular disease during the acute event and one year later. SERPINC1 sequencing was done in cases with antithrombin deficiency. RESULTS: High salt concentrations specifically restricted the pentassacharide-induced activation of antithrombin to the ß glycoform. ß-antithrombin displayed a normal distribution in the general population (89.5%-103.5%), with no significant variations according to age or sex. In patients, whole antithrombin values remained within the normal range. Only five cases had antithrombin deficiency during the thrombotic event, one carrying the L99F mutation in SERPINC1. Interestingly, both ß-antithrombin and the ß/whole antithrombin ratio were significantly higher in patients during the acute event but normalized after one year. CONCLUSIONS: We have developed a rapid, simple, sensitive and specific method to quantify ß-antithrombin activity using 1µL of plasma. ß-antithrombin significantly increases in patients with ischemic cerebrovascular disease during the acute event, probably by its release from the vasculature.

Prothrombotic state and elevated levels of plasminogen activator inhibitor-1 in mitral stenosis with and without atrial fibrillation.

Patients with mitral stenosis in sinus rhythm are in a prothrombotic state and have fibrinolytic dysfunction, shown by an increase in levels of the inhibitor of tissue plasminogen activator, D-dimer, and modified antithrombin III. This state may be observed even in patients without dilated left atria (diameter < or =45 mm).

Tissue factor/tissue factor pathway inhibitor system and long-term prognosis after acute myocardial infarction.

UNLABELLED: The tissue factor and tissue factor pathway inhibitor (TFPI) system has been studied in the acute phase of coronary disease but its prognostic importance has been less well assessed. We evaluated its association with recurrent coronary events during long-term follow-up after a myocardial infarction. METHODS: We studied 55 consecutive patients with the following criteria for inclusion: (1) first myocardial infarct; (2) aged < 70 years; (3) non-complicated infarct; (4) low risk effort-test. Blood samples were taken 60-80 days after infarction. Tissue factor, total and free-TFPI were measured. A 4-year follow-up was carried out. Death, unstable angina and new myocardial infarction were considered as poor prognosis. RESULTS: There were no statistical differences in tissue factor/TFPI levels between patients and controls. Total-TFPI showed statistical correlation with total cholesterol (r = 0.59), triglycerides (r = 0.34), LDL-cholesterol (r = 40) and Lipoprotein(a) (r = 0.48). Patients with high levels of cholesterol, LDL-cholesterol and triglycerides showed elevated levels of total-TFPI with no differences in free-TFPI. During follow-up, 8 patients showed poor prognosis. There were no statistical associations between tissue factor/TFPI levels and prognosis. CONCLUSIONS: After acute myocardial infarction, we did not find any differences in the tissue factor/TFPI system between controls and patients. The tissue factor/TFPI system showed little value as a prognostic factor.

Does chronic kidney disease improve the predictive value of the CHADS2 and CHA2DS2-VASc stroke stratification risk scores for atrial fibrillation?

Chronic Kidney Disease (CKD) constitutes an adverse risk factor in chronic anticoagulated atrial fibrillation (AF) patients, being related to adverse cardiovascular events, mortality and major bleeds. It is unclear if CKD adds independent prognostic information to stroke risk stratification schemes, as the risk factor components of the CHADS2 and CHA2DS2-VASc scores are themselves related to renal dysfunction. The aim of our study was to determine if CKD independently improves the predictive value of the CHADS2 and CHA2DS2-VASc stroke stratification scores in AF. We recruited consecutive patients (n=978) patients (49% male; median age 76) with permanent or paroxysmal AF on oral anticoagulants with acenocoumarol, from our out-patient anticoagulation clinic. After a median follow-up of 875 (IQR 706-1059) days, we recorded stroke/transient ischaemic attack (TIA), peripheral embolism, vascular events (acute coronary syndrome, acute heart failure and cardiac death) and all-cause mortality. During follow-up, 113 patients (4.82%/year) experienced an adverse cardiovascular event, of which 39 (1.66%/year) were strokes, 43 (1.83%/year) had an acute coronary syndrome and 32 (1.37%/year) had acute heart failure. Also, 102 patients (4.35%/year) died during the following up, 31 of them (1.32%/year) as a result of a thrombotic event. Based on c-statistics and the integrated discrimination improvement (IDI), CKD did not improve the prediction for stroke/systemic embolism, thrombotic events and all-cause mortality using the CHADS2 and CHA2DS2-VASc scores. In conclusion, evaluating renal function in AF patients is important as CKD would confer a poor overall prognosis in terms of thromboembolic events and all-cause mortality. Adding CKD to the CHADS2 and CHA2DS2-VASc stroke risk scores did not independently add predictive information.

High sensitivity cardiac troponin T and interleukin-6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation.

UNLABELLED: There are limited data on the prognostic role of biomarkers in anticoagulated patients with atrial fibrillation (AF). We evaluated the prognostic value of high sensitivity TnT (hsTnT) and high-sensitivity interleukin-6 (hsIL6) in a large cohort of AF patients taking oral anticoagulant therapy (OAC) as both biomarkers have been associated with adverse cardiovascular events. METHODS: We studied 930 patients (51% male; median age 76) with permanent/ paroxysmal AF who were stabilized (for at least 6 months) on OAC (INRs 2.0-3.0). Plasma hsTnT and hsIL6 levels were quantified by electrochemiluminescense immunoassay at baseline. Patients were followed-up for up to 2 years, and adverse events (thrombotic and vascular events, mortality and major bleeding) were recorded. RESULTS: At follow-up, 96 patients (3.97%/year) died whilst 107 had an adverse cardiovascular event (3.14%/year). On multivariate analysis, high hsTnT and high hsIL6 remained significantly associated with prognosis even after adjusting for CHADS2 score: HR 2.21 (1.46-3.35, P<0.001) for high hsTnT and 1.97 (1.29-3.02, P=0.002) for high hsIL6, for adverse cardiovascular events. For all-cause mortality, the HRs were 1.79 (1.13-2.83, P=0.013) and 2.48 (1.60-3.85, P<0.001), respectively. The integrated discrimination index (IDI) values of clinical scores (CHADS2 and CHA2 DS2-VASc) were improved by the addition of hsTnT and/or hsIL6 (all P<0.05). CONCLUSION: In a large 'real world' cohort of anticoagulated AF patients, both hsTnT and hsIL6 levels provided prognostic information that was complementary to clinical risk scores for prediction of long-term cardiovascular events and death, suggesting that these biomarkers may potentially be used to refine clinical risk stratification in AF.