Juan Antonio Vílchez

The HAS-BLED Score Has Better Prediction Accuracy for Major Bleeding Than CHADS2 or CHA2DS2-VASc Scores in Anticoagulated Patients With Atrial Fibrillation

OBJECTIVES The aim of this study was to test the hypothesis that a specific bleeding risk score, HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly), was better at predicting major bleeding compared with CHADS2 (congestive heart failure, hypertension, 75 years of age or older, diabetes mellitus, and previous stroke or transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, 65 to 74 years of age, female) in anticoagulated atrial fibrillation (AF) patients. BACKGROUND The CHADS2 and CHA2DS2-VASc scores are well-validated stroke risk prediction scores for AF, but are also associated with increased bleeding and mortality. METHODS We recruited 1,370 consecutive AF patients (49% male; median age, 76 years) receiving oral anticoagulation therapy from our outpatient anticoagulation clinic, all of whom were receiving acenocoumarol and had an international normalized ratio between 2.0 and 3.0 during the preceding 6 months. During follow-up, major bleeding events were identified by the 2005 International Society on Thrombosis and Haemostasis criteria. Model performance was evaluated by calculating the C-statistic, and the improvement in predictive accuracy was evaluated by calculating the net reclassification improvement and integrated discrimination improvement. RESULTS After a median follow-up of 996 (range, 802 to 1,254) days, 114 patients (3.0%/year) presented with a major bleeding event; 31 of these events were intracranial hemorrhages (0.8%/year). Based on the C-statistic, HAS-BLED had a model performance superior to that of both CHADS2 and CHA2DS2-VASc (both p < 0.001). Both net reclassification improvement and integrated discrimination improvement analyses also show that HAS-BLED was more accurately associated with major bleeding compared with CHADS2 and CHA2DS2-VASc scores. CONCLUSIONS In anticoagulated AF patients, a validated specific bleeding risk score, HAS-BLED, should be used for assessing major bleeding. The practice of using CHADS2 and CHA2DS2-VASc as a measure of high bleeding risk should be discouraged, given its inferior predictive performance compared with the HAS-BLED score.

Growth differentiation factor-15, a novel biomarker related with disease severity in patients with hypertrophic cardiomyopathy

BACKGROUND The growth differentiation factor 15 (GDF-15) has been shown up-regulated in stress conditions and to have regulatory actions in myocyte hypertrophy. We hypothesized that GDF-15 could be related to disease severity and functional status in patients with hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS We performed a study which includes 102 consecutive outpatient HCM subjects, 73% males, aged 47.1±14.6 years. A complete history and clinical examination was performed, including 12-lead electrocardiogram, echocardiography, symptom-limited treadmill exercise, 24-hour ECG-Holter monitoring, and magnetic resonance with Gadolinium. Several biomarkers, associated with myocardial remodeling and damage, were compared to GDF-15 levels. The assays were performed with commercial ELISAs or standardized methods when available. There was a significant association between GDF-15 levels and comorbidities, being higher in hypertension (p=0.001), diabetes (p=0.030), atrial fibrillation (p=0.012), dyspnea (p=0.020) and NYHA≥II functional class (p=0.037). GDF-15 levels were positively correlated with clinical variables (age, worse exercise capacity and mild renal dysfunction) and biomarkers of interstitial remodeling, such as metalloproteinase-2 (r: 0.40; p=0.009), N-terminal pro-B-type natriuretic peptide (r: 0.28; p=0.049), high-sensitivity troponin T (r: 0.30; p=0.003) and von Willebrand factor (r: 0.33; p=0.001). Multivariate analysis was assessed to estimate the involvement of these different factors in the GDF-15 levels, confirming the independent implication of severe dyspnea and functional status. CONCLUSIONS The present results show that higher levels of GDF-15 are associated to conditions of severe disease in HCM. Hence, GDF-15 is suggested as a novel marker related to the severity and could represent a further useful tool in monitoring functional capacity of HCM patients.

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.

Usefulness of N-Terminal Pro–B-Type Natriuretic Peptide Levels for Stroke Risk Prediction in Anticoagulated Patients With Atrial Fibrillation

Background and Purpose— Oral anticoagulation is highly effective in reducing stroke and mortality in atrial fibrillation (AF). Several risk stratification schemes have been developed using clinical characteristics. Elevated levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP) are important markers of increased mortality and morbidity in congestive heart failure and general community population. The aim of our study was to assess the predictive value of NT-proBNP levels in an unselected real-world cohort of anticoagulated patients with AF. Methods— We studied 1172 patients (49% male; median age, 76 years) with permanent AF who were well stabilized on oral anticoagulation (international normalized ratio, 2.0–3.0). Plasma NT-proBNP levels were quantified at baseline. We recorded thrombotic and vascular events, mortality, and major bleeding. The best cutoff points were assessed by receiver-operating characteristic curves. Results— Median levels (interquartile range) of NT-proBNP were 610 (318–1037) pg/mL. Median follow-up was 1007 (806–1279) days. On multivariate analysis, high NT-proBNP was significantly associated with the risk of stroke (hazards ratio, 2.71; P=0.001) and composite vascular events (acute coronary syndrome or acute heart failure; hazards ratio, 1.85; P=0.016), as well as a significant association with mortality (adjusted hazards ratio, 1.66; P=0.006). No association with bleeding was found (P=0.637). The integrated discrimination improvement (IDI) analysis demonstrated that NT-proBNP improved the Congestive heart failure, Hypertension, Age≥75 (doubled), Diabetes mellitus, Stroke (doubled)–Vascular disease and Sex category (female); CHA2DS2–VASc score for predicting embolic events (relative IDI, 2.8%; P=0.001) and all-cause death (relative IDI, 1.8%; P=0.001). Conclusions— In real-world cohort of anticoagulated patients with AF, NT-proBNP provided complementary prognostic information to an established clinical risk score (CHA2DS2–VASc) for the prediction of stroke/systemic embolism. NT-proBNP was also predictive of all-cause mortality, suggesting that this biomarker may potentially be used to refine clinical risk stratification in anticoagulated patients with AF.

High-sensitivity troponin T as a biomarker for the development of atrial fibrillation after cardiac surgery.

OBJECTIVES Atrial fibrillation (AF) occurs in ∼ 30% of patients undergoing coronary artery bypass grafting (CABG) and in 40% of patients after valve surgery. High-sensitivity cardiac troponin T (hsTnT) is a specific and high-sensitivity marker of myocardial injury, while N-terminal proB-type natriuretic peptide (NT-proBNP) is an established biomarker for wall remodelling. We investigated whether hsTnT and NT-proBNP levels could be used as valuable biomarkers for AF occurrence after cardiac surgery. METHODS We included consecutive haemodynamically stable patients undergoing programmed cardiac surgery with cardiopulmonary bypass pump. We determined hsTnT and NT-proBNP levels before and after cardiac surgery and recorded AF development by prolonged electrocardiogram monitoring. RESULTS We included 100 patients with predominantly aortic valve (n = 42) or ischaemic heart (n = 58) diseases. Twenty-nine patients (29%) developed post-surgical AF. Patients developing AF had a longer hospital stay (P = 0.005). hsTnT levels increased after surgery [P < 0.001], indicating perioperative myocardial injury, with higher presurgery levels in patients who developed AF [P = 0.015]. Body mass index and EuroSCORE risk scale were independently associated with higher hsTnT levels presurgery. On univariate analysis, age (P = 0.048), male sex (P = 0.031), indexed left atrial volume (P = 0.042), β-blockers treatment (P = 0.024), type of surgery (valve surgery vs CABG; P = 0.034), EuroSCORE risk scale (P = 0.025) and higher preoperative hsTnT levels (P = 0.009) were predictors of AF development, but NT-proBNP did not reach statistical significance (P = 0.060). hsTnT levels in blood samples obtained the day after surgery were not associated with post-surgical AF development (P = 0.165). In a multivariate model, only higher hsTnT levels before cardiac surgery (>11.87 ng/l) [Odds Ratio, OR; (95% Confidence interval, CI) 4.27 (1.43-12.77), P = 0.009] and male sex [OR 5.10 (1.72-15.13), P = 0.003)] were independently associated with the occurrence of post-surgical AF. CONCLUSION High presurgical hsTnT levels were independently predictive of patients developing AF after cardiac surgery. hsTnT levels determined post-surgery suggest that cardiac perioperative myocardial injury is not associated with postoperative AF development. NT-proBNP did not reach statistical significance as a biomarker for AF prediction.

The real role of prediagnostic high‐density lipoprotein cholesterol and the cancer risk: a concise review

In several observational and clinical studies, the association between serum cholesterol levels and cancer is still unsettled although serum total cholesterol has been associated with increased mortality from cancer. Moreover, the importance of abnormal levels of serum lipid components as the main features of dyslipidemia and the risk of individual cancers is unclear.

The prognostic role of the adiponectin levels in atrial fibrillation

Patients with atrial fibrillation (AF) have a high morbidity and mortality from vascular events, even despite oral anticoagulation (OAC). Rather than being a risk factor, AF has been proposed as a risk marker, being a signal of advanced atherosclerosis. Circulating adiponectin levels, a cytokine with anti‐inflammatory and cardioprotector roles, are related to different atherosclerotic risk factors. The aim is to evaluate whether plasma adiponectin can be predictive of cardiovascular risk in anticoagulated patients with AF.

Plasma levels of Von Willebrand factor are increased in patients with hypertrophic cardiomyopathy

UNLABELLED Hypertrophic cardiomyopathy (HCM) is characterised by inappropriate hypertrophy, small-vessel coronary artery disease, myocyte disarray and increased interstitial fibrosis. Microvascular dysfunction is a common finding in HCM and its extent has been proposed as an important prognostic marker. Plasma von Willebrand factor (vWf) is an established marker of endothelial damage or dysfunction; however it has scarcely been studied in HCM. We hypothesised that vWf could be raised in patients with HCM and be related to different variables associated with severity of HCM. METHODS We included 124 HCM patients, 93 males, aged 48+/-15 years, 59 healthy control subjects with similar age and sex and 20 patients with ischemic heart disease but clinical stability for the last 6 months. A complete history and clinical examination was performed, including 12-lead electrocardiogram, echocardiography, 24 hours ECG-Holter monitoring, and symptom limited treadmill exercise test. Risk factors for sudden death were evaluated. A blinded cardiac MRI was performed with late enhanced study with Gadolinium. Plasma vWf levels were assayed by commercial ELISA. RESULTS Patients showed higher levels of vWf (140.0+/-65.0 UI/ml vs 105.0+/-51.0 UI/ml, p<0.001) even after adjusting for ABO blood group. vWf levels were found raised in patients with severe functional class (168.4+/-65.9 UI/mL vs 132.4+/-60.7 UI/mL, p=0.020), atrial fibrillation (175.8+/-69.4 UI/mL vs 133.0+/-59.0 UI/mL, p=0.005), hypertension (161.4+/-60.8 vs 128.9+/-60.5, p=0.010) obstruction (153.9+/-67.9 vs 128.2+/-57.4 UI/mL, p=0.046) and non sustained ventricular tachycardia (159.3+/-59.1 vs 133.0+/-63.0, p=0.049). vWf correlated with age (r:0.26; p=0.006) and obstruction (r:0.22; p=0.021). CONCLUSIONS We show, for the first time, patients with HCM present significantly raised levels of vWf. These are associated with different conditions related to the severity of the disease.

Comparative determination and monitoring of biomarkers of necrosis and myocardial remodeling between radiofrequency ablation and cryoablation.

Biomarkers of necrosis and inflammation have been found raised after radiofrequency ablation (RF). There is scarce information on biomarkers’ behavior after cryoablation. Our aim was to study biomarkers of necrosis, inflammation, and interstitial remodeling after two different approaches: RF versus cryoablation.

β-Trace Protein and Prognosis in Patients With Atrial Fibrillation Receiving Anticoagulation Treatment

BACKGROUND Atrial fibrillation (AF) is associated with a high risk of mortality and morbidity and it commonly coexists with chronic kidney disease. A biomarker of renal function, β-trace protein (BTP), has been implicated in the progression of cardiovascular disease. The aim of our study was to evaluate the association of BTP with adverse cardiovascular events, bleeding, and mortality in patients with AF. METHODS In a consecutive cohort of patients with nonvalvular AF receiving anticoagulation treatment, plasma BTP was determined using an automated nephelometer BN ProSpec System (Siemens) and related to estimated glomerular filtration rate (eGFR). We recorded adverse cardiovascular events (stroke, acute coronary syndrome, and acute pulmonary edema), major bleeding, and mortality. RESULTS We included 1,279 patients (48.6% men), aged 76 years (IQR, 71-81 years), who were followed up for 996 days (IQR, 802-1,254 days). During the follow-up, there were 150 cardiovascular events (annual rate, 3.99%), 57 embolisms (annual rate, 1.54%), and 114 major bleeding events (annual rate, 3.04%), and 161 patients died (annual rate, 4.32%). BTP levels were inversely associated with eGFR (P < .001). High BTP concentrations were significantly associated with embolic events (hazard ratio [HR], 4.64 [1.98-10.86]; P < .001), composite adverse cardiovascular events (HR, 1.93 [1.31-2.85]; P = .001), and mortality (HR, 2.08 [1.49-2.90]; P < .001), even after adjusting for CHAD2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes mellitus, stroke [doubled], vascular disease, age 65 to 74 years, sex category) score and renal function. High BTP was associated with major bleeding events (HR, 1.88 [1.18-3.00]; P = .008), even after adjusting for the HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or redisposition, labile international normalized ratio, elderly [> 65 years], drugs/alcohol concomitantly) score. CONCLUSIONS We suggest that BTP, a proposed renal damage biomarker, may be a novel predictor of adverse cardiovascular events, major bleeding, and mortality in patients with AF. BTP may help refine clinical risk stratification in these patients.