Dynamic changes of cardiovascular biomarkers after ablation for atrial fibrillation: observations from AXAFA-AFNET5

Abstract Background The dynamic changes and stability of blood biomarkers over time and after treatment are not well known. In this study, we describe changes in 12 centrally quantified known and novel cardiovascular biomarkers, prior to and 3 months after ablation for atrial fibrillation (AF). Purpose In patients enrolled in the AXAFA-AFNET5 trial, we 1) characterised changes in 12 biomarker levels pre and post-ablation, 2) ascertained if biomarker changes are consistent between males and females, and 3) identified biomarkers which predict recurrent AF post-ablation. Methods and results Of the 674 patients who were recruited and randomised, 633 received the study drug and underwent ablation. Peripheral blood samples were available for 488 patients at baseline and 434 at 3 months follow-up (median age [Q1, Q3] 64 [58, 70] years; 34% female). Between baseline (BL) and follow-up (FU), paired comparisons revealed that 3 biomarkers decreased, ANG2 (median [Q1, Q3] BL 2.185 [1.711, 3.115], FU 1.827 [1.457, 2.297] ng/mL, p<0.001), BMP10 (BL 2.056 [1.810, 2.380], FU 1.986 [1.757, 2.260] ng/mL, p<0.001), and NTproBNP (BL 2.219 [0.858, 5.731] per 100pg/mL, p<0.001), while 1 biomarker increased, FABP3 (BL 2.911 [2.425, 3.508], FU 2.911 [2.462, 3.521], p=0.005). The remaining 8 biomarkers remained unchanged. Significant differences in ANG2, BMP10, NTproBNP and FABP3 were driven by patients who remained arrhythmia free at follow-up whereas biomarker levels remained unchanged in 121 patients who experienced recurrent AF (39%; Figure). Change scores were mainly consistent between males and females, however, CRP decreased significantly more in females. Recurrent AF episodes were not different between males and females (p=0.319). Cox proportional hazards model assessed the relationship of individual biomarkers at baseline for predicting recurrent AF. Elevated ANG2 (hazard ratio, HR per ng/mL [95% confidence interval] 1.214 [1.113, 1.325]), BMP10 (HR per ng/mL 1.516 [1.039, 2.214]), and NTproBNP (HR per 100 pg/mL 1.050 [1.025, 1.076]) significantly predicted increased risk for recurrent AF, after adjustment for age, sex, body mass index, hypertension, diabetes, chronic obstructive pulmonary disease, stroke, heart failure, ablation type (PVI, PVI and other, other), ablation energy (radiofrequency, cryoablation, other), and treatment arm. Conclusion In this study, most cardiovascular biomarkers are unchanged after ablation for AF, however, ANG2, BMP10, and NTproBNP decreased at follow-up. These effects are driven by patients who remained arrhythmia free and could potentially reflect improvement in vascular (ANG2), endothelial (BMP10), and myocardial load (NTproBNP) parameters post-ablation. This outcome corresponds with the observation that elevated levels of these biomarkers at baseline predict recurrent AF at 3 months. Both males and females demonstrate similar changes in biomarker profiles and benefit equally from ablation for AF. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DZHK (German Centre for Cardiovascular Research) and BMBF (German Ministry of Education and Research) to AFNET.Additional support from European Union [grant agreement No. 633196 (CATCH ME)]. Biomarker changes

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Incidence and Predictors of Hospitalization in Patients with Atrial Fibrillation: Results from the Chinese Atrial Fibrillation Registry Study

10.21203/rs.3.rs-123416/v1 ◽

2020 ◽

Author(s):

Zhaojie Dong ◽

Xin Du ◽

Shangxin Lu ◽

Chao Jiang ◽

Shijun Xia ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cardiovascular Diseases ◽

Proportional Hazards Model ◽

Cox Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Chronic Obstructive ◽

Unique Identifier ◽

Clinical Trial Registration

Abstract Background: Patients with atrial fibrillation (AF) underwent a high risk of hospitalization, which, however, has not been paid much attention in clinic. Therefore, we aimed to assess the incidence, causes and predictors of hospitalization in AF patients.Methods: From August 2011 to December 2017, 20,172 AF patients from the Chinese Atrial Fibrillation Registry (China-AF) Study were enrolled in this study. We described the incidence, causes of hospitalization according to age and gender categories. The Cox proportional hazards model was employed to identify predictors of first all-cause and first cause-specific hospitalization. Results: After a mean follow-up of 37.3 ± 20.4 months, 7,512 (37.2%) AF patients experienced one or more hospitalizations. The overall incidence of all-cause hospitalization was 24.0 per 100 patient-years. Patients aged < 65 years were predominantly hospitalized for AF (42.1% of the total frequency of hospitalizations); while patients aged 65-74 and ≥ 75 years were mainly hospitalized for non-cardiovascular diseases (43.6% and 49.3%, respectively). Multivariate Cox model analysis verified the higher risk of hospitalization in patients complicated with heart failure (HF)[hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.08-1.24], established coronary artery disease (CAD) (HR 1.26, 95%CI 1.19-1.34), ischemic stroke/transient ischemic attack (TIA) (HR 1.26, 95%CI 1.18-1.33), diabetes (HR 1.16, 95%CI 1.10-1.22), chronic obstructive pulmonary disease (COPD) (HR 1.41, 95%CI 1.13-1.76), gastrointestinal disorder (HR 1.39, 95%CI 1.23-1.58), and renal dysfunction (HR 1.31, 95%CI 1.16-1.48). Conclusions: More than one-third of AF patients included in this study were hospitalized at least once during almost 3 years of follow-up. The main cause for hospitalization among elderly patients (≥65 years) is non-cardiovascular diseases rather than AF. Multidisciplinary management of comorbidities should be advocated as strategies to reduce hospitalization in AF patients.Clinical Trial Registration: URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.

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Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa324 ◽

2020 ◽

Author(s):

Yuko Yamaguchi ◽

Marta Zampino ◽

Toshiko Tanaka ◽

Stefania Bandinelli ◽

Yusuke Osawa ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Differentiation Factor ◽

Hazards Model ◽

Increased Risk ◽

The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

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Abstract WP79: Choice Of Treatment And Effect On Hemorrhage Rates Of Unruptured Intracranial Aneurysms

Stroke ◽

10.1161/str.44.suppl_1.awp79 ◽

2013 ◽

Vol 44 (suppl_1) ◽

Author(s):

James Torner ◽

Jie Zhang ◽

David Piepgras ◽

John Huston ◽

Irene Meissner ◽

...

Keyword(s):

Intracranial Aneurysms ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Interventional Procedure ◽

Careful Consideration ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Unruptured Intracranial Aneurysms ◽

Increased Risk

INTRODUCTION: The decision regarding whether to perform an interventional procedure as a strategy to prevent hemorrhage of an unruptured intracranial aneurysm (UIA) requires careful consideration of procedural risk and the UIA natural history. No randomized trial data are available. The International Study of Unruptured Intracranial Aneurysms (ISUIA) included a prospective cohort, examining hemorrhage risk and treatment risk. Hypothesis: The purpose of this analysis was to compare the factors related to treatment selection and determination of the number of hemorrhages prevented. Methods: Patients were allocated into the initial treatment and untreated cohorts based upon observation or treatment practices in 61 centers from 1991-1998. 1691 patients were in the observational cohort, 471 were in the endovascular cohort and 1917 patients were in the surgical cohort. The cohorts were followed for a median follow-up of 9.2 years. Outcomes were determined prospectively and with central review. The data were grouped together and analyzed to determine treatment decisions. A Cox proportional hazards model predicting hemorrhage developed in the observation cohort and was applied to the surgery and endovascular cohorts across the follow-up period. Results: Significant baseline variable differences between treated and observed patients were aneurysm size, symptoms, age, prior SAH group, geographical region, treatment percentage, aneurysm daughter sacs or multiple lobes, and history of hypertension, smoking and myocardial infarction. Aneurysm site and family history were not significant. Site, size, and aspirin use were significant predictors of hemorrhage. Long-term the predicted hemorrhage rates were 6.7% at 5 years and 8.0% at 10 years in the surgery group and 8.1% and 9.6% for the endovascular group, respectively. For comparison the rates in the observed cohort were 4.1% and 4.8%, respectively. Conclusions: Decisions for treatment are influenced by patient characteristics such as age and medical history, aneurysm characteristics such as size and morphology and center and regional practices. Patients in the treated cohorts were at moderately increased risk for hemorrhage compared to those in the observed cohort.

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Cross-sectional and longitudinal characterisation of cognitive function and outcomes in patients presenting to hospital with cardiovascular risk factors

European Heart Journal ◽

10.1093/eurheartj/ehab724.0481 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

W Chua ◽

P Brady ◽

F Nehaj ◽

Y Purmah ◽

A Khashaba ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Cognitive Function ◽

Cognitive Dysfunction ◽

Clinical Decision Making ◽

Proportional Hazards Model ◽

Cox Proportional Hazards Model ◽

Co Morbidity ◽

Artery Disease

Abstract Background/Introduction Cardiovascular (CV) diseases including atrial fibrillation and arteriosclerosis are associated with impaired cognitive function. Cognitive dysfunction can impact the process of shared clinical decision making, reduce adherence to polypharmacy, and decrease quality of life. The prevalence of cognitive dysfunction in contemporary patients with CV diseases and its implication on future CV events is not well known. Purpose We 1) quantified cognitive function in patients presenting to hospital with CV diseases, 2) identified clinical variables and blood biomarkers associated with cognitive dysfunction, and 3) quantified the hazard of abnormal cognitive function for predicting MACCE (major adverse CV and cerebrovascular events). Methods and results Of 1625 consecutive patients presenting acutely to a large teaching hospital with CV diseases, 614 patients (median age [Q1, Q3] 68 [58, 76] years; 66% male) who completed the Montreal Cognitive Assessment (MoCA) were analysed. The median [Q1, Q3] MoCA score was 25 points [21, 27]. 360 patients (59%) had an abnormal score (<26). At baseline, patients with abnormal scores were more likely to be female (odds ratio, OR [95% confidence intervals], 1.874 [1.287, 2.728]), have BMI<30 (OR 0.584 [0.410, 0.831]), heart failure (OR 1.492 [1.043, 2.135]), diabetes (OR 2.212 [1.529, 3.199]), chronic kidney disease (CKD-EPI<60 ml/min, OR 1.553 [1.021, 2.361]), and have more CV co-morbidities (OR per additional co-morbidity 1.415 [1.246, 1.605]). Amongst 12 CV biomarkers tested, elevated Bone Morphogenetic Protein 10 (OR 1.325 [1.022, 1.719]) and Growth Differentiation Factor 15 (OR 1.419 [1.054, 1.912]) increased odds of abnormal scores. Cox proportional hazards model adjusted for competing risk of non-CV death assessed the relationship between abnormal cognitive function and MACCE (stroke, TIA, myocardial infarction, hospitalisation for heart failure, CV death). Follow-up time ranged from 2.7 to 6.1 years. Patients were censored at 2.5 years for this analysis. 130 out of 614 patients experienced a MACCE (21%) and 71 had a non-CV death (12%). Patients with abnormal MoCA scores were at higher risk for MACCE (subhazard ratio, sHR [95% CI] 1.827 [1.253, 2.664]). The hazard remained significant after adjustment for age, sex, obesity, atrial fibrillation, stroke, heart failure, hypertension, coronary artery disease, diabetes, peripheral artery disease and renal dysfunction (sHR 1.367 [1.056, 2.326]; Figure). All-cause mortality was 1.785 times higher for those with abnormal MoCA scores [1.061, 3.002]. Conclusion In this study, 3 out of 5 patients with CV diseases had abnormal MoCA scores at baseline. Abnormal cognitive scores significantly predicted patients who went on to experience a MACCE within 2.5 years of follow-up. These observations call for further research and action to provide additional diagnostics, support and early intervention to address cognitive dysfunction in CV patients. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU H2020 CATCH ME Cumulative incidence function

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Survival of Captive Chimpanzees: Impact of Location and Transfers

10.1101/068858 ◽

2016 ◽

Author(s):

Michael S. Lauer

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Premature Mortality ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Increased Risk ◽

Random Survival Forests ◽

Survival Forests

AbstractTo inform the retirement of NIH-owned chimpanzees, we analyzed the outcomes of 764 NIH-owned chimpanzees that were located at various points in time in at least one of 4 specific locations. All chimpanzees considered were alive and at least 10 years of age on January 1, 2005; transfers to a federal sanctuary began a few months later. During a median follow-up of just over 7 years, there were 314 deaths. In a Cox proportional hazards model that accounted for age, sex, and location (which was treated as a time-dependent covariate), age and sex were strong predictors of mortality, but location was only marginally predictive. Among 273 chimpanzees who were transferred to the federal sanctuary, we found no material increased risk in mortality in the first 30 days after arrival. During a median follow-up at the sanctuary of 3.5 years, age was strongly predictive of mortality, but other variables – sex, season of arrival, and ambient temperature on the day of arrival – were not predictive. We confirmed our regression findings using random survival forests. In summary, in a large cohort of captive chimpanzees, we find no evidence of materially important associations of location of residence or recent transfer with premature mortality.

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P6355The behavior of atrial fibrillation in patients with heart failure hospitalization

European Heart Journal ◽

10.1093/eurheartj/ehz746.0951 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M Fukunaga ◽

K Hirose ◽

A Isotani ◽

T Morinaga ◽

K Ando

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Cardiovascular Disease ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Significant Difference ◽

The Impact

Abstract Background Relationship between atrial fibrillation (AF) and heart failure (HF) is often compared with proverbial question of which came first, the chicken or the egg. Some patients showing AF at the HF admission result in restoration of sinus rhythm (SR) at discharge. It is not well elucidated that the restoration into SR during hospitalization can render the preventive effect for rehospitalization. Purpose To investigate the impact of restoration into SR during hospitalization for readmission rate of the HF patients showing AF. Methods We enrolled consecutive 640 HF patients hospitalized from January 2015 to December 2015. Patients data were retrospectively investigated from medical record. Patients showing atrial fibrillation on admission but unrecognized ever were defined as “incident AF”; patients with AF diagnosed before admission were defined as “prevalent AF”. Primary endpoint was a composite of death from cardiovascular disease or hospitalization for worsening heart failure. Secondary endpoints were death from cardiovascular disease, unplanned hospitalization related to heart failure, and any hospitalization. Results During mean follow up of 19 months, 139 patients (22%) were categorized as incident AF and 145 patients (23%) were categorized as prevalent AF. Among 239 patients showing AF on admission, 44 patients were discharged in SR (39 patients in incident AF and 5 patients in prevalent AF). Among incident AF patients, the primary composite end point occurred in significantly fewer in those who discharged in SR (19% vs. 42% at 1-year; 23% vs. 53% at 2-year follow-up, p=0.005). To compare the risk factors related to readmission due to HF with the cox proportional-hazards model, AF only during hospitalization [Hazard Ratio (HR)=0.37, p<0.01] and prevalent AF (HR=1.67, p=0.04) was significantly associated. There was no significant difference depending on LVEF. Conclusion Newly diagnosed AF with restoration to SR during hospitalization was a good marker to forecast future prognosis.

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Hemorrhage From Arteriovenous Malformations During Pregnancy

Neurosurgery ◽

10.1227/neu.0b013e318256c34b ◽

2012 ◽

Vol 71 (2) ◽

pp. 349-356 ◽

Cited By ~ 59

Author(s):

Bradley A. Gross ◽

Rose Du

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Venous Drainage ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Cox Proportional Hazards Model ◽

Relative Paucity ◽

Increased Risk ◽

Risk Of Hemorrhage

Abstract BACKGROUND: Previous hemorrhage, deep venous drainage, and deep location are established risk factors for arteriovenous malformation (AVM) hemorrhage. Although pregnancy is an assumed risk factor, there is a relative paucity of data to support this neurosurgical tenet. OBJECTIVE: To elucidate the hemorrhage rate of AVMs during pregnancy. METHODS: We reviewed the records of 54 women with an angiographic diagnosis of an AVM at our institution. Annual hemorrhage rates were calculated as the ratio of the number of bleeds to total number of patient-years of follow-up. Patient-years of follow-up were tallied assuming lesion presence from birth until AVM obliteration. The Cox proportional hazards model for hemorrhage with pregnancy as the time-dependent variable was used to calculate the hazard ratio. RESULTS: Five hemorrhages in 4 patients occurred over 62 pregnancies, yielding a hemorrhage rate of 8.1% per pregnancy or 10.8% per year. Over the remaining 2461.3 patient-years of follow-up, only 28 hemorrhages occurred, yielding an annual hemorrhage rate of 1.1%. The hazard ratio for hemorrhage during pregnancy was 7.91 (P = 2.23 × 10−4), increasing to 18.12 (P = 7.31 × 10−5) when limiting the analysis to patient follow-up up to age 40. CONCLUSION: Because of the increased risk of hemorrhage from AVMs during pregnancy, we recommend intervention in women who desire to bear children, particularly if the AVM has bled. If the AVM is discovered during pregnancy, we recommend early intervention if it has ruptured; if it is unruptured, we recommend comprehensive counseling, weighing risks of intervention against continuation of pregnancy without intervention.

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P3781Prognostic impact of body mass index on mortality and its causes in patients with atrial fibrillation: the Fushimi AF Registry

European Heart Journal ◽

10.1093/eurheartj/ehz745.0630 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

Y An ◽

M Iguchi ◽

M Ishii ◽

N Masunaga ◽

Y Aono ◽

...

Keyword(s):

Atrial Fibrillation ◽

Body Mass Index ◽

Body Mass ◽

Obesity Paradox ◽

Chronic Obstructive ◽

Inverse Association ◽

Community Based ◽

Increased Risk ◽

All Cause Mortality

Abstract Background Obesity has been shown to be related to an increased risk for incidence and progression of atrial fibrillation (AF). Meanwhile, the inverse association between body mass index (BMI) and mortality, so-called “obesity paradox”, is well-known among patients with AF, as well as other cardiovascular diseases. However, data regarding the relationship between BMI and specific causes of death in AF patients remain scarce. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. The inclusion criterion for the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time. We started to enroll patients from March 2011, and baseline characteristics including BMI and follow-up data were available for 3,805 patients by the end of November 2018. Patients were categorized into 3 groups depending on the BMI value; underweight (<18.5 kg/m2; 419 patients), normal (18.5 to <25.0 kg/m2; 2,283 patients), overweight (≤25.0 kg/m2; 1,103 patients). Results In the entire population, the mean BMI level was 23.1±4.0 kg/m2. The lower BMI was associated with higher age (78.5±10.3, 74.0±10.3, and 71.3±10.9 years in Underweight, Normal, and Overweight, respectively; p<0.001) and with higher prevalence of various comorbidities and CHA2DS2-VASc scores (3.83±1.67, 3.43±1.70, and 3.29±1.64, p<0.001). Oral anticoagulants were less frequently prescribed in those with lower BMI (46%, 56%, and 58%, p<0.001). During a median follow-up of 1,464 days (interquartile range: 727–2,228 days), all-cause mortality was lower in accordance with higher BMI (14.3, 5.3, and 3.5 per 100 person-years, respectively; p<0.001). The proportion of infection as a cause of death was prominently higher in the Underweight group than the others (25.7%, 16.7%, and 13.4%, p<0.001) (Figure A). Furthermore, the mortality due to infection was consistently higher in Underweight than in the others in any of the age subgroups (Figure B). Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the BMI value for mortality, adjusted by age, sex, chronic kidney disease, anemia, chronic obstructive pulmonary disease, history of major bleeding, and other components of CHA2DS2-VASc score. Higher BMI was related to lower all-cause mortality (per 5 kg/m2 increase: HR 0.71 [95% CIs 0.63–0.78], p<0.001), and also lower mortality due to infection (per 5 kg/m2 increase: HR 0.48 [95% CIs 0.37–0.61], p<0.001). Figure 1 Conclusions In a Japanese community-based AF cohort, obesity paradox was also observed on all-cause mortality. In particular, lower BMI was strongly associated with the mortality due to infection regardless of age. Acknowledgement/Funding Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi-Sankyo, Novartis Pharma, MSD, Sanofi-Avent

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P5708Balancing risk and benefit in patients with atrial fibrillation: the GARFIELD-AF risk score

European Heart Journal ◽

10.1093/eurheartj/ehz746.0649 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

K Fox ◽

S Virdone ◽

K Pieper

Keyword(s):

Atrial Fibrillation ◽

Adverse Events ◽

Major Bleeding ◽

Proportional Hazards Model ◽

Haemorrhagic Stroke ◽

Cox Proportional Hazards Model ◽

Large Set ◽

Risk Of Death ◽

Major Bleed

Abstract Background The GARFIELD-AF risk tool was originally developed to predict future risk of adverse events in patients with atrial fibrillation (AF) using a range of baseline clinical variables. In the present work a new, improved risk tool was developed using data from all five GARFIELD cohorts gathered over 2 years' follow-up. Purpose To derive a new integrated risk tool for predicting mortality, stroke/systemic embolism (SE), and major bleeding in AF patients up to 2 years after enrolment and compare the risk tool versus CHA2DS2-VASc and HAS-BLED. Methods GARFIELD-AF is an international prospective registry of nonvalvular AF patients diagnosed within 6 weeks prior to enrolment and having at least one risk factor for stroke. In this study only the first occurrence of events was considered. Event rates were estimated using a Poisson model. Potential predictors of events including a large set of demographics, clinical characteristics, choice of treatment, and lifestyle factors were identified, and a Cox proportional hazards model chosen for each outcome by least absolute shrinkage and selection operator (LASSO). Indices were compared versus models of CHA2DS2-VASc and HAS-BLED. Results Among a total 52,080 patients enrolled 52,032 (male, 55.8%; median age, 71 years) had available follow-up data. At 2 years, 3702 patients had died (event rate, 3.82 [95% CI, 3.70–3.95] per 100 patient-years) whereas non-haemorrhagic stroke/SE was noted in 957 patients (rate, 1.00 [95% CI, 0.94–1.06] per 100 patient-years) and major bleed/haemorrhagic stroke in 673 patients (rate, 0.70 [95% CI, 0.65–0.75] per 100 patient-years). The GARFIELD risk tool outperformed CHA2DS2-VASc and HAS-BLED at predicting all adverse events in the overall population and pre-selected subpopulations over 2 years. Notably, the new model identified use of OAC therapy, which is not included in CHA2DS2-VASc, as one of the strongest predictors of risk of mortality and stroke, and unlike HAS-BLED, could discriminate a lower risk of bleeding in patients treated with NOACs versus VKAs. Population All-cause mortality Stroke/SE Major bleeding* GARFIELD CHA2DS2-VASc GARFIELD CHA2DS2-VASc GARFIELD CHA2DS2-VASc Overall 0.76 (0.75–0.76) 0.66 (0.65–0.67) 0.68 (0.67–0.70) 0.64 (0.62–0.66) – – AC treated 0.74 (0.73–0.75) 0.65 (0.64–0.66) 0.68 (0.66–0.70) 0.65 (0.62–0.67) 0.67 (0.64–0.69) 0.63 (0.61–0.65) *Model only considers AC-treated patients. Conclusions The GARFIELD-AF risk tool demonstrated good calibration and discrimination, outperforming CHA2DS2-VASc at predicting risk of death and non-haemorrhagic stroke and HAS-BLED for major bleed in AF patients over 2 years. Acknowledgement/Funding The GARFIELD-AF registry is funded by an unrestricted research grant from Bayer AG.

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Blood pressure levels and risk of haemorrhagic stroke in patients with atrial fibrillation and anticoagulants: results from a primary care cohort with hypertension

European Heart Journal ◽

10.1093/ehjci/ehaa946.2725 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J.-E Bager ◽

L Schioler ◽

K Manhem ◽

P Hjerpe ◽

H Odesjo ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Primary Care ◽

Proportional Hazards Model ◽

Haemorrhagic Stroke ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Funding Source ◽

Spline Curve ◽

Increased Risk

Abstract Background Haemorrhagic stroke (HS) is a serious condition that kills and debilitates many of those afflicted by it. Hypertension and oral anticoagulation (OAC) are independent risk factors for HS. Many patients with atrial fibrillation (AF) have hypertension and OAC. The concomitance of hypertension and OAC confers an even higher risk of haemorrhagic stroke, but less is known about the association between specific blood pressure levels and the risk of HS in patients with AF and OAC. Purpose To assess the risk of haemorrhagic stroke at different systolic blood pressure (SBP) levels in a primary care population with hypertension, AF and OAC. Methods We identified 3972 patients with hypertension, AF and OAC in a primary care database in southern Sweden. We followed patients from Jan 1, 2006 until a first event of HS, death, cessation of OAC or Dec 31, 2016. HS was defined as ICD-10 diagnosis codes: I60, I61, and I62. We analysed the association between SBP levels and HS by dividing SBP into five categories: <130, 130–139, 140–159, 160–179 and ≥180 mmHg. We also fitted a spline curve to visualise the relationship between SBP and HS. Hazard ratios (HR) were calculated for the SBP categories with a Cox proportional hazards model. The 130–139 group was used as a reference in the model. We identified age, sex, previous stroke, platelet inhibitor treatment, alcohol abuse and smoking as possible confounders with a directed acyclic graph and included them as co-variates in the model. Results We identified 51 cases of HS during follow-up. In the categorical analysis of SBP, point estimates of HRs for HS increased gradually from the lowest SBP category to the 160–179 category. Only the 160–179 category had a significantly different HR (3.76, CI 1.56–9.04) than the reference 130–139 category, however. See Table 1. No other co-variates were significantly associated with HS. The spline curve, Figure 1, illustrates a significantly increased HR for HS in the 140–175 SBP range. Conclusions In this real-world primary care cohort with hypertension, AF and OAC, we found that SBP in the 160–179 mmHg range was significantly associated with an increased risk of haemorrhagic stroke. Our findings emphasise the importance of blood pressure control in this patient category. Figure 1. Continuous and categorical SBP & HS risk Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): The study was financed by grants from the Swedish state under the agreement between the Swedish government and the country councils, the ALF-agreement.

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