Underweight predicts poststroke cardiovascular events in patients without atrial fibrillation

Background and purposeThe purpose of this study was to determine whether underweight is associated with poststroke cardiovascular events and whether such association is different according to the presence of atrial fibrillation (AF).MethodsPatients with acute stroke or transient ischemic attack who were prospectively registered in a multicenter stroke database from April 2008 to July 2020 were analyzed, excluding those aged 75 or older and those who were overweight. We prospectively captured major adverse cardiovascular events (MACE) within one year after stroke. Cox-proportional hazard regression analysis was conducted for each subgroup with or without AF after adjusting for predetermined vascular risk factors and potential confounders.ResultsAmong 30,912 patients, 1494 (4.8%) cases were underweight and 29,418 (95.2%) cases were normal weight. The cumulative event rate of 1-year MACE was higher in the underweight group (9.0%) than in the normal weight group (5.6%). In Cox-proportional regression, underweight was associated with significantly higher MACE (adjusted hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.26–2.09) and recurrent stroke (adjusted HR: 1.42, 95% CI: 1.02–1.98) in all study patients. In patients with AF, the risk of MACE for the underweight group was not significantly increased. In contrast, in patients without AF, the underweight group had a consistently higher risk of MACE (adjusted HR: 1.66, 95% CI: 1.25–2.22) and recurrent stroke (adjusted HR: 1.50, 95% CI: 1.05–2.14).ConclusionsUnderweight increased the risk of MACE and recurrent stroke within one year after acute stroke, especially in stroke without AF.     

Pre-admission warfarin use in patients with acute ischemic stroke and atrial fibrillation: The appropriate use and barriers to oral anticoagulant therapy

INTRODUCTION: Warfarin reduces the risk of stroke in patients with atrial fibrillation. Despite strong guideline recommendations, studies continue to demonstrate the under-use of warfarin in clinical practice. PURPOSE: To determine the prevalence and predictors of warfarin use in patients presenting with atrial fibrillation and acute ischemic stroke who do not have a documented contraindication to anticoagulants. METHODS: We conducted a retrospective chart review of all patients admitted to the Hamilton General Hospital with a primary diagnosis of ischemic stroke and a coded diagnosis of atrial fibrillation between 1999 and 2004. Using a standardized data abstraction form, the following variables were recorded: baseline demographics, past medical history including risk factors for stroke and major bleeding and known predictors of warfarin under-use. In cases where warfarin was not prescribed, charts were also reviewed for documented contraindications to warfarin use. The following were considered valid contraindications to warfarin: patient refusal, non-compliance with INR monitoring, bleeding diathesis, history of major bleeding or significant alcohol consumption. RESULTS: In total, 196 patients with ischemic stroke and atrial fibrillation were identified. Of these patients, 106 were considered to be appropriate candidates for anticoagulation after excluding patients with no known diagnosis of atrial fibrillation prior to admission (N=59), a valid contraindication to warfarin use (N=18), a CHADS2 score <1 (N=6) or a competing diagnosis for warfarin use (N=7). Of the patients deemed to be suitable candidates for warfarin, 57 (54%) were receiving warfarin therapy on admission. On multivariable analyses, increasing age (OR 0.7; 95% CI 0.5-0.9) was associated with a reduced odds of warfarin use while a history of stroke or TIA (OR 2.6; 95% CI 1.1-6.5) and a history of congestive heart failure (OR 3.2; 95% CI 1.1-9.0) were associated with an increased odds of warfarin use in patients without a contraindication to warfarin. While 75% of patients <75 years old were anticoagulated, only 33% of those >85 years were prescribed warfarin on admission to hospital. CONCLUSIONS: early half of all patients presenting with atrial fibrillation and acute ischemic stroke who were suitable candidates for anticoagulation were not prescribed warfarin. In patients not prescribed warfarin, very few had a documented contraindication. Advanced age appears to be the strongest predictor of warfarin non-use.     

Circulating osteocalcin during oral anticoagulant therapy

In this paper we present the following observations: 1) In sheep vitamin K-antagonists like phenprocoumon induce a decrease of the serum levels of osteocalcin (bone Gla-protein) and of the affinity of the circulating osteocalcin for hydroxyapatite. 2) In sheep vitamin K counteracts the effect of phenprocoumon on the blood coagulation system, but not that on the osteocalcin production. 3) In human subjects vitamin K-antagonists also lead to decreased levels of serum osteocalcin and a low affinity of the protein for hydroxyapatite. 4) These two variables reached steady-state levels within 24 h after the start of oral anticoagulant treatment and--at continuation of the therapy--they remained low for at least several years.     

Asymptomatic cerebral infarction in patients with chronic atrial fibrillation

A retrospective analysis of 54 patients with atrial fibrillation presenting with symptoms of cerebral ischemia between 1980 and 1985 was performed. Seven patients (13%) had computed tomographic evidence of previous, clinically silent cerebral infarction. In a control group of 168 persons (studied prospectively) in sinus rhythm presenting with symptoms of cerebral ischemia, seven (4%) had computed tomographic evidence of previous, clinically silent cerebral infarction (p less than 0.05). In those patients with atrial fibrillation all infarcts were peripheral and consistent with embolism, while in three of the seven patients in sinus rhythm the asymptomatic infarcts were lacunes.     

Oral anticoagulant therapy in patients with nonrheumatic atrial fibrillation and risk of bleeding. A Multicenter Inception Cohort Study

Oral anticoagulants (OA) are the drug of choice for stroke prevention in patients with non-rheumatic atrial fibrillation (NRAF). This clear benefit/risk ratio comes from several randomized clinical trials (RCT) in which highly selected patients were strictly monitored. The aim of this study was to ascertain whether the safety of OA was also obtained outside the setting of clinical trials in consecutive patients starting treatment and routinely followed at Italian anticoagulation clinics. A total of 433 patients with NRAF were enrolled in the ISCOAT study and followed up for a mean of 1.4 years. Two patients (0.3% per year) suffered from a complete non-fatal ischemic stroke, 8 patients (1.3% per year) died of thrombosis-related vascular death, and 11 patients (11 events, 1.8% per year) suffered from major bleedings (2 fatal). Major bleeding occurred more frequently in patients >75 years of age (6 events, 5.1% per year) than in younger patients (5 events, 1.0% per year). The cumulative incidence of major bleeding in patients over 75 years of age (10.8%; 95% CI, 1.8-19.8) was significantly higher than in younger patients (2.8%; 95% CI, 0.3-5.3, p = 0.006). Major primary bleeding unrelated to organic lesions (7 patients, 1 male and 6 females) occurred in 5 elderly patients (>75 years old) with a cumulative incidence (9.6%; 95% CI 0.8-18.4) significantly higher than in younger patients (1.2%; 95% CI, 0-3.0, p = 0.0003). Univariate analysis revealed a higher frequency of major primary bleeding in females, in diabetic patients and in in those who had suffered a previous thromboembolic event. Multivariate analysis revealed that only age grater than 75 years was independently related to major primary bleedings (RR 6.6; 95% CI 1.2-37, p = 0.032). Minor bleedings (n = 27) were not more frequent in elderly patients (6% vs 4% per year, p = ns). Patients were kept at optimal intensity of treatment for 63% of the time. These data confirm the efficacy of OA but identify elderly patients as a high risk group of major bleeding.     

D-dimer: a characteristic of the coagulation state of each patient with chronic atrial fibrillation

BACKGROUND AND OBJECTIVE: It is accepted that patients with atrial fibrillation (AF) are characterised by increased levels of plasmatic D-dimers, with a wide inter-individual variability depending on the patients and therapeutic characteristics, but it has not been established if this level was predictive of the risk of arterial thromboembolic event. In order to answer such a question, it has to be established if the D-dimer level in a given patient is characteristic of such a patient (stable over time) if also fluctuating with time (and useless to characterise the patient). METHODS AND RESULTS: One hundred thirty clinically stable patients with chronic AF were recruited (anticoagulant: group 1, antiaggregant aspirin: group 2, no antithrombotic: group 3). During the follow-up of patients without clinical events (n=63), it is notable that in patients with D-dimer levels <500 ng/ml, these remained <1000 ng/ml, in patients with levels between 500 and 1000 ng/ml, these did not reach 1590 ng/ml, and in those with D-dimers >1000 ng/ml, the levels remained relatively stable. Mean age and D-dimer levels were lower in group 1 (74.4 years and 509.1 ng/ml, respectively) than in group 2 (82.4 years, p=0.0003 and 1015.7 ng/ml, p<0.0001, respectively) and in group 3 (79.3 years and 1289.3 ng/ml, p<0.0001, respectively). The effect of the antithrombotic therapy was independent of the age of patients (p=0.017). CONCLUSION: D-dimer levels in patients with chronic AF remain in the same range over time. They are lower on anticoagulant therapy than on antiaggregant or no antithrombotic therapy, irrespective of age. Thus, D-dimers appear to be a useful parameter for assessing the degree of hypercoagulability of patients whatever their age.     

IV t-PA therapy in acute stroke patients with atrial fibrillation

Background and purposeAtrial fibrillation (AF) is a predictor for severe stroke. Intravenous administration of tissue plasminogen activator (t-PA) can improve clinical outcomes in patients with acute ischemic stroke. We investigated clinical characteristics and patient outcome in patients with and without AF after t-PA therapy.MethodsConsecutive ischemic stroke patients treated with t-PA within 3 h of stroke onset were studied prospectively. MRI examinations, including diffusion weighted imaging and MRA, were performed before t-PA thrombolysis. NIHSS scores were obtained before and 7 days after t-PA infusion. The patients were divided into two groups (AF group and Non-AF group). Their clinical characteristics and outcome 7 days and 3 months after t-PA therapy were compared.Results85 patients (56 males, mean age, 73.4 ± 11.5 years) were enrolled in the present study. The AF-group had 44 patients, and the Non-AF group had 41 patients. Fewer patients with AF had dramatic improvement at 7 days and favorable outcome (mRS 0–1) at 3 months after t-PA therapy than patients without AF (31.8% vs. 61.0%, P = 0.007, and 15.9% vs. 46.3%, P = 0.002). On the other hand, worsening at 7 days and poor outcome (mRS > 3 and death) at 3 months after t-PA therapy were more frequently observed in AF group than Non-AF group (22.7% vs. 9.8%, P = 0.107, and 70.5% vs. 41.5%, P = 0.007). After adjusting age and gender, patients with AF more frequently had worsening and poor outcome than those without AF (adjusted OR; 4.54, 95% CI 1.04–19.75, P = 0.044, and adjusted OR; 2.8, 95% CI 1.10–7.28, P = 0.032).ConclusionThe present study found that acute ischemic stroke patients with AF more frequently had poor outcome after IV-t-PA therapy compared with those without AF.     

Clopidogrel and warfarin: absence of interaction in patients receiving long-term anticoagulant therapy for non-valvular atrial fibrillation

The effect of concomitantly administered clopidogrel on anti-coagulation status was investigated in patients receiving long-term warfarin therapy. Forty-three patients with non-valvular atrial fibrillation who were receiving long-term warfarin and had a stable international normalized ratio (INR) between 2 and 3 were randomly assigned to clopidogrel 75 mg daily or placebo for 8 days (Days 1-8). INR (primary endpoint) and plasma levels of warfarin enantiomers (secondary endpoint) were evaluated at Days 3, 6, 9, 13 and 22. Mean INR remained extremely stable in the clopidogrel group, the maximum percentage change from baseline being 0.6% at Day 6. Plasma levels of R- and S-warfarin also remained very stable in those receiving clopidogrel. No serious adverse events, premature discontinuations of study drug or bleeding occurred with clopidogrel. In conclusion, the stable anticoagulation status of patients receiving long-term warfarin therapy is unaffected by concomitant administration of clopidogrel 75 mg daily.     

Bleeding time is prolonged during oral anticoagulant therapy

We have performed the BT test in 55 patients undergoing oral anticoagulant therapy monitored by means of Thrombotest (TT). Patients in steady state of anticoagulation showed longer BT than normal controls; patients in overdose phase had longer BT values than either controls or patients in steady state. After recovery the overdose phase patients showed BT values not different from those of the controls. Moreover we were able to find in our patients a significant linear correlation between BT and TT. Impairment in primary haemostasis could be due either to a scarce fibrin deposition in the haemostatic plug or to deficiency of a possible vitamin K dependent vascular “bleeding factor”.     

心房颤动患者口服华法林相关脑出血危险因素分析

目的分析心房颤动(AF)患者口服华法林相关脑出血危险因素及预后情况,从而减低华法林相关脑出血(WAICH)的发生率与死亡率。方法本研究通过哈尔滨医科大学附属第一医院电子病历系统查找从2015年1月至2017年12月在神经内科、外科住院AF患者WAICH患者20例和AF口服华法林无颅内出血患者30例为调查对象。记录患者基本信息、既往史、危险因素、实验室检查、出院转归等方面进行整理。同样方法搜集无出血组资料。对上述资料进行SAS9.4软件统计学分析。结果经分析,出血组与无出血组在高血压病、缺血卒中史、出血史、治疗时间≤1年、血浆凝血酶原时间(PT)为30.36±22.53、活化部分凝血活酶时间(APTT)为43.88±17.75、国际标准化比值(INR)2.93±1.80、INR异变率、合并使用抗血小板药物、HAS-BLED评分为3.30±0.73有统计学差异(P <0.05),将上述单因素有意义的变量放入多因素Logistic模型中,采用逐步回归,结果表明PT,APTT,治疗时间长短是独立因素。结论高血压病、缺血卒中史、出血史、PT升高、APTT升高、INR增高、有INR异变率、治疗时间≤1年、合并应用抗血小板药物患者、HAS-BLED评分高是非瓣膜房颤(NVAF)患者口服华法林相关脑出血的危险因素;PT增高,APTT增高,治疗时间≤1年为NVAF口服华法林致WAICH的独立危险因素。     

Cystatin C and creatinine as markers of bleeding complications,cardiovascular events and mortality during oral anticoagulant treatment

Introduction

Impaired kidney function has been linked to both ischemic events as well as bleeding complications in several clinical conditions. Our aim was to investigate if cystatin C, creatinine and calculated glomerular filtration rate (eGFR) were related to future risk of bleeding complications, cardiovascular events or all-cause mortality during oral anticoagulant treatment.

Materials and methods

In a cohort study, 719 patients on long-term vitamin K antagonist (VKA) treatment were followed for a mean of 4.2 years. Blood sampling was taken at inclusion and patients were followed prospectively. Cystatin C and creatinine were analysed and eGFR was calculated. All medical records were reviewed. Major bleeding events, myocardial infarctions, strokes, arterial emboli, and deaths were recorded and classified.

Results

After adjustment for age, no association between cystatin C, creatinine or eGFR and major bleeding was found. Cystatin C was independently associated with cardiovascular events (hazard ratio 1.50 (95% CI: 1.27-1.77)) and all-cause mortality (hazard ratio 1.62 (95% CI: 1.38-1.90)).Creatinine was only associated with all-cause mortality, while eGFR was not associated with any of the outcomes.

Conclusions

Our findings underscore the superiority of cystatin C as a marker of cardiovascular risk compared to creatinine or eGFR. VKA-treated patients with increased cystatin C levels should be considered to be at an increased risk of cardiovascular events, and not bleeding complications.