Vascular Disease and Risk Stratification for Ischemic Stroke and All-Cause Death in Heart Failure Patients without Diagnosed Atrial Fibrillation: A Nationwide Cohort Study

Background

Stroke and mortality risk among heart failure patients previously diagnosed with different manifestations of vascular disease is poorly described. We conducted an observational study to evaluate the stroke and mortality risk among heart failure patients without diagnosed atrial fibrillation and with peripheral artery disease (PAD) or prior myocardial infarction (MI).

Methods

Population-based cohort study of patients diagnosed with incident heart failure during 2000–2012 and without atrial fibrillation, identified by record linkage between nationwide registries in Denmark. Hazard rate ratios of ischemic stroke and all-cause death after 1 year of follow-up were used to compare patients with either: a PAD diagnosis; a prior MI diagnosis; or no vascular disease.

Results

39,357 heart failure patients were included. When compared to heart failure patients with no vascular disease, PAD was associated with a higher 1-year rate of ischemic stroke (adjusted hazard rate ratio [HR]: 1.34, 95% confidence interval [CI]: 1.08–1.65) and all-cause death (adjusted HR: 1.47, 95% CI: 1.35–1.59), whereas prior MI was not (adjusted HR: 1.00, 95% CI: 0.86–1.15 and 0.94, 95% CI: 0.89–1.00, for ischemic stroke and all-cause death, respectively). When comparing patients with PAD to patients with prior MI, PAD was associated with a higher rate of both outcomes.

Conclusions

Among incident heart failure patients without diagnosed atrial fibrillation, a previous diagnosis of PAD was associated with a significantly higher rate of the ischemic stroke and all-cause death compared to patients with no vascular disease or prior MI. Prevention strategies may be particularly relevant among HF patients with PAD.     

Cardioversion and Risk of Adverse Events with Dabigatran versus Warfarin—A Nationwide Cohort Study

Aim

Cardioversion can rapidly and effectively restore sinus rhythm in patients with persistent atrial fibrillation. Since 2011 dabigatran has been available as an alternative to warfarin to prevent thromboembolic events in patients with non-valvular atrial fibrillation undergoing cardioversion. We studied time to cardioversion, risk of adverse events, and risk of readmission with atrial fibrillation after cardioversion according to anticoagulation therapy.

Methods and Results

Through the nationwide Danish registries we included 1,230 oral anticoagulation naïve patients with first time non-valvular atrial fibrillation and first time cardioversion from 2011 to 2012; 37% in the dabigatran group (n = 456), and 63% in the warfarin group (n = 774). Median time to cardioversion was 4.0 (interquartile range [IQR] 2.9 to 6.5) and 6.9 (IQR 3.9 to 12.1) weeks in the dabigatran and warfarin groups respectively, and the adjusted odds ratio of cardioversion within the first 4 weeks was 2.3 (95% confidence interval [CI] 1.7 to 3.1) in favor of dabigatran. The cumulative incidence of composite endpoint of stroke, bleeding or death were 2.0% and 1.0% at 30 weeks in the warfarin and dabigatran groups respectively, with an adjusted hazard ratio of 1.33 (95% CI 0.33 to 5.42). Cumulative incidence of readmission with atrial fibrillation after 30 weeks were 9% and 11% in the warfarin and dabigatran groups, respectively, and an adjusted hazard ratio of 0.66 (95% CI 0.41 to 1.08).

Conclusion

Anticoagulation treatment with dabigatran allows shorter time to cardioversion for atrial fibrillation than warfarin, and appears to be an effective and safe alternative treatment strategy to warfarin.     

Frequency and Risk Factors for Under- and Over-Treatment in Stroke Prevention for Patients with Non-Valvular Atrial Fibrillation in General Practice

Objective

To determine adequacy of antithrombotic treatment in patients with non-valvular atrial fibrillation. To determine risk factors for under- and over-treatment.

Design

Retrospective, cross-sectional study of electronic health records from 36 general practitioners in 2008.

Setting

General practice in the Netherlands.

Subjects

Primary care physicians (n = 36) and patients (n = 981) aged 65 years and over.

Main Outcome Measures

Rates of adequate, under and over-treatment, risk factors for under and over-treatment.

Results

Of the 981 included patients with a mean of age 78, 18% received no antithrombotic treatment (under-treatment), 13% received antiplatelet drugs and 69% received oral anticoagulation (OAC). Further, 43% of the included patients were treated adequately, 26% were under-treated, and 31% were over-treated. Patients with a previous ischaemic stroke were at high risk for under-treatment (OR 2.4, CI 1.6–3.5), whereas those with contraindications for OAC were at high risk for over-treatment (OR 37.0, CI 18.1–79.9). Age over 75 (OR 0.2, CI: 0.1–0.3]), diabetes (OR 0.1, CI: 0.1–0.3), heart failure (OR 0.2, CI: 0.1–0.3), hypertension (OR 0.1, CI: 0.1–0.2) and previous ischaemic stroke (OR 0.04, CI: 0.02–0.11) protected against over-treatment.

Conclusions

In general practice, CHADS₂-criteria are being used, but the antithrombotic treatment of patients with atrial fibrillation frequently deviates from guidelines on this topic. Patients with previous stroke are at high risk of not being prescribed OAC. Contraindications for OAC, however, seem to be frequently overlooked.     

Risk of Ischemic Stroke after Intracranial Hemorrhage in Patients with Atrial Fibrillation

Background

We aimed to estimate the risk of ischemic stroke after intracranial hemorrhage in patients with atrial fibrillation.

Materials and Methods

Using discharge data from all nonfederal acute care hospitals and emergency departments in California, Florida, and New York from 2005 to 2012, we identified patients at the time of a first-recorded encounter with a diagnosis of atrial fibrillation. Ischemic stroke and intracranial hemorrhage were identified using validated diagnosis codes. Kaplan-Meier survival statistics and Cox proportional hazard analyses were used to evaluate cumulative rates of ischemic stroke and the relationship between incident intracranial hemorrhage and subsequent stroke.

Results

Among 2,084,735 patients with atrial fibrillation, 50,468 (2.4%) developed intracranial hemorrhage and 89,594 (4.3%) developed ischemic stroke during a mean follow-up period of 3.2 years. The 1-year cumulative rate of stroke was 8.1% (95% CI, 7.5–8.7%) after intracerebral hemorrhage, 3.9% (95% CI, 3.5–4.3%) after subdural hemorrhage, and 2.0% (95% CI, 2.0–2.1%) in those without intracranial hemorrhage. After adjustment for the CHA₂DS₂-VASc score, stroke risk was elevated after both intracerebral hemorrhage (hazard ratio [HR], 2.8; 95% CI, 2.6–2.9) and subdural hemorrhage (HR, 1.6; 95% CI, 1.5–1.7). Cumulative 1-year rates of stroke ranged from 0.9% in those with subdural hemorrhage and a CHA₂DS₂-VASc score of 0, to 33.3% in those with intracerebral hemorrhage and a CHA₂DS₂-VASc score of 9.

Conclusions

In a large, heterogeneous cohort, patients with atrial fibrillation faced a substantially heightened risk of ischemic stroke after intracranial hemorrhage. The risk was most marked in those with intracerebral hemorrhage and high CHA₂DS₂-VASc scores.     

Selection of Patients and Anesthetic Types for Endovascular Treatment in Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Background

and Purpose Recent randomized controlled trials have demonstrated consistent effectiveness of endovascular treatment (EVT) for acute ischemic stroke, leading to update on stroke management guidelines. We conducted this meta-analysis to assess the efficacy and safety of EVT overall and in subgroups stratified by age, baseline stroke severity, brain imaging feature, and anesthetic type.

Methods

Published randomized controlled trials comparing EVT and standard medical care alone were evaluated. The measured outcomes were 90-day functional independence (modified Rankin Scale ≤2), all-cause mortality, and symptomatic intracranial hemorrhage.

Results

Nine trials enrolling 2476 patients were included (1338 EVT, 1138 standard medical care alone). For patients with large vessel occlusions confirmed by noninvasive vessel imaging, EVT yielded improved functional outcome (pooled odds ratio [OR], 2.02; 95% confidence interval [CI], 1.64–2.50), lower mortality (OR, 0.75; 95% CI, 0.58–0.97), and similar symptomatic intracranial hemorrhage rate (OR, 1.12; 95% CI, 0.72–1.76) compared with standard medical care. A higher proportion of functional independence was seen in patients with terminus intracranial artery occlusion (±M1) (OR, 3.16; 95% CI, 1.64–6.06), baseline Alberta Stroke Program Early CT score of 8–10 (OR, 2.11; 95% CI, 1.25–3.57) and age ≤70 years (OR, 3.01; 95% CI, 1.73–5.24). EVT performed under conscious sedation had better functional outcomes (OR, 2.08; 95% CI, 1.47–2.96) without increased risk of symptomatic intracranial hemorrhage or short-term mortality compared with general anesthesia.

Conclusions

Vessel-imaging proven large vessel occlusion, a favorable scan, and younger age are useful predictors to identify anterior circulation stroke patients who may benefit from EVT. Conscious sedation is feasible and safe in EVT based on available data. However, firm conclusion on the choice of anesthetic types should be drawn from more appropriate randomized controlled trials.     

Predictors of early and late stroke following cardiac surgery

Background:

Much is known about the short-term risks of stroke following cardiac surgery. We examined the rate and predictors of long-term stroke in a cohort of patients who underwent cardiac surgery.

Methods:

We obtained linked data for patients who underwent cardiac surgery in the province of Ontario between 1996 and 2006. We analyzed the incidence of stroke and death up to 2 years postoperatively.

Results:

Of 108 711 patients, 1.8% (95% confidence interval [CI] 1.7%–1.9%) had a stroke perioperatively, and 3.6% (95% CI 3.5%–3.7%) had a stroke within the ensuing 2 years. The strongest predictors of both early and late stroke were advanced age (≥ 65 year; adjusted hazard ratio [HR] for all stroke 1.9, 95% CI 1.8–2.0), a history of stroke or transient ischemic attack (adjusted HR 2.1, 95% CI 1.9–2.3), peripheral vascular disease (adjusted HR 1.6, 95% CI 1.5–1.7), combined coronary bypass grafting and valve surgery (adjusted HR 1.7, 95% CI 1.5–1.8) and valve surgery alone (adjusted HR 1.4, 95% CI 1.2–1.5). Preoperative need for dialysis (adjusted odds ratio [OR] 2.1, 95% CI 1.6–2.8) and new-onset postoperative atrial fibrillation (adjusted OR 1.5, 95% CI 1.3–1.6) were predictors of only early stroke. A CHADS₂ score of 2 or higher was associated with an increased risk of stroke or death compared with a score of 0 or 1 (19.9% v. 9.3% among patients with a history of atrial fibrillation, 16.8% v. 7.8% among those with new-onset postoperative atrial fibrillation and 14.8% v. 5.8% among those without this condition).

Interpretation:

Patients who had cardiac surgery were at highest risk of stroke in the early postoperative period and had continued risk over the ensuing 2 years, with similar risk factors over these periods. New-onset postoperative atrial fibrillation was a predictor of only early stroke. The CHADS₂ score predicted stroke risk among patients with and without atrial fibrillation.Stroke remains a devastating complication following cardiac surgery, with substantial functional and economic impact.^1–3 Stroke research in cardiac surgery has focused on the immediate postoperative period;^4–9 however, most patients undergoing cardiac surgery have conditions such as hypertension, diabetes and atrial fibrillation, which place them at long-term risk of stroke.Early and late outcomes among patients undergoing cardiac surgery could be improved if the risk of postoperative stroke was defined and predictors of stroke identified. With this information, clinicians could optimize medical therapy for stroke risk factors such as hypertension,^10,11 improve the evidence-based use of oral anticoagulation in patients with atrial fibrillation and evaluate intraoperative surgical strategies (e.g., removal of the left atrial appendage¹²) in patients whose clinical characteristics predict an increased risk of stroke. We examined the rate and predictors of long-term stroke within 2 years after cardiac surgery.     

Cardiovascular Disease Rates,Outcomes, and Quality of Care in Ontario Métis: A Population-Based Cohort Study

Background

The burden of cardiovascular disease in the Métis, Canada’s fastest growing Aboriginal group, is not well studied. We determined rates of five cardiovascular diseases and associated outcomes in Ontario Métis, compared to the general Ontario population.

Methods

Métis persons were identified using the Métis Nation of Ontario Citizenship Registry. Métis citizens aged 20–105 were linked to Ontario health databases for the period of April 2006 to March 2011. Age- and sex-standardized prevalence and incidence of acute coronary syndromes (ACS), congestive heart failure (CHF), cerebrovascular disease (stroke), atrial fibrillation, and hypertension were compared between the Métis and the general population. Secondary outcome measures included one-year hospitalizations and mortality following the incident cardiovascular diagnosis, as well as quality-of-care measures.

Results

There were 12,550 eligible Métis persons and 10,144,002 in the general population. The adjusted prevalence of each disease was higher (p<0.05) among the Métis compared to the general population: ACS 5.3% vs. 3.0%; CHF 5.1% vs. 3.9%; stroke 1.4% vs. 1.1%; atrial fibrillation 2.1% vs. 1.4%; hypertension 34.9% vs. 29.8%. Incident ACS, stroke, and atrial fibrillation were also higher (p<0.05) among the Métis: ACS 2.4% vs. 1.5%; stroke 0.8% vs. 0.6%; atrial fibrillation 0.6% vs. 0.3%. One-year all-cause and cardiovascular-related mortality were not significantly different. Hospitalizations were higher for Métis persons with CHF (OR 1.93; 95% CI 1.34–2.78) and hypertension (OR 2.27; 95% CI 1.88–2.74). Métis with CHF made more emergency department (ED) visits in the year after diagnosis compared to non-Métis with CHF, while Métis aged ≥65 with ACS were more likely to be on beta-blockers following diagnosis.

Conclusions

The burden of cardiovascular disease was markedly higher in the Métis compared to the general population: prevalence rates for five cardiovascular conditions were 25% to 77% higher. Métis persons with CHF had more frequent hospitalizations and ED visits following their diagnosis.     

Impact of Antithrombotic Therapy in Atrial Fibrillation on the Presentation of Coronary Artery Disease

Background

Little is known about whether atrial fibrillation is a presentation of coronary disease. There is a paucity of knowledge about their causal relationship and also the impact of different antithrombotic strategies on the subsequent presentation of symptomatic coronary disease.

Methods and Results

We studied 7,526 Chinese patients diagnosed with non-valvular atrial fibrillation and no documented history of coronary artery disease. The primary endpoint was the new occurrence of coronary artery disease—either stable coronary artery disease or acute coronary syndrome. After a mean follow-up of 3.2±3.5 years (24,071 patient-years), a primary endpoint occurred in 987 patients (13.1%). The overall annual incidence of coronary artery disease was 4.10%/year. No significant differences in age, sex, and mean CHA₂DS₂-VASc score were observed between patients with and without the primary endpoint. When stratified according to the antithrombotic strategies applied for stroke prevention, the annual incidence of coronary artery disease was 5.49%/year, 4.45%/year and 2.16%/year respectively in those prescribed no antithrombotic therapy, aspirin, and warfarin. Similar trends were observed in patients with acute coronary syndromes. Diabetes mellitus, smoking history and renal failure requiring dialysis were predictors for primary endpoint in all antithrombotic therapies.

Conclusion

In patients with non-valvular atrial fibrillation, there is a modest association with coronary artery disease. Patients prescribed warfarin had the lowest risk of new onset coronary artery disease.     

Comorbidities against Quality Control of VKA Therapy in Non-Valvular Atrial Fibrillation: A French National Cross-Sectional Study

Background

Given the prevalence of non-valvular atrial fibrillation in the geriatric population, thromboembolic prevention by means of vitamin K antagonists (VKA) is one of the most frequent daily concerns of practitioners. The effectiveness and safety of treatment with VKA correlates directly with maximizing the time in therapeutic range, with an International Normalized Ratio (INR) of 2.0-3.0. The older population concentrates many of factors known to influence INR rate, particularly concomitant medications and concurrent medical conditions, also defined as comorbidities.

Objective

Determine whether a high burden on comorbidities, defined by a Charlson Comorbidity Index (CCI) of 3 or greater, is associated a lower quality of INR control.

Study-Design

Cross-sectional study.

Settings

French geriatric care units nationwide.

Participants

2164 patients aged 80 and over and treated with vitamin K antagonists.

Measurements

Comorbidities were assessed using the Charlson Comorbidity Index (CCI). The recorded data included age, sex, falls, kidney failure, hemorrhagic event, VKA treatment duration, and the number and type of concomitant medications. Quality of INR control, defined as time in therapeutic range (TTR), was assessed using the Rosendaal method.

Results

487 patients were identified the low-quality control of INR group. On multivariate logistic regression analysis, low-quality control of INR was independently associated with a CCI ≥3 (OR = 1.487; 95% CI [1.15; 1.91]). The other variables associated with low-quality control of INR were: hemorrhagic event (OR = 3.151; 95% CI [1.64; 6.07]), hospitalization (OR = 1.614, 95% CI [1.21; 2.14]).

Conclusion

An elevated CCI score (≥3) was associated with low-quality control of INR in elderly patients treated with VKA. Further research is needed to corroborate this finding.     

Predictors of Severe Sepsis among Patients Hospitalized for Community-Acquired Pneumonia

Background

Severe sepsis, may be present on hospital arrival in approximately one-third of patients with community-acquired pneumonia (CAP).

Objective

To determine the host characteristics and micro-organisms associated with severe sepsis in patients hospitalized with CAP.

Results

We performed a prospective multicenter cohort study in 13 Spanish hospital, on 4070 hospitalized CAP patients, 1529 of whom (37.6%) presented with severe sepsis. Severe sepsis CAP was independently associated with older age (>65 years), alcohol abuse (OR, 1.31; 95% CI, 1.07–1.61), chronic obstructive pulmonary disease (COPD) (OR, 1.75; 95% CI, 1.50–2.04) and renal disease (OR, 1.57; 95% CI, 1.21–2.03), whereas prior antibiotic treatment was a protective factor (OR, 0.62; 95% CI, 0.52–0.73). Bacteremia (OR, 1.37; 95% CI, 1.05–1.79), S pneumoniae (OR, 1.59; 95% CI, 1.31–1.95) and mixed microbial etiology (OR, 1.65; 95% CI, 1.10–2.49) were associated with severe sepsis CAP.

Conclusions

CAP patients with COPD, renal disease and alcohol abuse, as well as those with CAP due to S pneumonia or mixed micro-organisms are more likely to present to the hospital with severe sepsis.     

Impact of Triple Therapy in Elderly Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

Background and Purpose

Selecting an ideal antithrombotic therapy for elderly patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) can be challenging since they have a higher thromboembolic and bleeding risk than younger patients. The current study aimed to assess the efficacy and safety of triple therapy (TT: oral anticoagulation plus dual antiplatelet therapy: aspirin plus clopidogrel) in patients ≥75 years of age with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI).

Methods

A prospective multicenter study was conducted from 2003 to 2012 at 6 Spanish teaching hospitals. A cohort study of consecutive patients with AF undergoing PCI and treated with TT or dual antiplatelet therapy (DAPT) was analyzed. All outcomes were evaluated at 1-year of follow-up.

Results

Five hundred and eighty-five patients, 289 (49%) of whom were ≥75 years of age (79.6±3.4 years; 33% women) were identified. TT was prescribed in 55.9% of patients at discharge who had a higher thromboembolic risk (CHA₂DS₂VASc score: 4.23±1.51 vs 3.76±1.40, p = 0.007 and a higher bleeding risk (HAS-BLED ≥3: 88.6% vs 79.2%, p = 0.02) than those on DAPT. Therefore, patients on TT had a lower rate of thromboembolism than those on DAPT (0.6% vs 6.9%, p = 0.004; HR 0.08, 95% CI: 0.01–0.70, p = 0.004). Major bleeding events occurred more frequently in patients on TT than in those on DAPT (11.7% vs 2.4%, p = 0.002; HR 5.2, 95% CI: 1.53–17.57, p = 0.008). The overall mortality rate was similar in both treatment groups (11.9% vs 13.9%, p = 0.38); however, after adjustment for confounding variables, TT was associated with a reduced mortality rate (HR 0.33, 95% CI: 0.12–0.86, p = 0.02).

Conclusions

In elderly patients with AF undergoing PCI, the use of TT compared to DAPT was associated with reduced thromboembolism and mortality rates, although a higher rate of major bleeding.     

Atrial Fibrillation as a Marker of Occult Cancer

Background

Recent studies suggest that cancer increases risk of atrial fibrillation. Whether atrial fibrillation is a marker for underlying occult cancer is unknown.

Methods

We conducted a cohort study (1980–2011) of all Danish patients with new-onset atrial fibrillation. To examine cancer risk, we computed absolute risk at 3 months and standardized incidence ratios (SIRs) by comparing observed cancer incidence among patients newly diagnosed with atrial fibrillation with that expected based on national cancer incidence during the period.

Results

Median follow-up time was 3.4 years among 269 742 atrial fibrillation patients. Within 3 months of follow-up, 6656 cancers occurred (absolute risk, 2.5%; 95% confidence intervals [CI], 2.4%–2.5%) versus 1302 expected, yielding a SIR of 5.11; 95% CI, 4.99–5.24. Associations were particularly strong for cancers of the lung, kidney, colon, ovary, and for non-Hodgkin''s lymphoma. The SIR within 3 months of follow-up was 7.02; 95% CI, 6.76–7.28 for metastatic and 3.53; 95% CI, 3.38–3.68 for localized cancer. Beyond 3 months of follow-up, overall cancer risk was modestly increased (SIR, 1.13; 95% CI, 1.12–1.15).

Conclusion

Patients with new-onset atrial fibrillation had a markedly increased relative risk of a cancer diagnosis within the next three months, however, corresponding absolute risk was small.     

Early Depression Screening Is Feasible in Hospitalized Stroke Patients

Background and Purpose

Post-stroke depression (PSD) is common but is not routinely assessed for in hospitalized patients. As a Comprehensive Stroke Center, we screen all stroke inpatients for depression, though the feasibility of early screening has not been established. We assessed the hypothesis that early depression screening in stroke patients is feasible. We also explored patient level factors associated with being screened for PSD and the presence of early PSD.

Methods

The medical records of all patients admitted with ischemic stroke (IS) or intracerebral hemorrhage (ICH) between 01/02/13 and 15/04/13 were reviewed. A depression screen, modified from the Patient Health Questionnaire-9, was administered (maximum score 27, higher scores indicating worse depression). Patients were eligible if they did not have a medical condition precluding screening. Feasibility was defined as screening 75% of all eligible patients.

Results

Of 303 IS and ICH inpatients, 70% (211) were eligible for screening, and 75% (158) of all eligible patients were screened. More than one-third of all patients screened positive for depression (score > 4). Women (OR 2.06, 95% CI 1.06–4.01) and younger patients (OR 0.97, 95% CI 0.96–0.99) were more likely to screen positive. Screening positive was not associated with poor discharge/day 7 outcome (mRS > 3; OR 1.45, 95% CI 0.74–2.83).

Conclusions

Screening stroke inpatients for depression is feasible and early depression after stroke is common. Women and younger patients are more likely to experience early PSD. Our results provide preliminary evidence supporting continued screening for depression in hospitalized stroke patients.     

Resting Heart Rate and Risk of Cardiovascular Diseases and All-Cause Death: The Kailuan Study

Background

Resting heart rate (RHR) predicts both cardiovascular and noncardiovascular death in different populations. However, the results of the association between RHR and cardiovascular diseases (CVDs) are inconsistent, especially for each subtype of CVDs.

Objective

The aim of this study was to prospectively explore the relationship between RHR and CVDs including myocardial infarction (MI), ischemic stroke, and hemorrhagic stroke and all-cause death in a general population.

Methods

The Kailuan study is a prospective longitudinal cohort study on cardiovascular risk factors and cardiovascular or cerebrovascular events. Hazard ratio (HR) with 95% confidence intervals (CI) were calculated using Cox regression modeling.

Results

We analyzed 92,562 participants (18–98 years old) in the Kailuan Study. CVDs were developed in 1,903 people during follow-ups. In multivariate analysis with adjustment for major traditional cardiovascular risk factors, HRs of the highest quintile group compared with the lowest quintile group of RHR for all-cause CVDs, MI, any stroke, ischemic stroke, hemorrhagic stroke, and all-cause death were 1.03 (95% CI, 0.98–1.07), 1.10 (95% CI, 1.01–1.20), 1.01 (95% CI, 0.97–1.06), 1.02 (95% CI, 0.96–1.07), 1.01 (95% CI, 0.92–1.11) and 1.18, (95% CI, 1.13–1.23), respectively.

Conclusions

The elevated RHR was independently associated with the increased risk for MI and all-cause death, but not for all-cause CVDs, any stroke, ischemic stroke, nor hemorrhagic stroke. This indicates that the elevated RHR might be a risk marker for MI and all-cause death in general populations.     

Extended Anticoagulant and Aspirin Treatment for the Secondary Prevention of Thromboembolic Disease: A Systematic Review and Meta-Analysis

Background

Patients who have had an unprovoked deep venous thrombosis (DVT) or pulmonary embolus (PE) are at a high risk for recurrent venous thromboembolism (VTE). Extended “life-long” anticoagulation has been recommended in these patients. However, the risk benefit ratio of this approach is controversial and the role of the direct oral anticoagulants (DOACs) and aspirin is unclear. Furthermore, in some patients with a “weak provoking factor” there is clinical equipoise regarding continuation or cessation of anticoagulant therapy after treatment of the acute VTE event.

Objective

A systematic review and meta-analysis to determine the risks (major bleeding) and benefits (recurrent VTE and mortality) of extended anticoagulation with vitamin k antagonists (VKA), DOACs and aspirin in patients with an unprovoked VTE and in those patients with clinical equipoise regarding continuation or cessation of anticoagulant therapy. In addition, we sought to determine the risk of recurrent VTE events once extended anti-thrombotic therapy was discontinued.

Data Sources

MEDLINE, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles.

Study Selection

Randomized placebo-controlled trials (RCTs) that compared the risk of recurrent VTE in patients with an unprovoked DVT or PE who had been treated for at least 3 months with a VKA or a DOAC and were then randomized to receive an oral anti-thrombotic agent or placebo for at least 6 additional months. We included studies that included patients in whom clinical equipoise existed regarding the continuation or cessation of anticoagulant therapy.

Data Extraction

Independent extraction of articles by both authors using predefined data fields, including study quality indicators. Data were abstracted on study size, study setting, initial event (DVT or PE), percentage of patients where the initial VTE event was unprovoked, the number of recurrent VTE events, major bleeds and mortality during the period of extended anticoagulation in the active treatment and placebo arms. In addition, we recorded the event rate once extended treatment was stopped. Meta-analytic techniques were used to summarize the data. Studies were grouped according to the type of anti-thrombotic agent.

Data Synthesis

Seven studies which enrolled 6778 patients met our inclusion criteria; two studies evaluated the extended use of Coumadin, three studies evaluated a DOAC and two studies evaluated the use of aspirin. The duration of followup varied from 6 to 37 months. In the Coumadin and aspirin studies 100% of the randomized patients had an unprovoked VTE, while in the DOAC studies between 73.5% and 93.2% of the VTE events were unprovoked. In the control group recurrent VTE occurred in 9.7% of patients compared to 2.8% in the active treatment group (OR 0.21; 95% CI 0.11–0.42, p<0.0001). VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with VKA and DOACs being significantly more effective than aspirin. Major bleeding events occurred in 12 patients in the control group (0.4%) and 25 of 3815 (0.6%) patients in the active treatment group (OR 1.64; 95% CI 0.69–3.90, NS). There were 39 (1.3%) deaths in control patients and 33 (0.9%) deaths in the anti-thrombotic group during the treatment period (OR 0.73; 95% CI 0.40–1.33, NS). Patients whose initial VTE event was a PE were more likely to have a recurrent PE than a DVT. The annualized event rate after discontinuation of extended antithrombotic therapy was 4.4% in the control group and 6.5% in the active treatment arm.

Conclusions

VKA, DOACs and aspirin significantly reduced the risk of recurrent VTE, with DOACs and VKA being more effective than aspirin. The decision regarding life-long anticoagulation following an unprovoked DVT or PE should depend on the patients’ risk for recurrent PE as well as the patients’ values and preferences.     

Depression in Atrial Fibrillation in the General Population

Background

Initial evidence suggests that depressive symptoms are more frequent in patients with atrial fibrillation. Data from the general population are limited.

Methods and Results

In 10,000 individuals (mean age 56±11 years, 49.4% women) of the population-based Gutenberg Health Study we assessed depression by the Patient Health Questionnaire (PHQ-9) and a history of depression in relation to manifest atrial fibrillation (n = 309 cases). The median (25th/75th percentile) PHQ-9 score of depressive symptoms was 4 (2/6) in atrial fibrillation individuals versus 3 (2/6) individuals without atrial fibrillation, . Multivariable regression analyses of the severity of depressive symptoms in relation to atrial fibrillation in cardiovascular risk factor adjusted models revealed a relation of PHQ-9 values and atrial fibrillation (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01–1.08; P = 0.023). The association was stronger for the somatic symptom dimension of depression (OR 1.08, 95% CI 1.02–1.15; P = 0.0085) than for cognitive symptoms (OR 1.05, 95% CI 0.98–1.11; P = 0.15). Results did not change markedly after additional adjustment for heart failure, partnership status or the inflammatory biomarker C-reactive protein. Both, self-reported physical health status, very good/good versus fair/bad, (OR 0.54, 95% CI 0.41–0.70; P<0.001) and mental health status (OR 0.61 (0.46–0.82); P = 0.0012) were associated with atrial fibrillation in multivariable-adjusted models.

Conclusions

In a population-based sample we observed a higher burden of depressive symptoms driven by somatic symptom dimensions in individuals with atrial fibrillation. Depression was associated with a worse perception of physical or mental health status. Whether screening and treatment of depressive symptoms modulates disease progression and outcome needs to be shown.     

Serum Levels of Monocyte Chemoattractant Protein-1 and All-Cause and Cardiovascular Mortality among Patients with Coronary Artery Disease

Background

Monocyte chemoattractant protein-1 (MCP-1) is an important chemokine at multiple phases of atherosclerosis in animals, but human studies are few and inconsistent. The aim of this study is to investigate the association of serum MCP-1with all-cause and cardiovascular disease (CVD) mortality among coronary artery disease (CAD) patients and determine whether this biomarker can add secondary prognostic value to standard risk predictors.

Methods

MCP-1 was measured at baseline in 1411 CAD patients who were 40–85 years of age. Cox proportional hazards regression models were used to estimate the association of MCP-1 levels with death risk.

Results

During a median follow-up of 3.3 years, 117 deaths were recorded, 88 of which were due to CVD. The multivariable-adjusted hazard ratios across tertiles of MCP-1 were 1.51 (95% confidence intervals [CI] 0.89–2.58), 1.00, and 2.11 (95% CI 1.31–3.40) for all-cause mortality, and 1.50 (95% CI 0.80–2.81), 1.00, and 2.21 (95% CI 1.27–3.87) for CVD mortality. The addition of serum MCP-1 to the fully adjusted model increased the C-index by 0.009 (p<0.0001) for all-cause mortality and 0.008 (p<0.0001) for CVD mortality and significantly improved the predictive ability by 12.1% (P = 0.006) on all-cause mortality and 12.6% (P = 0.003) on CVD mortality using the net reclassification improvement method.

Conclusions

Both lower and higher MCP-1 levels are associated with an increased risk of all-cause and CVD mortality among CAD patients. More research is needed to confirm its clinical relevance.