Categories
Stroke

How much does clopidogrel increase the bleeding risk of aspirin?

Risk for major hemorrhages in patients receiving clopidogrel and aspirin compared with aspirin alone after transient ischemic attack or minor ischemic stroke: a secondary analysis of the POINT randomized clinical trial.

Tillman H, Johnston SC, Farrant M, et al.

JAMA Neurol 2019; 76:774-782.

Abstract

IMPORTANCE:

Results show the short-term risk of hemorrhage in treating patients with acute transient ischemic attack (TIA) or minor acute ischemic stroke (AIS) with clopidogrel plus aspirin or aspirin alone.

OBJECTIVE:

To characterize the frequency and kinds of major hemorrhages in the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial.

METHODS:

This secondary analysis of the POINT randomized, double-blind clinical trial conducted in 10 countries in North America, Europe, and Australasia included patients with high-risk TIA or minor AIS who were randomized within 12 hours of symptom onset and followed up for 90 days. The total enrollment, which occurred from May 28, 2010, through December 17, 2017, was 4881 and constituted the intention-to-treat group; 4819 (98.7%) were included in the as-treated analysis group. The primary safety analyses were as-treated, classifying patients based on study drug actually received. Intention-to-treat analyses were performed as secondary analyses. Data were analyzed in April 2018.

INTERVENTIONS:

Patients were assigned to receive clopidogrel (600 mg loading dose on day 1 followed by 75 mg daily for days 2-90) or placebo; all patients also received open-label aspirin, 50 to 325 mg/d.

MAIN OUTCOMES AND MEASURES:

The primary safety outcome was all major hemorrhages. Other safety outcomes included minor hemorrhages.

RESULTS:

A total of 269 sites worldwide randomized 4881 patients (median age, 65.0 years [interquartile range, 55-74 years]; 2195 women [45.0%]); the primary results have been published previously. In the as-treated analyses, major hemorrhage occurred in 21 patients (0.9%) receiving clopidogrel  plus aspirin and 6 (0.2%) in the aspirin alone group (hazard ratio, 3.57; 95% CI, 1.44-8.85; P = .003; number needed to harm, 159). There were 4 fatal hemorrhages (0.1%; 3 in the clopidogrel plus aspirin group and 1 in the aspirin alone group); 3 of the 4 were intracranial. There were 7 intracranial hemorrhages (0.1%); 5 were in the clopidogrel plus aspirin group and 2 in the aspirin plus placebo group. The most common location of major hemorrhages was in the gastrointestinal tract.

CONCLUSIONS:

The risk for major hemorrhages in patients receiving either clopidogrel plus aspirin or aspirin alone after TIA or minor AIS was low. Nevertheless, treatment with clopidogrel plus aspirin increased the risk of major hemorrhages  over aspirin alone from 0.2% to 0.9%.

This paper is cited in the neurochecklist:

Secondary stroke prevention: antiplatelets

Abstract link

By MarinaVladivostokOwn work, CC0, Link
Categories
Headaches

Does IIH increase the risk of cerebrovascular events?

Association between idiopathic intracranial hypertension and risk of cardiovascular diseases in women in the United Kingdom.

Adderley NJ, Subramanian A, Nirantharakumar K, et al.

JAMA Neurol 2019 (Epub ahead of print).

Abstract

BACKGROUND:

Cardiovascular disease (CVD) risk has not been previously evaluated in a large matched cohort study in idiopathic intracranial hypertension (IIH).

OBJECTIVES:

To estimate the risk of composite cardiovascular events, heart failure, ischemic heart disease, stroke/transient ischemic attack (TIA), type 2 diabetes, and hypertension in women with idiopathic intracranial hypertension and compare it with the risk in women, matched on body mass index (BMI) and age, without the condition; and to evaluate the prevalence and incidence of IIH.

METHODS:

This population-based matched controlled cohort study used 28 years of data, from January 1, 1990, to January 17, 2018, from The Health Improvement Network (THIN), an anonymized, nationally representative electronic medical records database in the United Kingdom. All female patients aged 16 years or older were eligible for inclusion. Female patients with IIH (n = 2760) were included and randomly matched with up to 10 control patients (n = 27 125) by BMI and age.

RESULTS:

In total, 2760 women with IIH and 27 125 women without IIH were included. Age and BMI were similar between the 2 groups, with a median (interquartile range) age of 32.1 (25.6-42.0) years in the exposed group and 32.1 (25.7-42.1) years in the control group; in the exposed group 1728 women (62.6%) were obese, and in the control group 16514 women (60.9%) were obese. Higher absolute risks for all cardiovascular outcomes were observed in women with IIH compared with control patients. The aHRs were as follows: composite cardiovascular events, 2.10 (95% CI, 1.61-2.74; P < .001); heart failure, 1.97 (95% CI, 1.16-3.37; P = .01); ischemic heart disease, 1.94 (95% CI, 1.27-2.94; P = .002); stroke/TIA, 2.27 (95% CI, 1.61-3.21; P < .001); type 2 diabetes, 1.30 (95% CI, 1.07-1.57; P = .009); and hypertension, 1.55 (95% CI, 1.30-1.84; P < .001). The incidence of IIH in female patients more than tripled between 2005 and 2017, from 2.5 to 9.3 per 100 000 person-years. Similarly, IIH prevalence increased in the same period, from 26 to 79 per 100 000 women. Incidence increased markedly with BMI higher than 30.

CONCLUSIONS:

Idiopathic intracranial hypertension in women appeared to be associated with a 2-fold increase in cerebrovascular disease risk; change in patient care to modify risk factors for CVD may reduce long-term morbidity for women with IIH and warrants further evaluation.

This paper is cited in the neurochecklist:

Idiopathic intracranial hypertension (IIH): typical clinical features 

Abstract link

Internet Archive Book Images on Flickr. https://www.flickr.com/photos/internetarchivebookimages/14586373420/
Categories
Stroke

Do artificial sweeteners increase the risk of stroke?

 

Artificially sweetened beverages and stroke, coronary heart disease, and all-cause mortality in the Women’s Health Initiative.

Mossavar-Rahmani Y, Kamensky V, Manson JE, et al.

Stroke 2019; 50:555-562.

Abstract

Background:

We examine the association between self-reported consumption of artificially sweetened beverages (ASB) and stroke and its subtypes, coronary heart disease, and all-cause mortality in a cohort of postmenopausal US women.

Methods:

The analytic cohort included 81 714 women from the Women’s Health Initiative Observational Study, a multicenter longitudinal study of the health of 93 676 postmenopausal women of ages 50 to 79 years at baseline who enrolled in 1993 to 1998. This prospective study had a mean follow-up time of 11.9 years (SD of 5.3 years.) Participants who completed a follow-up visit 3 years after baseline were included in the study.

Results:

Most participants (64.1%) were infrequent consumers (never or <1/week) of ASB, with only 5.1% consuming ≥2 ASBs/day. In multivariate analyses, those consuming the highest level of ASB compared to never or rarely (<1/wk) had significantly greater likelihood of all end points (except hemorrhagic stroke), after controlling for multiple covariates. Adjusted models indicated that hazard ratios and 95% confidence intervals were 1.23 (1.02-1.47) for all stroke; 1.31 (1.06-1.63) for ischemic stroke; 1.29 (1.11-1.51) for coronary heart disease; and 1.16 (1.07-1.26) for all-cause mortality. In women with no prior history of cardiovascular disease or diabetes mellitus, high consumption of ASB was associated with more than a 2-fold increased risk of small artery occlusion ischemic stroke hazard ratio =2.44 (95% confidence interval, 1.47-4.04.) High consumption of ASBs was associated with significantly increased risk of ischemic stroke in women with body mass index ≥30; hazard ratio =2.03 (95% confidence interval, 1.38-2.98).

Conclusions:

Higher intake of artificially sweetened beverages was associated with increased risk of stroke, particularly small artery occlusion subtype, coronary heart disease, and all-cause mortality. Although requiring replication, these new findings add to the potentially harmful association of consuming high quantities of ASB with these health outcomes.

This paper is cited in the neurochecklist:

Ischaemic stroke: non-genetic risk factors

Abstract link

Not sugar. Pascal on Flickr. https://www.flickr.com/photos/pasukaru76/3630414292
Categories
Stroke

How does living close to a motorway increase the risk of stroke?

Residential proximity to major roadways and risk of incident ischemic stroke in NOMAS (The Northern Manhattan Study).

Kulick ER, Wellenius GA, Boehme AK, Sacco RL, Elkind MS.

Stroke 2018; 49:835-841.

Abstract

BACKGROUND:

The evidence supporting the deleterious cardiovascular health effects of living near a major roadway is growing, although this association is not universal. In primary analyses, we hypothesized that residential proximity to a major roadway would be associated with incident ischemic stroke and that cardiovascular risk factors would modify that association.

METHODS:

NOMAS (The Northern Manhattan Study) is an ongoing, population-based cohort study designed to measure cardiovascular risk factors, stroke incidence, and other outcomes in a multiethnic urban population. Recruitment occurred from 1993 to 2001 and participants are followed-up annually by telephone. Residential addresses at baseline were geocoded and Euclidean distance to nearest major roadway was estimated and categorized as in prior studies. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals for the association of this distance to incidence of stroke and other outcomes, adjusting for sociodemographic and cardiovascular risk factors, year at baseline, and neighborhood socioeconomic status. We assessed whether these associations varied by age, sex, smoking status, diabetes mellitus, and hypertension.

RESULTS:

During a median follow-up period of 15 years (n=3287), 11% of participants were diagnosed with ischemic stroke. Participants living <100 m from a roadway had a 42% (95% confidence interval, 1.01-2.02) higher rate of ischemic stroke versus those living >400 m away. This association was more pronounced among noncurrent smokers (hazard ratio, 1.54; 95% confidence interval, 1.05-2.26) and not evident among smokers (hazard ratio, 0.69; 95% confidence interval, 0.23-2.06). There was no clear pattern of association between proximity to major roadways and other cardiovascular events including myocardial infarction, all-cause death, or vascular death.

CONCLUSIONS:

In this urban multiethnic cohort, we found evidence supporting that within-city variation in residential proximity to major roadway is associated with higher risk of ischemic stroke. An individual’s smoking history modified this association, with the association remaining only among participants not currently smokers.

This paper is cited in the neurochecklist:

Ischaemic stroke: non-genetic risk factors

Abstract link

By Rept0n1xOwn work, CC BY-SA 3.0, Link
Categories
Vasculopathy

Do lipid lowering drugs reduce the risk of intracranial aneurysm rupture?

Lipid-lowering agents and high HDL (high-density lipoprotein) are inversely associated with intracranial aneurysm rupture

Stroke 2018; Epub ahead of print

Can A, Castro VM, Dligach D, et al.

 

Abstract

Background:

Growing evidence from experimental animal models and clinical studies suggests the protective effect of statin use against rupture of intracranial aneurysms; however, results from large studies detailing the relationship between intracranial aneurysm rupture and total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), and lipid-lowering agent use are lacking.

Methods:

The medical records of 4701 patients with 6411 intracranial aneurysms diagnosed at the Massachusetts General Hospital and the Brigham and Women’s Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to determine the effects of lipids (total cholesterol, LDL, and HDL) and lipid-lowering medications on intracranial aneurysm rupture risk. Propensity score weighting was used to account for differences in baseline characteristics of the cohorts.

Results:

Lipid-lowering agent use was significantly inversely associated with rupture status (odds ratio, 0.58; 95% confidence interval, 0.47-0.71). In a subgroup analysis of complete cases that includes both lipid-lowering agent use and lipid values, higher HDL levels (odds ratio, 0.95; 95% confidence interval, 0.93-0.98) and lipid-lowering agent use (odds ratio, 0.41; 95% confidence interval, 0.23-0.73) were both significantly and inversely associated with rupture status, whereas total cholesterol and LDL levels were not significant. A monotonic exposure-response curve between HDL levels and risk of aneurysmal rupture was obtained.

Conclusions:

Higher HDL values and the use of lipid-lowering agents are significantly inversely associated with ruptured intracranial aneurysms.

This reference is cited in the Neurochecklist:

Cerebral aneurysms: risk factors for rupture

Abstract link

By Tiago Etiene QueirozOwn work, CC BY-SA 3.0, Link
Categories
Vasculopathy

What are the risk factors for multiple intracranial aneurysms?

Risk factors for and clinical consequences of multiple intracranial aneurysms: a systematic review and meta-analysis

Jabbarli R, Dinger TF, Darkwah Oppong M, et al.

Stroke 2018; (Epub ahead of print).

Abstract

BACKGROUND AND PURPOSE:

Multiple intracranial aneurysms (MIAs) are common findings of cerebral angiographies; however, MIA prevalence varies in different patient cohorts. We sought to elucidate risk factors influencing MIA prevalence and the clinical consequences.

METHODS:

We systematically searched PubMed, Scopus, Embase, and Cochrane Library databases for publications before January 15, 2017, reporting MIA prevalence and risk factors. We used random-effects meta-analysis and multivariate regression analysis to assess the impacts of individual, study, and population characteristics.

RESULTS:

We included 174 studies reporting on MIA (mean overall prevalence, 20.1%; range, 2%-44.9%) in 134 study populations with 86 989 intracranial aneurysm (IA) patients enrolled between 1950 and 2015. Studies from Europe and North America (P<0.001) and more recent enrolment years (P=0.046) were independently associated with higher MIA prevalence. In meta-analysis, MIA correlated with female sex (odds ratio [OR], 1.59; 95% confidence interval [CI], 1.4-1.8), higher patient age (>40 years; OR, 1.6; 95% CI, 1.14-2.25), arterial hypertension (OR, 1.51; 95% CI, 1.17-1.94), smoking (OR, 1.89; 95% CI, 1.37-2.6) and familial IA (OR, 2.02; 95% CI, 1.47-2.77), and formation of de novo (OR, 3.92; 95% CI, 1.95-7.87) and growth of initial IA (OR, 3.47; 95% CI, 1.87-6.45). Risk of subarachnoid hemorrhage in MIA patients was higher only in longitudinal studies from Japan and Korea (OR, 2.08; 95% CI, 1.46-2.96).

CONCLUSIONS:

Female sex, higher age, arterial hypertension, smoking, and familial IA are major risk factors for multiple intracranial aneurysms. In addition, MIA patients are at risk for enhanced IA formation. Further studies are needed to evaluate rupture risk and the role of ethnicity, especially in the context of increased MIA identification with improved neurovascular imaging.

This reference is cited in the neurochecklist:

Cerebral aneurysms: risk factors for formation

 

Abstract link

By HellerhoffOwn work, CC BY-SA 3.0, Link
Categories
Stroke

How does serum potassium affect stroke risk and outcome?

Serum potassium is positively associated with stroke and mortality in the large, population-based malmö preventive project cohort.

Johnson LS, Mattsson N, Sajadieh A, Wollmer P, Söderholm M

Stroke 2017; 48:2973-2978.

 

Abstract

BACKGROUND AND PURPOSE:

Low serum potassium is associated with stroke in populations with cardiovascular disease, hypertension, and diabetes mellitus but has not been studied in a mainly healthy population. We aimed to study the relation between serum potassium and incident stroke and mortality in the Malmö Preventive Project, a large cohort with screening in early mid-life and follow-up >25 years.

METHODS:

Serum potassium measurements and covariates were available in 21 353 individuals (79% men, mean age 44 years). Mean follow-up time was 26.9 years for stroke analyses and 29.3 years for mortality analyses. There were 2061 incident stroke events and 8709 deaths. Cox regression analyses adjusted for multiple stroke risk factors (age, sex, height, weight, systolic blood pressure, fasting blood glucose, serum sodium, current smoking, prevalent diabetes mellitus, prevalent coronary artery disease, and treatment for hypertension) were fitted.

RESULTS:

There was an independent, linear association between serum potassium, per mmol/L increase, and both stroke (hazard ratio, 1.33; 95% confidence interval, 1.17-1.52; P<0.0001) and mortality (hazard ratio, 1.20; 95% confidence interval, 1.13-1.28; P<0.0001). This was significant in subjects both older and younger than the median age (46.5 years), and there was evidence of an interaction with serumsodium. The association was positive and significant for both ischemic stroke and intracerebral hemorrhage and in both hypertensive and normotensive subjects.

CONCLUSIONS:

Serum potassium, measured in early mid-life, was linearly associated with both incidence of ischemic stroke and intracerebral hemorrhage and all-cause mortality. An interaction with serum sodium implies that factors related to electrolyte balance and incident hypertension may be mediating factors.

This reference is cited in the neurochecklists:

Ischaemic stroke: non-genetic risk factors

Ischaemic stroke: prognosis and outcome

Intracerebral haemorrhage (ICH): causes and risk factors

 

Abstract link

By Dnn87Self-photographed, CC BY 3.0, Link
Categories
Vasculopathy

What factors predispose to recurrent cerebral vein thrombosis?

Venous thrombotic recurrence after cerebral venous thrombosis: a long-term follow-up study

Palazzo P, Agius P, Ingrand P, et al.

Stroke 2017; 48:321-326.

Abstract

BACKGROUND AND PURPOSE:

After cerebral venous thrombosis (CVT), the risk of venous thrombotic events was estimated at 2% to 3% for a new CVT and 3% to 8% for extracranial events. However, because of the paucity of prospective studies, the clinical course of CVT is still largely unknown. We aimed to prospectively evaluate the rate of thrombosis recurrence in a cohort of CVT patients with a long-term follow-up and to detect predisposing factors for recurrence.

METHODS:

Consecutive CVT patients with complete clinical, radiological, biological, and genetic data were systematically followed up. New venous thrombotic events were detected after hospital readmission and imaging confirmation.

RESULTS:

One-hundred eighty-seven patients (mean age 45±18 years, 67% women) with angiographically confirmed CVT were included. Cause was found in 73% of patients. Coagulation abnormality and JAK2 gene mutation were detected in 20% and 9%, respectively. Median follow-up length was 73 months (range 1-247 months). Mean duration of the oral anticoagulant treatment was 14 months. Mortality rate was 2.5% per year, with 2% in-hospital mortality. During follow-up, CVT reoccurred in 6 patients, whereas 19 subjects had a symptomatic extracranial venous thrombotic event, with cumulative venous thrombotic recurrence rates of 3% at 1 year, 8% at 2 years, 12% at 5 years, and 18% at 10 years. A previous venous thrombotic event (hazard ratio, 2.8; P=0.018), presence of cancer or malignant hemopathies (hazard ratio, 3.2; P=0.039), and unknown CVT causes (hazard ratio, 2.81; P=0.024) were independently associated with recurrence.

CONCLUSIONS:

In our cohort of CVT patients followed on average for >6 years, subjects with a previous venous thrombotic event, cancer/malignant hemopathies, and unknown CVT causes were found to be at higher risk of recurrence.

This reference is cited in the neurochecklist:

Cerebral vein thrombosis (CVT): clinical features

Abstract link

By HellerhoffOwn work, CC BY-SA 3.0, Link
Categories
Stroke

How may serum troponin help in the diagnosis of stroke?

Early elevated troponin levels after ischemic stroke suggests a cardioembolic source

Yaghi S, Chang AD, Ricci BA, et al.

Stroke 2018; 49:121-126.

Abstract

BACKGROUND AND PURPOSE:

Elevated cardiac troponin is a marker of cardiac disease and has been recently shown to be associated with embolic stroke risk. We hypothesize that early elevated troponin levels in the acute stroke setting are more prevalent in patients with embolic stroke subtypes (cardioembolic and embolic stroke of unknown source) as opposed to noncardioembolic subtypes (large-vessel disease, small-vessel disease, and other).

METHODS:

We abstracted data from our prospective ischemic stroke database and included all patients with ischemic stroke during an 18-month period. Per our laboratory, we defined positive troponin as ≥0.1 ng/mL and intermediate as ≥0.06 ng/mL and <0.1 ng/mL. Unadjusted and adjusted regression models were built to determine the association between stroke subtype (embolic stroke of unknown source and cardioembolic subtypes) and positive and intermediate troponin levels, adjusting for key confounders, including demographics (age and sex), clinical characteristics (hypertension, hyperlipidemia, diabetes mellitus, renal function, coronary heart disease, congestive heart failure, current smoking, and National Institutes of Health Stroke Scale score), cardiac variables (left atrial diameter, wall-motion abnormalities, ejection fraction, and PR interval on ECG), and insular involvement of infarct.

RESULTS:

We identified 1234 patients, of whom 1129 had admission troponin levels available; 10.0% (113/1129) of these had a positive troponin. In fully adjusted models, there was an association between troponin positivity and embolic stroke of unknown source subtype (adjusted odds ratio, 4.46; 95% confidence interval, 1.03-7.97; P=0.003) and cardioembolic stroke subtype (odds ratio, 5.00; 95% confidence interval, 1.83-13.63; P=0.002).

CONCLUSIONS:

We found that early positive troponin after ischemic stroke may be independently associated with a cardiac embolic source. Future studies are needed to confirm our findings using high-sensitivity troponin assays and to test optimal secondary prevention strategies in patients with embolic stroke of unknown source and positive troponin.

Also see

Merkler AE, Gialdini G, Murthy SB, et al. Association between troponin levels and embolic stroke of undetermined source. J Am Heart Assoc 2017; pii: e005905.

Both references are cited in the neurochecklist:

Embolic stroke of undetermined source (ESUS)

Abstract link 1

Abstract link 2

By MetskasLAOwn work, CC0, Link