Global study shows stroke largely preventable

Micrograph showing cortical pseudolaminar necrosis, a finding seen in strokes on medical imaging and at autopsy. H&E-LFB stain. Credit: Nephron/Wikipedia

Ten risk factors that can be modified are responsible for nine of 10 strokes worldwide, but the ranking of those factors vary regionally, says a study led by researchers of the Population Health Research Institute (PHRI) of McMaster University.

16 july 2016--Prevention of stroke is a major public health priority, but the variation by region should influence the development of strategies for reducing stroke risk, say the authors of the study published in The Lancet today.
Stroke is a leading cause of death and disability, particularly in low-income and middle-income countries. The two major types of stroke include ischaemic stroke caused by blood clots, which accounts for 85% of strokes, and haemorrhagic stroke or bleeding into the brain, which accounts for 15% of strokes.
The study led by Dr. Martin O'Donnell and Dr. Salim Yusuf of the Population Health Research Institute at McMaster and collaborators from 32 countries, builds on findings from the first phase of the INTERSTROKE study which identified ten modifiable risk factors for stroke in 6,000 participants from 22 countries. This full-scale INTERSTROKE study added 20,000 individuals from 32 countries in Europe, Asia, America, Africa and Australia, and sought to identify the main causes of stroke in diverse populations, young and old, men and women and within subtypes of stroke.
"This study has the size and scope to explore stroke risk factors in all major regions of the world and within key populations," said O'Donnell, a principal investigator for the PHRI and professor of translational medicine at HRB-Clinical Research Facility, NUI Galway.
"We have confirmed the ten modifiable risk factors associated with 90% of stroke cases in all regions, young and older and in men and women. The study also confirms that hypertension is the most important modifiable risk factor in all regions, and the key target in reducing the burden of stroke globally."
The investigators looked at the different risk factors, and determined the proportion of strokes which would be cut if the risk factor disappeared.
The number of strokes would be practically cut in half (48%) if hypertension was eliminated; trimmed by more than a third (36%) if people were physically active; and shaved by almost one fifth (19%) if they had better diets. In addition, this proportion was cut back by 12% if smoking was eliminated; 9% for cardiac (heart) causes, 4% for diabetes, 6% for alcohol intake, 6% for stress, and 27% for lipids (the study used apolipoproteins, which was found to be a better predictor of stroke than total cholesterol).
Many of these risk factors are known to also be associated with each other (such as obesity and diabetes), and when were combined together, the total for all 10 risk factors was 91%, which was similar in all regions, age groups and in men and women.
However, the importance of some risk factors appeared to vary by region. For example, the importance of hypertension ranged from practically 40% in Western Europe, North America, and Australia to 60% in Southeast Asia. The risk of alcohol was lowest in Western Europe, North America and Australia but highest in Africa and south Asia, while the potential impact of physical inactivity was highest in China.
An irregular heart rhythm, or atrial fibrillation, was significantly associated with ischaemic stroke in all regions, but was of greater importance in Western Europe, North America and Australia, than in China or South Asia.
However, when all 10 risk factors were included together, their collective importance was similar in all regions.
"Our findings will inform the development of global population-level interventions to reduce stroke, and how such programs may be tailored to individual regions," said Yusuf, a professor of medicine of McMaster's Michael G. DeGroote School of Medicine and director of the PHRI. "This includes better health education, more affordable healthy food, avoidance of tobacco and more affordable medication for hypertension and dyslipidaemia."
Along with the study, The Lancet published a related comment from New Zealand researchers Valery L. Feigin and Rita Krishnamurthi of the National Institute for Stroke and Applied Neurosciences, of Auckland's University of Technology.
They said the key messages from the study were that stroke is a highly preventable disease globally, regardless of age and sex; that the relative importance of modifiable risk factors means there should be development of regional or ethnic-specific primary prevention programs, and that additional research on stroke risk factors is needed for countries and ethnic groups not included in INTERSTROKE.
"Now is the time for governments, health organizations, and individuals to proactively reduce the global burden of stroke. Governments of all countries should develop and implement an emergency action plan for the primary prevention of stroke," they wrote.

More information: The Lancet, DOI: 10.1016/S0140-6736(16)30506-2


Provided by McMaster University

Guidelines issued for stroke prevention in women

18 jun 2014--—New guidelines have been released that highlight unique stroke risk factors for women and address prevention strategies, according to a synopsis article published in the June 17 issue of the Annals of Internal Medicine.

Cheryl Bushnell, M.D., M.H.S., from the Wake Forest Baptist Medical Center in Winston-Salem, N.C., and Louise McCullough, M.D., Ph.D., from the University of Connecticut Health Center in Farmington, discuss the newly released American Heart Association/American Stroke Association guideline focusing on stroke prevention in women. Members of a multidisciplinary expert panel reviewed the literature and devised evidence-based tables and developed recommendations.

The researchers discuss stroke risk factors for women, including hypertension, atrial fibrillation, diabetes, and migraine headache, which are stronger risk factors or more prevalent among women; hormonal contraception; menopause and hormone replacement; and depression and psychosocial stress, which may be a stronger risk factor in women. Stroke prevention strategies include maintenance of a healthy lifestyle, with recommendations for lifestyle intervention identical for men and women; treatment of carotid stenosis, with similar guideline recommendations for both sexes; and use of aspirin. Gaps in the literature limit the ability to provide strong, sex-specific recommendations. New recommendation were provided for pregnancy and pregnancy-associated complications.

"We hope that this guideline will spur additional research to determine the best approaches to stroke prevention for both men and women," the authors write.

One author disclosed financial ties to Genentech.

More information: Full Text

Very Elderly Age Group: Need For Routine Stroke Prevention Therapies And Research In Epilepsy

06 oct 2009--A review published Online First and in the November edition of The Lancet Neurology reports that routine stroke prevention therapies are underused in the very elderly, but could be very effective in this age group. The article is the work of Dr Nerses Sanossian of the University of Southern California and Dr Bruce Ovbiagele of the UCLA Stroke Center and Department of Neurology, Los Angeles, CA, USA.

The average human lifespan is extending and as a result there are more individuals above 80 years old who have a high quality of life. However, these very elderly individuals are particularly vulnerable to stroke. There have been substantial advances in stroke research, with several therapeutic drugs able to enhance clinical outcomes in people with stroke or who are at risk of stroke. But still, the very elderly seem to be given fewer vascular protection interventions that have been shown to be effective in their younger counterparts. These treatments might be of benefit to this group of patients. However, there has been an under-representation of the very elderly in studies of stroke therapy. In fact, new data indicate that the use of several of these therapies in routine clinical practice in the very elderly can be useful.

The authors write in conclusion: "With the rapidly growing population of individuals above 80 years, future stroke trials need to include the very elderly to facilitate ready generalisability of results and to convince sceptical clinicians that all patients with stroke should benefit from prompt evidence-based treatment, regardless of age."

A second Lancet Neurology review discusses epilepsy in later life. It is written by Professor Martin Brodie, Western Infirmary, Glasgow, UK, and colleagues. They remark: "Epilepsy is most likely to develop in later life. The burden of this disorder on health-care resources will rise further as the world's population continues to age."

There is growing prevalence and potentially deep physical and psychosocial effects of new-onset epilepsy in elderly people. However shockingly, this disorder has received little research attention. There is growing agreement that future treatment strategies should move beyond symptomatic relief like seizure control. Instead, they should focus on achieving cure and prevention for those at risk. In accordance with this objective, the European scientific community has recently identified a number of research priorities. Some of the aspects that are particularly relevant to the elderly population include:

• preventing the development of epilepsy after brain trauma
• translating genetic knowledge to optimise care of patients
• reducing the life-burden of seizures
• improving treatment and prognosis

The authors write in conclusion: "Old age has become the most common time in life to develop epilepsy in high-income societies. Because of the often atypical presentation, concomitant cognitive impairment, and non-specific abnormalities in routine investigations, establishing a correct diagnosis can be particularly challenging. A multispecialty, multi-professional strategy can help to facilitate rapid diagnosis and ensure a comprehensive approach in ameliorating the physical as well as the psychosocial effects of the diagnosis of epilepsy on elderly patients and their families."

A complementary Lancet Neurology editorial comments: "The rapidly increasing elderly population poses a major challenge for future health-care systems. Many of the diseases of old age are neurological disorders, so neurological practice is likely to be disproportionately affected by an ageing society...there is a dearth of clinical trials among older people - indeed, very elderly patients are systematically excluded from many clinical trials. If we are to meet the challenge of caring for rising numbers of elderly patients in the future, more good-quality trials in older people are needed to inform clinical practice."

"Prevention and management of stroke in very elderly patients"
Nerses Sanossian, Bruce Ovbiagele
DOI: 10.1016/S1474-4422(09)70259-5

"Neurology in the elderly: more trials urgently needed"
DOI: 10.1016/S1474-4422(09)70265-0
The Lancet Neurology

Secondary Stroke Prevention Lower in Elderly Patients

Study emphasizes need for secondary stroke prevention in patients of all ages

18 april 2009-- In stroke survivors, secondary prevention is essential regardless of age, according to a study published online April 16 in BMJ.
Rosalind Raine, Ph.D., of the University College London in the United Kingdom, and colleagues studied 12,830 patients aged 50 years and older who had a stroke between 1995 and 2005 and survived the first 30 days afterward.
The researchers found that secondary prevention rates were low in both men and women (25.6 percent and 20.8 percent, respectively). They also found that secondary prevention was significantly lower among patients aged 80 to 89 years than in those aged 50 to 59 years (adjusted odds ratio, 0.53), even though secondary prevention was associated with a 50 percent reduction in mortality risk in all age groups.
"The evidence suggests that concerns about the trade-off between benefits and risks in elderly people may be exaggerated and that one-year survival benefit is not modified by age," the authors write. "Therefore under-treatment of older people cannot be justified, unless it is explained by informed patient choice."
AbstractFull Text

Age Should Not Rule Out the Use of Warfarin for Stroke Prevention

BIRMINGHAM, England, Aug. 9 -- Warfarin (Coumadin) is more effective than aspirin for stroke prevention among elderly patients with atrial fibrillation, and it does not seem to increase the risk for major bleeds, according to investigators here.
In a randomized trial of nearly 1,000 patients ages 75 and older with atrial fibrillation, those who took warfarin had a 52% lower risk of an ischemic stroke, hemorrhagic stroke, intracranial hemorrhage or significant arterial embolism than did those who received aspirin.
Moreover, warfarin did not increase the risk of major hemorrhages compared with aspirin, reported Jonathan Mant, M.D., of the University of Birmingham, and colleagues, in the Aug.11 issue of The Lancet.
"These data lend support to the use of anticoagulation for all people aged over 75 years who have atrial fibrillation, unless there are contraindications or the patient decides that the size of the benefit is not worth the inconvenience of the treatment," the authors wrote.
In the Birmingham Atrial Fibrillation Treatment of the Age (BAFTA) study, patients with a mean age of 81.5 were randomized to 75 mg/day of aspirin or to warfarin therapy with a target international normalized ratio (INR) of 2-3.
During approximately 2.7 years of follow-up, there were 24 events in the 488 patients taking warfarin including 21 strokes, two intracranial hemorrhages and one systemic embolus. By contrast, there were 49 events seen in the 485 patients taking daily aspirin including 44 strokes, one intracranial hemorrhage and three systemic emboli.
The yearly risk of stroke was 1.8% among patients taking warfarin, compared with 3.8% among those patients who were taking aspirin therapy to reduce their risk of stroke (P=0.003). The absolute risk reduction of warfarin was only 2% per year because of the low event rates seen in the study (95% CI 0.7-3.2). The number needed to treat for one year to prevent one primary event was 50, the researchers reported.
Although there had been concern that warfarin would increase the risk of major bleeds compared with other treatments in the elderly, the BAFTA study showed that warfarin was no more dangerous than aspirin. There was a 1.9% yearly rate of major hemorrhage including intracranial bleed and hemorrhagic stroke in the warfarin group, compared with a 2.0% yearly rate in the aspirin users (RR 0.96; 95% CI 0.53-1.75).
The yearly risk of major bleed did, however, increase with age in both arms. The yearly risk of extracranial hemorrhage was 1.4% in patients taking warfarin, compared with 1.6% among their counterparts who tool aspirin (RR 0.87; 95% CI 0.43-1.73), The absolute risk reduction for extracranial hemorrhage was 0.2%, the study showed.
In an accompanying editorial, David Garcia, M.D., of the University of New Mexico in Albuquerque, and Elaine Hylek, M.D., of Boston University pointed out that patients could not be included in this trial if warfarin was considered the only effective stroke prevention treatment for them. These patients thus had a lower risk of stroke than those in other studies. The study shows that even in low-risk groups, the benefits of anticoagulation exceed those seen with antiplatelet therapy, they wrote.
"In the future our greatest challenge will be to identify this patients (elderly or not) who are truly at the highest risk of major bleed, particularly intracranial hemorrhage," they added. "For everyone else the benefits of well-managed warfarin substantially outweigh its risks."
The relative contraindications to warfarin use in elderly patients are prior intracranial hemorrhages, in particular cerebral amyloid angiopathy, but also hypertensive bleeds and subdural hematoma and extensive small vessel disease such as periventricular white matter demyelination, commented Derk W. Krieger, M.D. Ph.D., a neurologist at the Cleveland Clinic.
"There is no question that warfarin is better than aspirin, and even aspirin plus clopidogrel (Plavix) for stroke prevention in atrial fibrillation," he said in an interview. "The BAFTA study nicely applies this 'dogma' to the elderly and even though many physicians are wary to prescribe warfarin to the elderly due to fall risk, the risk-benefit analysis is in favor of warfarin."
One of the researchers reported receiving funds for educational support, research and consulting from AstraZeneca, Sanofi-Aventis, Bayer, Astellas, and Daiichi-Sanko. The same researcher helped develop guidelines for the treatment of atrial fibrillation and is on the writing committee for the American College of Chest Physicians' guidelines on anti-thrombotic therapy for atrial fibrillation. The remaining study authors declared no conflicts of interest. Primary source: LancetSource reference: Jonathan Mant, FD Richard Hobbs, Kate Fletcher, Andrea Roalfe, David Fitzmaurice, Gregory YH Lip, Ellen Murray, on behalf of the BAFTA investigators* and the Midland Research Practices Network (MidReC)* Lancet 2007; 370: 493-503

Oral Anticoagulants Top Antiplatelet Drugs for Stroke Prevention in A-Fib

ROCHESTER, Minn., July 18 -- Patients with nonvalvular atrial fibrillation have about a 33% lower risk of stroke and major vascular events when treated with oral anticoagulants rather than antiplatelet therapy, findings from a systematic review of clinical trials suggest.
The magnitude of the advantage ranged from 29% for disabling or fatal strokes to 52% for systemic emboli. The two types of therapy had equivalent effects on vascular death and all-cause mortality, according to a review published online in issue 3 of The Cochrane Library.
The reduction in clinical events with oral anticoagulants came at a price, however: a doubling of the risk of intracranial hemorrhage compared with the risk from antiplatelet drugs, reported Maria Aguilar, M.D., of the Mayo Clinic, and colleagues.
Despite the advantages demonstrated by the review, physicians should use a risk-adjusted strategy for clinical decision-making about anticoagulants, the researchers said.
"The threshold of benefit that would warrant anticoagulation remains controversial and depends on patient preferences and availability of optimal anticoagulation monitoring," Dr. Aguilar and colleagues concluded.
"In most cohorts of [atrial fibrillation] patients without prior stroke or TIA, about 40% have a sufficiently low stroke rate during antiplatelet therapy that the absolute benefits of oral anticoagulants would be small (below 1% per year)."
The review was undertaken because of uncertainty surrounding the suspected cardioembolic nature of most strokes in atrial fibrillation patients. Oral anticoagulants and antiplatelet agents have demonstrated stroke prevention efficacy in high-risk patients, however, primary prevention in patients with non-valvular atrial fibrillation merited separate consideration, the authors stated.
A search of the Cochrane databases, published literature, and information on published clinical studies yielded eight randomized trials that involved a total of 9,598 patients treated with adjusted dose warfarin or aspirin in doses ranging from 75 to 325 mg/day. All of the trials limited enrollment to patients who had no history of stroke or TIA. Follow-up averaged 1.9 years.
As compared with aspirin, oral anticoagulants significantly reduced the risk of:
All stroke (odds ratio 0.68)
Ischemic stroke (OR 0.53 ), and
Systemic emboli (OR 0.48)
Treatment with oral anticoagulants versus aspirin also led to nonsignificant reductions in disabling or fatal strokes (OR 0.71) and myocardial infarction (OR 0.69). Vascular death (OR 0.93) and all-cause mortality (0.99) were similar with the two prevention strategies.
Oral anticoagulants were associated with a statistically significant increased risk of intracranial hemorrhage (OR 1.98) compared with aspirin. However, the authors noted, CNS bleeding occurred infrequently with either type of therapy.
For primary prevention of stroke in patients with atrial fibrillation, the absolute benefit of oral anticoagulants versus antiplatelet therapy is modest, Dr. Aguilar and co-authors stated. In the clinical arena of secondary prevention, oral anticoagulants continue to offer larger absolute benefits.
Dr. Aguilar reported no potential conflicts. Her co-authors disclosed that they had participated in two of the trials included in the review. The review had no commercial support.Primary source: Cochrane ReviewSource reference: Aguilar MI et al. "Oral anticoagulants versus antiplatelet therapy for preventing stroke in patients with non-valvular atrial fibrillation and no history of stroke or transient ischemic attacks." Cochrane Database of Systematic Reviews 2007, Issue 3, Art. No.: CD006186. DOI: 10.1002/14651858.CD006186.pub2.

Why Aerobic Exercise Is Good For The Heart

Aerobic exercise is widely recognized to reduce the risk of coronary heart disease, but until now, researchers have not fully understood the biological mechanisms behind the effect of exercise on cardiovascular health. Findings of a new study show how exercise decreases inflammation, which reduces the risk of atherosclerosis – fatty build-ups in the arteries – that cause most cases of heart disease.
In a study led by Richard P. Sloan, Ph.D., professor of behavioral medicine at Columbia University Medical Center, whole blood samples were taken from 46 healthy young adults (20-45 years old) both before and after participating in moderate or high intensity aerobic exercise, over a 12-week period.
The blood samples were stimulated with the infectious agent lipopolysaccharide (LPS) – gram negative bacteria – and then analyzed for levels of tumor necrosis factor (TNF) – an initial step in the inflammatory cascade. Substantially lower levels of TNF were found after aerobic training, in both the moderate and high intensity groups.
http://www.sciencedaily.com/releases/2007/03/070320073101.htm