Zoster ups stroke risk in patients with autoimmune disease

05 feb 2017—For patients with autoimmune diseases, the risk of stroke is increased in the few months subsequent to incident herpes zoster (HZ), according to a study published online Jan. 28 in Arthritis & Rheumatology.

Leonard H. Calabrese, D.O., from the Cleveland Clinic, and colleagues identified patients with autoimmune disease using Medicare data from Jan. 1, 2006, through Dec. 31, 2013. The authors examined whether the incidence of hospitalized stroke was increased immediately following HZ compared with incidence at later time points.
The researchers found that the crude incidence of stroke varied from 2.30 per 100 patient-years (95 percent confidence interval [CI], 0.96 to 5.52) within 90 days of HZ in patients who had HZ-related cranial nerve complications and did not receive treatment, to 0.87 per 100 patient-years (95 percent CI, 0.75 to 1.02) at 366 to 730 days for those who did not have complications and who received treatment. The overall incidence rate ratio (IRR) was 1.36 (95 percent CI, 1.10 to 1.68) for stroke in the first 90 days versus at 366 to 730 days after HZ, after multivariable adjustment for multiple stroke-related factors. Patients with zoster and cranial nerve complications had greater risk (IRR, 2.08; 95 percent CI, 0.99 to 4.36). The incidence of subsequent stroke was lower with prompt antiviral therapy (IRR, 0.83; 95 percent CI, 0.70 to 0.98).
"These data underscore the urgency of developing strategies for reducing the risk of varicella-zoster virus," the authors write.

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Eating up to 100 g of chocolate daily linked to lowered heart disease and stroke risk

Chocolate. Credit: Wikimedia Commons

Eating up to 100 g of chocolate every day is linked to lowered heart disease and stroke risk, finds research published online in the journal Heart.

16 JUN 2015--There doesn't seem to be any evidence for cutting out chocolate to lower the risk of cardiovascular disease, conclude the researchers.

They base their findings on almost 21,000 adults taking part in the EPIC-Norfolk study, which is tracking the impact of diet on the long term health of 25,000 men and women in Norfolk, England, using food frequency and lifestyle questionnaires.

The researchers also carried out a systematic review of the available international published evidence on the links between chocolate and cardiovascular disease, involving almost 158,000 people—including the EPIC study participants.

The EPIC-Norfolk participants (9214 men and 11 737 women) were monitored for an average of almost 12 years, during which time 3013 (14%) people experienced either an episode of fatal or non-fatal coronary heart disease or stroke.

Around one in five (20%) participants said they did not eat any chocolate, but among the others, daily consumption averaged 7 g, with some eating up to 100 g.

Higher levels of consumption were associated with younger age and lower weight (BMI), waist: hip ratio, systolic blood pressure, inflammatory proteins, diabetes and more regular physical activity —all of which add up to a favourable cardiovascular disease risk profile.

Eating more chocolate was also associated with higher energy intake and a diet containing more fat and carbs and less protein and alcohol.

The calculations showed that compared with those who ate no chocolate higher intake was linked to an 11% lower risk of cardiovascular disease and a 25% lower risk of associated death.

It was also associated with a 9% lower risk of hospital admission or death as a result of coronary heart disease, after taking account of dietary factors.

And among the 16,000 people whose inflammatory protein (CRP) level had been measured, those eating the most chocolate seemed to have an 18% lower risk than those who ate the least.

The highest chocolate intake was similarly associated with a 23% lower risk of stroke, even after taking account of other potential risk factors.

Of nine relevant studies included in the systematic review, five studies each assessed coronary heart disease and stroke outcome, and they found a significantly lower risk of both conditions associated with regular chocolate consumption.

And it was linked to a 25% lower risk of any episode of cardiovascular disease and a 45% lower risk of associated death.

This is an observational study so no definitive conclusions about cause and effect can be drawn. And the researchers point out that food frequency questionnaires do involve a certain amount of recall bias and underestimation of items eaten.

Reverse causation—whereby those with a higher cardiovascular disease risk profile eat less chocolate and foods containing it than those who are healthier—may also help to explain the results, they say.

Nevertheless, they add: "Cumulative evidence suggests that higher chocolate intake is associated with a lower risk of future cardiovascular events."

And they point out that as milk chocolate, which is considered to be less 'healthy' than dark chocolate, was more frequently eaten by the EPIC-Norfolk participants, the beneficial health effects may extend to this type of chocolate too.

"This may indicate that not only flavonoids, but also other compounds, possibly related to milk constituents, such as calcium and fatty acids, may provide an explanation for the observed association," they suggest.

And they conclude: "There does not appear to be any evidence to say that chocolate should be avoided in those who are concerned about cardiovascular risk."

More information: Habitual chocolate consumption and risk of cardiovascular disease among healthy men and women

Provided by British Medical Journal

Green tea, coffee may help lower stroke risk

Green tea. Credit: Wikimedia Commons

Green tea and coffee may help lower your risk of having a stroke, especially when both are a regular part of your diet, according to research published in Stroke: Journal of the American Heart Association.

18 mar 2013--"This is the first large-scale study to examine the combined effects of both green tea and coffee on stroke risks," said Yoshihiro Kokubo, M.D., Ph.D., F.A.H.A., F.A.C.C., F.E.S.C., lead author of the study at Japan's National Cerebral and Cardiovascular Center. "You may make a small but positive lifestyle change to help lower the risk of stroke by adding daily green tea to your diet."

Researchers asked 83,269 Japanese adults about their green tea and coffee drinking habits, following them for an average 13 years. They found that the more green tea or coffee people drink, the lower their stroke risks. 

• People who drank at least one cup of coffee daily had about a 20 percent lower risk of stroke compared to those who rarely drank it.
• People who drank two to three cups of green tea daily had a 14 percent lower risk of stroke and those who had at least four cups had a 20 percent lower risk, compared to those who rarely drank it.
• People who drank at least one cup of coffee or two cups of green tea daily had a 32 percent lower risk of intracerebral hemorrhage, compared to those who rarely drank either beverage. (Intracerebral hemorrhage happens when a blood vessel bursts and bleeds inside the brain. About 13 percent of strokes are hemorrhagic.)

Participants in the study were 45 to 74 years old, almost evenly divided in gender, and were free from cancer and cardiovascular disease.

During the 13-years of follow-up, researchers reviewed participants' hospital medical records and death certificates, collecting data about heart disease, strokes and causes of death. They adjusted their findings to account for age, sex and lifestyle factors like smoking, alcohol, weight, diet and exercise.

Green tea drinkers in the study were more likely to exercise compared to non-drinkers.

Previous limited research has shown green tea's link to lower death risks from heart disease, but has only touched on its association with lower stroke risks. Other studies have shown inconsistent connections between coffee and stroke risks.

Initial study results showed that drinking more than two cups of coffee daily was linked to increasing coronary heart disease rates in age- and sex-adjusted analysis. But researchers didn't find the association after factoring in the effects of cigarette smoking—underscoring smoking's negative health impact on heart and stroke health.

A typical cup of coffee or tea in Japan was approximately six ounces. "However, our self-reported data may be reasonably accurate, because nationwide annual health screenings produced similar results, and our validation study showed relatively high validity." Kokubo said. "The regular action of drinking tea, coffee, largely benefits cardiovascular health because it partly keeps blood clots from forming."

Tea and coffee are the most popular drinks in the world after water, suggesting that these results may apply in America and other countries.

It's unclear how green tea affects stroke risks. A compound group known as catechins may provide some protection. Catechins have an antioxidant anti-inflammatory effect, increasing plasma antioxidant capacity and anti-thrombogenic effects.

Some chemicals in coffee include chlorogenic acid, thus cutting stroke risks by lowering the chances of developing type 2 diabetes. Further research could clarify how the interaction between coffee and green tea might help further lower stroke risks, Kokubo said.

More information: For additional information on stroke:

newsroom.heart.org/news/672 
www.heart.org/HEAR… _Article.jsp

Provided by American Heart Association

Statins cut stroke risk by a fifth, study finds

LONDON16 april 2009 - Cholesterol-lowering drugs cut the risk of strokes by about a fifth, according to a pooled analysis of 24 past clinical studies involving 165,000 people.

The hugely successful class of drugs -- a mainstay for millions of people with heart disease -- also slow the movement of blockages in the carotid artery carrying blood to the brain, French researchers reported in the journal Lancet Neurology.

The meta-analysis concluded that stroke risk fell by 21 percent for each one millimole per liter decrease in the level of "bad" low-density lipoprotein (LDL) cholesterol in the blood.

Previous individual clinical trials have not always given a clear picture of the benefits of using statins in stroke prevention. Leading statins include Pfizer's Lipitor, AstraZeneca's Crestor and cheaper generics, such as simvastatin.

Lead researcher Pierre Amarenco from Paris-Diderot University said the next step in the field should be to assess the safety and effectiveness of further reductions in LDL cholesterol after a stroke.

Healthy Behaviors Associated with Halving of Stroke Risk

22 feb 2009--Four behaviors combined — exercise, not smoking, healthy eating, and moderate drinking — are associated with a significant drop in stroke risk among older people, according to a BMJ study.

U.K. researchers ascertained the health behaviors of a cohort of some 20,000 adults aged 40 to 79. The group was then followed for an average of 11 years.

Over that period, those not engaging in any of four specific healthy behaviors had more than twice the risk for stroke as those engaging in all four — exercising regularly (or having a nonsedentary occupation), not smoking, eating five or more portions of fruits and vegetables daily, and drinking moderately. (The risk for stroke increased linearly with increasing numbers of unhealthy behaviors.)

An editorialist comments that modifying lifestyle behaviors "across a population has a greater potential for overall reduction in stroke than modifying more powerful risk factors (such as carotid stenosis and atrial fibrillation) in a smaller number of people."

LINK(S):

BMJ article (Free)

BMJ editorial (Subscription required)

Airborne Fine Particulate Matter Linked to Stroke Risk

By Todd Neale
ANN ARBOR, Mich., 31 may 2008Even low levels of airborne fine particulate matter appear to be associated with an increased risk of cerebrovascular events, researchers found.Levels of particulate matter in a southeast Texas county were associated with "borderline significant" increases in the risk of ischemic stroke and transient ischemic attack, Lewis Morgenstern, M.D., of the University of Michigan, and colleagues reported online in the Annals of Neurology.When levels of fine particulate matter rose by 5.1 mg/m3 the risk of suffering one of the events increased by 3% that day (RR 1.03, 95% CI 0.99 to 1.07) and the day after (RR 1.03, 95% CI 1.00 to 1.07).
"Although the magnitude of increased risk for stroke/[transient ischemic attack] because of [particulate matter] exposure was relatively small," the researchers said, "most of the public is exposed to ambient air pollution at the levels observed in this community or greater every day, suggesting a potentially large public health impact."
The median particulate matter level was 7.0 mg/m3, less than half the standard set by the Environmental Protection Agency (15 mg/m3).
The results, therefore, "call into question current standards for fine particulate matter and whether these standards are sufficient to protect the public from stroke," the researchers said.
Past studies have found a link between air pollution and cardiovascular disease in general but data on the association with stroke have been more limited, the researchers said.
Fine particulate matter -- a diameter less than 2.5 mm -- can penetrate airways and alveoli and enter the circulation because of its smaller size and chemical activity, they said.
The particles may raise the risk for cerebrovascular events by inducing arterial vasoconstriction or acute increases in blood pressure and plasma viscosity, they said.
To explore the issue, Dr. Morgenstern and colleagues turned to the Brain Attack Surveillance in Corpus Christi Project, which is designed to capture all strokes in Nueces County, Tex. There are a large number of oil refineries, chemical plants, and other sources of particulate matter pollution in this area.
Nevertheless, the level of particulate matter during the study was low, most likely because of the prevailing winds and coastal location, they said.
Air pollution and meteorological data were obtained from the Texas Commission on Environmental Quality.
From Jan. 1, 2001 through Dec. 31, 2005, the researchers identified 2,350 ischemic strokes and 1,158 transient ischemic attacks in patients ages 45 and older (median age 72). Half of the patients were Mexican-American, 44% were white, and 5% were African American.
The increased risk of suffering a stroke or transient ischemic attack was independent of ozone levels after accounting for temperature, day of the week, and temporal trends in cerebrovascular events.
Season did not modify the association.
"These data contribute to the literature because there is currently a scarcity of data on the effect of environmental exposures on risk for stroke in the United States," the researchers said.
Future studies on the effects of particulate air pollution on the risk for subtypes of ischemic stroke could reveal the biological mechanisms at work, they said.
The authors acknowledged some limitations to the study, including the fact that, as an ecological study, it should be used primarily for generating hypotheses. The results should be replicated, they said, and future studies should take into account any unmeasured confounders.
In addition, measurement of particulate matter is subject to error. The values obtained in this study may not be generalizable over a wider geographic area, they said.
Finally, they said, residual confounding by other pollutants may have occurred.
The study was funded by a grant from the National Institute of Neurological Disorders and Stroke.
The authors made no disclosures.
Primary source: Annals of NeurologySource reference:Lisabeth L, et al "Ambient air pollution and risk for ischemic stroke and transient ischemic attack" Ann Neurol 2008; DOI: 10.1002/ana.21403.

Deaths Higher for Strokes Treated at Night, on Weekends

Susan Jeffrey
Two new studies again suggest that stroke mortality is higher in patients who are admitted to the hospital during nights and on weekends.
The results were presented here during the International Stroke Conference 2008.
In 1 report, researchers led by Matthew J. Reeves, PhD, associate professor of neurology at Michigan State University, in East Lansing, researchers found that the risk for in-hospital mortality was higher for all patients who presented after hours and on weekends, but particularly so for hemorrhagic stroke patients.
The other study, with lead author David S. Liebeskind, MD, associate professor of neurology at the University of California, Los Angeles, showed that mortality was higher for patients with any stroke admitted to the hospital on a weekend vs a weekday.
The findings, both researchers speculated, may reflect differences in the quality of care offered to stroke patients during these off-hours.
"There are differences here that shouldn't be," Dr. Liebeskind told reporters here. These findings "set the course for items to address to make sure that these inequalities are not persisting."
Dr. Reeves pointed out that roughly half of stroke patients in his study were treated during off-hours. Based on this, they calculated the population-attributable risk of this differential between on- and off-hours. "It's about 5%, so theoretically, if you could get rid of the difference between on-hours and off-hours, you could lower the mortality rate by 5%," Dr. Reeves said. "Probably there are not many things you'll see at this conference this week that could do that."
Weekend Presentation a Hazard
Previous studies in Canada and Europe have suggested that patients admitted for stroke on the weekends have poorer care and higher risk-adjusted mortality, Dr. Liebeskind said. In the study presented here, the researchers looked at stroke outcomes in the United States, comparing weekend and weekday admissions.
They used data on more than 2.4 million stroke admissions from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project between 1988 and 2004 based on International Statistical Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 430 to 438. Annual percentages and trends analyses were conducted for demographic variables, admission characteristics, procedures, and outcomes. Of 2,409,043 total admissions, 1,397,883 were ischemic strokes.
Patients admitted on weekends vs weekdays did not differ in age, race, sex, or socioeconomic status, they note. Weekend patients were more often admitted emergently (70.2% vs 53.5%), but length of stay was similar between cohorts.
The researchers found that the mortality rate for all stroke patients admitted on weekdays was "remarkably lower," they write, than weekend admissions, a pattern that was also seen in the ischemic stroke subgroup.
Patients were also more likely to be routinely discharged if they were admitted on weekdays compared with weekends (53.2% vs 43.8%; P < .001). Again, this was also true of the ischemic stroke subgroup.
Dr. Liebeskind noted that the cohorts had a similar number of procedures done, but those in the weekend cohort underwent their first procedure almost 1 day later than the weekday group, with the first procedure at 2.65 days after the event, vs 1.76 days for the weekday group.
He added that although stroke mortality did go down during the 15-year period, the differential in mortality between those admitted on the weekend vs weekdays persisted.
Their analysis ended in 2004, during a time when primary stroke centers were still being developed and mobilized throughout the country, he added. "We don't know how things will sit in coming years with stroke centers that have been developed and tailored, so that remains to be seen, but the hope is that we standardize care irrespective of the day of the week."
Increased Risk with "Off-Hour" Admissions
In a separate report, Dr. Reeves and colleagues looked at outcomes among 308,545 stroke admissions at 857 US hospitals participating in the Get With the Guidelines — Stroke (GWTG-Stroke) program, a continuous quality-improvement program through the American Heart Association/American Stroke Association (ASA). They included hospitals that submitted at least 20 cases between October 2001 and April 2007.
For this analysis, 883 cases were excluded because they did not arrive at the emergency department, and 6701 cases that did not have data on mortality status were also excluded. A total of 187,669 ischemic stroke and 34,845 hemorrhagic stroke cases were included in the final analysis.
"On-hour" presentation was defined as presentation between 7 AM and 6 PM on weekdays, and "off-hour" presentation as presentation at any other time. The relationship between time of presentation and in-hospital mortality was examined using generalized estimating equation methods, adjusted for a variety of patient and hospital variables.
They found 50% of ischemic stroke cases and 57% of hemorrhagic stroke cases presented during off-hours. In-hospital mortality was higher for both ischemic and hemorrhagic stroke cases who presented during off-hours.
After adjustment for demographic factors, stroke risk factors, arrival mode, and hospital characteristics, presentation during off-hours was still associated with a small but statistically significant increase in the risk for in-hospital mortality for both stroke types.
They did see a trend to some improvement during the study period, suggesting an effect of the GWTG-Stroke quality-improvement program, he noted. "We did see a narrowing of the difference between off-hour higher mortality and longer program participation. It's observational data, and I'm not saying that's causal, but there is a trend."
However, he noted, "You'd think that if you participate in a quality-improvement program there would be some spillover; that you wouldn't just see improvement from Monday to Friday, but you would see improvement on weekends as well," he said. But he said, "We really don't know the mechanisms of this and really need better data to say exactly what's causing it."
More precise measures, for instance, such as the delay in imaging seen in Dr. Liebeskind's data, would be helpful in pinpointing the problems, he added.
"I think it's a public health issue about why we find this acceptable, that hospitals can provide basically a different business model on the weekends," Dr. Reeves said.
Dr. Liebeskind agreed. "Instead of looking for a magical therapy, fix the weekend problem."
Room for Improvement
In a statement from the ASA, advisory chair Ralph Sacco, MD, from the University of Miami, in Coral Gables, Florida, said, "Although we are improving our rapid treatment approaches for acute stroke and improving outcomes, these new studies suggest that we may have room for improvement for those cases who present during off-hours. The outcome disparities, however, were greatest for hemorrhagic stroke patients, for whom we have the least successful treatments to offer."
Dr. Liebeskind has disclosed that he has received funding from the National Institute of Neurological Disorders and Stroke. Dr. Reeves has disclosed no relevant financial relationships.
International Stroke Conference: Abstracts P174, P540. Presented February 20, 2008 and February 21, 2008.

Vitamin C Levels in Plasma May Predict Stroke Risk

Susan Jeffrey
January 17, 2008 — A new analysis from a prospective cohort study suggests that higher plasma levels of vitamin C are associated with a reduced risk for stroke. Researchers report that those in the highest quartile for plasma vitamin C had a 42% reduced risk for stroke compared with those in the lowest quartile.
The results, from the prospective European Prospective Investigation into Cancer (EPIC)–Norfolk study, are published in the January 1 issue of the American Journal of Clinical Nutrition.
Whether the causal link between plasma vitamin C and stroke can be identified, plasma vitamin C concentrations may nevertheless be a good predictive indicator of stroke risk, lead author Phyo Kyaw Myint, MRCP, from the clinical gerontology unit at Addenbrooke's University Hospital in Cambridge, United Kingdom, told Medscape Neurology and Neurosurgery.
"Vitamin C is a biomarker of fruit and vegetable consumption, which have many nutrients which may be biologically active and protective for stroke; high fruit and vegetable consumption has been reported in previous studies to be protective for stroke," he said. "Measuring plasma vitamin C levels may identify those who will most benefit from established risk factor management such as blood pressure control."
Trials Negative to Date
Because of its antioxidant activity, higher levels of ascorbic acid are thought to be associated with reduced cardiovascular disease risk, the authors write. However, randomized trials of supplementation with antioxidant vitamins including beta-carotene, vitamin E and vitamin C, including the Heart Outcomes Prevention Evaluation (HOPE) study and the Finnish Alpha-Tocopherol, Beta Carotene Cancer Prevention Study, have shown no effect in reducing cardiovascular risk.
Previous prospective studies have shown that high fruit and vegetable intakes, for which plasma vitamin C is a good biomarker, are associated with lower stroke risk. However, few studies have examined the relationship between plasma vitamin C concentrations and stroke risk, and those that have were limited in their ability to account for potential confounding factors, Dr. Myint and colleagues write. "We explored the relation between baseline plasma vitamin C concentrations and future stroke risk in British participants in the European Prospective Investigation into Cancer (EPIC)–Norfolk," study, a population-based prospective study.
The study included 20,649 men and women aged 40 to 79 years, who were free of prevalent stroke at baseline. Participants completed a health questionnaire and attended a clinic between 1993 and 1997, when baseline measurements of plasma vitamin C were taken. They were then followed up for incident strokes through March of 2005.
For 196,713 person-years of follow-up and average follow-up of 9.5 years, 448 incident strokes occurred.
In a Cox proportional hazards model, those in the highest quartile for plasma vitamin C concentrations had a 42% lower risk for stroke (P = .001) compared with those in the lowest quartile. The association was independent of confounding factors, including age, sex, smoking, body mass index, systolic blood pressure, cholesterol, physical activity, prevalent diabetes and myocardial infarction, social class, alcohol consumption, and any supplement use.
The results were not substantially different after exclusion of those with illnesses, those taking supplements containing ascorbic acid, and those with a history of early stroke during the first 2 years of follow-up, they note.
Their study does have limitations, they note, including that the vitamin C levels were taken in a single measurement at baseline.
"We believe that these findings are of interest for several reasons," Dr. Myint and colleagues conclude. "First, the strong inverse association between plasma vitamin C and stroke suggests that plasma vitamin C is likely to be a good biomarker of whatever causal factors affect stroke risk, most plausibly the dietary intake of plant foods," although they add that identification of the relevant factors may lead to better stroke prevention.
"Second, irrespective of any causal associations, plasma vitamin C appears to be a good predictive risk indicator of stroke, independent of known risk factors such as age, BP [blood pressure], smoking, lipids, diabetes and BMI [body mass index]," they conclude. "Given that about half of the risk of stroke is unexplained by conventional cardiovascular disease risk factors, and that the predictive validity of traditional cardiovascular disease risk factors appears to diminish with age, risk markers that may help identify those persons at greatest risk of stroke for targeted preventive interventions with established therapies, such as BP (blood pressure) reduction, may be of interest."
The Message? Eat Your Fruit and Veg
In an editorial accompanying the article, Sebastian J. Padayatty, MRCP, PhD, and Mark Levine, MD, from the Molecular and Clinical Nutrition Section of the National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, call the study by Myint and colleagues, "refreshing in that its findings are both clear and not overstated."
"On the basis of the evidence presented, the investigators did not advocate an increased intake of vitamin C to prevent stroke," they note. "Such strict interpretation of the data avoids a confusing correlation with causation and allows improved hypothesis generation, but is not sufficient grounds to advocate unfounded and possibly useless treatments."
What can be said to patients and the public at this point is that high intakes of fruits and vegetables are associated with many health benefits, including a reduction in stroke, they conclude. "Because we do not know why or how the benefit occurs or what fruit and vegetables are effective, it is prudent to consume a wide variety. The optimum intake for reduction of stroke and cardiovascular disease is unknown, but an intake of 5 - 9 servings daily is associated with benefit, and the public should aim toward the higher intakes."
The EPIC-Norfolk study is supported by research program grant funding from Cancer Research UK and the Medical Research Council, with additional support from the Stroke Association, British Heart Foundation, Research Into Ageing, Academy of Medical Sciences, and Wellcome Trust. The authors and editorialists have disclosed no relevant financial relationships.
Am J Clin Nutr. 2008;87:5-7, 64-69.

Studies tout treating mini-strokes fast

By MARIA CHENG, AP Medical WriterMon Oct 8, 7:00 PM ET
Treating patients quickly for mini-strokes could dramatically cut the risk of a major stroke later, report two studies that could change standard treatment and potentially save millions of people from stroke's damaging effects.
In research published Tuesday, British and French doctors found that patients treated within 24 hours of having a mini-stroke cut their chances by 80 percent of having a more serious stroke in the next three months.
Such large reductions in risk are rare, said Dr. Peter Rothwell of Oxford University, lead author of a study published in The Lancet medical journal. "We normally get excited about 10 to 15 percent."
Rothwell said that minor strokes should now be classified as medical emergencies. "The health care system needs to be changed to respond to these people quickly," he said. "The current delays in treatment in the United Kingdom are no longer acceptable."
In the U.K., most patients who have small strokes are referred by their doctors to specialist clinics. Many wait several weeks before being treated.
In the United States too, many people are sent home within a day if their symptoms seem to resolve.
Worldwide, nearly 15 million people have a stroke every year, and it is one of the leading killers in the industrialized world.
Mini-strokes, or transient ischemic strokes, have the same symptoms as a big stroke, including facial numbness, slurred speech, paralysis on one side of the body, blurry vision or a sudden headache. But in small strokes, the symptoms last less than a day.
Rothwell's research was drawn from a larger population of nearly 100,000 people being studied for vascular disease. Of 1,278 patients who had a stroke or a mini-stroke, he and colleagues examined roughly 600 people who had mini-strokes.
In the first part of the study, 310 mini-stroke patients were observed as they received standard care, under British medical guidelines. They were referred to an outpatient clinic. After a normal wait of about three weeks, these patients were typically prescribed drugs, including aspirin, to lower their blood pressure and cholesterol, and to prevent clotting.
In the second part of the study, about 281 other patients were given these same medications within 24 hours of their suspected mini-stroke.
The researchers found that the patients treated immediately had only about a 2 percent chance of having a major stroke in the next three months. In comparison, patients who weren't treated as quickly had about a 10 percent chance of having a major stroke in the next three months.
And among those who got delayed treatment, 32 had a bigger stroke. Among those in the group that got fast treatment, only six had a more serious stroke.
The study was funded by Oxford University. Rothwell has occasionally consulted for pharmaceutical companies that make drugs used in stroke prevention.
Similar research was published in Lancet Neurology. Dr. Pierre Amarenco of Bichat-Claude Bernard University Hospital in Paris and colleagues set up a 24-hour clinic to treat patients with suspected mini-strokes.
Among the 1,085 patients followed, the chance that patients would have another stroke within 90 days was a little over 1 percent. That compares to a predicted stroke rate of nearly 6 percent, based on historical medical data.
The Paris study was funded by a French non-profit organization. The authors said they had no conflicts of interest.
Doctors increasingly say that small strokes should be seen as warning signals for a more dangerous stroke later on, in the same way that chest pain can be a red flag for an imminent heart attack.
"We need to think of transient ischemic strokes as the 'angina' or 'acute coronary syndrome' equivalent for the brain," said Dr. Ralph L. Sacco, chairman of neurology at the University of Miami, who was not connected to the study. Sacco said that patients who have mini-strokes are at high risk of a more serious stroke and should be monitored more carefully.
The British Stroke Association said that Rothwell's study should lead to faster treatment of mini-strokes.
"We clearly should not be evaluating stroke symptoms in a leisurely sort of way," said Dr. Larry Goldstein, director of Duke University's Center for Cerebrovascular Disease, who was not connected to the studies. "The main message from these studies is that treatment delays can be dangerous."

Heavy Alcohol Use Increases Stroke Risk, Mortality

August 24, 2007 — Heavy consumption of alcohol has been linked to a significantly increased risk for stroke and stroke-related death in Chinese men.
In a large, population-based study of 64,338 men participating in the China National Hypertension Study, researchers at Tulane University School of Public Health and Tropical Medicine in New Orleans, Louisiana, found those who consumed 35 or more alcoholic drinks per week had a 22% increased risk for stroke and a 30% increased risk for stroke-related death vs nondrinkers.
"We found a progressive, nearly linear, increase in risk of stroke across the categories of drinking. It was significantly higher among individuals who consumed at least 35 drinks per week. But the risk was also increased in moderately heavy drinkers. So the risk was increased in those who were drinking more than 3 drinks per day and was greatly increased among those who consumed more than 5 drinks per day," principal investigator Lydia Bazzano, MD, PhD, told Medscape.
The study is published in the August 20 Online First issue of the Annals of Neurology.
Leading Cause of Death, Disability
In China, stroke is the leading cause of death in men and the leading cause of long-term disability. According to Dr. Bazzano, previous research has not completely clarified the link between the risk for stroke and alcohol consumption.
"We felt this study provided us with an excellent opportunity to look at this relationship in a population that has very high rates of stroke and stroke-related death," she said.
The prospective cohort study included men older than age 40 years who were free of stroke at the outset of the study. At baseline examination in 1991, participants provided information about their demographic characteristics, medical history, and lifestyle risk factors including alcohol consumption.
The follow-up evaluation, which was conducted from 1999 to 2000, included determining vital status, interviewing participants or proxies, and obtaining hospital and medical records for incident and fatal strokes.
Important Implications
During the course of the study, there were 3434 incident strokes and 1848 deaths from stroke. After adjusting for other risk factors including age, body mass index (BMI), physical activity, cigarette smoking, geographic variation, urbanization, history of diabetes, and education, researchers found alcohol consumption was significantly related to increased incidence of stroke as well as mortality.
"We know drinking alcohol can induce hypertension, so we expected to see some increased stroke risk in the highest category, but it was interesting to see this very linear correlation across the board between alcohol consumption and stroke risk," said Dr. Bazzano.
She added that the study's results have important public health implications that are likely generalizable to other populations.
"This study has shown that heavy, or even moderately heavy, drinkers have a much greater risk of stroke and stroke-related death than the general population. For this reason, doctors should advise patients who consume more than 3 alcoholic drinks per day to cut back," she said.
The authors have disclosed no relevant financial relationships.
Ann Neurol. Published online August 20, 2007.

Migraine With Aura Tied to Stroke Risk for Women

BALTIMORE, Aug. 9 -- Women who have migraine with visual symptoms have a 50% greater risk of ischemic stroke than women without the headaches, researchers reported.
Smoking, use of oral contraceptives, and onset of the headaches with aura a year before the stroke also increased the risk, Leah R. MacClellan, M.S.P.H., of the University of Maryland, and colleagues, reported in the Aug. 10 issue of Stroke: Journal of the American Heart Association.
On the other hand, the researchers found no association between stroke and migraine without aura.
And the chance that a young woman in the 15-to-44-age group with migraine and aura will have an ischemic stroke is low-one-to-two for every 10,000 women each year, said Steven J. Kittner, M.D., a study co-author and director of the Maryland Stroke Center here.
Clarifying the clinical features of the headache-stroke relationship may provide useful insights into the association, the researchers said. For example, the effects of migraine frequency, lifetime duration of migraine, and the time of migraine onset and stroke risk, and a possible anatomic predilection are unclear.
To assess these relationships, the researchers analyzed data from a population-based case-control study of young white and African-American women, the Stroke Prevention in Young Women Study (recruitment 1992 to 1996; 2001 to 2003).
Their study included 386 women, ages 15 to 49, with a first ischemic stroke. They were matched in a 1:2 ratio with 614 age- and ethnicity-matched controls with no history of stroke.
After answering a questionnaire, the women were classified as having no migraine, probable migraine without visual aura, or probable migraine with visual aura.
Women with migraine and aura had 1.5 greater odds of ischemic stroke (95% CI, 1.1-2.0). The risk was highest among those with no history of hypertension, diabetes, or myocardial infarction compared with nonmigraineurs, the researchers reported.
Compared with women with no migraine history, women with a migraine and aura history of 12 or more years had a 1.3-fold greater stroke risk.
For women who reported new migraine and aura starting within a year before their stroke or study enrollment, the adjusted odds ratio was 6.9 times higher (CI, 2.3 to 21.2).
Women with migraine and aura who smoked and were current users of oral contraceptives had seven times the stroke risk of women with migraines who neither smoked nor used oral contraceptives (OR 7.0, CI, 1.3 to 22.8).
With regard to the location of a migrainous infarct, the data showed no appreciable anatomic difference in risk of stroke between circulation in the anterior and posterior regions in relation to the migraine.
Also, they said patent foramen ovale has been implicated as a possible mechanism for the stroke risk because it is a risk factor for young-onset stroke and is associated with migraine prevalence.
However, in this study no evidence for the role of the defect was found because the data were insufficient, they said.
Study limitations included the self-reported migraine history, which lacked specific data on untreated duration of headache, or time and duration of aura symptoms, for example.
The proportion of migraineurs in this study was high compared with the prevalence in the general population, possibly because of misclassification of migraine status. Also, the researchers noted that they did not control for factors such as medication use, cholesterol, alcohol consumption, and physical activity.
Given the contributing risk factors, the researchers advised neurologists and physicians to encourage their patients with migraine and aura to minimize their stroke risk by not smoking and finding alternatives to estrogen-containing contraceptives.
The association indicates a high-risk population for which appropriate management strategies are warranted, they concluded.
No financial conflicts were reported.
This study was supported in part by the Office of Research and Development, Medical Research Service, the Research Enhancement Award Program in Stroke, the Geriatrics Research, Education, and Clinical Center, Department of Veterans Affairs; a cooperative agreement with the Cardiovascular Health Branch, Division of Adult and Community Health, Centers for Disease Control, the National Institute of Neurological Disorders and Stroke, the National Institutes of Health Office of Research on Women's Health; the National Institute on Aging Pepper Center Grant, the University of Maryland General Clinical Research Center Grant, General Clinical Research Centers Program, National Center for Research Resources, and the National Institutes of Health. Primary source: StrokeSource reference: MacClellan LR, et al "Probable Migraine With Visual Aura and Risk of Ischemic Stroke: The Stroke Prevention in Young Women Study" Stroke 2007; 38: doi.1161/strokeaha.107.488395

Oral Anticoagulants Trump Antiplatelet Therapy for Primary Stroke Prevention in Nonvalvular AF

August 6, 2007 — Oral anticoagulants are superior to antiplatelet therapy for primary stroke prevention in patients with nonvalvular atrial fibrillation (AF), according to a new report published in the Cochrane Database of Systematic Reviews July 18.
The meta-analysis, which included 8 randomized controlled trials and almost 10,000 patients, found warfarin and other anticoagulants reduced primary stroke risk in patients with AF by about 33% compared with antiplatelet therapies. Patients who received antiplatelet therapy had a 20% reduction in primary stroke risk compared with their counterparts who received no preventive treatment.
"When it comes to secondary stroke prevention, it's well-known warfarin is superior to aspirin or other antiplatelet therapy, but we wanted to compare the efficacy of these agents in primary prevention. We found warfarin or other anticoagulant therapy reduced the risk of stroke and other ischemic vascular events in patients with nonvalvular AF and that this effect was superior to the effect of antiplatelet therapy in this patient population," study investigator Maria Aguilar, MD, from the Mayo Clinic in Scottsdale, Arizona, told Medscape.
"Anticoagulants reduced [stroke] risk 10% to 20% more than antiplatelet therapy, including aspirin, clopidogrel, and other antiplatelet agents. Based on these results, we think warfarin is probably the best option for primary stroke prevention in patients who can take it safely," she added.
For the review, the investigators included all unconfounded, randomized trials in which long-term (more than 4 weeks), adjusted-dose oral anticoagulant treatment was compared with antiplatelet therapy in patients with chronic nonvalvular AF.
Management Challenges
The 8 trials included 9598 patients without prior stroke or transient ischemic attack (TIA) and looked at warfarin vs adjusted-dose aspirin (in doses ranging from 75 to 325 mg/day). The mean overall follow-up was 1.9 years per study participant.
Oral anticoagulants were associated with lower risk of all stroke, ischemic stroke, and systemic emboli. In addition, the authors report that all disabling or fatal strokes and myocardial infarction (MI) were substantially, but not significantly, reduced by oral anticoagulants.
Vascular death and all-cause mortality outcomes were similar between the 2 treatments; intracranial hemorrhage was increased by anticoagulant therapy.
While the study's results are not unexpected, said Dr. Aguilar, she hopes that the findings will help strengthen physicians' confidence in the benefits of anticoagulant therapy in this patient group.
Admittedly, said Dr. Aguilar, warfarin is not a benign agent and can cause devastating complications, including death. In addition, there are significant challenges associated with its management.
"Treating patients with warfarin requires an anticoagulation clinic, access to a lab, and a significant commitment from the patient and the patient's family. As a result, most general practitioners favor antiplatelet therapy," she said.
Only Available Option
Nevertheless, she added, at this point it is the only available option for stroke prevention in this patient group and, when administered correctly, is safe and effective.
"I hope these results will help clinicians who are still reluctant to use anticoagulation therapy take a more open-minded approach toward it," she said.
What is needed ultimately, she said, is an agent that combines the efficacy of warfarin with the safety of aspirin. The best recent hope for this was ximelagatran.
The one-size-fits-all drug promised to overcome the monitoring, drug interaction, and dietary issues associated with warfarin therapy. Unfortunately, said Dr. Aguilar, the agent turned out to be hepatotoxic and never made it to market.
"At this point, there are no new therapies in the pipeline to prevent stroke in this growing population of older patients with nonvalvular atrial fibrillation. We will have to learn to live with what we have and do our best to prevent stroke using existing antithrombotic therapy," she said.
Cochrane Database Syst Rev. Published online July 18, 2007.

VAS-COG: Lowering Angiotensin II May Raise Stroke Risk

SAN ANTONIO, July 16 -- Drugs that lower angiotensin II may increase the risk of stroke, contrary to conventional wisdom, an investigator asserted here.
A review of 26 clinical trials involving 206,632 patients revealed a consistent pattern of benefit with drugs that increase levels of angiotensin II compared with those that reduce angiotensin II (P=0.003), Albert Fournier, M.D., reported at the International Society for Vascular Behavioral and Cognitive Disorders.
Dr. Fournier, of University Hospital in Amiens, France, and colleagues did separate analyses of placebo-controlled trials, comparisons against angiotensin II-neutral drugs, and direct comparisons of angiotensin II-raising and angiotensin II-lowering agents.
"Classical and graphical meta-analysis of the large clinical trials that evaluated antihypertensive drugs in primary and secondary stroke prevention support the hypothesis that angiotensin II-increasing drugs are better for stroke prevention than are angiotensin II-decreasing drugs," said Dr. Fournier.
"Although [angiotensin II-raising] drugs decrease systolic blood pressure to a greater extent than angiotensin II-decreasing drugs," he said, "this blood pressure difference does not fully explain the better stroke prevention."
An abundance of data from experimental models of stroke suggests a protective effect from activation of receptors for angiotensin II and angiotensin IV, said Dr. Fournier. However, the hypothesis that angiotensin activation is cerebroprotective has not been specifically evaluated in clinical trials.
For the current analysis investigators grouped studies according to medications' effect on angiotensin II:
Drugs that increase angiotensin II: diuretics, dihydropyridine calcium-channel blockers, short-acting non-dihydropyridine calcium channel blockers, and angiotensin Ireceptor blockers
Drugs that decrease angiotensin II: beta-blockers, ACE inhibitors, and long-acting dihydropyridine calcium channel blockers
Angiotensin-neutral drugs: alpha-blockers and the combination of a thiazide diuretic and a beta-blocker
The 26 trials excluded patients with heart failure, and a cumulative total of 7,108 strokes were reported in the studies.
Placebo-controlled trials demonstrated an overall hazard ratio for stroke of 0.67 for drugs that increase angiotensin II versus 0.87 for drugs that lower angiotensin II drugs.
In trials that involved active comparators with angiotensin II-neutral effects, drugs that decrease angiotensin II levels had a cumulative relative risk for stroke of 1.04. In contrast, angiotensin II-lowering drugs had a relative risk of 0.84 compared with the neutral agents.
Finally, in direct clinical comparisons, drugs that lower angiotensin II had a relative risk for stroke of 1.17 compared with drugs that increase angiotensin II levels.
Only one trial (a comparison of a beta-blocker and a thiazide diuretic) showed a stroke advantage for drugs that lower angiotensin II.
The remaining eight studies demonstrated a relative risk of 1.03 to 2.28 for drugs that decrease levels of angiotensin II.
The difference in stroke risk in clinical trials that compared angiotensin II-raising and angiotensin II-lowering drugs was statistically significant (P=0.003). A test for heterogeneity among the studies was not significant (P<0.07).
The investigators declared no conflicts of interest or outside funding sources for the study. Primary source: International Society for Vascular Behavioral and Cognitive DisordersSource reference: A Fournier et al. "Blood pressure (BP)-independent stroke prevention is better when angiotensin-II is increased by antihypertensive drugs: a graphical evidence." International Society for Vascular Behavior and Cognitive Disorders Annual Meeting, July 11-14, San Antonio. Final Program. Abstract P-114.

VAS-COG: Mild Cognitive Impairment May Increase Stroke Risk

SAN ANTONIO, July 13 -- Mild impairment of the executive function domain of cognition may represent an early marker of increased stroke risk, according to data from the Framingham Study.
Mildly impaired executive function conferred a stroke hazard ratio of 2.4 compared with normal executive function in the original Framingham cohort, Sudhas Seshadri, M.D., of Boston University reported at the International Society of Vascular Behavioral and Cognitive Disorders meeting here.
An even greater effect was seen in the Framingham Offspring cohort, as mildly impaired executive function increased the relative risk of stroke almost five-fold, the investigators added
Mild impairment in the verbal memory or amnestic domain of cognitive function was associated with an increased risk of dementia and Alzheimer's disease in the original Framingham cohort but not stroke.
"We know that vascular risk factors increase the risk of stroke and independently increase the risk of impaired cognitive function in people who have not had a stroke," said Dr. Seshadri. "It could be that poorer cognitive function is a marker of the duration or severity of exposure to vascular risk factors. It might also be a marker of susceptibility to these risk factors."
The study consisted of 1,312 original Framingham participants who underwent cognitive testing during 1976 to 1978 and 1,941 Framingham Offspring participants who had cognitive evaluations during 1998 to 2004. All participants were free of stroke and dementia at baseline, and the offspring participants also were known to be free of such neurologic conditions.
Neuropsychological assessment of the study participants comprised five domains of cognition, but Dr. Seshadri and colleagues looked for mild cognitive impairment in two domains-- verbal memory and executive function. They defined mild impairment as 1.5 standard deviations below adjusted means scores for the population.
Multivariate proportional hazards models were used to estimate the 10-year risk of incident stroke for participants with mild impairment in either of the two domains.
During 10 years of follow-up, 92 strokes and 84 cases of dementia occurred in the original Framingham cohort. In the younger offspring cohort, 25 strokes occurred, and dementia occurred too infrequently to assess.
In the original cohort, mild impairment in executive function independently predicted stroke risk (P<0.05) but not dementia or Alzheimer's disease. Mild impairment in verbal memory as associated with almost a six-fold increase in the relative risk of dementia or Alzheimer's disease (P<0.001), but did not predict stroke risk.
In the offspring cohort mildly impaired executive function with a stroke hazard ratio of 4.8 (P<0.001). Impaired verbal memory did not predict stroke risk.
Cognitive function was assessed by means of simple, office-based tests that could easily be incorporated into stroke risk assessment, Dr. Seshadri said.
Dr. Seshadri and her co-investigators had no disclosures to report. Primary source: International Society of Vascular Behavioral and Cognitive DisordersSource reference: S Seshadri et al. "Mild vascular cognitive impairment predicts risk of incident stroke in the Framingham Study." International Society of Vascular Behavioral and Cognitive Disorders meeting. Final Program. Abstract P-6.

Increased BMI Boosts Total and Ischemic Stroke Risk

July 11, 2007 — An analysis of data from a large Finnish cohort, with follow-up of almost 20 years and more than 3200 incident stroke events, shows that increased body mass index (BMI) is a risk factor for both total and ischemic stroke.
Abdominal adiposity, defined as the highest quartile for waist circumference or waist-hip ratio, however, was a risk factor for total and ischemic stroke for men but not for women.
The findings provide yet another reason for those with higher BMIs to try and control their weight, lead author Gang Hu, MD, PhD, from the National Public Health Institute and the University of Helsinki in Finland, told Medscape. "We believe they should reduce their weight because obesity is a very strong risk factor for stroke from this study."
The study is published in the July 9 issue of the Archives of Internal Medicine.
Conflicting Results
Although adiposity is an established risk factor for cardiovascular disease, the relationship with cerebrovascular disease has been less clear, the authors write.
Some studies have shown an association between high BMI and total stroke, particularly ischemic stroke. However, the association disappeared after adjustment for other risk factors, suggesting the effect of BMI might be mediated through those other factors, particularly hypertension, they write. Other studies showed no such association or showed that a low BMI might increase stroke risk.
Several studies have suggested that indicators of abdominal adiposity, such as waist circumference or waist-hip ratio, may be a stronger predictor of stroke than BMI, they note.
This Finnish study, a cross-sectional population survey, is one of the largest cohorts in the world, Dr. Hu said. For this analysis, they investigated the association of BMI, waist circumference, and waist-hip ratio with total and ischemic stroke incidence among 49,996 Finnish men and women who were aged 25 to 74 years and free of coronary heart disease and stroke at baseline.
During an average follow-up of 19.5 years, 3228 subjects (1673 men and 1555 women) had an incident stroke. Of these, 674 were hemorrhagic and 2554 were ischemic.
Data were analyzed dividing BMI levels by World Health Organization (WHO) categories: lean or underweight (BMI, < 18.5 kg/m2), normal weight (BMI, 18.5 - 24.9 kg/m2), overweight (BMI, 25.0 - 29.9 kg/m2), and obese (BMI, ≥ 30.0 kg/m2).
They found that, after adjustment for age, study year, smoking status, physical activity, educational level, family history of stroke, and alcohol consumption, increasing BMI was a risk factor for total and ischemic stroke in both men and women, compared with individuals of normal weight.
Additional adjustment for other factors, including systolic blood pressure, total cholesterol level, and history of diabetes, appeared to attenuate the association, they note, but it remained statistically significant for both sexes.
For hemorrhagic stroke, they found no association with BMI for either men or women if they used the WHO categories. However, when they divided BMI into 7 categories, a U-shaped risk pattern emerged, with increased risk for hemorrhagic stroke seen in women with BMIs at both the lowest and highest BMI levels.
Positive associations of total and ischemic stroke across quartiles of waist circumference or waist-hip ratio were seen for men but not for women. No association of hemorrhagic stroke with either of those variables was seen.
"In conclusion, the present study demonstrates that BMI is associated with an increased risk of total and ischemic stroke in men and women," the researchers write. "Furthermore, a substantial additional risk is mediated through adiposity-related risk factors, such as blood pressure, total cholesterol level and diabetes mellitus."
The study was supported by a grant from the Finnish Academy and by the Finnish Foundation for Cardiovascular Research. The authors have disclosed no relevant financial relationships.
Arch Intern Med. 2007;167:1420-1427.

Midlife Strokes More Common Among Women

LOS ANGELES, June 21 -- Strokes in middle age strike women more than twice as often as they do men, researchers found.
Stroke prevalence was 2.39-fold higher for women than men at ages 45 to 54 (2.5% versus 1.0%, P=0.004), Amytis Towfighi, M.D., of the University of California at Los Angeles, and colleagues, reported online in Neurology.
In their analysis of the 1999 to 2004 National Health and Nutrition Survey (NHANES), modifiable risk factors, including heart disease and waist circumference appeared to be factors in the gender difference.
Because women are known to receive less preventive and diagnostic cardiovascular care than men, the findings reaffirm the need for improved risk factor modification among women, the researchers suggested.
"Prompt and close attention may need to be paid to the cardiovascular health of women in their mid-30s to mid-50s with a goal of mitigating this burden," they wrote.
The researchers analyzed data from a nationally representative sample of 17,061 adults in NHANES. Among the participants, 606 (4%) reported during the household interview that a physician had ever told them that they had experienced a stroke. About half were women (49%).
Respondents were not asked about transient ischemic attacks or stroke type.
The stroke rate was consistently higher among women than men in middle age, though the difference was only significant for the age range 45 to 54. The findings were:
Similar rates between women and men at age 35 to 44 (1.2% versus 1.0%, OR 1.2142, 95% confidence interval 0.4715 to 3.1268, P=0.6876).
Significantly higher rates among women than men at age 45 to 54 (2.5% versus 1.0%, OR 2.3903, 95% CI 1.3205 to 4.3267, P=0.0040).
Similar rates between genders at age 55 to 64 (3.4% versus 3.0%, OR 1.1256, 95% CI 0.6218 to 2.0376, P=0.6961).
The increasing stroke rate with age-"a well-established predictor of higher stroke risk"-for both genders was not surprising, the researchers said.
Women in the 45 to 54 and 55 to 64 age groups were more likely to experience stroke than those in the 35 to 44 group (OR 2.1346, P=0.0667, and OR 2.9818, P=0.0078, respectively).
Men in the 55 to 64 age group were significantly more likely to have a stroke than those 35 to 44 (OR 3.2165, P=0.0034) or those 45 to 54 (OR 2.9665, P=0.0011).
There were also significant gender differences in the factors that contributed to stroke risk in a multivariate analysis that adjusted for race, ethnicity, waist circumference, systolic blood pressure, homocysteine, glycohemoglobin, total cholesterol, and history of hypertension, diabetes, smoking, and coronary artery disease.
For men ages 45 to 54, a history of smoking was the only independent predictor of stroke. For women, the only independent predictors were coronary artery disease (OR 12.79, P=0.0088) and waist circumference (OR 1.543, P=0.0489) after further adjustment for any use of hormone replacement therapy, which was not a significant predictor of stroke in the 45 to 54 age group.
In a separate multivariate analysis for severe headache or migraine (reported for the three months prior to the survey), this measure was an independent predictor of stroke as well among women (OR 4.859, 95% CI 1.864 to 12.669, P=0.0012).
"This sex difference in stroke predictors may not be surprising because we observed a steeper rise in several conventional vascular biomarkers over the course of midlife in women compared with men, with the biggest changes frequently occurring between 45 and 54 years," Dr. Towfighi and colleagues noted.
Blood pressure increased seven to 10 points per decade among women but four to five points with each decade among men. At age 35 to 54, the average systolic blood pressure was significantly higher among men (119.9254 versus 113.9440 mm Hg, P<0.0001). But by age 55 to 64, the opposite was true (128.6503 versus 131.9976 mm Hg, P=0.0082).
Total cholesterol levels followed the same pattern-increasing by 10 to 12 points each decade among women but remaining stable among men. Men had significantly higher levels at age 35 to 54, (208.6748 versus 197.5985 mg/dL, P<0.0001) but were overtaken by women by age 55 to 56 (208.6748 versus 197.5985 mg/dL, P<0.0001).
Likewise, homocysteine, glycohemoglobin, and triglyceride levels and the atherosclerosis biomarker ankle-brachial pulsatility index increased faster with age among women than men in midlife.
The investigators noted that these trends are in keeping with stroke trends seen over time in observational studies in the United States.
In the one study using the Swedish Hospital Discharge Register, women ages 30 to 65 had a 33% rise in strokes in 1998 to 2000 compared with 1989 to 1991, whereas men had only a 19% increase. Notably, most of the increases in this study were seen in patients younger than 60.
Dr. Towfighi and colleagues cautioned that the study's cross-sectional design "may limit any strong inferences from being drawn at this time" as to the reasons for the gender disparities in midlife stroke. Further study is needed, they said.
"In the meantime, our study suggests a substantial toll of stroke among women aged 45 to 54 years that may be amenable to optimal control of modifiable vascular risk factors," they concluded.
The researchers reported no financial conflicts of interest. Primary source: NeurologySource reference: Towfighi A, et al "A midlife stroke surge among women in the United States" Neurology 2007;69.

Type 2 Diabetes Doubles Short-Term Stroke Risk

June 21, 2007 — Research shows individuals who develop type 2 diabetes have a 2-fold increased stroke risk within the first 5 years of diagnosis compared with the general population.
Investigators at the University of Alberta, Canada, found an almost 10% absolute risk for stroke within 5 years of diabetes diagnosis vs an approximate 4.5% absolute risk in the general population.
Previous research examining the association between diabetes and stroke risk has typically looked at long-term cardiovascular outcomes — usually after 10 years or more — where it has been shown associated with a 2- to 3-fold increased risk. However, this study is the first to investigate the short-term risk.
"These results show stroke risk is high, even very early in the course of diabetes. This study strongly supports aggressive management of cardiovascular risk factors immediately after diagnosis," principal investigator Thomas Jeerakathil, MD, MSc, told Medscape.
The study is published in the June 1, 2007, issue of Stroke.
Suboptimal Risk Factor Management
According to Dr. Jeerakathil, scientific evidence suggests management of cardiovascular risk factors leaves a lot to be desired, both in individuals with diabetes as well as the general population.
"With respect to diabetes we thought perhaps one of the reasons for this phenomenon was due to a perception that cardiovascular risk does not accumulate until a decade or more after disease onset. We thought it would be useful to see whether in fact, there was an upfront stroke risk following a new diagnosis of diabetes," he said.
Data for the large population-based cohort study were derived from linkable health databases from the province of Saskatchewan, Canada, which has a publicly funded health system and a population of 1 million. Stroke hospitalizations are documented yearly by age and sex, which allows investigators to compare stroke rates between the study group and the general population.
The diabetes cohort included 12,272 subjects aged 30 years or older who were recently diagnosed with type 2 diabetes. Outcomes for the diabetes study cohort included only the first stroke-related event, whereas all stroke hospitalizations were included in the population comparator group, including recurrent events.
Younger Individuals at Higher Risk
The average age of the diabetes cohort was 64 years, and 55% were men. One of the study's surprising findings, said Dr. Jeerakathil, was that the relative risk for stroke was much higher in younger individuals than in their older counterparts.
Those aged 30 to 44 years had a relative short-term risk of 5.6 vs 1.8 in subjects older than 75 years. "This was surprising to us and suggests the diabetic state in younger people is a major cause of stroke in this population," he said.
Dr. Jeerakathil added that a better understanding of the short-term risk for stroke in patients with type 2 diabetes may improve the motivation of clinicians and patients to adhere to proven therapies to lower stroke risk in patients with type 2 diabetes.
Furthermore, he pointed out that because of the population-based design of the study, which included an entire population covered under a universal health care system, the results are highly generalizable.
"I hope this study will outline to people there is a risk for stroke even in the first few years after diagnosis and treatment [of diabetes] and I hope it will highlight to both physicians and patients that major cardiovascular risk factors need to be aggressively managed right from the time a patient is diagnosed," said Dr. Jeerakathil.
Stroke. 2007;38:1739-1743.

FASTER: Clopidogrel Plus Aspirin May Reduce Secondary Stroke Risk, But No Preventive Effect With Statins

June 13, 2007 (Glasgow) — Results of the pilot phase of the Fast Assessment of Stroke and Transient Ischemic Attack to Prevent Early Recurrence (FASTER) trial suggest that the addition of clopidogrel to aspirin administered within 24 hours of a transient ischemic attack (TIA) or minor stroke is associated with a reduced risk for recurrent stroke. However, immediate statin use following such events has no significant impact on secondary stroke prevention.
Presented recently at the 16th European Stroke Conference, FASTER — the first randomized trial to evaluate the effects of early aggressive intervention with combination antiplatelet therapy and high-dose statin therapy immediately after minor stroke or TIA — showed a 3.7% reduction in recurrent stroke among individuals on active clopidogrel, compared with placebo.
In contrast, study subjects on active simvastatin had a 3.3% increased risk for recurrent stroke, compared with placebo (10.6% vs 7.3%).
Minor Stroke, Major Risk
"These results suggest that the addition of clopidogrel to aspirin is associated with a reduction in stroke following TIA or minor stroke, [but] it appears unlikely that there is a significant effect of stroke prevention with early statin use. However, both of these conclusions need to be compared in a larger study," said the study's principal investigator, James Kennedy, MB, MSc, from the University of Oxford, in the United Kingdom.
Previous research has shown the risk for recurrent stroke following a TIA or minor stroke is high: approximately 8% at 7 days, 12% at 30 days, and up to 20% at 90 days.
Despite the high risk for recurrence, many patients with TIA or minor stroke are not considered appropriate candidates for tissue plasminogen activator because their symptoms are too "mild" to assume the risks associated with aggressive thrombolysis. However, according to Dr. Kennedy, about one third of these patients ultimately end up either dead or dependent.
Encouraged by results of recent trials in patients with unstable angina, which have shown a benefit of early combination therapy (aspirin and clopidogrel and statin therapy), the aim of the FASTER trial was to determine whether this same benefit would occur in patients with acute symptomatic cerebrovascular disease.
Early Closing
The primary end point of the pilot phase of the study was any stroke at 90 days and stroke severity.
A total of 2885 patients were assessed for study inclusion in the multicenter trial, which included 19 centers in Canada and 1 in the United States. Of these subjects, 2489 were excluded; the remaining 396 participated in the study.
According to Dr. Kennedy, the eligibility criteria for the study focused on those individuals considered to be at highest risk for subsequent deterioration, with either weakness or speech disturbance at the time of symptom onset and symptom duration lasting 5 minutes or longer.
Subjects were ineligible if they were currently on statin therapy, antiplatelet therapy (excluding aspirin), or anticoagulation. Subjects were also excluded if they were candidates for thrombolysis or other acute intervention, or if their stroke was suspected to have a cardioembolic source.
The majority of subjects were excluded because they were on clopidogrel, anticoagulation, or statin therapy. In fact, said Dr. Kennedy, the increasing use of statins over the course of the study, which began in May 2003 and ended in December 2006, played a large role in its failure to meet its enrollment target of 500 subjects, which resulted in its early closing.
Hypothesis Generating
All participants were taking aspirin. Those who weren't taking aspirin at trial entry were given a loading dose of 162 mg and subsequently 81 mg per day. Subjects were randomized to receive clopidogrel (300 mg loading dose plus 75 mg/day) or its placebo, or simvastatin (40 mg/day) or simvastatin placebo within 24 hours of TIA or minor stroke onset for 90 days.
A total of 35 recurrent strokes occurred during the 90-day study period, 2 of which occurred within the first 7 days.
In terms of safety, 2 patients on active clopidogrel experienced intracranial hemorrhage and 4 had systemic hemorrhages (1 severe, 2 moderate, and 1 mild); none of the patients taking placebo experienced hemorrhage.
In addition, 61 (30.8%) subjects in the clopidogrel group experienced asymptomatic hemorrhages or bruising, whereas only 27 (13.9%) in the placebo group did.
The increased use of statins, which ultimately hampered study enrollment, means FASTER is not a feasible trial. However, added Dr. Kennedy, the results of the pilot phase are hypothesis-generating and will inform future resear

Blood pressure predicts stroke risk for all groups

Thu Mar 29, 2007 4:39PM EDT
NEW YORK (Reuters Health) - Systolic blood pressure is an important predictor of stroke risk among men and women and across racial groups, according to a report in the American Journal of Hypertension.
Systolic blood pressure -- the top reading of the blood pressure -- has been shown to be a better predictor of stroke than diastolic blood pressure - the lower reading -- among apparently healthy white men, the authors explain, but it is unclear whether this holds true for women and African Americans.
Dr. David W. Brown and colleagues from the Centers for Disease Control and Prevention in Atlanta, investigated whether various blood pressure parameters -- individually and in combination -- improved the prediction of stroke events, using data from the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study.
The study population included 3295 men and 3462 women. Over a median follow-up of nearly 15 years, 113 fatal strokes occurred.
Brown's team found that increasing systolic blood pressure, diastolic blood pressure, pulse pressure, and mean arterial pressure were individually associated with an increased risk of fatal stroke.