Monday, June 21, 2010

Risk factors for stroke

Stroke animation

This animation explains how a stroke happens, the different types of stroke, and how lifestyle changes may help to reduce the risks.
Just 10 lifestyle choices and medical conditions account for the majority of strokes, the Daily Mail reported. It said that a study had found that 80% of cases were caused by high blood pressure, smoking, a fat stomach, poor diet and lack of exercise. Another 10% could be attributed to diabetes, excessive alcohol consumption, stress and depression, heart disorders and a higher concentration of molecules in the blood (apolipoproteins) that are involved in the transportation of bad cholesterol.
The newspaper report is accurate and importantly highlights that the majority of the risk factors for stroke are modifiable. In other words, they are a risk that can be changed.
This was a well-conducted international study. The researchers say that in future, they will address some of the study’s shortcomings, including recruiting an additional 10,000 stroke patients and matching controls, making the results more robust and allowing comparison between countries. Their conclusion that ‘targeted interventions that reduce blood pressure and smoking, and promote physical activity and a healthy diet, could substantially reduce the global burden of stroke’, seems sensible.

Where did the story come from?

The study was carried out by researchers from McMaster University and other medical and academic institutions around the world, including in China, India, Uganda, Mozambique, Colombia and Australia. The study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, Pfizer, Merck, AstraZeneca and Boehringer Ingelheim. The study was published in the peer-reviewed medical journal The Lancet.
The Daily Mail has covered this research appropriately.

What kind of research was this?

This story is based on the INTERSTROKE study, a multinational case control study in 6,000 people recruited from 22 countries between 2007 and 2010. The study’s aim was to determine which factors are associated with stroke and how much risk each factor contributes. To do this, researchers compared the exposures in 3,000 people who had an acute first stroke with a control group that had no history of stroke (matched on age and sex).

What did the research involve?

People who had experienced their first acute stroke were recruited from 84 centres in 22 countries. Patients were included after an acute stroke within five days of stroke symptoms first appearing or from when they were last seen without symptoms, within 72 hours of admission to hospital and if a brain scan (CT or MRI) was planned for within one week of initial diagnosis.
Stroke patients were asked to complete a questionnaire at the beginning of the study. For those who were incapable of this, a proxy respondent was identified (spouse or first-degree relative living in the same home). A control was identified for each case and matched in terms of sex and age (within five years). The control group were based either in hospital or in the community and had no history of a stroke. The researchers identified which type of stroke the participant had (ischaemic [blood clot] or intracerebral haemorrhagic [bleed into the brain]), based on clinical assessment and neuroimaging (CT or MRI).
The questionnaire assessed the participants’ risk factors, measuring key vascular risk factors, including hypertension (high blood pressure) or diabetes, anthropometrical measurements (waist, hip circumference, height and weight), physical activity, diet, alcohol, smoking and psychosocial factors.
To assist with defining hypertension, blood pressure and heart rate were recorded on three occasions for all cases. Physical activity and diet risk scores (including that associated with drinking) were calculated depending on responses to the questionnaires. Smoking was categorised as current, former or never. Depression was also ranked. Other measures, such as blood glucose and cholesterol, were assessed.
The researchers then used statistical models to determine which factors were linked with the risk of stroke. All of the findings took into account geographical region, gender, age and all potential confounders that had been measured. The researchers were interested in the association between stroke (all strokes and ischaemic and haemorrhagic stroke) and the following factors: hypertension, smoking status, diabetes mellitus, physical activity, diet, psychosocial factors, abdominal obesity, alcohol intake, and apolipoprotein concentrations (protein molecules linked to the transport of good and bad cholesterol). For each of these factors, the researchers calculated the population attributable fraction (PAF), an assessment of how much each factor contributes to the overall risk of the outcome.

What were the basic results?

Several factors were associated with an increased risk of stroke: history of hypertension, current smoking, waist-to-hip ratio, diet risk score (increased risk associated with increased consumption of red meat, organ meats or eggs, fried foods and cooking with lard), lack of physical activity, history of diabetes mellitus, more than 30 alcoholic drinks per month or binge drinking, psychological stress, other heart problems, and cholesterol. A model indicated that these factors accounted for 90% of the risk for all types of stroke. The following table shows the level of increased risk with each factor (individually these do not add up to 90% because of interactions between variables).
When they looked at the two different types of stroke separately, all of these factors were linked with ischaemic stroke. Only hypertension, smoking waist-to-hip ratio, diet and alcohol were linked to intracerebral haemorrhagic stroke.
The PAFs for stroke for this population were calculated as follows:
  • 51.8% - Hypertension (self-reported history of hypertension or blood pressure >160/90mmHg)
  • 18.9% - Smoking status
  • 26.5% - Waist-to-hip ratio
  • 18.8% - Diet risk score
  • 28.5% - Regular physical activity
  • 5% - Diabetes mellitus
  • 3.8% - Alcohol intake
  • 4.6% - Psychosocial stress
  • 5.2% - Depression
  • 6.7% - Cardiac causes (atrial fibrillation, previous MI, rheumatic valve disease, prosthetic heart valve)
  • 24.9% - Ratio of ApoB to ApoA (reflecting cholesterol levels)

How did the researchers interpret the results?

The researchers note that their findings suggest that ‘10 risk factors are associated with 90% of the risk of stroke’. They say that targeting interventions to reduce blood pressure and smoking and to promote physical activity and a healthy diet could substantially reduce the burden of stroke.


This is an important study that quantifies the contribution of different factors to the overall risk of stroke. As the researchers note, it provides information on the relative importance of different factors, building on the findings of previous epidemiological studies. Finding that hypertension is the biggest risk factor for all stroke types is important because, like many other factors, it is a modifiable risk that can be addressed by appropriate medication and lifestyle changes. They say that this is particularly important in low-income settings as screening programmes need relatively little training, and resources and interventions are inexpensive.
It also confirmed that stopping smoking greatly reduces the risk of stroke, and that intake of fish and fruits were the dietary components most associated with risk reduction. Surprisingly, there was no association between vegetable intake and stroke, and the researchers say that this needs further exploration. The researchers also highlighted inconsistencies in the research base, and point out the following limitations of their study:
  • A case-control design, as employed here, has several biases, including recall bias (participants’ responses being affected by their own memory or personal biases) and problems with selecting participants. The people in this study were all in hospital, so the findings may not be relevant for those with less or more severe strokes.
  • A reliance on hospital records for the type of stroke participants had. This potentially differs between countries.
  • Importantly, they note the small sample size and state that in the next phase they will include an additional 10,000 case-control pairs. This will be large enough to allow them to analyse patients by region and provide more information on how this profile of risk differs according to geography.
The researchers say that in subsequent phases of their research, they will address some of these shortcomings.
Overall, this study provides key information about the relative importance of the risk factors for overall stroke and for the different types of stroke. The conclusion that ‘targeted interventions that reduce blood pressure and smoking, and promote physical activity and a healthy diet, could substantially reduce the global burden of stroke’, seems sensible.

Ninety percent of stroke risk due to 10 risk factors

A large international study has found that 10 risk factors account for 90 percent of all the risk of stroke, with high blood pressure playing the most potent role.

Of that list, five risk factors usually related to lifestyle -- high blood pressure, smoking, abdominal obesity, diet and physical activity -- are responsible for a full 80 percent of all stroke risk, according to the researchers.

The findings come the INTERSTROKE study, a standardized case-control study of 3,000 people who had had strokes and an equal number of healthy individuals with no history of stroke from 22 countries. It was published online June 18 in The Lancet.

The study -- slated to be presented Friday at the World Congress on Cardiology in Beijing -- reports that the 10 factors significantly associated with stroke risk are high blood pressure, smoking, physical activity, waist-to-hip ratio (abdominal obesity), diet, blood lipid (fat) levels, diabetes, alcohol intake, stress and depression, and heart disorders.

Across the board, high blood pressure was the most important factor, accounting for one-third of all stroke risk.

“It's important that most of the risk factors associated with stroke are modifiable,” said Dr. Martin J. O'Donnell, an associate professor of medicine at McMaster University in Canada, who helped lead the study. “If they are controlled, it could have a considerable impact on the incidence of stroke.”

Controlling blood pressure is important, he said, because it plays a major role in both forms of stroke: ischemic, the most common form (caused by blockage of a brain blood vessel), and hemorrhagic or bleeding stroke, in which a blood vessel in the brain bursts.

In contrast, levels of blood lipids such as cholesterol were important in the risk of ischemic stroke, but not hemorrhagic stroke.

“The most important thing about hypertension is its controllability,” O'Donnell said. “Blood pressure is easily measured, and there are lots of treatments.”

Lifestyle measures to control blood pressure include reduction of salt intake and increasing physical activity, he said.

He added that the other risk factors -- smoking, abdominal obesity, diet and physical activity -- in the top five contributors to stroke risk were modifiable as well.

High intake of fish and fruits, for example, were associated with a lower risk of stroke, according to the study.

The researchers pointed out several potential limitations of the study, including the sample size, which they said “might be inadequate to provide reliable information” about the importance of each risk factor in different regions and ethnic groups.

Many of the same risk factors have cropped up in other studies, but this is the first stroke risk study to include both low- and middle-income participants in developing countries and to include a brain scan of all participating stroke survivors, according to the researchers.

The countries joining in the study were Argentina, Australia, Brazil, Canada, Chile, China, Colombia, Croatia, Denmark, Ecuador, Germany, India, Iran, Malaysia, Mozambique, Nigeria, Peru, Philippines, Poland, South Africa, Sudan and Uganda.

The INTERSTROKE study confirms that high blood pressure “is the leading cause of stroke in developing countries” as well as developed nations, Dr. Jack V. Tu, of the University of Toronto, wrote in an accompanying editorial. He added that it highlighted the need for health authorities in those countries to develop strategies to reduce high blood pressure, salt intake and other risk factors.

A second phase of the INTERSTROKE study is underway, with researchers looking at the importance of risk factors in different regions, ethnic groups and types of ischemic stroke. They'll also study the association between genetics and stroke risk. The researchers plan to enroll 20,000 participants.

Dr. Larry B. Goldstein, director of the Duke Stroke Center, noted that the study underscored what's already known about stroke risk.

“The bottom line is that the risk factors for low- and middle-income countries seem to be pretty similar to those of Western countries,” Goldstein said. “The findings reiterate the importance of attention to lifestyle factors in stroke risk -- diet, smoking, physical activity.”

Curiosities: Do cell phones cause health problems?

Does cell phone use increase the chances of brain cancer or other health problems? Jack Dempsey
Q. I've heard that cell phones produce unhealthy electromagnetic waves that can cause health problems. Is this true?
A. The major concern with the electromagnetic radiation from cell phones is brain cancer, but most studies find "nothing definitive," says Bruce Thomadsen, a professor of medical physics and human oncology at UW-Madison.
The issue is very difficult to study for many reasons. For example, cell phone technology changes; phone users devote a varying amount of time to phoning. Nevertheless, Thomadsen notes that Interphone, a large series of studies on the topic, reported on May 17 that most cell phone users have little or no risk of brain cancer.
Interphone, which was sponsored by the World Health Organization, is one of many studies that shows "no consistent evidence for a relationship between cell phone use and brain cancers," Thomadsen says. However, several recent studies suggest that cell phone radiation may reduce the movement of sperm, which could link heavy cell phone use to male infertility and perhaps other problems.
"It's troubling, and there's nothing incredibly definitive, but the effect on human sperm warrants more research," he says. The worst health hazard of cell phones, Thomadsen adds, is likely to appear on our roads, in the form of auto accidents caused by inattentive, cell phone-obsessed drivers.

Is Exercise the Best Drug for Depression?

At his research clinic in Dallas, psychologist Jasper Smits is working on a somewhat unorthodox treatment for depression. It is not yet widely accepted, but his treatment is free and has no side effects. Compare that with antidepressant drugs, which cost Americans $10 billion each year and have many common side effects: sleep disturbances, nausea, tremors, changes in body weight.
This intriguing new treatment? It's nothing more than exercise.
That physical activity is crucial to good health — both mental and physical — is nothing new. As early as the 1970s and '80s, observational studies showed that Americans who exercised were not only less likely to be depressed than those who did not, but were also less likely become depressed in the future.
In 1999, Duke University researchers demonstrated in a randomized controlled trial that depressed adults who participated in an aerobic exercise plan improved as much as those treated with sertraline, the drug that was marketed as Zoloft, and was earning Pfizer more than $3 billion annually before its patent expired in 2006.
Subsequent trials have repeated these results, showing again and again that patients who undergo aerobic exercise regimens see comparable improvement in their depression as those treated with medication, and that both groups do better than patients given only a placebo. But exercise trials on the whole have been small and most have run only for a few weeks; some are plagued by methodological problems. Still, despite limited data, the trials all seem to point in the same direction: Exercise boosts mood. It not only relieves depressive symptoms, but appears to prevent them from recurring.
"I was really surprised that more people weren't working in this area when I got into it," says Smits, an assistant professor of psychology at Southern Methodist University.
Molecular biologists and neurologists have also begun to show that exercise may alter brain chemistry in much the same way that antidepressant drugs do — regulating the key neurotransmitters serotonin and norepinephrine. At the University of Georgia, neuroscience professor Philip Holmes and colleagues have shown that over the course of several weeks, exercise can switch on certain genes that increase the brain's level of galanin, a peptide neurotransmitter that appears to tone down the body's stress response by regulating another brain chemical, norepinephrine.
The result is that exercise primes the brain to show less stress in response to new stimuli. In the case of lab rats and mice, that stimuli include being plunged into very cold water or being suspended by the tail. And while those are not exactly problems that most people face, the thinking is that the human neurochemical response may well react similarly, with exercise leaving our brain less susceptible to stress in the face of harmless but unexpected events, like a missed appointment or getting a parking ticket. A little bit of mental strain and excess stimulation from exercise, in other words, may help us to keep day-to-day problems in perspective.
Researchers also wonder whether this interaction between body and brain may, evolutionarily speaking, be hard-wired. "It occurs to us that exercise is the more normal or natural condition, and that being sedentary is really the abnormal situation," Holmes says.
Humans (and lab rats) never evolved to be cooped up, still, all day long. Our brains simply may not be built for an environment without physical activity. Research has also suggested that exercise may be an effective treatment not just for depression, but also against related anxiety disorders and even substance dependence.
Other scientists have found that, in mammals, exercise also boosts the production of brain-derived neurotrophic factor (BDNF), a substance that supports the growth and maintenance of brain cells. In depressed patients, BDNF has been shown to help repair brain atrophy, which can lift symptoms of the disease.
Back in Dallas, Smits says his exercise treatment appeals to patients for two main reasons. First, exercise doesn't carry the same stigma among patients (and some providers) that depression medication and psychotherapy do. Second, the mood-enhancing benefits of exercise can kick in fast — a lot faster than, say, its impact on weight loss or cardiovascular health. "By and large, for most people, when they exercise 30 minutes — particularly when it's a little bit more demanding, and they get their heart rate up — they feel better," Smits says. "You get an immediate mood lift."
That effect doesn't reflect the longer-term changes in the brain that Holmes studies. But Smits uses the immediate mood boost as a way to motivate patients with depression (which, of course, manifests in a chronic lack of motivation) to get moving. Instead of a barrier to exercise, Smits suggests, depression becomes a reason to exercise. "You feel crappy, so you get on the treadmill, and you look back and you say, 'Wow I feel much better,'" he says.
Yet for all the potential clinical benefits, the big questions about exercise treamtent remain unanswered: How much? How long? In which patients? In their recent book for therapists, Exercise for Mood and Anxiety Disorders (Oxford University Press, 2009), Smits and co-author Michael Otto at Boston University suggest precise exercise doses that they hope will aid psychologists and primary-care doctors in prescribing exercise as treatment, which can be administered in combination with other treatments, of course.
Smits and Otto recommend the familiar 30 minutes of moderate-intensity aerobic exercise, like walking, five times per week, or 30 minutes of high-intensity aerobic exercise three times a week. These doses, which are regularly recommended for physical fitness, are the only ones that have been well tested for depression. "But we can't say at this point that more wouldn't be better," Smits says. "Or maybe less would be better. We really don't know." Too few tests have been run. It is also unclear whether anaerobic exercise, like weight lifting, would have the same mood-lifting effects — or whether exercise works as well in severely depressed patients as it does in sufferers of mild or moderate depression.
For now, then, data on exercise are only suggestive. The clinical literature on antidepressant drugs is massive, since large-scale, rigorous studies are required for market approval from the Food and Drug Administration (FDA). The trials on exercise have all been smaller, perhaps in part because it needs no government approval. "If you look at FDA standards [for evidence], it's not clear that exercise would meet that standard," says James Blumenthal, the Duke University professor of medical psychology who ran Duke's 1999 exercise study, as well as a 2007 follow-up with more than 200 patients, which Blumenthal believes is the largest-ever such trial to date.
But the evidence is mounting, and it's hard to argue with a free treatment that is exempt from side effects for a pervasive and debilitating mental health scourge — especially when so many other health benefits of exercise are incontrovertible. "I think that we have reason to be optimistic. For people who at least want to consider exercise as a possible treatment, and for whom exercise is safe, it's definitely worth a shot," Blumenthal says.