Johns Hopkins Medicine
Media Relations and Public Affairs

FOR IMMEDIATE RELEASE

CHOCOLATE "OFFENDERS" TEACH SCIENCE A SWEET LESSON
-- Study helps explain heart benefits from daily - but small - dose of chocolate

(Oral presentation #11865, Room S106b, Chicago Convention Center)

Some "chocoholics" who just couldn't give up their favorite treat to comply with a study to test blood stickiness have inadvertently done their fellow chocolate lovers - and science - a big favor.

Their "offense," say researchers at Johns Hopkins led to what is believed to be the first biochemical analysis to explain why just a few squares of chocolate a day can almost halve the risk of heart attack death in some men and women by decreasing the tendency of platelets to clot in narrow blood vessels.

"What these chocolate 'offenders' taught us is that the chemical in cocoa beans has a biochemical effect similar to aspirin in reducing platelet clumping, which can be fatal if a clot forms and blocks a blood vessel, causing a heart attack," says Diane Becker, M.P.H., Sc.D., a professor at the Johns Hopkins University's School of Medicine and Bloomberg School of Public Health.

Becker cautions that her work is not intended as a prescription to gobble up large amounts of chocolate candy, which often contains diet-busting amounts of sugar, butter and cream. But as little as 2 tablespoons a day of dark chocolate - the purest form of the candy, made from the dried extract of roasted cocoa beans - may be just what the doctor ordered.

Researchers have known for nearly two decades that dark chocolate, rich in chemicals called flavonoids, lowers blood pressure and has other beneficial effects on blood flow. The latest Johns Hopkins findings, to be presented Nov. 14 at the American Heart Association's annual Scientific Sessions in Chicago, identified the effect of normal, everyday doses of chocolate found in ordinary foods, unlike previous studies that found decreased platelet activity only at impractically high doses of flavonoids equivalent to eating several pounds of chocolate a day.

"Eating a little bit of chocolate or having a drink of hot cocoa as part of a regular diet is probably good for personal health, so long as people don't eat too much of it, and too much of the kind with lots of butter and sugar," says Becker.

In the study, 139 people Becker - whom Becker somewhat tongue in cheek calls "chocolate offenders" - were disqualified from a much larger study looking at the effects of aspirin on blood platelets. The Genetic Study of Aspirin Responsiveness (GeneSTAR) was conducted at johnd Hopkins from June 2004 to November 2005 and enrolled more than 500 men and 700 women participants nationwide.

Shortly before aspirin dosing began for the subjects, they were told to stay on a strict regimen of exercise and to refrain from smoking or using foods and drinks known to affect platelet activity. These included caffeinated drinks, wine, grapefruit juice - and chocolate.

The non-compliers - who admitted to eating chocolate - were a diverse group who got their flavonoid "fix" from a variety of sources, including chocolate bars, cups of hot cocoa, grapes, black or green tea, and strawberries. And while they were excluded from the aspirin study, Becker and her team scoured their blood results for chocolate's effect on blood platelets, which the body recycles on a daily basis.

When platelet samples from both groups were run through a mechanical blood vessel system designed to time how long it takes for the platelets to clump together in a hair-thin plastic tube, the chocolate lovers were found to be less reactive, on average taking 130 seconds to occlude the system. Platelets from those who stayed away from chocolate as instructed clotted faster, at 123 seconds.

In another key test of urine for waste products of platelet activity, primarily urinary thromboxane (11-dehydro-thromboxane B2), scientists found that chocolate eaters showed less activity and waste products on average, at 177 nanograms per millimol of creatinine, versus an average of 287 nanograms per millimol of creatinine in the group that abstained.

Participants ranged in age from 21 to 80; 31 percent were black and the rest were white. In total, more than 200 different tests of platelet reactivity were performed and analyzed in the study. Because whole blood contains other cells that affect platelet aggregation, testing was repeated using a purified version of test samples made up of strictly platelet-rich plasma.

None of the "offenders" had previous histories of heart problems, such as a heart attack, but all were considered to be at slightly increased risk of heart disease because of family history. Fifty percent of women participants were postmenopausal.

"These results really bring home the point that a modest dietary practice can have a huge impact on blood and potentially on the health of people at a mildly elevated risk of heart disease," says study co-author Nauder Faraday, M.D., an associate professor at Johns Hopkins. "But we have to careful to emphasize that one single healthy dietary practice cannot be taken alone, but must be balanced with exercise and other healthy lifestyle practices that impact the heart."

Johns Hopkins Medicine
Media Relations and Public Affairs

FOR IMMEDIATE RELEASE

ADULT PIG STEM CELLS SHOW PROMISE IN REPAIRING ANIMALS' HEART ATTACK DAMAGE
(Oral presentation #732, Room E354b, Chicago Convention Center)

Johns Hopkins scientists have successfully grown large numbers of stem cells taken from adult pigs' healthy heart tissue and used the cells to repair some of the tissue damage done to those organs by lab-induced heart attacks. Pigs' hearts closely resemble those in humans, making them a useful model in such research.

Following up on previous studies, Johns Hopkins cardiologists used a thin tube to extract samples of heart tissue no bigger than a grain of rice within hours of the animals' heart attacks, then grew large numbers of cardiac stem cells in the lab from tissue obtained through biopsy, and within a month implanted the cells into the pigs' hearts. With help from a blue-dye tracking system, the scientists have shown that within two months the cells had developed into mature heart cells and vessel-forming endothelial cells.

"This is a relatively simple method of stem cell extraction that can be used in any community-based clinic, and if further studies show the same kind of organ repair that we see in pigs, it could be performed on an outpatient basis," says Eduardo Marbán, M.D., Ph.D., senior study author and professor and chief of cardiology at the Johns Hopkins University School of Medicine and its Heart Institute. "Starting with just a small amount of tissue, we demonstrated that it was possible, very soon after a heart attack, to use the healthy parts of the heart to regenerate some of the damaged parts."

Marbán cautions that no overall improvements in heart function have yet been shown in these studies, which were not designed to establish such changes and used relatively low numbers of infused cells (10 million or less). "But we have proof of principle, and we are planning to use larger numbers of cells implanted in different sites of the heart to test whether we can restore function as well," he says. "If the answer is yes, we could see the first phase of studies in people in late 2007."

The latest Johns Hopkins findings are scheduled to be presented Nov. 13 at the American Heart Association's annual Scientific Sessions in Chicago. They are believed to be the first results in animal studies to show that so-called cardiac stem cell therapy can be successfully applied with minimally invasive methods to circumstances closely resembling those in humans. Scientists say the results build on earlier studies with cardiac stem cells in mice and humans that demonstrated success in regenerating infarcted heart muscle and restoring heart cell function post-infarct.

For the study, cardiac stem cells were extracted by tissue biopsy from eight pigs whose main arterial blood supply was tightened for more than two hours, duplicating the effects and damage caused by heart attack.

Using techniques developed in Marbán's lab, researchers extracted about a million cardiac stem cells from undamaged heart tissue, growing them without the use of potentially dangerous chemical stimulators.

After three weeks, the stem cells turned into spherical balls of cells that mimicked the electrical properties of heart muscle cells. The so-called cardiospheres yielded on average more than 14 million cells.

Within a month after the initial heart attack, a catheter tube was inserted into an artery in the pig leg for infusing the cardiospheres. Previous research had shown that they would on their own migrate to the damaged zones of the heart. Marbán's team was able to confirm this because they had labeled the stem cells with a gene that codes for an enzyme producing a blue dye, which could be seen under a microscope.

Months later, when researchers examined the hearts to see if any damaged tissue had been repaired, they found blue spots indicating where the stem cells had taken root.
Closer examination of results revealed that stem cells had matured and grown in the border zones of the damaged area, where researchers suspect both dead and living tissue mingle and some blood supply remains.

"The goal is to repair heart muscle weakened not only by heart attack but by heart failure, perhaps averting the need for heart transplants," says Peter Johnston, M.D., study author and a Reynolds Foundation postdoctoral cardiology research fellow at Johns Hopkins' Heart Institute. "By using a patient's own adult stem cells rather than a donor's, there would be no risk of triggering an immune response that could cause rejection."

No Heart Risk for Women Who Favor Protein Over Carbs - MedPage Today
Women who say no to carbs, but yes to protein as recommended in the South Beach and Zone diets, do not increase their risk of coronary heart disease, according to researchers here.

And women who consume low-carbohydrate diets that emphasize vegetables rather than animals as the source of protein and fat may be rewarded with a moderate reduction in risk of heart disease.
Women whose diets consisted mainly of vegetable protein and fat were are about 30% less likely to develop coronary heart disease than women who whose diets contained either more carbohydrates or more animal protein and fat (P for trend=0.002), Thomas L. Halton, Sc.D. of the Harvard School of Public Health, and colleagues reported in the Nov. 9 issue of the New England Journal of Medicine.MORE

Lower Income Means Higher Risk for Heart Disease: USC PRESS RELEASE
Protein linked to heart disease found to be more prevalent in low-income people, minorities and women. Findings may help explain why the poor age faster, say USC and UCLA researchers.

Low-income adults are more likely to have very high levels of C-reactive protein (CRP), a risk factor for heart disease, according to a study led by researchers at the University of Southern California.

The study, published in the current issue of Brain, Behavior and Immunity, finds that among adults with income levels at or below the poverty line, 15.7 percent had very high levels of CRP, compared to only 9.1 percent of those in families above the poverty line.

"We have long known that poor people have worse health," said Eileen Crimmins, corresponding author and professor in the USC Leonard Davis School of Gerontology. "This paper provides evidence that people living at or near the poverty line are almost twice as likely to have very high CRP, which poses risks for long-term, chronic conditions like heart disease and cognitive loss. This may be one of the explanations for why poor people age faster."

CRP is produced as part of the immune response to inflammation. In healthy individuals, CRP levels return to normal after infection or injury subsides. However, some people have chronically elevated levels of CRP. Recent studies have shown high levels of CRP to be a useful predictor of heart disease.

Recent illness, chronic conditions and lifestyle account for some but not all of the explanations for the association between high CRP levels and socioeconomic standing.

"We found that even after accounting for various risk factors, people in poverty still had higher CRP," said Dawn Alley, another corresponding author and a recent doctoral graduate from the USC Davis School. "This suggests that even beyond issues like health behaviors and chronic conditions, there is something about poverty that makes people sick, and at least part of this effect is working through CRP."

The study also found that African Americans, Hispanics and women are more likely to have high levels of CRP, and that obesity is the largest contributor to above normal CRP levels.

The findings, which were funded by the National Institutes of Health, provide a better understanding about risk factors for poor health outcomes later in life.

The Division of Geriatrics at the UCLA School of Medicine also contributed to the study.

News Review From Harvard Medical School -- Value of Sealing Hole in Heart Debated
Makers of a device that seals a small hole in the heart are being told to prove that it is helpful. Until the studies are done, the U.S. Food and Drug Administration has tightened rules on marketing the devices, the Associated Press reported October 30. About 1 in 5 adults has a small hole in the heart called a patent foramen ovale. Such a hole is present in about 60% of younger adults who have strokes. However, it's not clear if the hole causes strokes or if sealing it prevents strokes. This is what the new studies would show.

By Howard LeWine, M.D.
Harvard Medical School

What Is the Doctor's Reaction?

A small hole between the two upper chambers of the heart has caused a big controversy.

Before we are born, all of our oxygen supply comes from our mothers' blood. So it doesn't matter if blood mixes between the two sides of the heart. It's normal for a fetus and newborn baby to have an opening that allows blood to move between the two upper chambers (the atria).

After we are born and need to breathe air to get oxygen, this connection is supposed to close. The heart has its own natural way to fix it. There is a flap on the upper left chamber wall. The pressure is higher in the upper left chamber than in the right chamber. So the higher pressure pushes the flap over the hole. In time, this flap usually gets permanently attached.

However, in 1 out of every 5 of us, the hole doesn't close permanently and completely. The opening is the foramen ovale, and when it stays open it is called a patent foramen ovale (PFO). Many millions of people who have this never know they have it, nor do they need to know.

The potential importance of a PFO was recognized in the 1960s. During this decade, doctors were regularly using ultrasound to take pictures of the heart (echocardiography) for many reasons, one of them to diagnose the cause of a stroke.

Doctors started seeing a higher-than-expected rate of PFO in people with strokes and TIAs (transient ischemic attacks, which can lead to a stroke). This seemed especially true for younger people not at traditional risk of stroke.

This association has led to an acceptance of PFO as a cause of TIA and stroke. The next natural step was to fix the hole either with surgery or by threading a device through the artery to close the hole. But now doctors are not so sure that this always needs to be done.

The waters have grown even muddier. More recently doctors have noticed that people with certain types of migraine (sometimes called complex migraine) also tend to have PFOs. The symptoms of a complex migraine can be just like those of a TIA or stroke.

What Changes Can I Make Now?

If you have complex migraine or symptoms that suggest of a TIA, your doctor may have ordered an echocardiogram as part of the evaluation. So what should you do if you are told you have a PFO?

There is no correct answer. Although it is not likely that the PFO is actually causing your symptoms, the two can have a direct relationship.

Here is one example of a direct relationship. If you have an untreated blood clot in a vein, a piece of that blood clot can break off and travel to the right side of your heart. If there is an opening between the upper right and left chambers, the clot can move across the PFO. It then travels into the lower left heart chamber, where it exits into the aorta. From here, the clot can travel to the brain and cause a TIA or stroke.

In this situation, the person takes blood thinners initially and then has a procedure to close the PFO.

In another example, a person with a PFO who has TIA-like symptoms and blood that clots too easily would be considered for PFO closure.

But most of the time, the situation is not so straightforward. You and your doctor will balance the risks and benefits of the options, usually taking an aspirin or other blood thinner or having the PFO closed.

Pretoria News: Three-hour rule would halve stroke burden
A stroke patient who is treated at a stroke unit within three hours of becoming ill has a 50% chance of full recovery, according to a German neurologist.

According to Professor Werner Hacke, chairman of the University of Heidelberg's department of neurology in Germany, the damage caused by stroke could be halved if patients (and their doctors) identified the problem quickly and sought help.

"Symptoms of stroke are well known. Can the patient lift both arms to an equal level? Can they say their name properly? Can they stand up and walk?" said Hacke.

Stroke is the biggest cause of disability in South Africa.

For this reason governments everywhere should do everything possible to improve stroke care to reduce the burden of stroke disability on the state, said Hacke.
javascript:void(0);
He said one solution for developing countries was to use the Internet more in the treatment of the illness.

This could involve sending live images of the patient to a neurologist based in a city hospital.

"The technology is so good now that a doctor can be in another city and still look into a patient's eyes," he said.

This technology was not expensive (R100 000 for a unit) but needed political co-operation to be installed and properly used.