DATA SHOT

$400

The approximate cost of genetic testing to predict a patient’s response to the commonly prescribed blood thinner warfarin

MIT Technology Review, March/April 2010, by Lauren Gravitz  —  The market for personalized medicine is growing: according to ­PricewaterhouseCoopers, the core market will reach $42 billion by 2015. However, that growth is not uniform. Some areas, such as genomic sequencing, are surging ahead; others, such as translating genetic data into clinically useful information, languish.

In this environment, startups developing sequencing technologies, such as Pacific Biosciences, Illumina, and Complete Genomics, have attracted sustained investor interest as they race to create ever cheaper ways to decode DNA (see “Faster Tools to Scrutinize the Genome“). In their most recent rounds of venture funding last summer, Pacific Biosciences and Complete Genomics received $68 million and $45 million, respectively.

Diagnostic technologies, too, are moving at a rapid pace. Startups from Boston to Silicon Valley have been pinning down disease-related genetic markers and creating many new tests that are already in the clinic or on their way. As these companies grow and bring more tests to market, large diagnostics companies are likely to acquire them, says venture capitalist Brook Byers of Kleiner Perkins Caufield and Byers.

One of the biggest undeveloped areas in personalized medicine, however, is the information technology needed to analyze and store the huge quantity of genetic data that is starting to pour forth (see “Drowning in Data“). Of the few bioinformatics companies working to digest the data, Proventys, based in Newton, MA, is among the furthest along. Its technology combines biomarkers and other information to make risk predictions about diseases.

Meanwhile, pharmaceutical companies are responding to the nascent market for personalized therapeutics in different ways. Pfizer, for example, is collaborating with existing biotech companies to develop drugs and diagnostics based on genetic testing. AstraZeneca recently announced a partnership with the Danish diagnostics company Dako, the first of many alliances it plans in a strategy for bringing genetic tests to market. Novartis is taking a different tack, dedicating a large portion of its own resources to developing personalized medicine.

In the United States, benefit management companies, which act as middlemen between patients and insurers or employers, are aggressively moving into the market. One of the largest, Medco, has established a personalized-medicine group to recommend which genetic tests insurers should pay for. In February it acquired DNA Direct, a firm that specializes in analyzing genetic diagnostics, to aid in this effort. One of its largest competitors, CVS Caremark, increased its stake in a similar company, Generation Health, last December. Because such companies serve millions of people, they will play a critical role in making genetic tests broadly available and educating doctors about the benefits of offering such tests to their patients.

landscape map

A machine for DNA sequencing was invented by Leroy Hood and his colleagues at Caltech. In 1992, Hood and several others were granted U.S. patent 5,171,534 for an “Automated DNA Sequencing Technique.” Replacing slow and expensive manual methods, this is one of the most important pieces of intellectual property in biotechnology; explore this interactive analysis by IPVision of the patent’s impact on the innovation landscape.

The FDA recommends genetic testing before patients are given prescriptions for Erbitux, a treatment for colorectal cancer.  Credit: Bristol Myers Squib

MIT Technology Review, February 24, 2010, by Courtney Humphries  —  Personalized medicine does not fit easily into established government procedures for approving drugs. After all, clinical trials are designed to test a drug on a large and diverse group of patients, and the whole point of personalized therapeutics is to target the specific genetic populations that will benefit most. The U.S. Food and Drug Administration is now trying to figure out how to judge the usefulness of a drug designed for particular genetic groups while also considering its safety for others who may receive it for off-label purposes.

Last fall the FDA created a post for a genomics advisor, who will coördinate the agency’s efforts to address the subject of genetic data and prescription drugs. Amy Miller, public-policy director of the nonprofit Personalized Medicine Coalition, says the agency has signaled that it’s “now ready to give the industry some guidance on how personalized-medicine products will be regulated in the future.”

One of the first challenges the FDA will probably tackle is how to evaluate genetic and biomarker-based tests aimed at identifying the patients most likely to benefit from a drug. The agency has begun adding recommendations for diagnostic tests to drug labels, and in a handful of cases it has mandated a genetic test before a drug can be prescribed, but there is currently no streamlined path for approving the combination of a drug and a diagnostic test. The FDA has indicated that it will develop guidelines, but so far it’s not clear how, or when, it will resolve the logistical difficulties involved in approving two very different products in one regulatory process.

March/April 2010

: Personalized Medicine

By MIT Technology Review Editors

Finding ways to analyze large amounts of genetic data and extract information related to diseases that involve multiple genes.

  • Project: Cancer Biology and Genetics Program
    Sloan-Kettering Institute
    www.mskcc.org

Testing a microfluidic chip that will measure differences in how genes are expressed in tumors.

  • Project: Coriell Personalized Medicine Collaborative
    Coriell Institute for Medical Research
    cpmc.coriell.org

Enrolling 100,000 participants in a research study to measure how genetic information can improve health.

Developing a genetic test that will identify patients at risk of sudden cardiac death who should receive an implantable defibrillator.

An EU-funded consortium seeking to standardize genetic testing and establish guidelines for doctors and patients.

An American-Japanese scientific alliance studying pharmacogenomics across a broad array of medical conditions, including depression, AIDS, and asthma.

  • Project: Pharmacogenomics Knowledge Base
    Stanford University Medical Center and others
    www.pharmgkb.org

An international consortium building a database detailing the influence of genetic variations on drug reactions.

Investigating whether using genetic tests to determine a patient’s sensitivity to certain drugs is more cost-effective than choosing drugs that are less affected by genetic variations.

  • Project: The 1000 Genomes Project
    Wellcome Trust Sanger Institute, Beijing Genomics Institute Shenzen, National Human Genome Research Institute
    www.1000genomes.org

Sequencing the genomes of about 1,200 people around the world to create a database of biomedically relevant genetic variation.

  • Project: The Cancer Genome Atlas
    National Cancer Institute, National Human Genome Research Institute
    cancergenome.nih.gov

Sequencing thousands of samples from over 20 types of tumors to understand the genetic changes that underlie these cancers.

Original Article:http://www.mayoclinic.com/health/pharmacogenomics/MY01192

MayoClinic.com, GoogleNews.com, February 24, 2010, by Carrie A. Zabel  —  Personalized medicine offered at your local drugstore?

Two large prescription drug companies have announced plans to offer genetic testing as part of the prescription-filling process. The testing will center on an emerging science, pharmacogenomics, which studies drug response based upon an individual’s genetic make-up. Pharmacogenomic testing is already used for some commonly prescribed drugs such as Tamoxifen and Warfarin.

The process would use a pharmacy benefits management company that would contract with large drugstore chains. When certain prescriptions come in, the company would contact the physician to let them know a genetic test is available, which may help them to more appropriately prescribe that medication. The individual may then be offered the genetic testing, but it wouldn’t be required.

Supporters say this will improve patient safety, health outcomes and decrease overall health care costs by using the right medications in the right patients. It may also provide an opportunity to advance the field of pharmacogenomics by collecting data on genetic testing results and drug effectiveness.

Others are concerned about the privacy of genetic testing information and say the science of pharmacogenomics is premature. Drug metabolism isn’t only based on our genetic make-up, but is affected by many additional factors, such as body size and age. And, since pharmacogenomics is a relatively new science, insurance companies may not reimburse for the cost of genetic testing.

About the writer………………..Carrie A. Zabel, M.S., C.G.C., Genetic Counselor

Carrie A. Zabel, M.S., C.G.C.


“We must begin now to prepare for the future; we cannot wait until the details are known or fully understood.”*

— David B. Schowalter, M.D., Ph.D., former Mayo geneticist, (*posthumous)

Carrie A. Zabel, M.S., C.G.C., is a board-certified genetic counselor who specializes in hereditary cancer syndromes. One of her main professional interests is the family medical history.

“Recognizing features in the family history which may suggest an underlying single gene disorder can have a huge impact on families,” she says. “Identifying a genetic susceptibility gene can allow family members to more accurately understand their risk of disease and empower those who have an increased genetic susceptibility to take control of their medical management and lifestyle factors which may influence this risk.”

She received her B.S. in biology from the University of Wisconsin-La Crosse in 2002 and M.S. in genetic counseling from the University of Minnesota in 2004.

She was a clinical genetic counselor at the Marshfield Clinic in Marshfield, Wis., before joining Mayo Clinic in August 2006 as a genetic counselor and educator for the grant-funded Mayo Eisenberg Genomics Education Program. During her time in Wisconsin, she was also an active member of the metabolic subcommittee of the state Newborn Screening Program and co-facilitated a phenylketonuria clinic.

At Mayo Clinic, she provides physician and staff education about clinically relevant topics in genomics. She also manages multiple education projects championed by Mayo Clinic physicians and is a faculty member for Mayo Medical School. In addition to her education roles, she sees adult patients in the Department of Medical Genetics.

Credit: Christopher Harting

Tests for this type of individual genetic variation have been available for a long time, but in many cases they cost too much and take too long. Nanosphere, a startup out of Northwestern University that’s based in Northbrook, IL, hopes to change that. Its Verigene system, which takes just a few hours to analyze DNA from blood or other material, allows doctors to test for genetic variations without having to send samples out to a lab.

 

A new device can rapidly test biological samples for genetic variations that could cause dangerous reactions to some drugs

MIT Technology Review, March/April 2010, by Erica Naone  —  Different people can react to drugs in different ways, and in some cases the response can be predicted from their genes. For example, the drug warfarin, often used to prevent blood clots, can cause dangerous bleeding in some patients. Researchers have identified two genetic variations that can increase this risk.

 
A. Disposable cartridge

A single-use cartridge uses a combination of chemical reactions to isolate fragments of DNA from a patient sample and test them for specific genetic characteristics. The top half of the cartridge is discarded after this process is complete, leaving a prepared glass slide behind.

B. Bar Code

To help keep track of samples, a bar code is printed on the test cartridge and the underlying slide.

C. Reagent Wells

The necessary ingredients for the chemical reactions used to process the DNA are stored in wells located around the edges of the test cartridge. After the DNA is extracted from a sample, the machine uses air pressure and mechanical valves to release the ingredients from the wells as needed. Strands of DNA that are complementary to the target sequences are used to bind those sequences to the glass slide below the cartridge, as well as to gold nanoparticles that will allow the DNA to be detected when exposed to light. The cartridge washes away any excess DNA or nanoparticles and then sets off a reaction that coats the remaining nanoparticles with silver, which makes it easier to scan for them.

D. DNA Loading chamber

A DNA sample is loaded into the port shown here. Sonic energy, applied when the cartridge is inserted into the machine that processes the samples, breaks the DNA into small fragments and separates it into its two complementary strands so that it can be captured on the surface of the glass slide.

E. Glass Slide (Microarray)

After the chemical reactions have finished, the target DNA remains on the surface of the prepared glass slide, tagged by silver-coated gold nanoparticles. The Verigene’s reader can read the slide by shining light into it and measuring how that light is scattered by the tagged DNA. The system can be used to look for single or multiple genetic targets.

Finding messengers: deResearchers use a specially designed sensor to detect the release of dopamine (lower green and purple band) and adenosine (upper green and purple band), both chemical messengers in the brain.
Credit: Kendall H. Lee, MD, PhD, director of Mayo Neural Engineering Laboratories, and Kevin Bennet, Chair of Mayo Division of Engineering.

 

A system to detect brain chemicals may improve therapies for Parkinson’s and other disorders

MIT Technology Review, February 24, 2010, by Emily Singer  —  Over the last decade, deep brain stimulation, in which an implanted electrode delivers targeted jolts of electricity, has given surgeons an entirely new way to treat challenging neurological diseases. More than 75,000 people have undergone the procedure for Parkinson’s and other disorders. But despite its success, scientists and surgeons know little about its actual effect on the brain or exactly why it works.

An implantable sensor designed to detect vital chemical signals in the brain, currently being tested in animals, could help scientists measure the impact of electrical stimulation and perhaps provide a way to enhance the effectiveness of the treatment. “For a long time in neurosurgery we’ve been dealing with the brain from purely an electrical perspective,” says Nader Pouratian, a neurosurgeon at the University of California, Los Angeles, who was not directly involved in the research. “This allows us to look at the brain as an electrochemical organ and understand the effect of interventions such as deep brain stimulation.”

During the conventional deep brain stimulation procedure, neurosurgeons insert a small electrode into the brain. The patient is awake during the surgery so that the surgeon can find the optimal location and level of stimulation to reduce the patient’s symptoms. In Parkinson’s patients, for example, muscle tremors are often immediately and visibly reduced with the appropriate stimulation.

However, the actual mechanisms behind its therapeutic effect are hotly debated. Recording the release of the brain’s signaling chemicals, known as neurotransmitters, could help to resolve the question, allowing neurosurgeons to better optimize the procedure.

The device consists of a custom-designed sensor electrode that is implanted along with the stimulating electrode, a microprocessor, a Bluetooth module to send data to a computer, and a battery. “It allows us to record dopamine and serotonin wirelessly in real time,” says Kendall Lee, a neurosurgeon at the Mayo Clinic, Rochester, MN, who helped develop the device. “That means we have tremendous control over the chemistry of the brain.”

To detect neurotransmitters, researchers apply a low voltage across the electrode. That oxidizes dopamine molecules near the electrode, triggering current flow at the electrode. “The amount of current flow gives a relative indication of concentration,” says Kevin Bennet, chairman of the division of engineering at the Mayo Clinic and one of Lee’s collaborators.

Preliminary research in pigs using the new system has shown that deep brain stimulation of the area targeted in Parkinson’s patients triggers release of dopamine. Researchers now aim to repeat these experiments in pigs that have some of the symptoms of the disease. For example, the sensors could detect whether certain patterns of dopamine correspond to improvements or worsening of Parkinson’s symptoms.

“We have to get more nuanced understanding of how electricity impacts brain chemistry at the microscopic circuit level,” says Helen Mayberg, a physician and neuroscientist at Emory University, in Atlanta, who was not involved in the research. “This type of technology gives us the opportunity to look precisely at very local changes in the chemical mix. As the technology is expanded to be able to detect an even wider range of neurochemical systems, it’s going to really catapult what we can learn about the mechanisms of brain stimulation and the diseases we treat with it.”

In addition to detecting dopamine, preliminary research shows the technology can also detect serotonin, a brain chemical implicated in depression. (Serotonin reuptake inhibitors such as Prozac target this neurotransmitter.) Deep brain stimulation is currently approved to treat Parkinson’s, the movement disorder dystonia, and severe obsessive-compulsive disorder, and is under study for epilepsy, depression, anorexia, and other disorders.

Lee says his team has now been granted approval to test the system in a patient, which they aim to do in the next few months. Initially, it will be tested only during the implantation surgery to determine how moving the electrode alters the level of dopamine released. But the ultimate goal is to incorporate the sensor into the deep brain stimulation system. Researchers are currently developing new sensor electrodes that function effectively over the long term, as well as shrinking the device so that it can be packaged and implanted onto the skull. Once researchers better understand the link between deep brain stimulation and neurochemistry, the accompanying chemical data may help neurosurgeons to better place the electrode.

But some say this step may be premature. “The technology is very intriguing, but we need a lot more research before it can be applied in humans,” says Ali Rezai, a neurosurgeon at Ohio State University, who was not directly involved with the research. He says that researchers need to show that using this technology alongside deep brain stimulation in animals with symptoms of Parkinson’s disease improves outcomes.

In the long term, Lee and his collaborators want to develop a so-called closed loop system, allowing the stimulation device to detect the chemical changes in the brain and adjust its response accordingly. This approach is analogous to cardiac pacemakers, which stimulate the heart only when the instrument detects an abnormality. While abnormalities in heart rhythms are fairly straightforward to detect, “in the brain, it’s much more complicated,” says Rezai.

Hepatitis model: Human liver cells (in green) that are injected into mice take over, creating a mostly human liver. When infected with hepatitis B, scientists can study its effects in vivo and test new drugs on the “humanized” liver.
Credit: Karl-Dimiter Bissig, Salk Institute for Biological Studies

Rodents could be an effective model for researchers looking for new hepatitis drugs

MIT Technology Review, February 23, 2010, by Jennifer Chu  —  Scientists at the Salk Institute for Biological Studies have engineered a mouse with a mostly human liver by injecting human liver cells, or hepatocytes, into genetically engineered mice. Researchers say the mouse/human chimera could serve as a new model for discovering drugs for viral hepatitis, a disease that has been notoriously difficult to replicate and study in the lab. The team exposed the altered mice to hepatitis B and C viruses and, after treating the rodents with conventional drugs, found that the mice responded much like human patients.

In the United States, 1.2 million Americans are infected with chronic hepatitis B, and 3.2 million with chronic hepatitis C. Searching for effective treatments and drug combinations for viral hepatitis has been a frustrating challenge for years.

In the laboratory, hepatitis and the liver cells it infects can be cagey and temperamental. Human liver cells immediately change character when taken out of the body, and are difficult to grow in a petri dish. What’s more, hepatitis only infects humans and chimps, having virtually no effect in other species, meaning conventional lab animals like mice and rats are useless as live models. “You could do chimp studies, but that is not very convenient, and it is of course an ethical issue,” says Karl-Dimiter Bissig, first author of the group’s paper, published in the Journal of Clinical Investigation. “There’s really a need to develop animal models where you can make a human chimerism and study the virus.”

Bissig says his group’s mouse/human chimera improves on a similar model developed several years ago that was genetically engineered to give human liver cells a growth advantage when injected into a mouse liver. Researchers engineered the mouse with a gene that destroyed its own liver cells. This programmed death gave human liver cells an advantage, and when researchers injected human hepatocytes, they were able to take over and repopulate the mouse liver. However, scientists found that the genetically engineered mice tended to die off early, which required injecting human liver cells within the first few weeks after birth–a risky procedure that often resulted in fatal hemorrhaging.

Instead, Bissig and his colleagues, including Inder Verma of the Salk Institute, sought to engineer a mouse chimera in which the introduction of human liver cells could be easily controlled. The group first engineered mice with several genetic mutations, which eliminated production of immune cells so that the mice would not reject human liver cells as foreign. The researchers made another genetic mutation that interfered with the breakdown of the amino acid tyrosine. Normally, tyrosine is involved in building essential proteins. To keep a healthy balance, the liver clears out tyrosine, keeping it from accumulating to toxic levels. Bissig engineered a mutation in mice that prevents tyrosine from breaking down, instead causing tyrosine to build up in liver cells, eventually killing the mouse cells, giving the human cells an advantage.

To avoid killing mouse liver cells too early (or killing the mice entirely), Bissig’s team administered a drug that blocks the toxic byproducts of tyrosine buildup from killing liver cells. By putting the mice on the drug, and taking them off the drug a little at a time, researchers found that they could control the rate at which rodent liver cells died off.

The team then injected mice with hepatocytes from various human donors, and found that the cells were able to take over 97 percent of the mouse liver. The “humanized” mice were then infected with hepatitis B and C, and researchers found high levels of the virus in the bloodstream–versus normal mice, which are impervious to the disease and are able to clear the virus out quickly.

Bissig and his colleagues went a step further and treated the infected mice with a drug typically used to treat humans with hepatitis C. They found that, after treatment, the mice exhibited a thousand-fold decrease in viral concentration in the blood, similar to drug reactions in human patients.

Charles Rice, who heads the laboratory for virology and infectious disease at Rockefeller University, says the new chimeric model is a robust improvement over existing study models for viral hepatitis. Further improvements, Rice explains, could include engineering human cell types, other than hepatocytes, that also appear in the human liver. While the majority of the human liver is composed of hepatocytes, there are a few other cell types that may interact with hepatocytes and affect how a virus infects the liver. Engineering other liver cells could more accurately depict a working human liver and its response to disease.

Raymond Chung, associate professor of medicine at Harvard Medical School, suggests another improvement in designing an accurate mouse/human liver: to engineer a mouse with a human immune system. “This is still not an ideal model,” says Chung of Bissig’s research. “You can’t necessarily accurately evaluate antiviral drugs given the lack of adaptive immune response in these animals.”

Bissig says that in the future, he and his team hope to add a human immune system to their mouse model, so they can see how hepatitis acts, not only in a human liver, but in the presence of a normal, healthy human immune system.

Harvard Medical School

 

FiercePharma.com, February 23, 2010, by Tracy Staton  —  A new survey quantifies a trend we’ve seen: Fewer medical schools are accepting gifts and support from drug and device makers. According to the study published in the Archives of Internal Medicine, 56 percent of internal medicine program directors say they accepted free food and teaching materials. That’s down from 89 percent in 1990.

And apparently, some of the program directors are accepting pharma support unwillingly: Seventy-two percent say taking offered food and gifts from drugmakers was undesirable.

The ties between medical schools and drugmakers have come up for plenty of debate in recent years. Some colleges–including, most recently, Harvard Medical School–have instituted new, more restrictive policies governing just what sort and how much aid they can take from companies. Some of those policies even ban small gifts such as pizza; some won’t let pharma reps distribute free samples directly to doctors’ offices.

Researchers now are suggesting that perhaps med-school students need to be taught how to work with drugmakers. “Despite the attention around conflict of interest with pharmaceutical support, we were surprised to find that only 29.2 percent of the responding program directors reported a specific curriculum to instruct residents about interactions with the pharmaceutical industry,” the researchers say.

TheWallStreetJournal.com, February 23, 2010, by Anna Wilde Mathews  —  If you’re taking a daily aspirin for your heart, you may want to reconsider.

For years, many middle-aged people have taken the drug in hopes of reducing the chance of a heart attack or stroke. Americans bought more than 44 million packages of low-dose aspirin marketed for heart protection in the year ended September, up about 12% from 2005, according to research firm IMS Health.

Now, medical experts say some people who are taking aspirin on a regular basis should think about stopping. Public-health officials are scaling back official recommendations for the painkiller to target a narrower group of patients who are at risk of a heart attack or stroke. The concern is that aspirin’s side effects, which can include bleeding ulcers, might outweigh the potential benefits when taken by many healthy or older people.

“Not everybody needs to take aspirin,” says Sidney Smith, a professor at the University of North Carolina who is chairing a new National Institutes of Health effort to compile treatment recommendations on cardiovascular-disease prevention. Physicians are beginning to tailor aspirin recommendations to “groups where the benefits are especially well established,” he says.

Doctors generally agree that most patients who have already suffered a heart attack or ischemic stroke, the type caused by a clot or other obstruction blocking an artery to the brain, should take regular low-dose aspirin. But for people without heart disease, the newest guidelines from the U.S. Preventive Services Task Force spell out much more clearly than before when aspirin should be administered.

The guidelines, announced last year, suggest aspirin for certain men 45 to 79 years old with elevated heart-disease risk because of factors like cholesterol levels and smoking. For women, the guidelines don’t focus on heart risk. Instead, the task force recommends certain women should take aspirin regularly if they are 55 to 79 and are in danger of having an ischemic stroke, for reasons that could include high blood pressure and diabetes.

The panel urged doctors to factor in conditions that could increase a patient’s risk of bleeding from aspirin, which tends to rise with age. The group didn’t designate a dose, but suggested that an appropriate amount might be 75 milligrams a day, which is close to the 81mg contained in low-dose, or “baby,” aspirin. The task force didn’t take a position on aspirin for people who are 80 and older because of a lack of data in this age group.

Other medical researchers dispute the idea that there should be different guidelines for men and women. Still, many experts agree that doctors may have been recommending aspirin to people for whom the risks might outweigh the benefits.

Aspirin acts as a blood thinner, which is believed to account for much of its benefit of protecting against heart attacks and strokes. But that same action, along with a tendency to deplete the stomach’s protective lining, can lead to a danger of gastrointestinal bleeding and possibly bleeding in the brain.

The task force issued its latest guidelines after reviewing the evidence from a number of studies on aspirin’s benefits and risks. The recommendations update the panel’s previous guidelines from 2002, which were more broadly written. Those suggested aspirin use for people of any age who were at elevated risk of heart disease.

“We would like doctors to re-look at their patients who are on aspirin and consider recommending stopping it where the chance of harm outweighs the benefit,” says Ned Calonge, a Colorado public-health official who serves as the task force’s chairman. He notes, however, that in studies of healthy people taking aspirin, the actual rates of bleeding and of prevented heart attacks were very low.

Not all patients accustomed to taking aspirin will want to stop. Maxine Fischer, 55 years old, recently figured out that under the new U.S. guidelines, she wouldn’t be encouraged to continue with the drug. Using an online calculator, which factored such data as her age, blood pressure and medical history, she learned she had just a 1% likelihood of a stroke in the next 10 years. Under the guidelines, only women in her age group with at least a 3% or higher stroke risk should take aspirin.

Ms. Fischer, who works as a manager for seniors’ lobby AARP in San Diego, has taken aspirin daily for two years after reading it could reduce the risk of stroke. For the moment, she says she’ll keep it up, partly because she’s more worried about strokes than ulcers. Strokes are “the big scary thing,” she says.

Other patients say they would stick with aspirin because of other benefits attributed to the drug; past research has suggested that regular aspirin may reduce the risk of colon cancer, for instance. Virginia Douglas, 64, a retired trade-association executive, takes aspirin a few times a week. In addition to the possibly reduced risk of stroke, Ms. Douglas hopes to avoid colon cancer, which affected her father and grandfather. “There’s always a new study with a new recommendation,” says Ms. Douglas, of Sacramento, Calif. “You have to do what’s best for you.”

In a separate analysis, published in medical journal Lancet last May, an international group of scientists reached a broadly similar conclusion as did the U.S. task force—that doctors may have been recommending aspirin too widely. “You really have to have a clear margin of benefit over hazard before you should be treating healthy people,” says Colin Baigent, a professor at Oxford University who coordinated the Lancet analysis.

Still, the Lancet authors disagreed with the U.S. panel on some important details, particularly about who should be taking aspirin. The two groups examined evidence largely from the same studies of the drug, although the international team analyzed the data differently. In the end, the international team of scientists, unlike the U.S. officials, concluded that aspirin’s effects on men and women were mostly the same.

Another disagreement between the two groups also emerged: The U.S. task force said that age is the biggest factor determining a person’s risk of internal bleeding from aspirin. But the international team said other factors, such as diabetes and high blood pressure, also play a significant role. Unfortunately, the scientists noted, the same factors that increase patients’ risk of bleeding also increase their risk of developing heart disease. This, in turn, can make it more difficult to calculate whether the benefits of aspirin would outweigh the risks of side effects.

The U.S. task force responded with a letter to the Lancet, defending its finding that men and women’s results did appear different. There is a “wealth of evidence that men and women have different cardiovascular disease manifestations and respond differently to aspirin,” the letter said. The panel also reiterated its position that bleeding risk is best parsed by age.

Amid the debate, some individual doctors are finding their own position. Rodney Hayward, who codirects a Veterans Affairs research center in Ann Arbor, Mich., says he’s not convinced that aspirin’s effects on men and women are so different. He says he continues to recommend aspirin for certain patients of both sexes with significant heart risk.

Write to Anna Wilde Mathews at anna.mathews@wsj.com

What Aspirin Does

Aspirin’s effects in the body can have good and bad implications.

  • Blood thinner: It inhibits clotting, which helps reduce the risk of heart attack and ischemic stroke but increases the danger of bleeding.
  • Inflammation reducer: It lessens pain and fever by preventing production of the hormone-like substances called prostaglandins. But this can also deplete a protective layer in the stomach and increase the risk of ulcers.

What You Can Do

If you want to figure out if the newest guidelines recommend aspirin for you, here’s where to check:

  • At ahrq.gov, type ‘aspirin and prevention’ into the search box, and the new guidelines will come up in the results. Click on ‘clinical summary’ for a table that explains what people of different ages should do, and includes links to online calculators to help you figure out your risk of heart attack or stroke. You should also speak to your doctor.

Aspirin Advice

Doctors have been scaling back their aspirin recommendations for people who don’t already have heart disease. Here are the current guidelines from the U.S. Preventive Services Task Force.

Aspirin recommended for:

  • Some men 45 and older with risk factors for heart disease, assuming no history of ulcers or other bleeding dangers.
  • Some women 55 and older with risk factors for stroke, and no history of bleeding danger.

Aspirin not recommended for:

  • Men younger than 45, and women younger than 55.
  • Anyone 80 and older.

Anatomy of the Heart

Harvard Medical School, February 23, 2010 — Women and men share most risk factors for heart disease — including high chole
sterol, inactivity, obesity, high blood pressure, and smoking — but there are some gender differences in its development, symptoms, and prognosis.

Men and women who want to live a heart-healthy life together can devise a single diet and exercise program that will suit them both. But their paths diverge at pill time and cocktail hour.

Aspirin. Baby aspirin should have a place on a man’s medicine shelf 10 years before a woman’s. Men at risk for heart attack are advised to take a low-dose aspirin daily starting at age 45, but women are told to hold off until they’re 55, and then to take it for the purpose of preventing strokes. For both genders, the protective effects of aspirin have to be weighed against the gastrointestinal risks.

Alcohol. While two drinks a day may keep a man’s cardiologist away, they may hasten a woman’s journey to the ER. Women are limited to a single drink because their bodies hang on to alcohol longer: lower levels of the liver enzymes that break down alcohol keep concentrations in a woman’s blood higher for longer periods. As a result, alcohol abuse has more serious effects on women’s hearts than on men’s, as evidenced by studies of patients with alcoholic cardiomyopathy — a weakening of the heart muscle.

Differences in symptoms

When the coronary arteries are obstructed or constricted so that the heart muscle isn’t receiving the oxygen it needs to do its work, the body feels the results. Both men and women may experience angina, the classic sign of coronary artery disease characterized by chest pain, a cold sweat, nausea, and other symptoms.

But women are more likely than men to have less dramatic symptoms, such as general fatigue and a flulike malaise. And variant angina — also known as Prinzmetal’s angina — which results from coronary artery spasm and is likely to strike in the wee hours during deep sleep, is more common in women than in men.

Differences in diagnosis

When someone shows up at a medical facility with cardiac symptoms, a number of tests can be used to determine the source, beginning with resting electrocardiography (ECG), followed by stress testing, in which a person walks on a treadmill while being monitored by ECG.

However, ECG stress tests are more likely to miss cardiovascular disease in women than in men. Nuclear stress tests, in which an image indicating blood flow to the heart is made before and immediately after exercise, cost more, but they’re more reliable than ECGs in women.

Coronary angiography — an X-ray that outlines blockages in coronary arteries — is considered the gold standard for identifying the location of blockages in people with positive stress tests. But all that glitters isn’t gold for women. Because they’re less likely than men to have discrete, bulging lesions and more likely to experience microvascular disease, their angiograms may show no obstructions. Women may need two additional tests, which can be performed during angiography:

Intravascular ultrasound (IVUS) involves threading a tiny transducer into a coronary artery to capture a cross-sectional image of the artery walls. It can find arteries that have been narrowed more uniformly by atherosclerotic plaque.

Coronary flow reserve studies, in which a catheter measures the change in coronary blood flow in response to increased demand, can indicate whether the microscopic vessels in the heart wall are delivering an adequate blood supply.

Differences in treatment

For women who have uniformly narrowed coronary arteries or microvascular disease, lifestyle changes and medications are the only treatment options. For women and men with obstructive coronary lesions, angioplasty with stenting and coronary bypass surgery are equally likely to succeed in opening their arteries, but women are less likely than men to be offered these procedures.

When women do have bypass surgery or get angioplasty, they tend to be a decade older than men undergoing similar procedures. Perhaps as a result, they require longer hospital stays, have higher death rates in the weeks following the procedure, and are less likely to be referred to coronary rehabilitation centers.

The bottom line

Heart disease is still the No. 1 killer of us all, although death rates have declined by 25% since the late 1990s. Heart disease has become less deadly for a variety of reasons:

better control of risk factors like cholesterol and blood pressure

faster diagnosis,

improvements in emergency care

advances in medications and procedures

If there’s a message for men, it’s that it’s all there for the taking. Diagnostic and therapeutic protocols are made for you. Whether you’ve had a heart attack or are trying to prevent one, your greatest challenge is to adhere to a healthful diet, exercise often, have regular check-ups, and take your medication as prescribed.

The message for women: A healthy lifestyle is key, especially if you have an inflammatory disorder or an expanding waistline. If you’re depressed, get help. And if you feel unusually tired, achy, or short of breath, don’t write it off as nothing — or blame it on aging. Check with your doctor to make sure it isn’t heart disease. If you’re diagnosed with heart disease, you may have to be a little more aggressive in getting the care you need. Seek out one of the women’s heart centers that are springing up in hospitals across the nation.

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