Family History May Be Key in Heart Risk

First appeared in the Wall Street Journal

Ecorse Heart Doctors often gloss over a key question for assessing a person's risk for coronary heart disease, according to a new study: What is the patient's family history of cardiovascular illness?

The study suggests some doctors may not be capturing the full extent of many patients' chances of developing heart disease. Detailed family information could help doctors better predict who is at risk and more accurately target patients for preventive care that may help avert the disease altogether, according to the study, due to be published Tuesday in the Annals of Internal Medicine. Routinely tracking family history sharply boosted the number of people in the study considered at high risk for heart disease.

A widely used scorecard for measuring heart risk, the Framingham Risk Score, fails to take family history directly into account. And while many doctors currently collect some information about the health of their patients' families, the data often lack the detail to be clinically useful for assessing risk and prescribing care.

Family history remains one of the most important predictors of an event for an individual. Still, most of the family history that experts are collecting is just the presence or the absence of heart disease, not the age of onset or the type of disease, according to Northville Cardiologists.

Guidelines for heart-risk screening, issued by the heart association in late 2010, encouraged doctors to take family histories into account. Doctors sometimes make judgment calls to treat people as high risk because of family history, even if it isn't part of the patient's risk score.

The study, funded by the United Kingdom Department of Health, included 748 patients aged 30 to 65. Up to 13% of patients were found to be at high risk of coronary heart disease using traditional assessment tools. After patients filled out enhanced questionnaires that sought more complete information, the percentage considered at high risk jumped to 18%. The traditional assessment could include general information, such as blood pressure, cholesterol level and basic information about whether a family member had a history of heart disease. The enhanced survey would identify, for instance, that a patient's mother had a heart attack at age 50.

It's a low cost way to target people who are at high risk for cardiovascular disease, say Romulus Heart Doctors.

Findings from the U.K.-based study reflect similar use of family history among doctors in the U.S., several U.S.-based physicians say.

Family history has been linked to higher risk for a number of illnesses, including cancer and diabetes. Unlike some other diseases, however, clear genetic markers for coronary heart disease, which accounts for 1 in 6 U.S. deaths, remain elusive. Family histories can be used as a proxy for detailed genetic work that may someday be used to help predict heart-disease risk, researchers say.

Another risk-measurement tool, known as the Reynolds Risk Score, developed by Harvard University researchers in the 1990s, does consider if a patient's parent had a heart attack and at what age. However, many medical practices don't yet use the tool, which became available in 2007.

Using the Reynolds system, the researchers tracked 25,000 initially healthy patients over a decade. They found that a 50-year-old male patient who, among other things, smoked, and had high blood pressure and cholesterol, but no family history of heart disease, had a 12%, or moderate, chance of having a heart attack in the 10-year period. But a similar patient with a parent who had a heart attack before age 60 had a 20% risk, putting that patient at high risk for heart disease. Heart risk wasn't significantly affected in patients with a parent who had a heart attack at the age of 60 or older.

Still, many medical practices continue to rely on the older Framingham Risk Score, which became available in the 1990s. Researchers believed that other factors, including blood pressure and cholesterol levels, provided all the information needed to determine a patient's risk for heart disease.

Doctors use the scoring systems to single out patients who could benefit from counseling about lifestyle changes, such as losing weight and quitting smoking, or from preventive interventions such as low-dose aspirin and cholesterol drugs, says Yul Ejnes, the chairman of the American College of Physicians board of regents. The college publishes the Annals of Internal Medicine.

Primary-care doctors say there are obstacles to gathering family histories from patients, including competing priorities for time in the examination room. And patients often don't know many details about their family members. In the Annals of Internal Medicine study, patients were mailed questionnaires and instructed to gather the material before seeing their doctor.

Patients should make a point of knowing the health histories of their parents, siblings and grandparents, he says. To identify clues about specific diseases, however Riverview Heart Doctors say that they sometimes asks patients questions like: "What do you remember about Grandpop's hospitalization? Were his legs swollen?"

A 33-year-old a senior marketing director at a Boston technology firm, says her family history has made her an advocate for her own health. She says she watches her diet and exercises regularly. And although she currently isn't on any heart medication, she regularly pushes her doctor to check thoroughly for signs of developing heart disease.

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Sleep Deprived? Your Reaction could be Genetic

LA Times

You and your co-worker have been burning the midnight oil for a week to complete a project, and your abbreviated sleep schedule has you feeling like a zombie. Your co-worker, by contrast, bounces through the workday looking and acting none the worse for wear. There are drugs that can do this, you tell yourself, but your co-worker waves off the suggestion. “I’ve always been able to get by with less sleep,”  she says.

Is she just more disciplined than you are? Did she train herself to “need” less sleep? Is she just saying that to make you feel like a slug? While you may too tired to decide, a study published this week in the journal Neurology supplies the likely answer: It’s in her genes. And your exhaustion is in yours, as well.

The Neurology study, conducted at University of Pennsylvania School of Medicine, found evidence that “interindividual differences” in the way we fall asleep, stay asleep and cope with sleep shortage can be predicted reliably by whether or not we have inherited an allele called DBQ1*0602.
You may very well be one of the more than one-in-four people who are positive for the DBQ1*0602 allele, which happens to be a genetic marker for narcolepsy--a sleep disorder that causes sufferers to fall deeply asleep during the day with little warning. Most narcoleptics have this genetic peculiarity, although being DBQ1*0602-positive is no assurance you’ll be narcoleptic. Compared to those without this allele, someone who’s positive for this allele is likely to fall fitfully into sleep even when she’s exhausted; break free from sleep’s hold several times a night, and feel miserably sleepy when he hasn’t gotten enough shut-eye.

That resilient co-worker, by contrast, appears to be in the genetic majority: DBQ1*0602-negative. Faced with the prospect of less sleep, her body and brain settle into sleep more quickly, slide seamlessly into deep sleep, and stay under until she has to wake up.

After putting 129 healthy adults through a five-night ordeal of partial sleep deprivation (four hours per night), the authors of the Neurology study found no actual differences in cognitive performance between those who were positive and those who were negative for the allele: the differences were in how sleepy and fatigued individuals in the two groups felt after five nights of abbreviated sleep.

In a world where sleep is in chronically short supply, this kind of research is of considerable interest to employers. In lines of work where hours can be long, sleep is had in short bursts, and alertness is non-negotiable—e.g. fighting wars, tending to the sick, driving trucks and flying commercial aircraft—finding people who can function well on little sleep is essential. As research refines how our genes influence our sleeping patterns, some ethicists worry research like this will be used to weed out those who genes predispose them to tolerate sleep deprivation poorly. (The Genetic Information Nondiscrimination Act—GINA—made law in 2008 makes such actions illegal. But that legal protection can potentially be short-circuited by arguments about public safety or national security.)

Namni Goel, the author of the Neurology study published this week, says that using such research to weed out employees who feel miserable when sleep deprived “would be a negative outcome.” She’d rather people use such information to help themselves function optimally: if they know they’re genetically vulnerable to sleep deprivation, they should have a cup of coffee or take a nap when they’ve failed get enough nighttime sleep, said Goel.

Genome Studies point to Cholesterol-Regulating Genes

Bloomberg / Business Week

Researchers caution any possible clinical application is many years away

Researchers have identified almost 100 genes in the human genome that may regulate cholesterol levels and the risk of coronary artery disease, according to a new study.

Reporting in the Aug. 5 issue of Nature, the authors suggest that studying these regions may illuminate the genetic basis of cholesterol levels in humans, but they caution that potential clinical applications are many years away.

"There's convincing evidence that at least some of these will be useful on a clinical level," said study co-author Dr. Sekar Kathiresan of Harvard Medical School, although exactly how most of them might regulate cholesterol metabolism remains an open question, he said.

Levels of two kinds of lipids -- cholesterol and triglycerides -- are known risk factors for heart disease, and about half of the variability in lipid levels is thought to result from genetic factors, said Kathiresan.

He and his colleagues measured lipid levels in more than 100,000 people and then scanned their genomes for genetic differences. They found 95 sites at which tiny differences in genetic sequence seemed to correlate consistently with differences in lipid levels. Together, an individual's genetic makeup at these 95 sites seems to explain about one-quarter of the genetic component of blood lipid levels, Kathiresan said.

Although the initial analysis was done in people of European descent, the researchers also performed their analyses on people of other ethnic backgrounds and found that most of the 95 regions appear to be important in individuals of African and Asian heritage as well.

About one-third of these sites were already known or suspected to be important for lipid metabolism; the other two-thirds had not been tied to lipid levels or coronary artery disease.

"We have now a long list of genes that are relevant in people, and we think it's time to start trying to understand each of those," Kathiresan said. "We think that some of these will in time turn out to be useful drug targets."

As a first step in understanding the biological mechanism through which one of these genes regulates lipid levels, the authors then conducted an in-depth analysis of one of the 95 sites. They found that the gene that had the strongest relationship to lipid levels was not actually part of the genome that codes for proteins. Instead, this "non-coding" gene is involved in regulating the expression of a different gene that directly influences lipid levels.

None of this mechanism was known before to be important in cholesterol metabolism, Kathiresan said. It's an "entirely new player in the lipid field."

Similar in-depth analysis of the other 94 sites may uncover other novel lipid regulators, Kathiresan said. "With that kind of effort, we think we'll be able to learn a lot about what is important for lipids in people," he said.

Dr. John LaRosa, of the State University of New York Downstate Medical Center in Brooklyn, cautioned that it may not be straightforward to tease apart how these genes influence lipid levels or risk of coronary artery disease. While a few of them may regulate lipid metabolism in a simple way, it's likely that many interact in extremely complex ways, which may be too much for even powerful computers to resolve, he said.

Some may be important only when triggered by an environmental factor, and others may simply be false positives that don't actually contribute to lipid metabolism, LaRosa added.

Still, the work is "great science," LaRosa said, and sets important groundwork for the future.

What does this mean for the average guy on the street?

"Probably not much," he said, "but they are important studies to do. They build up a database that we need in order to be able to dissect how the genome influences something as remote from the individual gene sites as having high cholesterol."

House Panel Probes Gene Tests

The Wall Street Journal

 

A House panel is investigating personal genetic test kits currently sold over the Internet after one company proposed selling its kits through stores operated by Walgreen Co. and CVS Caremark Corp.

Last week, Pathway Genomics, a closely held firm based in San Diego, announced plans to sell its Insight Saliva Collection Kit through 6,000 Walgreens stores for between $20 to $30 a test. Saliva collected from the test would be sent to the company and analyzed for an additional price of $79 to $249.

The test, which Pathway currently sells through its website, is designed to predict a person's risk for developing certain diseases or how they might respond to certain drugs. It can also predict the risk of 37 genetic diseases caused by recessive genes that might be passed to a child from parents.

But after the Food and Drug Administration raised concerns about the test, Walgreen and CVS Caremark both said they would hold off on selling the kits until all the regulatory issues are worked out with the agency.

The test isn't FDA-approved, but Pathway Genomics has said it didn't think the test needed agency approval. The company said it's currently working with the FDA to make sure it is compliant with agency rules.

Now, the House Energy and Commerce Committee is seeking information about Pathway's test along with tests from 23andMe Inc. and Navigenics, two other closely held firms based in California.

All three companies sell tests on the Internet that analyze a person's salvia to determine their risk of certain health conditions. The tests also allow people to obtain genetic ancestry data.

Rep. Henry Waxman, D-Calif., the chairman of the Energy and Commerce Committee, along with other lawmakers on the House panel, sent letters to the three companies Wednesday requesting information about how they analyze the test and how accurate the test results are. The panel is also seeking information about how the firms collect, process and store individual genetic samples collected from consumers.

It wasn't immediately clear if the panel planned to hold a hearing on the genetic tests.

Walgreens to Begin Selling Genetic Testing Kits

The Chicago Tribune

Scientists, bio-ethicists and genetic counselors worry consumers will misuse or misunderstand test results

 

 

Coming soon to a drugstore near you, alongside the aspirin and greeting cards, will be the promise of answers to some of life's most personal mysteries: Am I at risk for Alzheimer's disease? Or breast cancer? Or obesity?

Starting Friday, Walgreens will begin selling Insight personal genetic testing kits, becoming the first major retail chain in the U.S. to offer home tests that say they assess the risk of developing one of dozens of different health conditions. CVS plans to have it in stores by August.

The product's introduction raises immediate concerns among scientists, bio-ethicists and genetic counselors. They worry that consumers will misuse or misunderstand the results of a test so open to interpretation it is potentially meaningless, or frightening, especially without a full medical assessment.

On Tuesday, the Food and Drug Administration told the Tribune it is investigating the medical claims the product's manufacturer, California-based Pathway Genomics, is making in marketing its genetic test, which hasn't been approved by U.S. regulators.

Pathway officials say the company's home genetic test meets federal regulations and doesn't require FDA approval.

"The tests conducted are not an in-vitro medical device and are not intended for use in diagnosis, treatment, mitigation or cure of disease. It does provide information that allows a person to learn about their health to make healthier lifestyle choices," said Ed MacBean, Pathway's vice president of product management. "If the FDA contacts us, we will discuss it and address any concerns they might have."

Drugstores already carry DNA paternity and gender prediction tests that can be done at home, and genetic test kits are sold online by several firms. But genetic testing typically requires a visit to the doctor's office, allowing for consultation with a health care professional.

Marketers think such kits could become as common as early pregnancy tests, helping consumers get initial information before going to the doctor.

"We recognize that for some people, genetic responses are becoming a more important component of managing their health care," said Jim Cohn, a spokesman for Deerfield-based Walgreens. "There are people who want to know more about their genetic makeup, and we pride ourselves on being convenient and accessible."

The Insight genetic test kit, priced at $20 to $30, comes with a vial and a shipping envelope. Buyers send a sample of their saliva to a Pathway Genomics laboratory and receive their results online. The report costs $79 to $179, depending on the type of test requested.

The kits will be appear on the shelves at about 6,000 of Walgreens' 7,500 stores nationwide.

Pathway Genomics Chief Executive Jim Plante said in a statement that his company is "revolutionizing" the way people access information about their genetics. "The value of knowing how genes play a role in our personal lives, and potentially the lives of our children, is critical for making well-informed health and wellness decisions," he said.

Pathway screens for genetic markers of more than 70 diseases, including diabetes, prostate cancer and cystic fibrosis. The company notes that "some markers have been researched more thoroughly than others, but scientific knowledge advances rapidly."

It recommends buyers discuss results with a doctor or one of Pathway's genetic counselors, particularly for complex health issues such as heart disease and cancer that have multiple causes, including lifestyle and environmental factors, MacBean said.

Scientists question the value of home genetic testing. For most diseases, no one knows exactly why one person gets it and another does not, said Peter Kraft, deputy director of the Program in Molecular and Genetic Epidemiology at Harvard School of Public Health.

"The company states, everyone has the right to know the secrets hidden within their DNA," he said. "Fair enough, but that is a lot of work. I don't think this is the way to go."

According to a paper published in The Lancet in May, a team of more than 30 researchers took a year to analyze the results from full-genome testing of a 40-year-old man with a family history of coronary artery disease who died suddenly. Although the amount of data they analyzed was far greater than that of Pathway's kit, the researchers used much of the same data on genetic health risks, disease risk and drug information.

Even then, the researchers acknowledged that the genetic information was incomplete, said Dr. Nilesh Samani, a professor of cardiology at the University of Leicester in England who wrote a commentary on the study.

Many of the risks have been calculated for the entire population, Samani said, but that doesn't mean it applies neatly to any one individual because of family history, lifestyle habits or, importantly, genetic variations.

Samani likened it to a card game in which you can only see a few cards. At first blush, you may be holding a bad hand, but what if the cards you can't see are all aces?

"You need to know the rest to know whether it is worthwhile," Samani said. "That is a limitation. It is a big limitation. [The companies] don't present it like this."

New Mutant Genes Linked to Rheumatoid Arthritis

Reuters

A large study of European populations has uncovered seven new clusters of defective genes which may be responsible for rheumatoid arthritis, a painful and disabling disease that affects mainly the joints.

The paper was published in Nature Genetics on Monday together with findings of a separate study in Japan, which identified one of the seven genetic clusters as possibly causing the chronic inflammatory disease among Japanese.

"The findings leverage us to better understand the basic biology of rheumatoid arthritis (RA), with the goals of developing new targets for therapy and new biomarkers for diagnosis and prognosis," wrote research scientist Eli Ayumi Stahl at the Brigham and Women's Hospital in Boston in the United States, who led the study on European populations.

The study was also intended "to develop better genetic tests for RA risk, especially in people already at risk (such as arthritis patients or relatives of patients with autoimmune disorders)," Stahl told Reuters.

RA affects about 1 percent of the world's population. Apart from the joints, it may affect the skin, heart, lungs, kidneys and blood vessels. Many end up with deformed hands and feet, resulting in loss of functions and movement. There are few alternatives in the way of rheumatoid arthritis relief.

In the European study, Stahl and colleagues repeated six previous studies involving 5,539 patients, analyzing their genes using the latest technology. They shortlisted 34 genetic variants which they considered most suspect in causing RA.

They then checked if those genetic defects were found in another batch of 6,768 RA patients in Canada, North America, the Netherlands and Britain. Ten of the 34 variants figured most prominently in this replication phase.

"Ten of the 34 variants tested were validated in the replication phase of our study. Three were previously implicated in RA, leaving the 7 new ones mentioned above," Stahl wrote.

"This is more RA risk variants discovered in a single study than any other study to date, underscoring the importance of large-scale studies and the collaborations that enable them in order to make progress in unraveling common, complex diseases."

"Our results further suggest that many more RA risk variants remain to be definitively identified," Stahl added.

In the Japanese study, researchers led by Yuta Kochi at the RIKEN Center for Genomic Medicine in Yokohama, Japan, analyzed genes of 7,039 RA patients and identified a common genetic mutant near the CCR6 gene.

The CCR6 gene was also identified in the European study.