Spotting Heart Disease Early

Roche and other companies are devising diagnostic tests that help more patients prevent heart attacks. The next frontier: genetics-based screens

Diagnosing heart failure is time-consuming, expensive, and often inaccurate. The condition, which occurs when the heart is unable to pump enough blood throughout the body, afflicts 5 million Americans, with 550,000 new cases reported each year.

But its symptoms -- shortness of breath, swollen ankles, and fatigue -- are vague and easily confused with other conditions such as lung or kidney problems. This complicates and delays diagnosis while increasing the chances of error. Missing a heart failure diagnosis puts patients at high risk of serious problems -- or death -- while overdiagnosis may lead patients to receive unnecessary and costly treatment.


Now, with a simple blood test, doctors can accurately diagnose or rule out heart failure in minutes. Launched two years ago by Swiss drug and diagnostics giant Roche Holding (RHHVF), the test measures the levels of two proteins, NT and BNP, which are elevated when the heart muscle is under stress. Levels of these proteins can be raised in cases of heart failure, heart attack, unstable angina, pulmonary embolism, and acute high blood pressure.

Initially, the test was used to diagnose heart failure and monitor its treatment. But last month researchers at Massachusetts General Hospital made a major breakthrough.

In clinical trials, the test proved able to predict long-term risk of death in patients with shortness of breath. The researchers found that patients with elevated levels of the proteins, regardless of the cause, had a higher risk of dying within one year.


As a result, they believe the test can be used not only to determine diagnosis but also to gauge long-term prognosis, allowing doctors to quickly identify patients needing more aggressive treatment and follow-up.

"The next logical step is to evaluate treatment interventions for those with higher NT-proBNP levels to see if we can reduce their considerable risk for death," says Dr. James Januzzi Jr., assistant professor of medicine at Harvard Medical School and a staff cardiologist at Massachusetts General Hospital, who led the research.

Such tests represent a major advance in the diagnosis of cardiovascular disease. Led by Roche, the world leader in cardiovascular testing, many companies now have diagnostic tools on the market to both measure a patient's risk of heart disease and detect existing heart disease. More tests can then distinguish the exact type of disease.


For instance, Roche was the first company to introduce a blood test for troponin, a protein released from dead or injured cells in the heart muscle. This test can determine not only whether a patient has had a heart attack but the exact extent of damage to the heart muscles.

Roche is now taking a much closer look at traditional risk factors for cardiovascular disease such as cholesterol, in the hopes of developing diagnostics that can pick up heart disease much earlier. So instead of just looking at LDL, the so-called bad cholesterol, the company is looking at the worst of the worst subsets of LDL to find very early indications of clogged arteries, says Dr. Hendrik Hüdig, head of Roche Centralized Diagnostics' marker program.

But pharmaceutical and diagnostic companies are moving beyond such traditional markers and exploring a range of proteins and genetic mutations to develop more sophisticated tools to enable earlier and more accurate diagnosis.


"What we're researching is how to assess which patients are at risk, when will they develop heart disease, how their disease is progressing, and whether treatment can be monitored," says Dr. Joachim Eberle, head of research and development at Roche Centralized Diagnostics.

Diagnostics is the first frontier in the ongoing quest for personalized medicine. But as scientists discover more about the exact proteins and genes involved in specific forms of heart disease, they will in turn discover potential targets for better and more effective medicines.

In the meantime, diagnostics companies are in a race to develop sophisticated tests to target with greater precision those most at risk for heart disease. It has proved a hard slog, since heart disease is not one disease but many, which are caused by a complex combination of genetics and environment.


But Celera, an Alameda (Calif.) biotech co-founded by genomics pioneer J. Craig Venter, is on the verge of introducing a new blood test to help predict whether a patient has a high or low risk of developing heart disease, independent of traditional risk factors such as high cholesterol or diabetes.

In conjunction with researchers at Harvard, the Cleveland Clinic, the University of California at San Francisco, and the University of Texas, Celera has examined the genetic profiles of more than 30,000 patients. By comparing genetic samples of patients who have had heart attacks with those who haven't, they have found a number of novel genetic variations that contribute to the development of coronary heart disease.

These variations form the basis of Celera's genetic risk score, which the company says will be available in "a matter of months, not years." "People will be able to determine definitively whether they carry incremental risk for heart attack," says Celera President Kathy P. Ordonez.


Such knowledge could even lead to preventative treatment. For instance, patients who have no symptoms of heart disease but have a high genetic risk score might be given cholesterol-lowering statins.

Currently, most doctors prescribe statins to patients exhibiting more than two of the standard risk factors such as high blood pressure, high cholesterol, or obesity. But as Ordonez points out, are more than 17 million Americans fall into the category of moderate risk and therefore wouldn’t be treated. If these patients were armed with their genetic risk score, doctors could intervene earlier and stop heart disease in its tracks.

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