By now we’ve all heard the admonitions about eating a low-fat diet and exercising regularly. We’ve welcomed the good news about a daily glass or two of red wine. But for those of us with a family history of heart disease, the statistics are frightening. One in five people have some form of cardiovascular disease, and one in three men can expect to develop some major cardiovascular disease before age 60. For women the odds are one in 10.
Cardiovascular disease, which has held the infamous title of No. 1 killer of Americans since 1919, shows no sign of relinquishing its position. In 1997, it claimed 953,110 lives, 41.2 percent of all deaths or one of every 2.4 deaths. More lives are lost to it each year than the next seven leading causes of death combined.
    While the downside of this is obvious, the silver lining is that medical researchers have had ample opportunity to study this nefarious killer, and this generation may be the one that knocks cardiovascular disease from its pedestal.
    As readers of this magazine know, there are a growing number of diagnostic tests available to help single out those patients who are most at risk for serious cardiac problems.
Cholesterol levels are a great starting point, but since half of all myocardial infarctions occur in patients who have never had elevated cholesterol levels, there are clearly more pieces to the puzzle. Tests for troponin, lipoprotein(a), myoglobin and homocysteine have begun to earn their place in the treatment protocols that many emergency rooms and chest pain centers have set up. Of course, the diagnostic tests are only useful if something can be done to help the patient, and today there are a host of drugs and therapies available for the well-armed cardiologist.
Once identified, those at risk can start a daily regimen that includes taking one or more of the latest LDL cholesterol-lowering drugs, which in some patients have proven to be as effective as angioplasty in relieving chest pain and other symptoms. Until the geneticists come to the rescue with the ultimate solution, cardiac markers are our best hope.
— Coleen Curran

dm01.jpg (11912 bytes)Cardiac markers: From diagnosis to prognosis
Every year in this country, about 6 million people visit the hospital complaining of chest pain. Some are clearly having a full blown heart attack, or myocardial infarction (MI), a diagnosis made on the basis of symptoms and the results of an electrocardiogram (ECG). Others may have only a bad case of heartburn or indigestion.
     But for those people with less severe cardiac problems, including the 1.3 million hospitalized each year with acute coronary syndrome, the situation is not as clear. This condition includes both unstable angina, a strangling pain that occurs even when a person is resting, and non-Q-wave MI, or a small heart attack. These are differentiated by the use of blood tests (cardiac markers) which demonstrate the death of heart tissue.
      With standard treatment, about one in 10 of these people will die or have a heart attack within one month of the initial symptoms. More aggressive treatments are available, but the challenge is to identify those patients who are at risk, and if so, how best to treat them.
      “This has really become the Holy Grail in cardiology,” said Robert Jesse, M.D., Ph.D., director of acute cardiac care at the Medical College of Virginia campus of Virginia Commonwealth University in Richmond. “If I’m confronted with someone who has severe chest pain, it does me no good merely to provide a diagnosis. I want to make decisions about possible treatments that I can use to make someone better.”
      Now it looks like a group of proteins known as troponins, which were originally used as cardiac markers to help diagnose these coronary conditions, may also have another use — guiding treatment decisions.

Acute coronary syndrome
Acute coronary syndrome occurs when plaque that has formed in a coronary artery ruptures. This can lead to blood clots that can impede blood flow to the heart. Not only can blood clots lead to a full-blown heart attack, but they also can reduce the effectiveness of interventional treatments such as balloon angioplasty. All too often, an interventional cardiologist will use angioplasty to open the artery, only to have it rapidly close up again as new clots form. The procedure must then be repeated, increasing the chances of complications.
     For most patients, the standard medical treatment to reduce blood clots — aspirin and heparin — is relatively effective and inexpensive. But unfortunately this is not sufficient for everyone. In select cases, thrombolitic “clot buster” drugs can be used to open the arteries. These are expensive and can be risky.
A new family of medications — platelet blockers (glycoprotein IIb/IIIa blockers) — are proving effective in many people. These drugs work by attaching to and blocking the GP IIb/IIIa receptors, which prevent clots from forming. Three platelet blockers have been approved by the FDA — tirofiban (Aggrastat), eptifibatide (Integrilin) and abciximab (Reopro).
     Jesse said some studies have shown that these drugs can reduce the risk of a second cardiac event by as much as 50 percent. But the question is, which patients will benefit? Part of the issue is therapeutic; part is driven by cost. “The platelet blockers cost $800 to $1,200 each. We can’t just give them to anyone,” Jesse said. “They’re relatively safe and effective, but at that price we have to make sure we give them to someone who will actually benefit.”

Levels of risk
To make treatment decisions easier, Jesse has developed a 5-level risk stratification system, with level 1 representing the highest risk (a patient with MI who will receive thrombolytic drugs or angioplasty) and level 5 representing the lowest risk (a non-cardiac patient).
     Levels 1 and 5 are relatively easy to determine, by looking at symptoms and the ECG. But many people with acute coronary syndrome fall in the middle range. These level 2 through 4 patients require additional laboratory testing for cardiac markers, which provide a rough measure of heart damage.
     Traditional cardiac markers include myoglobin and creatine kinase myocardial band (CK-MB). More recently, a group of proteins known as troponins are being widely used as cardiac markers.
     Troponins, which normally help to regulate muscle contractions, are located in all types of muscle tissue. But when the heart is injured in some way, the injured tissues release cardiac troponin I and T. Both can be detected four to six hours after a cardiac event. Depending on the severity of the event, troponin I and T may remain detectable for up to seven days afterwards.
     “Initially the troponins were used to differentiate someone with a heart attack from other chest pain,” Jesse said. “But the troponins didn’t meet expectations for specificity in the early studies. Then they re-analyzed the data, and saw these also were elevated in approximately one-third of the unstable angina patients, suggesting another use for them.”

From diagnosis to prognosis
It turns out that troponin levels determine prognosis as well as diagnosis. “What we learned is that the higher the level of troponin, the worse the outcome,” Jesse said. More important, research revealed that people whose troponins were elevated were also more likely to benefit from treatment with platelet blockers.
“We found that the troponin negative patients did no better on the platelet blockers than they did on placebo,” Jesse explained. “About 1 to 2 percent of them would later have another cardiac event, whether they received these drugs or not.”
     “But if you look at the troponin positive patients,” he said, “there’s a dramatic difference. About 4.5 to 5 percent of the people who are troponin positive and do not receive platelet blockers will have a second cardiac event. But if they are given platelet blockers, it drops to 0.9 percent. So clearly identifying at-risk patients helps guide treatment.”
     Tests for troponin can be done quickly. And that is important. “Fifteen years of studies show that the faster MI treatment begins, the better the outcome.”
     “In the past, we used to be more passive. We’d collect the data, run it in the laboratory, then meet with the patient the next morning and start therapy based on the results.” Now, Jesse said, the test results are available within hours. “We can check the markers over a six to eight hour period, and if they are positive, we can treat patients most likely to improve from aggressive therapy.”
     The FDA has approved a number of troponin assays that all are valuable, according to Jesse. There are even some point-of-care tests for small hospitals where more expensive devices are not available.
     The main point, he said, is to test for troponins in some way. “We’ve reached a point now where laboratory tests are not only identifying at-risk patients, but we are actually using this data to drive care,” Jesse said.
— Ann MacDonald

Troponin’s Capability to Identify Patients Who Will Benefit From Therapy
The 3,232-patient PRISM* trial demonstrated that when unstable angina patients with elevated troponin levels are given the glycoprotein IIb/IIIa receptor antagonist tirofiban, they experience a reduced rate of cardiac events such as acute myocardial infarction and even death. The study showed that this benefit was significant in patients with elevated levels of either troponin I or troponin T.
   In a 2,240-patients sub-study of that trial, the researchers investigated whether the improved patient outcome after 30 days was related to the treatment regime chosen after patients were infused with a clot-busting therapy for 48 hours.
   The study found that when troponin I-positive patients were treated with tirofiban, differences in surgery rates and hospitalization days were no longer observed between patients with elevated troponin I levels and those without.
   The PRISM trial showed that the assessment of tryponin status can direct therapy that results in improved patient outcomes such as a reduction in major cardiac events and the necessity for coronary intervention.

Source: Supplement to the Journal of the American College of Cardiology, February 2000, Vol. 35, Issue 2, Suppl. A. page 393.

* Platelet Receptor Inhibition in Ischemic Syndrome Management

dm02.jpg (11662 bytes)Fewer cardiac tests done on women
According to a recent study at the Mayo Clinic and Foundation in Rochester, Minn., women who go to the emergency room seeking treatment for chest pain are less likely than men to undergo procedures used to diagnose heart disease.
     The study included 1,306 men and 965 women in Olmstead County, Minn. who went to hospital emergency rooms because of unstable angina. Unstable angina can occur at rest and is regarded as a sign of worsening heart disease and increased risk for heart attack.
     The vast majority of participants — 85 percent of the men and 72 percent of the women — underwent some sort of procedure to test for heart disease within 90 days of visiting the emergency room, the researchers reported.
      But when the investigators took into account other factors besides sex — such as age, type of chest pain and several measures of heart function — they found that men were 24 percent more likely than women to undergo any type of cardiac procedure. Men also were about 40 percent more likely to undergo coronary angiography.
      Researcher Veronique L. Roger, M.D., of the Mayo Clinic said there is no evidence that women’s health is jeopardized by receiving fewer cardiac tests. Despite the fewer tests, the study showed that over the following six years, women in the study had fewer heart attacks and were less likely to die than men. During the six-year study, men were somewhat more likely to die, although the difference in death rates was not statistically significant, meaning that it could have occurred by chance. Men were 21 percent more likely to have heart-related problems, like a heart attack and heart failure, a difference which was statistically significant.
— Melissa Mac

dm03.jpg (9952 bytes)Cardiac markers are key to clinical protocols that improve outcomes for chest pain patients
After several decades of treating and researching the human cardiovascular system, the consensus among clinicians is that diagnostic protocols or treatment algorithms are the best approach for patients with chest pain. Stephen Kahn, Ph.D., director of the Chemistry/Clinical Lab and departments of pathology and biochemistry at Loyola University Medical Center, agrees. Dr. Kahn, a past-president of the American Association for Clinical Chemistry, is an outspoken advocate of standardization and the use of clinical treatment pathways. CLP talked with him about cardiac markers’ role in chest pain triage and how they are improving outcomes.

Q. With all the research into cardiac markers and their capability to predict MI, how prevalent are treatment algorithms?
A. Several leading institutions use accelerated diagnostic protocols (ADPs) or treatment algorithms. These ADPs may be in use at large teaching hospitals, community hospitals or academic medical centers, but there are still a lot of hospitals that are not at the stage of using these types of protocols. The treatment algorithms can be very different from one hospital to the next.

Q. How is it handled at Loyola?
A. We categorize our chest pain patients into low-, middle- and high-risk based on a variety of clinical criteria. Key criteria include a patient’s history, clinical presentation, the EKG and laboratory results. Once patients are enrolled in the chest pain protocol, there is still the question of whether or not they really had an acute myocardial infarction (AMI). The laboratory test component of the ROMI (rule out of myocardial infarction) protocol is begun. The lab tests are important, but still only one part of the overall treatment pathway.

Q. So most institutions probably have some type of treatment protocol for chest pain?
A. One can find institutions that are not utilizing ADPs. One also could find institutions that firmly believe in categorizing patients into no fewer than five different risk categories. All sorts of variations are out there.

Q. Is it ideal to shorten the protocol?
A. Ideally, you want to abbreviate it as much as possible, but the key is to accurately determine if the patient has had a heart attack. In many studies, (including our outpatient population), roughly 90 percent of the patients who present to emergency rooms for chest pain have not had a heart attack. You don’t want to miss any of them, particularly those who have had an AMI. But you don’t want to admit any individuals whose health status does not require it. It is just not appropriate clinical care, and significant but unnecessary costs can be incurred.
    It is clinically and financially desirable for institutions to treat patients on an outpatient basis. At our institution, selected patients can be categorized as a 23-hour admission if it can be determined within 23 hours that the patient is not suffering from an AMI or any other clinical problems requiring admission. This reduces the unnecessary use and cost of an inpatient bed by ensuring that the individual who does not need to be admitted remains an outpatient. The major issue, however, is not a financial concern. Most important is maintaining the quality of clinical care and recognizing that the majority of chest pain patients likely do not require inpatient admission.

Q. When did you start your program?
A. We’ve had our chest pain program in place for a little over two years, and it has helped us effectively triage all chest pain patients. We use an aggressive, patient-focused protocol with defined and regimented lab testing provisions. Depending on the risk category and other factors, chest pain patients may be further evaluated using a stress treadmill test or an imaging technique to determine if they have any blockages of blood vessels or necrotic areas in the heart. While our cost-per-AMI patient is somewhat higher now than it was prior to implementing the ADPs, the overall cost-per-patient for all the patients in the chest pain category, including patients ruled out for an MI, is far less.
Considering that about 90 percent of the patients who present at the ER are not having an AMI, the overall cost-per-patient savings can be considerable as has been reported in selected studies in the scientific and clinical literature. There was a study at Cook County Hospital in Chicago a couple of years ago where the use of a chest pain evaluation unit with accelerated treatment protocols had been initiated. The authors claimed to have saved more than $500,000 a year by implementing these protocols and effectively triaging all their chest pain patients. They included the majority of patients who didn’t need to be admitted. The program also provided an improved approach to identifying those individuals who did have an AMI so that they could get effective medical care.

Q. What does it take to implement a treatment algorithm at an institution?
A. First, it takes a significant amount of effort to bring together personnel from different departments to agree upon and establish these protocols. There also is information in the clinical and scientific literature. The key individuals on our institution’s Chest Pain Committee believe that it is best clinical practice to set up treatment plans or care paths and/or treatment algorithms. But it takes a lot of teamwork to design them, and regardless of any literature study, to ensure that treatment guidelines are appropriate for your own patient population. Establishing any treatment protocol that involves people from different departments is always a significant undertaking.

Q. How did you do it?
A. A lot of advance planning and teamwork. We started our chest pain management program in the summer of 1997 with the formation of the Chest Pain committee. This group met twice a month for almost six months prior to the start of the program.
— Coleen Curran

High Blood Pressure Facts

  1. High blood pressure was listed as the primary cause of death on the death certificates of 42,565
    Americans in 1997.
  2. About 50 million Americans age 6 and older have high blood pressure.
  3. • 31.6% don’t know they have it
    • 27.4% control it with medication
    • 26.2% are on medication but don’t have it under control
    • 14.8% are not on medication
  4. High blood pressure is two to three times more common in women taking oral contraceptives.

From the Sixth Report of the Joint National
Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure

FDA clears lipoprotein test as a predictive marker for premature myocardial infarction
The U.S. Food and Drug Administration has good news for people with a family history of heart disease. A new automated method for measuring lipoprotein(a) (Lp(a)) was cleared by the government agency in January. An excess of lipoprotein(a) in human serum has been associated with premature myocardial infarction and death among people with a family history of heart disease.

dm04.jpg (8127 bytes)Lipoproteins transport cholesterol and triacylglycerols through the blood stream. Lipoproteins can be divided into five broad categories: VLDL (very low density), LDL (low density), IDL
(intermediate density), HDL (high density), and Chylomicrons.

Lipoprotein(a) appears to raise the odds of random clots, which can block blood flow to the heart. Experts believe that 15 to 20 percent of the population has an elevated level of Lp(a) cholesterol. Those with elevated levels run a much higher risk of heart disease. Testing for Lp(a) levels is crucial because one out of every two heart-attack victims has completely normal cholesterol levels. “Testing for Lp(a) in people who have normal levels of cholesterol but who also have a strong inherited risk of heart disease will likely save lives,” according to Richard Stein, M.D., a cardiologist at Lennox Hill Hospital in New York City.
     The Macra Lp(a) is a microtiter plate assay used to measure lipoprotein(a) in human serum. It is manufactured by Trinity Biotech USA of Jamestown, N.Y., a subsidiary of Trinity Biotech of Dublin, Ireland. It is distributed in the United States through Wampole Laboratories of Cranbury, N.J.
While there are other tests on the market that measure lipoprotein, the Irish assay has been approved by the FDA under three banners, according to Andrew Shine, marketing manager at Trinity Biotech.
     “First, it is approved as a marker of cardiac disease, which others (test manufacturers) have as well. Secondly, we also have clearance for use in automated systems,” Shine said. Since the automated systems market is considerably larger than the manual tests market, this clearance significantly improves opportunities for the test to become more widespread.
     Risk assessment is the third banner of FDA approval. “It’s been cleared for prediction,” Shine said. “It’s a predictive marker, and it’s the only [test] cleared for that.”
     Cardiovascular disease (CVD), the leading cause of death in the United States, causes many more deaths than all cancers combined, according to the American Heart Association. Fifty-eight million Americans have one or more types of CVD, including 12.2 million with coronary heart disease, according to AHA statistics. Approximately 225,000 people a year die of cardiac arrest.
     Trinity Biotech’s Lp(a) assay is the same test used in the renowned Framingham Offspring Study, Shine said. Pinpointing potential heart disease in patients can greatly reduce the risk of CVD, he said.
     “It uses a pretty standard methodology, and just about every laboratory would have the equipment to do the test,” Shine said. “If not, the majority of those [without the equipment] could do it manually.”

dm05.jpg (10411 bytes) Structure of a lipoprotein
A lipoprotein is a complex spherical structure with a hydrophilic coating composed of
phospholipid, cholesterol and proteins (so called apolipoproteins). Within the hydrophobic
core of lipoproteins are triacylglycerols (triglyceride) and cholesterol esters.

The most widely used and most widely tested cardiac marker — cholesterol — is not to be ignored, according to Shine, but he notes that Trinity Biotech’s test is far more accurate and specific in looking for potential CVD. Lipoprotein is a test that should be used alongside cholesterol to help further define the at-risk population since 50 percent of people with normal cholesterol levels will some day have a heart attack.
     “Cardiac markers have been very indistinct,” he said. “Cholesterol was first, but apparently not very accurate. It was split into other lipoproteins, low-density lipoprotein (LDL) and high-density lipoprotein (HDL).
     “Lp(a) differs from LDL in that it contains an additional block of protein that is much more specific,” Shine said. The bottom line is that the test will point out who is most at risk for CVD, he said.
     “Many doctors might look at patients who are overweight or have high cholesterol and say ‘Cut down on fatty foods, etc.’,” Shine said. “This test is more specific. It points out who is at risk, and there are diets that can help cut down on lipoprotein.”
     With the Lp(a) test specifically pointing out to doctors what patients may be at risk for CVD, Shine said, “Doctors can then say to their patients, with confidence, ‘if you don’t do this or cut down on that, you will be in trouble.’ ”
— Paul Kandarian

dm07.jpg (8244 bytes)From homocysteine to C Reactive Protein, the list of accurate tools for cardiac diagnosticians continues to grow
Nader Rafai, Ph.D., director of clinical chemistry at the Children’s Hospital of Boston and associate professor of pathology at Harvard Medical School, talks about the complexity of atherosclerosis and some of the latest cutting edge markers for cardiac risk. These markers are helping clinicians to identify earlier and more accurately those patients who are at high risk for having myocardial infarction.

Q. We hear that homocysteine is one of the markers that researchers are currently looking at as a predictor of cardiac problems.
A. Homocysteine is used like cholesterol, CRP (C Reactive Protein) or Lp(a) (Lipoprotein (a)) at the front end to help assess someone’s risk of developing a coronary event. It’s done when you are in a metabolically steady state and healthy. It helps assess the likelihood of developing stroke or MI.

Q. How long has it been used to asses stroke or MI risk?
A. There are several requirements for a test to be accepted clinically as a coronary heart disease risk marker. First, you have to be able to measure it reliably and well. You also want a marker that has been shown to be consistent and useful in prospective studies. And you have to be able to do something with the information. Cholesterol is a perfect example that fits all three. It’s measured very well, it’s standardized and there are tons of prospective, epidemiological clinical studies showing that high cholesterol correlates with coronary heart disease. Finally, there are cholesterol-lowering drugs that can lower the risk of coronary heart disease. Homocysteine was suggested for the first time in the mid-60s as being associated with atherosclerosis. It has been popular over the last several years. But when you look at the three requirements for homocysteine, its measurement is not standardized yet, and most are homemade assays.

Q. What do you mean by homemade?
A. Individual labs make them. They are not subjected to the rigid quality assurance that manufacturers are subjected to when they develop products. So the level of variability from lab to lab is usually high. So this is one issue.

Q. Is homocysteine a promising marker?
A. The data from prospective studies is not very consistent. Some excellent studies have shown that homocysteine is a predictor of myocardial infarction. Other equally well designed studies found that it is not. So it is a risk factor, but whether it will make it in the long run remains to be determined. One interesting thing about homocysteine is that folate supplements seem to lower homocysteine levels. We don’t know yet if lowering homocysteine levels through folate supplements will help lower the risk of MI. There are studies on-going right now to document that.
      A couple of years ago, the FDA increased the amount of folate added to cereals. Several reports have since documented that the median and the mean levels of homocysteine in the U.S. population are going down. So it’s going to be interesting to see how many of those who have elevated homocysteine levels will remain elevated down the line.
     When studying a disease as complex as atherosclerosis, you want to identify the most promising risk factors, so you can add them to the net to increase your likelihood of identifying the individuals who are at risk. So as far as routine use for homocysteine, I don’t know. Certainly there are no national recommendations for screening for coronary risk. There are populations with a family history of atherosclerosis where the measurement of homocysteine is justified, but clearly not on the entire population.

Q. Can you explain the homocysteine study you were involved in.
A. We were trying to see how much discrepancy there was between commercial and in-house methods. We were pleasantly surprised. There’s still some variability among methods that will affect the clinical utility of the tests. So there is a great need for standardization. It’s a risk factor, but I don’t think it is the most promising one among the newly emerging risk factors.

Q. So you don’t think homocysteine is very promising as a risk factor marker?
A. It might prove to be useful in a specific
patient population such as diabetics and patients with chronic renal failure but not for the population at large.

Q. Which of the newly emerging risk factors do you think is promising?
A. CRP or C-Reactive Protein. We have a lot of studies with CRP using high sensitivity methods. We have six or seven prospective studies going, and there are several others in the U.S., and at least two in Europe. All of them were very, very positive. Those males in the highest quintile of CRP levels had a three-fold higher risk of MI and up to five to six times the risk in females with high CRP compared to those with low CRP.
     Remember that half of those people who end up having a myocardial infarction have normal lipid levels. So certainly other things are involved. Whatever markers we’re going to bring in need to add value to cholesterol measurements. With homocysteine, that was not apparent. With CRP, it was apparent. It almost doubled the risk predictability when you add CRP to total cholesterol and HDL ratio.
    In fact, we have a paper that should be coming out in the New England Journal of Medicine very soon. We did a sub-study of the Women’s Health Study, 28,000 women who are being followed for up to five years. We have baseline samples on them. Now five years later, we know who developed MI. So we went back to their baseline samples and measured 12 risk factors to see which ones were predictors for MI. We found that by far the strongest predictor was CRP and next to it was total cholesterol to HDL ratio. The lowest two were Lp(a) and homocysteine.
    Those with the highest CRP levels were at three times the risk of developing MI than those with low CRP concentrations. So homocysteine is an interesting factor, but when you put it in contrast with the other emerging factors, I don’t think it’s that impressive.

Q. So how can CRP be controlled? Is it a function of diet?
A. One study came out saying that aspirin, which besides having anti-platelet activities also has an anti-inflammatory effect, will lower CRP. Another study shows that Pravastatin lowers the CRP level. Since late summer 1999, there have been at least three Wall Street Journal articles on CRP. They said that pharmaceutical companies are now retaining inflammation experts to look for new drugs or at old drugs that were shelved and that may be ideal for this particular situation. This goes along with the whole new theory of atherosclerosis as a chronic, sub-clinical inflammatory process.

Q. Are there any problems with CRP?
A. CRP has a very bad reputation. It is viewed as a non-specific lousy marker. It’s not used widely in the U.S. The new high-sensitivity assays will measure fine in normal individuals but if you have an infection, the CRP level is going to be high. But for any test to assess someone’s risk of heart disease, the person has to be in a metabolically steady state. Even cholesterol is affected if you have cold or are sick. For example, a normal level of CRP is between .01 and .04. If you have cold, the level will be 1 or 2 or 3 or 4. So you will know that the levels are far too high, so you will repeat the test when the patient is not sick.
    If it had a different name, people would probably accept it much quicker. So you just have to convince people now to look at it from a completely different point of view. That should be relatively easy because the data coming out from laboratories around the world is so consistent and so strong that you really have to believe it. There has not been a single negative study so far. It’s very powerful.

Q. Are CRP tests being done?
A. It’s very new. The data is just coming out. People are just learning about it. To tell you the truth, I think laboratories are lagging behind in this. I get phone calls from frustrated cardiologists all the time. They heard a talk about CRP, and they send a sample to the lab, and the lab has either not heard of high-sensitivity CRP or they send back results below the detection limit because they are using the old assays. There needs to be a significant educational effort. Clinicians are more aware of it at this point than the labratorians and manufacturers are more aware of it than their customers. So of the three groups, the labratorians are clearly the ones that are lagging behind the most.

Q. What’s the difference between older and newer assays?
A. Older assays have a sensitivity limit of .5 or .3 mg/dL. The newer ones have a sensitivity limit from about .015 or lower.
— Coleen Curran

dm08.jpg (7780 bytes)Study links hair loss and heart disease
As if losing your hair is not enough to worry about, now baldness has been implicated as correlating with a tendency toward heart disease. Men, who are losing hair on the crowns of their heads, have up to a 36 percent greater risk of coronary heart disease than men with full heads of hair or even receding hairlines, according to a recent study.
     The risk of coronary heart disease is even greater in men with other risk factors, said JoAnn E. Manson, M.D., endocrinologist and chief of the Division of Preventive Medicine at Brigham and Women’s Hospital in Boston, and co-author of the study.
      “The link between extensive baldness and heart disease was even stronger among men with existing hypertension or high cholesterol,” said Manson. The latest findings of the Brigham and Women’s Hospital-based Physicians’ Health Study was published in the Jan. 24, 2000, issue of the Archives of Internal Medicine, a specialty journal of the American Medical Association.
      Researchers looked at the occurrence of male-pattern baldness and heart disease among 19,112 male doctors aged 40 to 84 years, who were free of cardiovascular disease at the start of the study. During the 11-year follow-up period, 1,226 coronary events were documented and balding men accounted for 62 percent of those. Study participants were evaluated according to their hair loss patterns at age 45. The break down showed that 43 percent had no hair loss, 23 percent had frontal baldness and 34 percent had mild, moderate or severe vertex (crown of the head) baldness.
     Extensively bald men, who also had high cholesterol, had a risk of heart disease that was nearly three-fold higher than men with high cholesterol and no hair loss. Those with extensive hair loss and hypertension had an 80 percent increase in risk, the study showed.
     A possible explanation for the link between baldness and cardiovascular disease, according to Manson, may be elevated levels of the male hormones testosterone and dihydrotestosterone and a higher density of male hormone receptors in the scalp. High testosterone and other male hormone levels may contribute to both atherosclerosis (fatty deposits that narrow the arteries) and an increased risk of blood clotting, she said. These also may adversely affect the risk factors of hypertension and high cholesterol.
     More research is needed to confirm the findings and further clarify the biological mechanisms that could explain the relationship between male pattern baldness and heart disease, Manson said.
     “There have been a few small studies on the subject, but this is the first large-scale study dealing with the pattern of baldness and heart disease,” she said.
     “The study doesn’t mean that if you’re a bald man, you’ll have a heart attack tomorrow,” Manson stressed. “It’s just that the risk may be increased.”
     Like any other disease marker, this one should be heeded and preventive measures followed, she said.
     “While baldness is not modifiable, men can do certain things to help reduce their risk of heart disease. And I’m not talking about hair implants or magic cures for baldness,” Manson said. “There is no evidence that any hair tonic or re-growth product will alter the risk of disease.”
— Paul Kandarian

dm09.jpg (8023 bytes)Defibrillator/monitor delivers life-giving shocks without human intervention
Cardiac Science Inc. of Irvine, Calif., has received 510(k) clearance from the U.S. Food and Drug Administration to market a first-of-its-kind combination heart monitor and defibrillator in the United States.
    The Powerheart ECD is a bedside defibrillator that continuously monitors hospital patients at risk for sudden cardiac arrest. It instantly detects the onset of a life-threatening tachyarrhythmia and automatically delivers a pre-programmed amount and number of defibrillation shocks without the aid of hospital personnel. Previous automatic external defibrillators could detect abnormal wave forms, but only after a human had applied electrodes or paddles. A person also was needed to press a button to deliver the shock.
     When it comes to heart attacks, a quick response can mean the difference between life or death when a patient is suffering from ventricular fibrillation. Unfortunately, too many hospitals have documented delays of five minutes or more from patient cardiac event to the arrival time of a medical team member. Each minute that passes after the onset of a life-threatening tachyarrhythmia reduces a patient’s chance of survival by 10 percent. The American Heart Journal recently published a report of 113 clinical studies that included 26,095 patients. It revealed that patients who suffered in-hospital cardiac arrest had a meager survival rate of 15.2 percent. And despite continuous monitoring and ready access to trained personnel and equipment, patients in intensive care units who suffered cardiac arrests did not have a better chance of surviving than those who suffer an arrest outside the hospital.
     Michael Gioffredi, vice president of sales and marketing at Cardiac Science, said the Powerheart is designed to be a proactive approach to the management of critically ill patients. “If a critical care unit patient goes into a life-threatening rhythm, there are a series of events that result in a code blue being called,” Gioffredi said. “The code blue would trigger additional events, including the arrival of a code blue team. It becomes a very high stress event centered around getting a defibrillator to the patient.
      “But precious time is ticking away,” Gioffredi said. “What happens depends on the skill level and availability of the hospital employees. Response time may depend on the time of day and can range from three to five minutes. The clinical data suggests that the survival rate for in-hospital cardiac arrests is still less than 20 percent. It’s still a major problem in hospitals.”
      In these instances, clinicians are fighting time. The staff has to react quickly, and since they do not know which patient is going to arrest, it’s always an unexpected situation.
      “Using the Powerheart addresses this problem from a proactive, prospective perspective,” Gioffredi said. “Patients that are admitted to the critical care or intensive care unit have been identified by their physician as being at risk for these events. We believe that pretty much every patient in a cardiac care unit and a lot of them in the ICU should be attached to a Powerheart.”
      Patients attached to a Powerheart via a set of electrodes are continuously monitored for their cardiac activity. If the patient goes into a ventricular tacharrythymia or fibrillation, it detects the arrhythmia, performs an analysis, then the internal software makes a decision on whether or not to shock based on clinical parameters pre-set into the device by a clinician. Then, if programmed to do so, it will deliver the defibrillation therapy automatically.
     “We get therapy to these patients in seconds as opposed to minutes,” Gioffredi said. “That is the key clinical difference. The staff can be a lot more relaxed about the patient management aspect.”
      Gioffredi compares the technology to driving a car with an airbag versus driving one without. “Nobody in his or her right mind would drive a car without an airbag, because you are just a lot safer,” Gioffredi said. “We believe it is much more effective and efficient and is going to result in a higher number of successful resuscitations in the hospital than doing it the other way.”
     The Powerheart has been available in Europe since late last year, and it is expected to begin U.S. shipment soon. Medtronic Physio-Control, a division of Medtronic of Minneapolis, has an exclusive agreement to distribute the Powerheart in the United States, Canada, and nine European countries. On Dec. 31, 1999, the company made its initial shipment totaling $102,900, which represented the first delivery against the company’s backlog of purchase orders of $1.2 million. Cardiac Science expects to fulfill its current backlog within the second quarter of 2000.
— Melissa Mac

Percentage Breakdown of Deaths From Cardiovascular Diseases

  • 1% Rhematic Fever/ Rheumatic Heart Disease
  • 1% Congenital Cardiovascular Defects
  • 2% Atherosclerosis
  • 5% Congestive Heart Failure
  • 5% High Blood Pressure
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  • 17% Stroke
  • 49% Coronary Disease
  • 20% Other