Clot blocker

Doctors prescribe warfarin (Coumadin, generic) for people prone to forming blood clots. This includes people with atrial fibrillation, artificial heart valves, or a previous episode of deep-vein thrombosis or pulmonary embolism (a blood clot in a leg or lung), as well as individuals recovering from a heart attack or surgery to replace a knee or hip.

A blood clot is the end result of a complex cascade of interlocking chemical reactions that turn a dissolved protein called prothrombin into a stringy, solid clump of thrombin. Several of the middle steps depend on vitamin K. Warfarin blocks the action of vitamin K, which makes it harder to generate thrombin.

How much warfarin a person needs depends on the results of a blood test called the international normalized ratio, or INR. A high INR indicates the blood is too “thin,” a situation that could lead to a bleeding episode capable of triggering a hemorrhagic (bleeding) stroke or other potentially life-threatening problem. A low INR indicates the blood is susceptible to clotting. For most people, the target is an INR between 2 and 3.

How much warfarin a person needs to get to the proper INR depends on his or her age, weight, liver function, health, diet, and use of other medications. Since there are so many variables, it’s important that a person who is starting warfarin go to a hospital or clinic twice a week for INR tests.

Researchers have discovered two genes that influence warfarin levels in the bloodstream. One, called CYP2C9, helps regulate how quickly the body inactivates warfarin. People with certain variants of this gene break down the drug more slowly than expected. That means the drug can build up in the bloodstream, boosting the INR and thus the chances of bleeding.

The other gene, called VKORC1, influences how efficiently the body mobilizes vitamin K. People with certain variants of this gene need lower doses of warfarin to hit their target INRs than people with the “normal” VKORC1 gene.

Label change

In August 2007, the FDA announced that information on genetic testing had been added to the warfarin label. This is the dense document that comes packaged with the drug. In tiny type it describes how the drug works, who should take it, and possible side effects and drug interactions. The new label says that lower starting doses “should be considered” in people with certain variations in the CYP2C9 and VKORC1 genes, and that they may need to have their blood tested more often. At the same time, an advisory from the FDA says that doctors aren’t required to order genetic tests for CYP2C9 and VKORC1, nor should they delay the start of treatment for such tests.

10 tips for warfarin safety

Genes aside, you have a huge effect on whether your warfarin dose stays in the target range or moves in and out to dangerous highs and lows. Here are some pointers for reaching and keeping a stable level:

1. Take your warfarin every day.

2. If you forget a dose, don’t double up the next day.

3. Check your INR on schedule. Better yet, see if you can get a home testing kit.

4. Try to keep your diet consistent, especially in the amount of green, leafy vegetables (like spinach, kale, and mustard greens) you eat.

5. Try to keep your alcohol intake consistent too.

6. Make sure your doctors know all of the medications you are taking.

7. Also tell your doctor about supplements, herbal remedies, and other nondrug health aids you are taking.

8. Don’t start or stop taking a drug or supplement without telling your doctor.

9. Let other people know you are taking warfarin. A medical ID bracelet is a good idea.

10. Call your doctor right away if you suspect the drug is making you bleed — a cut that won’t stop bleeding, bruising for no apparent reason, a nosebleed, brownish urine, or stools that look red or black.

Testing and safety

Genetic testing, sometimes known as personalized medicine, may well be the wave of the future. For warfarin, right now, it’s barely a ripple.

The tests for CYP2C9 and VKORC1 could, indeed, spot some folks who need lower starting doses. But whether the tests work better than having your warfarin managed in a high-quality anticoagulation clinic, or testing your INR at home, is up in the air. The tests are expensive, not readily available, and take time.

We’ll know more about the value of these genetic tests when the Creating an Optimal Warfarin Nomogram (CROWN) trial, under way at several Harvard-affiliated hospitals, is finished. It is examining whether genetic testing improves the safety and efficiency of warfarin therapy among people just starting the drug.

Until then, don’t feel like you must have a genetic test, especially if your health plan isn’t paying for it (not all are). If your doctor wants you to have the test, go ahead. If he or she doesn’t, that’s fine, too — careful monitoring of your INR will help you use warfarin safely. And if it’s a toss-up between starting warfarin quickly and waiting 10 days for test results, you’re better off starting warfarin without the test.

Protecting the heart during noncardiac surgery

New guidelines simplify ways to protect the heart before and after general surgery.

It would only be fair if trouble with your ticker guaranteed good health elsewhere in the body. Sadly, it doesn’t work that way. Most people with heart disease have other ailments, including some that require surgery.

New guidelines from the American College of Cardiology and American Heart Association aim to take some of the stress — and stress testing — out of noncardiac surgery. They don’t, of course, offer a one-size-fits-all approach. Instead, the strategies outlined depend on the urgency and type of the planned operation, as well as the status of an individual’s heart disease and his or her general function.
In general, the guidelines limit the use of pre-surgery stress testing and encourage the use of beta blockers before and after surgery.

Nine key questions

Answers to the following questions can help you learn what will help you have the safest surgery possible.

How urgent is the operation? Emergency surgery to fix a burst appendix or control a brain tumor doesn’t leave any time to second-guess cardiac risk. Go straight to the operating room. If the operation is something that can be delayed, like having a knee replaced, then cardiac considerations may become more important.

Do you have an active cardiac condition? If so (see “Who needs pre-surgery cardiac care?”), it should be evaluated and treated, if necessary, before having the operation. If you don’t, then the cardiac hazard posed by the operation is the next thing to consider.

How dangerous is the operation for the heart? There’s no need for a stress test or cardiac workup before a low-risk operation (see “Cardiac threat of surgery”) such as cataract removal, as long as you don’t have an active cardiac condition. For more stressful operations, the status of your heart disease and general function (see the next questions) determine what, if anything, you need to do before noncardiac surgery.

What’s your functional status? If you can climb stairs or do housework without needing to stop because of chest pain or other heart-related symptoms, it’s safe to undergo even an intermediate- or high-risk operation without a stress test or other workup. But if you have trouble doing daily activities, then clinical factors (see the next item) come into play.

Do you have any clinical risk factors? Five of these — controlled heart failure, angina (chest pain) or other forms of ischemic heart disease, diabetes, kidney disease, or a prior stroke — increase the chances of heart trouble during or after an operation. If you don’t have any of these, you don’t need special precautions before an operation. If you do, your doctor may want to test your heart function before you go under the knife.

Are you taking a beta blocker? If not, you probably should be. A number of studies have shown that starting a beta blocker before noncardiac surgery and taking it for a while afterward lowers the risk of cardiac complications.

Do you take a cholesterol-lowering statin? If so, keep taking it up until the day of surgery and start taking it again right afterward. Statins somehow protect against heart-related complications following noncardiac surgery.

Have you recently gotten an artery-opening stent? If it was a drug-coated stent, you should be taking aspirin plus Plavix for 12 months to prevent a blood clot from forming in or around the wire-mesh stent. If you must have an operation while you are still taking this combination, the guidelines recommend staying on the aspirin and stopping the Plavix for the shortest time possible.

Do you have a pacemaker or implantable cardioverter-defibrillator? If you do, have it checked before the operation and after, since some of the equipment used to remove tissue or stop bleeding can interfere with these sensitive electrical devices.

A blood pressure problem that’s isolated in name only

Isolated systolic hypertension should demand your attention.

Stiff joints are an outward sign of aging. They’re a pain, literally, and can slow you down or keep you from doing the things you want to do. Stiff arteries are equally problematic. They are the main culprit behind the gradual rise in blood pressure with age. You can’t feel high blood pressure, but it can stop you just as surely as stiff joints can, and sometimes more permanently.

A blood pressure reading contains two numbers. The top number is the systolic pressure. It gauges the pressure in the arteries when the heart contracts and pushes a wave of blood along the arterial tree. The bottom number is the diastolic pressure. It reflects the pressure during the lull between waves, as the heart relaxes in between beats.

It takes a fair amount of pressure to push blood through miles of arteries. Too much pressure, though, is a bad thing. It injures cells lining the inside of arteries. It also makes them vulnerable to the microscopic changes that lead to atherosclerosis. In other words, high blood pressure sets the stage for cardiovascular catastrophes like heart attack and stroke.

We usually think of systolic and diastolic pressure rising in tandem, but that isn’t necessarily the case. In fact, by age 60, most people with high blood pressure have what’s called isolated systolic hypertension — a systolic blood pressure above 140 with a normal (under 90) diastolic pressure (see “Age and hypertension”).

Some experts don’t like the name isolated systolic hypertension. They worry that the word “isolated” sends a message that this condition isn’t much of a problem. But it is. Every 20-point increase in systolic blood pressure (and every 10-point increase in diastolic) doubles the chances of having a stroke. This hazard is seen even among people with mildly elevated blood pressure, what is now being called prehypertension (see “Quick guide to hypertension treatment”). In fact, a study published online in the medical journal BMJ suggests that heart attacks, strokes, and deaths from cardiovascular disease are twice as common among women with what used to be called high normal blood pressure (a systolic pressure between 130 and 139 and/or a diastolic pressure between 85 and 89) as among those with normal blood pressure.

A variety of medical conditions can lead to, or contribute to, systolic hypertension. These include anemia, an overactive thyroid or adrenal gland, a malfunctioning aortic valve, kidney disease, and even obstructive sleep apnea. Most of the time, though, it stems from the gradual stiffening of large arteries. This occurs for many reasons. A key cause is the development of cholesterol-filled patches in artery walls, part of the artery-clogging process known as atherosclerosis. Atherosclerosis is exacerbated by smoking, inactivity, and high blood pressure itself.

Improving pressure

If the top number of your blood pressure reading is above 140 and the bottom number is under 90, you have isolated systolic hypertension. Your doctor should run tests to rule out anemia and the other medical conditions that can cause isolated systolic hypertension. He or she should also evaluate your cardiac risk factors (weight, cholesterol, etc.) and see if you are showing any signs of hypertension-related damage to the eyes and kidneys.

Then it’s time to do battle with blood pressure. It isn’t an entirely straightforward process. That’s reflected in the fact that only about one-third of people diagnosed with high blood pressure have it under control.

The best place to start is with the choices you make in your daily life. Smoking, carrying too many pounds, eating too much salt, drinking an excess of alcohol, not exercising — all contribute to high blood pressure. By trading these in for their healthier alternatives, you can watch your blood pressure drift downward. Diets that emphasize fruits, vegetables, lean protein, and whole grains also help lower blood pressure.

Don’t be too quick to skip the lifestyle changes and head straight for medicines that lower blood pressure. While drug therapy targets blood pressure, the benefits of positive lifestyle changes reverberate throughout the body. They don’t just improve your heart and arteries, but are also good for your lungs, muscles, bones, brain, and parts in between.

If lifestyle changes aren’t enough to get your blood pressure under control, the best type of drug therapy depends on your starting systolic blood pressure. If it is between 140 and 159 (called stage 1 hypertension), guidelines suggest starting with a thiazide diuretic (water pill) such as chlorothiazide (Aldoclor, Diupres, Diuril), chlorthalidone (Hygroton), or hydrochlorothiazide (Esidrix, HydroDiuril, Microzide).

That general advice is tempered by any other medical troubles you may be having. If you’ve had a heart attack or are at high risk of having one, or you have heart failure, diabetes, or kidney disease, your doctor might start you off with an ACE inhibitor or calcium-channel blocker, with or without a diuretic. Beta blockers have long been considered excellent drugs for fighting high blood pressure, but recent evidence suggests they shouldn’t be used as first, or even second, choices.

If your systolic blood pressure is above 160 (stage 2 hypertension), your doctor won’t wait for lifestyle changes to kick in, but will probably start you on medication right away. Keep in mind that drug therapy is meant to work with lifestyle changes; it isn’t a replacement for them.

Don’t be surprised if you are asked to take two or even three blood pressure–lowering drugs. Attacking high blood pressure from different directions is more effective than coming at it from just one. And taking lower doses of three drugs often causes fewer side effects than taking a higher dose of one medication.

You may not respond to a particular blood pressure medicine the same way your spouse or a friend does. It takes some trial and error to find the drug or drug combination that works best for you. You may need to shepherd this process along. Doctors can fall victim to what’s known as clinical inertia — the failure to intensify therapy when needed. Some others don’t think that isolated systolic hypertension is a big deal.

Why bother?

Treating isolated systolic hypertension — or any type of hypertension, for that matter — is good medicine. An analysis of three large trials that compared a placebo against a blood pressure–lowering medicine among nearly 12,000 men and women, most of them over age 65, showed

• a 17% decrease in total mortality
• a 25% decrease in heart attacks and sudden cardiac deaths
• a 30% decrease in stroke.

But wait, there’s more. Data from one of the largest and longest trials of treatment for isolated systolic hypertension showed that individuals in the treatment group reported fewer limitations in their daily activities. The same study also showed that treatment reduced the chances of developing dementia (which is partly related to stiff, cholesterol-clogged arteries) and heart failure, two leading causes of disability among older people.

There are still some unanswered questions about isolated systolic hypertension. To begin with, should individuals over age 80 be treated for it? Few studies have examined this question. The ongoing Hypertension in the Very Elderly Trial should yield some answers.

What’s the benefit of drug treatment among those with systolic pressures between 140 and 159? Again, few studies have looked at this. The benefits of drug treatment in this group have been estimated from observational studies, not direct head-to-head trials. The benefits of lifestyle changes, though, are known.

How low should you go? National guidelines set two goals for treating high blood pressure: under 130/80 for those with diabetes or kidney disease, and under 140/90 for people without these conditions. One worry is that aggressively lowering systolic blood pressure may lower diastolic pressure too much.
That’s a problem because blood enters the coronary arteries when the heart relaxes between beats. If diastolic pressure drops too low, blood flow through cholesterol-clogged coronary arteries could slow to a trickle.

These controversies aside, the evidence squarely supports keeping your blood pressure under control or working to get it there. That’s true for isolated systolic hypertension, which, once it gains a foothold, becomes entangled with many aspects of health.
Finally, it also means you should know your blood pressure, especially if you’ve been diagnosed with hypertension. If you can afford one, get a $50 home blood pressure monitor and have your doctor check to make sure it is accurate, then use it at home.

Heart Beat

Teachable moment

What should family members do after a brother, sister, or parent has what doctors call a “premature” heart attack (one before age 55 in a man or 60 in a woman)? Provide support, for sure. After that, though, each family member should talk with a doctor to gauge his or her own cardiac risks. That’s what Scottish researchers propose in the Sept. 8, 2007 issue of the medical journal BMJ.
Heart disease tends to run in families. In a national study of more than 130,000 families, those having one or more members with heart disease represented only 14% of the general population but accounted for a staggering 70% of premature heart attacks and 86% of early strokes. How much of this is due to shared genes and how much to shared lifestyles or habits isn’t yet known.
While a heart attack or stroke at any age is frightening, it is even more so when it strikes early. The Scottish researchers suggest that these events can be powerful motivators for family members to see a doctor. By doing that, and then making changes to fight heart disease, up to half of premature heart attacks could be prevented, the Scottish researchers estimated.
Recommending checkups for family members is commonly done when a person develops an inheritable kind of cancer. It makes sense to do the same thing when heart disease rears its head at an early age.

Heart Beat

Steering clear of pacemaker infections

As the number of people who get pacemakers and implantable cardioverter-defibrillators (ICDs) grows year after year, so too does the number of people who develop infections from them. Up to 6% of people who get a pacemaker or ICD develop an infection from it, and the infection rate is growing faster than the implantation rate. Some of these infections are minor; some are very serious.
Finding factors that promote or prevent infection can help reduce this complication. French researchers did just that by combing through a database that included information on more than 6,000 people who had a pacemaker or ICD implanted. In this group, the chance of developing a post-procedure infection was increased by

• having a fever 24 hours before the device was implanted
• the use of temporary wires to keep the heart beating steadily before implantation
• an early follow-up procedure to remove a blood clot, fix a dislodged or broken wire, or replace a pacemaker or ICD generator.

Taking antibiotics before having a pacemaker or ICD implanted was one thing that significantly reduced the chances of later infection, something earlier studies have also shown.
If you need to have a pacemaker or ICD implanted, schedule the procedure, if possible, for a time when you aren’t recovering from a cold, the flu, or some other infection. And if your doctor doesn’t mention taking antibiotics beforehand, ask him or her about this.

Heart Beat

Newer bypass technique may be safer for women

Bypass surgery isn’t easy for anyone, but it seems to be especially hard on women. Women are more likely than men to have a heart attack or stroke or die during the operation or soon after it. A large study from Emory University in Atlanta suggests that off-pump bypass surgery, which is done without stopping the heart or using a machine to circulate the blood, mitigates some of these hazards in women.
The researchers looked at the results of 11,413 consecutive bypass operations done at Emory and its affiliated hospitals between 1997 and 2005. Women, who made up one-third of the group, tended to be older and sicker than the men. As in other studies, they didn’t fare as well as men. But when the researchers broke down the results by type of operation, something interesting emerged: Women who had off-pump bypass operations did much better than those who had traditional operations (see “On versus off”). The difference remained even after the researchers accounted for 31 other factors known to influence bypass results. Men benefited from off-pump bypass, too, but not nearly as much as women did.

Off-pump bypass isn’t for everyone. But it is worth asking your doctor about, especially if you are a woman.

Heart Beat

ACE, ARB duet questioned

An overproduction of stress hormones contributes to the symptoms of heart failure. ACE inhibitors and angiotensin-receptor blockers (ARBs) counteract the effects of these hormones in different ways. Does that mean taking an ACE inhibitor and an ARB offers double protection?

A report in the Oct. 8, 2007 Archives of Internal Medicine warns that the side effects of combining them might outweigh the benefits. In this analysis of four large trials, heart failure patients taking both drugs were more likely than those taking just an ACE inhibitor to develop kidney trouble, a high potassium level, or experience dizziness or falls due to low blood pressure. In the trials, taking an ACE inhibitor and an ARB reduced hospitalizations for heart failure but didn’t improve survival. While not the final answer, this study is sure to spark more research on the benefits and risks of this increasingly popular drug combination.

Heart Beat

Take a shot against heart disease

Heart disease deaths seem to follow flu outbreaks like Jeff follows Mutt. How closely connected are they? Researchers in Houston and St. Petersburg, Russia, compared weekly deaths from heart disease — all confirmed by autopsy — in St. Petersburg between 1993 and 2000. In each year, the peak of heart disease deaths coincided perfectly with the peak of flu and respiratory infections.

At the time this study was done, few people in Russia were vaccinated against the flu or were taking heart-protecting statins. Do the results apply here? Indeed, they do. In spite of aggressive vaccination campaigns, a University of Alabama study showed that barely half of people with heart disease get a yearly flu shot. That’s one reason influenza remains a killer, responsible for causing more than 90,000 deaths a year by triggering heart attacks and strokes.

Getting vaccinated is one way to avoid the misery of the flu and its often disastrous effects on the heart and circulatory system.

If you have heart disease, get the flu shot, not the nasal spray vaccine. The spray contains a live but disabled virus that isn’t recommended for people over age 50 or those at high risk for complications of the flu. That includes anyone with heart disease, diabetes, kidney disease, asthma, or a depressed immune system.

Heart Beat

Too few get the best therapy for an ailing heart

After having a heart attack or a stent put in to hold open a blocked coronary artery, what’s the best thing you can do for your heart, arteries, and long-term health? Give yourself a gold star if you answered “go through a cardiac rehabilitation program.”

Such programs have been shown to reduce deaths by up to 25% during the few years following the heart attack or procedure. That’s at least as good as taking aspirin, a beta blocker, a statin, or a combination of these. And the benefits of cardiac rehabilitation go beyond survival and heart health. These programs improve muscle strength, lung function, and endurance, all of which are essential for returning to an active life after a heart attack or other cardiac event. They also offer knowledge and the possibility of new personal connections that can keep all parts of you healthy. Yet barely 20% of people who are eligible for cardiac rehabilitation (see “Is cardiac rehab for you?”) take part in a program.

Doctors, the very people who should be promoting cardiac rehabilitation, aren’t very good at referring their patients to it. New standards set out by the American Heart Association, American Association of Cardiovascular and Pulmonary Rehabilitation, and 10 other organizations aim to make referring a patient to a cardiac rehab program as automatic as giving aspirin during a heart attack.
If you qualify for cardiac rehabilitation but your doctor hasn’t said anything to you about it, start badgering him or her. While most people start a program a few weeks after a heart attack or heart surgery, some insurance companies let you start as long as nine to 12 months afterward. For the best experience, try to find a program that goes beyond medically supervised exercise to include weight management, stress reduction, nutrition education, and smoking cessation (if you need it).

Ask the doctor

How do I handle conflicting advice about exercise?

Q. In 1989, at age 45, I had my aortic valve replaced. Last year, I had an aortic dissection. My surgeon tells me not to do any cardio or resistance exercise and to keep my heart rate down. My cardiologist says I can do light cardio and resistance exercise but to watch my blood pressure. Which one should I believe?

A. Your excellent question gets to the very core of how modern medicine is practiced. The “art of medicine” is gradually being nudged aside for the “evidence of medicine.” More and more, doctors try to rely on evidence-based medicine, meaning practices for which there is direct scientific evidence.
Unfortunately, most questions that patients raise haven’t been answered by rigorous scientific studies. So doctors make their best judgment based on their understanding of the disease, their own experiences, and listening to peers who have more experience with that particular question. As a result, recommendations in these gray areas can vary quite a bit from doctor to doctor.
Exercise is such an area. Specific types of exercise often haven’t been compared directly, even in patients with the most common diseases. So it isn’t surprising that your surgeon, who is more attuned to mechanical issues like your aortic tissue possibly tearing again, wants you to avoid strenuous exercise that might stress the aorta. It also isn’t surprising that your cardiologist, who is more attuned to the long-term issues of your cardiovascular conditioning and general fitness, has a different recommendation.

The bottom line here — and I’m sorry to tell you this — is that no one knows the right answer. In circumstances like these, you have to weigh all of the information you are getting, consider who is giving you that information, and make the best choice for your health. You should know that the American Heart Association has struggled with the very issue you are asking about — who needs what kind of exercise. The lack of data has led the AHA to offer some fairly conservative recommendations. Its guidelines list aortic dissection as one of the conditions for which resistance exercise should be avoided. Note, though, that the AHA doesn’t say what to do after the dissection has been repaired or how long resistance exercise should be avoided.

See if you can get your surgeon to talk with your cardiologist. Perhaps they can find some middle
ground and give you a unified recommendation on what kind of exercise is safe, and healthy, for you.

— Richard Lee, M.D.
Associate Editor, Harvard Heart Letter

Ask the doctor

Is yerba mate good for my heart?

Q. Is it true that drinking yerba mate can lower blood pressure and cholesterol?

A. It is true — in rabbits. I wouldn’t count on it doing the same thing for yourself, though.
Yerba mate (YAIR-ba MAH-tay) is a tea made from the leaves and twigs of Ilex paraguariensis, a holly tree that grows in South America. It’s a popular brew in some South American countries, where it is drunk much as coffee is drunk here. Promoters claim that yerba mate lowers blood pressure and cholesterol, aids weight loss, fights cancer, and sweetens bad breath. Those claims are based on small studies in animals and cell cultures. There’s no evidence that it does the same things in humans.
If you like the earthy taste of yerba mate or the flavored mate products being marketed in the United States, drink it (in moderation) because you enjoy it. But don’t turn to it as a health drink or depend on it to improve your blood pressure or cholesterol.

— Richard Lee, M.D.
Associate Editor, Harvard Heart Letter