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Heart, Blood Vessels, and Circulation
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Coronary Artery Disease

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Killer snow

Every winter, about 1,200 Americans die from a heart attack or some other cardiac event during or after a big snowstorm, and shoveling is often the precipitating event.

Why is shoveling so hazardous?

  • Shoveling uses your shoulders and arms, and upper body exercise tends to put strain on the heart because those muscles aren’t well conditioned.
  • Working in an upright position adds to the arduousness because blood pools in the legs and feet, so to maintain blood pressure, your heart must work harder.
  • Much of snow shoveling is isometric exercise: your muscles are working, but there's little actual movement until you finally heave a shovelful up on the bank. During isometric exercise of any type, your heart rate goes up, and your blood vessels constrict, presumably to send more blood to the straining muscles. As a result, your blood pressure goes up.
  • Without knowing it, shovelers sometimes perform a version of the Valsalva maneuver, bearing down as they would during a bowel movement while holding their breath. Waiting to exhale while straining like that can lead to abrupt changes in your heartbeat and blood pressure.
  • First thing in the morning, the time when many people dig out from a storm, stress hormone levels tend to be higher, platelets in the blood “stickier,” and heart attacks more likely.
  • Shoveling involves exposure to the cold, another cardiac stressor.
  • People who are out of shape often shovel, making the sudden intense exercise even harder on the heart.
  • Most people don’t warm up before they shovel or cool down afterward.

If you have a heart condition, you shouldn’t shovel under any circumstances. People older than 50 should also try to avoid it. Contact your local council on aging to see if they provide a list of teens in your neighborhood who you can hire to do the job for you. Or buy a snow blower. If you must shovel, take it easy. Rest often. Dress warmly and stay well hydrated. Wherever possible, push the snow rather than lift it. Clear only the snow that blocks your path into the house, the rest will melt on its own. And of course, listen to your body. Head home if you experience potential signs of heart trouble, including chest pain, palpitations, undue shortness of breath, fatigue, lightheadedness, or nausea. Also stop if your fingers or toes get numb or hurt — you could have frostbite.

January 2003 Update

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Food labels to list trans fat

Sometime next year the Food and Drug Administration will require food makers to list how much artery-damaging trans fat their products contain.

Trans fats, also called trans fatty acids, are found in hydrogenated or partially hydrogenated vegetable oils. Trans fatty acids are the byproduct of partial hydrogenation, a process that solidifies unsaturated oils. Hydrogenation increases the shelf life of products made with these oils, yet it also turns the relatively “safe” unsaturated fats into trans fatty acids, which are no better (and possibly worse) than saturated fat. Saturated fat had long been heralded as the “bad” kind of fat until research in the 1990s showed that trans fat is actually worse.
In a report to the FDA earlier this year, the Institute of Medicine said Americans should cut back their intake of trans fats but there was not enough research to recommend a safe daily level.

According to federal officials, trans fat will be labeled on a separate line from saturated fat, telling people exactly how much of each they are eating. Until food labels are changed, however, the only way to know what you're eating is to read food labels carefully. If partially hydrogenated oil is listed as one the first ingredients, the product likely has a lot of trans fat. Deep fried foods, such as donuts and French fries, top the list of food with high levels of trans fats.

There are also many “hidden” sources of trans fats, including vegetable shortening and stick margarines. The rule of thumb with margarines and spreads is the softer, the better (that is the lower in trans fats). Trans fats also occur naturally in meat, but at much lower levels.

November 2002 Update

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Stenting versus surgery for angina

Patients with angina — chest pain caused by plaque build-up in the coronary arteries — have a few choices of treatment. Though that choice may bring freedom, it can also bring confusion. Should you treat it with drugs, bypass surgery, angioplasty, or stents? A study published in the August 22, 2002 issue of the New England Journal of Medicine may help you and your physician start to make that decision. This study focused on two of the treatments — minimally invasive bypass surgery and stenting.

Minimally invasive bypass surgery, a relatively new technique, involves a smaller incision than traditional bypass surgery. This offers the doctor limited access to the heart. As in traditional bypass surgery, the surgeon takes a blood vessel from another part of the patient’s body and either replaces the clogged artery with it, or uses it to reroute blood away from the blocked section, much like a detour reroutes traffic away from a blocked roadway. Using this technique, doctors don’t need to stop a patient’s heart as they do in traditional bypass surgery. Stenting involves widening the narrowed artery by temporarily inflating a tiny balloon in the blood vessel. The surgeon then places a circular wire mesh in the artery to flatten the plaque and hold the artery open.

In the study, researchers randomly assigned 220 heart disease patients to receive either the surgery or stenting. Doctors monitored the subjects following the procedures and saw them again six months later. Both treatments proved to be effective, but their success rates and longevity differed. Stenting was successful and without complication in all of the 110 patients who got it, whereas surgery was successful in 95% of the patients. Five of the 110 patients in the surgery group experienced complications during the procedure and a few required reoperation soon after their initial surgery.

While surgery had more early complications, its effects lasted longer than the effects of stenting. At six months 79% of the patients in the surgery group were free from angina, compared to only 62% of patients in the stenting group. Narrowing of the arteries reoccurred in a larger number of patients who received stents than those who underwent surgery. This caused 29 of the patients in the stenting group to require further intervention, compared to only five patients in the surgery group.

The results of this study offer perspective on two of the available treatments for angina. Of course, when making this decision, you and your doctor should also take into account your age, your medical history, and the condition of your coronary arteries.

October 2002 Update

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New Developments in Hormone Replacement Therapy

In July 2002, the government halted a major study of hormone therapy three years early because of a slight but significant increase in the risk of invasive breast cancer. Researchers concluded that the long-term risks of taking hormones outweigh the benefits for a woman who still has her uterus.

More than 16,000 women took part in the study, known as the Women's Health Initiative, the largest to compare postmenopausal hormones with a placebo. The therapy was a combination of estrogen and progestin (Prempro), a treatment used by an estimated six million women to replace the declining levels of hormones at menopause.

The study sought to determine whether this combination hormone therapy could prevent such ailments as osteoporosis and heart disease. But while there were small decreases in hip fractures and colorectal cancer, the increases in breast cancer, heart attacks, strokes, and blood clots were too unsettling.

The data suggested that for every 10,000 women on the estrogen-progestin combination, an additional 8 will develop invasive breast cancer, when compared with women not taking the therapy. An additional 7 will have cardiovascular disease, 8 will have a stroke, and 8 will have blood clots in the lungs (pulmonary embolism).

In the aftermath of the trial, it seems that many doctors will be reconsidering prescribing estrogen and progestin. Some women may want to lower their doses or limit the duration of the use of these combinations, while others will elect to try other treatments to combat their hot flashes, vaginal dryness, and other menopausal symptoms.

However, it is important for women already on hormone replacement therapy (HRT) to know that there is no urgency to stop, and waiting until an annual exam to discuss it with a doctor is fine. There is also no harm in stopping immediately, if a woman is more comfortable doing so.

It's important to remember that only combination therapy appears to have these effects. Estrogen alone taken by women who have had a hysterectomy has not displayed such risks. A separate trial, with 10,000 women who have had a hysterectomy randomly assigned to either estrogen or a placebo, has not indicated an increased breast cancer risk. The trial is scheduled to go until 2005.

The full report on the Women's Health Initiative appeared in the Journal of the American Medical Association on July 17, 2002.

July 2002 Update

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Drinking Tea Benefits Heart and Bones

The health benefits of drinking tea have been well publicized lately, and recent studies point to two newly discovered advantages to consuming this beverage. One shows that drinking tea can help prevent death after a heart attack. The other reports that tea may increase bone mineral density, which helps prevent fractures and osteoporosis.

In the first study, published in Circulation, researchers questioned 1,900 patients hospitalized for heart attacks about the amount of caffeinated tea they drank in the past year. After adjusting for age, gender, and other variables, researchers found that those who drank 14 or more cups of tea per week were 39% less likely to die of cardiovascular disease in the 3.8 years following their heart attack than non-tea drinkers. Patients who consumed 1–14 cups of tea per week were 31% less likely to die from cardiovascular causes during that period than non-tea drinkers.

When researchers further looked into subjects' caffeine intake, they found that caffeine from sources other than tea did not affect death rates.

In the second study, published in the Archives of Internal Medicine, researchers surveyed 1,037 men and women age 30 and older about their tea consumption. Subjects who drank tea at least once a week for the preceding six months were labeled "habitual tea drinkers." This group was asked about their tea-drinking history, the kind of tea they drank, how often they drank it, and how much they drank in each sitting.

Researchers then measured the bone mineral density (BMD) of the lumbar spine, hip, neck, and total body of both the habitual tea drinkers and the non-drinkers.

The researchers found that people who consumed tea regularly for more than 10 years had the highest BMD scores compared to the other groups, after they adjusted for sex, age, weight, and lifestyle variables that may affect BMD. Those who drank tea regularly for the past 6–10 years also had significantly higher lumbar spine BMDs than the nonhabitual tea drinkers. People who consistently drank tea for the past 1–5 years did not have any significant differences in BMD score compared to the nonhabitual drinkers.

It didn't seem to matter what type of tea the person drank, and neither did the amount of tea consumed each time. Only duration of habitual tea consumption was an independent predictor of BMD score. Tea contains several components, including fluoride and flavonoids, which may work separately or in concert to maintain or restore bone density.

Although BMD score is often a good gauge of the risk of fracture from osteoporosis, this study did not actually test the link between tea consumption and bone fracture.

July 2002 Update

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Aspirin and heart disease

Should you take aspirin to prevent a heart attack? According to a new study, aspirin helps lower cardiovascular risk, but whether or not you should take it depends on a bevy of factors.

The study, published in the May 9, 2002, issue of the New England Journal of Medicine, analyzes the major trials on the subject. Four out of five of the randomized trials show a reduction in cardiovascular events (especially heart attacks) with aspirin use. (In randomized trials, researchers randomly assign patients to one of the treatments being tested.) But the studies' statistics vary wildly. For example, risk reduction ranged from 4%–44%, depending on the study. All but one trial showed that aspirin use increased the risk of bleeding, most commonly in the stomach.

Two large observational studies also showed that aspirin use decreased coronary events in both people with and without heart disease. (In observational studies, researchers simply monitor subjects' behaviors and health, they do not test a specific treatment on them.) Subjects' ages had an impact in both studies, with aspirin's benefit on the heart kicking in when subjects hit 50 years old in one, 60 years old in the other. Other trials have found that aspirin has the greatest effect on patients with high risk for heart disease.

So what should you do? That depends a lot on your heart disease risk. To calculate your risk go to this downloadable scoring system on the National Institutes of Health Web site.

Then, if you answer yes to any of these questions, talk to your doctor about starting aspirin therapy:

  • Is your risk for heart disease 1.5% or higher per year?
  • Is your risk between 0.7% and 1.4% per year? If so, and you answer yes to one or more of the following questions, ask your doctor about treatment:
    • Are you in poor physical shape?
    • Do you have diabetes or high blood pressure and damage to your organs?
    • Do you strongly want to start aspirin therapy?

But if your risk is 0.6% or lower per year, you're probably not a good candidate for aspirin therapy. You should also avoid the therapy if you're allergic to aspirin, prone to bleeding, or suffer from platelet disorders or ulcers. Your own preference is another important factor in making this decision.

Keep in mind that if you have high blood pressure, you'll need to take extra care to control it in order to get the most benefits from aspirin. Also, besides stomach bleeding, aspirin use may cause hemorrhagic stroke.

July 2002 Update

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Blood Pressure Medication May Affect Stroke Risk

Your choice of high blood pressure medication may affect your risk of stroke. Research published in the March 23, 2002, issue of The Lancet comparing the effectiveness of two high blood pressure is the first with solid evidence showing the importance of how we treat high blood pressure.

In the trial, called the LIFE study, researchers compared the number of strokes, heart attacks, and deaths due to cardiovascular events in over 9,000 patients taking either losartan or atenolol.

According to the results, both losartan and atenolol decreased blood pressure effectively, but patients who took losartan had a 25% lower risk of stroke than patients taking atenolol. In an accompanying study, researchers found similar results in patients with diabetes and high blood pressure.

Researchers believe the difference in effectiveness may be a result of the mechanisms by which each drugs works. Losartan belongs to a newer class of drugs, called angiotensin II receptor blockers (ARBs). ARBs lower blood pressure by preventing the smooth muscles of the arteries from contracting. Atenolol, on the other hand, is a beta-blocker and works to lower blood pressure by blocking substances that would otherwise speed up the heart and increase the pressure at which it pumps blood.

Results of the LIFE study also showed that losartan provided benefits beyond lowering blood pressure and reducing cardiovascular events. Patients on this drug had a 25% lower incidence of new-onset diabetes compared to patients on atenolol. In addition, patients in the losartan group were less likely to discontinue the drug due to side effects than were patients in the atenolol group.

Based on these findings, losartan or another ARB may quickly become a vital part of the first line of treatment for high blood pressure. Up until now, treatment with a beta-blocker, such as atenolol, and a diuretic has been regarded as the best intervention. The results of an upcoming National Institutes of Health study (due out in December) comparing a larger array of high blood pressure medications may shed even more light on the subject.

June 2002 Update

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Fish for Good Health

In April, three studies delivered powerful evidence that fish is good for you — and could even save your life. The key is omega-3 (or n-3) fatty acids, beneficial polyunsaturated fats provided by many kinds of fish and certain plant foods.

Researchers in the Nurses' Health Study examined 16 years of data involving almost 85,000 women and found an association between fish intake and a lower risk for heart disease and death. Women who ate fish just once a week had a heart attack risk 29% lower than those who ate it less than once a month. Women who ate fish five times a week had nearly half the risk of death from a heart attack.

The Harvard's Physicians' Health Study, which involves more than 22,000 male doctors who initially had no heart disease, analyzed blood levels of omega-3 fatty acids and risk for sudden cardiac death. Researchers found that such deaths were 81% less likely in men with the highest levels of omega-3s. Over half of such deaths occur in people without prior symptoms of heart disease — a compelling reason for adding more fish to your diet.

Finally, Italian researchers reported that heart attack survivors who took fish-oil supplements had a lower risk of sudden death. This trial studied omega-3 fatty acids and vitamin E in 11,000 men and women who had recently suffered heart attacks. Researchers found that 1 gram of omega-3 fatty acids daily reduced the risk for sudden coronary death by up to 42%. This benefit apparently reflects their calming effect on arrhythmias, potentially fatal heartbeat irregularities. Omega-3 fatty acids may also inhibit clotting and improve blood vessel function. The American Heart Association recommends four servings of fish per week but doesn't endorse supplements because of too few data on the subject.

May 2002 Update

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On-Pump and Off-Pump Coronary Bypass Surgeries Have Similar Cognitive Outcomes

Coronary artery bypass graft (CABG) surgery is performed to bypass blood around clogged arteries and improve the flow of blood and oxygen to the heart. But while these surgeries help the heart, they may be harming the brain. A study published in 2000 suggested that 23% of patients suffer from cognitive decline two months after CABG surgery.

The cardiopulmonary bypass, or "on-pump" procedure, has often been blamed for this decline, in part because it generates tiny clots that may affect cognitive function. Recent advances have allowed for CABG surgery to be performed on a beating heart ("off-pump" CABG). A study in the Journal of the American Medical Association examined whether off-pump CABG surgery results in a lower incidence of cognitive decline than on-pump CABG surgery.

Researchers from the Octopus Study Group (named for an off-pump procedure called the Octopus method) randomly assigned 281 patients scheduled for their first CABG surgery to either an on-pump or off-pump procedure. They then administered neuropsychological tests to the patients one day before surgery and then 3 and 12 months after surgery. The tests assessed major areas of cognitive function including verbal memory; visuospatial and motor capacity; selective, sustained, and divided attention; working memory; and information processing. Cognitive decline was defined as a 20% decrease in performance from the baseline score in at least 3 of the areas tested.

At three months after surgery, cognitive decline was found to be 35% more likely after on-pump surgery; it occurred in 29.2% of patients who had the on-pump surgery, compared to 21.1% of patients who had the off-pump procedure. At twelve months, however, the differences in cognitive decline between the two groups were no longer statistically significant — 33.6% of patients who had on-pump surgery compared to 30.8% of patients who had off-pump surgery.

The difference in cognitive decline of off-pump versus on-pump surgery was smaller than expected, and the researchers speculated that factors other than the cardiopulmonary bypass might be responsible for the cognitive decline. They proposed that general surgical trauma may be to blame, or that the off-pump technique itself may be a new source of cognitive decline. They also noted that the mean age of patients in this study (61 years) was younger than the average age (66 years) of patients who have had CABG surgery in the past decade. The off-pump technique may have additional benefits for older patients with more advanced coronary artery disease and who often suffer from additional, unrelated medical conditions.

May 2001 Update

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Periodontitis and Heart Disease

The question of whether gum disease is associated with heart disease is controversial. The first research to suggest a connection, published in 1989, found that even after controlling for such cardiovascular disease risk factors as smoking and diabetes, heart-attack patients had significantly worse dental health than control subjects. Since then, several studies have also suggested a link, but the nature of the relationship — is it causative or coincidental? — remains in question.

In 2001, researchers sought an answer to this question, examining data from 4,027 people who participated in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. During 17 years of follow-up, there were 1,238 cases of heart disease, 538 of which proved fatal. The rate of heart disease was three times higher in those with periodontitis than in those with healthy gums.

However, the connection became less prominent once investigators adjusted the numbers to account for other risk factors for cardiovascular disease — smoking, cholesterol levels, high blood pressure, and diabetes. After this adjustment, the heart disease risk among people with and without chronic dental infections was similar.

In fact, even those people who had eliminated any potential of dental infection through extraction of all teeth didn't have a lower heart disease risk when compared to those diagnosed with periodontitis (inflammation of the gums). The risk of developing CHD didn't decrease over time among those with no dental infections or increase over time among people with periodontitis.

A higher rate of other heart-disease risk factors among people with periodontitis might explain this relationship between gum disease and heart disease. For example, those with periodontitis were more likely to have high blood pressure and diabetes, and to smoke cigarettes.

These findings support the theory that the presence of periodontitis may occur coincidentally with increased cardiovascular risk but it is not its cause.
March 2002 Update

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Simvastatin and Niacin, But Not Antioxidants, Reduce Risk of Coronary Heart Disease

High levels of low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol both increase risk of coronary heart disease (CHD). Studies have shown that simvastatin, one of the statin medications, can lower levels LDL cholesterol and that niacin, a B vitamin, can raise levels of HDL cholesterol. Less consistent evidence indicates that antioxidant vitamins, such as vitamin E or vitamin C, may also help reduce the risk of CHD. In a study published in the New England Journal of Medicine, researchers sought to determine whether combining lipid-altering therapy with antioxidant vitamin therapy would have benefits that exceeded those of either therapy alone.

One hundred and sixty patients, all of whom had coronary heart disease, low HDL levels, and normal LDL levels, participated in the study. The average age of the study participants was 53 years. The researchers assigned the subjects to one of four treatment regimens: simvastatin plus niacin, antioxidants alone, simvastatin and niacin plus antioxidants, or placebo. The antioxidant therapy was comprised of vitamin E, vitamin C, beta carotene, and selenium.

After three years of treatment, the researchers used an imaging technique called coronary angiography to measure the amount of atherosclerotic plaque in the patient's arteries and compared it to angiographic measurements taken prior to the initiation of treatment. They found plaque formation increased by 3.9% in the placebo group, by 1.8% in patients taking antioxidants alone, and by 0.7% in the simvastatin and niacin plus antioxidant group. The amount of plaque decreased by 0.4% in the group that was assigned to simvastatin plus niacin therapy.

The laboratory results correlated with actual coronary events. In this study, the primary endpoint was defined as death from coronary causes, heart attack, stroke, or revascularization. The frequency of that endpoint was 24% in the placebo group, 21% in the antioxidant only group, 14% in the group taking simvastatin, niacin, and antioxidants, and 3% in the simvastatin plus niacin group. Only the simvastatin plus niacin group had a statistically significant decrease in clinical events.

These findings were somewhat surprising because not only did the addition of antioxidant therapy to lipid-altering therapy not improve the clinical outcome, it actually worsened the risk of a coronary event. One explanation proposed by the authors suggested that antioxidants might limit the increase of HDL2, a subtype of HDL believed to be the most protective HDL constituent. Additional study is needed to determine whether therapy with individual antioxidants would have a different result than the harmful effect of the combination antioxidant therapy tested in this analysis.

Side effects from niacin therapy led to the withdrawal of two participants from the study, while another two remained in the study but stopped taking niacin.
January 2002 Update

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Long or Irregular Menstrual Period and Diabetes Risk

Women with long or highly irregular menstrual periods face twice the risk of developing adult-onset diabetes compared with women with regular periods, a new study suggests.

More than 100,000 women with no prior history of diabetes recorded their menstrual cycles and were tracked for eight years as part of the Nurse's Health Study.

One in every 95 subjects with cycles 40 days or longer developed diabetes, while only 1 in every 297 women with cycles of 26 to 31 days did. Women with cycles too irregular to measure also showed a significant increase in the occurrence of diabetes. The risk was modestly greater for women with a cycle length less than 21 days, though there were few women in this category and the connection was only found when there was a family history of the disease.

The link between a long menstrual cycle and diabetes was even stronger in obese women. Oral contraception use had no effect on risk. This was particularly interesting, because oral contraceptives may adversely affect insulin sensitivity and glucose tolerance, therefore increasing the woman's risk for diabetes.

In light of these findings, researchers suggest women with irregular or long menstrual cycles make an extra effort to control other risk factors for diabetes, such as excessive weight and lack of exercise.
January 2002 Update

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Aggressive Therapy for Older Hearts

There's no question coronary artery bypass grafting and angioplasty can relieve the pain of angina, prevent heart attacks, and add years to the lives of people with blocked coronary arteries. But most studies have excluded people over age 70, so the benefits of aggressive therapy is less clear in the older patient.

Two studies from Switzerland and Canada provide good news for older people who may need bypass surgery or angioplasty. Swiss researchers compared the effects of medical therapy and invasive therapy among more than 300 men and women with angina, all of whom were age 75 or over. They reported the results in the journal Lancet. After six months, the frequency and severity of chest pain had lessened and the quality of life had improved in both groups. But the improvements were substantially greater, and the heart attack rate substantially lower, among those who had undergone bypass surgery or angioplasty.

The Canadian study, which appeared in the Canadian Medical Association Journal, compared the effects of bypass surgery on patients in their 80s and those in their 70s. The investigators found it as safe and effective for octogenarians as it was for septuagenarians and reported that it cost about the same in either group.

Neither of these studies provides blanket assurance that an invasive procedure like bypass surgery or angioplasty is right for every older person with blocked coronary arteries. Older candidates for bypass surgery or angioplasty may want to focus on quality-of-life issues. Recovery, for example, may be a completely different experience for older people.
December 2001 Update

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Normal ECG May Not Mean Everything is Fine

An electrocardiogram (ECG) graphically records the electrical current running through the heart muscle. By examining the graph, physicians can detect injury to the heart, abnormal heart rhythms, thickening or thinning of the heart muscle wall, and other conditions. Doctors use an ECG — along with a physical exam and blood tests for heart muscle enzymes — to diagnose a suspected heart attack. ECGs that clearly indicate a heart attack are known as diagnostic ECGs. But in some cases, patients who are having a heart attack may have a normal or nonspecific ECG. Doctors had assumed heart attack patients with normal or nonspecific ECGs would have a better short-term survival rate than heart attack patients with diagnostic ECGs. And that is, in fact, the case. But a new study in the Journal of the American Medical Association shows the absolute number of heart attack patients with normal or nonspecific ECGs who die during hospitalization is much higher than expected.

The study authors analyzed data, collected by the National Registry of Myocardial Infarction (NRMI) between June 1994 and June 2000, on 391,208 patients who had been hospitalized for a heart attack. As expected, heart attack patients with a normal ECG were 41% less likely to die in the hospital than heart attack patients with a diagnostic ECG, and patients with a nonspecific ECG were 30% less likely to die. Surprisingly, however, 5.7% of heart attack patients with a normal ECG and 8.7% with a nonspecific ECG did die in the hospital.

The researchers noted heart attack patients with normal ECGs are less likely to be treated with aspirin and heparin, blood-thinners that help prevent new blood clots, or with beta-blockers, which slow the heart rate and prevent abnormal heart rhythms. Though the study did not investigate whether aggressive post-heart attack treatment would lower the mortality rate in this group, it does open up the question for further research.

The exceptions in this study - who had normal ECGs and low mortality rates - were men younger than 65 years and patients with an ejection fraction of 40% or greater. An ejection fraction measures how much blood the heart empties when it contracts, relative to the volume of blood in the heart when it expands.
November 2001 Update

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H. pylori Infection May Aggravate GI Injury in Patients Taking Low-dose Aspirin

Doctors commonly prescribe low-dose aspirin for the prevention of heart disease, but it may also be responsible for some potentially serious side effects when taken frequently. Among the most common of these are gastrointestinal erosions and ulcers.

A recent study in The American Journal of Gastroenterology sought to determine whether certain people taking low-dose aspirin — specifically, people infected with Helicobacter pylori, a common bacterium that can cause ulcers — are more susceptible to gastrointestinal erosions and ulcers than people who are not infected with H. pylori.

Researchers from the University of Texas Southwestern Medical School and Baylor College of Medicine recruited 61 healthy volunteers between the ages of 18 and 61. Of these, 29 volunteers were infected with H. pylori. Forty-six of the volunteers were then randomly selected to receive low-dose aspirin (either 81 mg daily or 325 mg every three days), while 15 received a placebo.

After 46 days of treatment, an upper GI endoscopy was performed on each subject to determine the extent of gastrointestinal injury. The researchers did not detect any injury in the stomach or duodenum (upper intestine) of the patients taking placebo. In the subjects taking aspirin, those patients who were infected with H. pylori were significantly more likely to have gastrointestinal injury than those who were not infected (50% vs. 16%).

However, there was no difference between the groups in complaints of pain, nausea, vomiting, indigestion, or heartburn. In addition, the difference in outcomes between patients taking 81 mg of aspirin daily and 325 mg every three days was not statistically significant.
The researchers caution that the results of this study may not hold for older people or those with gastrointestinal diseases such as peptic ulcer disease, because the volunteers were healthy and aged 61 or younger. However, this study does suggest eradicating H. pylori infection may help prevent gastrointestinal erosions and ulcers in patients taking low-dose aspirin on a long-term basis.
October 2001 Update

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Smoking Cessation and Congestive Heart Failure

Quitting smoking greatly reduces your risk of death from congestive heart failure within two years.

Despite a lack of evidence, physicians have long advised patients with congestive heart failure to quit smoking to improve their chances of survival. Now, a recent study provides the necessary proof.

Researchers in Canada investigated the rates of death, hospitalization for heart failure, and heart attack in smokers, ex-smokers of less than 2 years, ex-smokers of more than 2 years, and non-smokers. All the participants in the study had congestive heart failure in the form of left ventricular dysfunction — failure of the left ventricle of the heart to properly pump oxygen-rich blood to the body.

The study found current smoking was associated with a substantial increase in the risk of death, rate of hospitalization, and heart attack. Patients who had quit smoking or never smoked had a 30% lower risk of dying during the time of the study (41 months). Moreover, ex-smokers had the same mortality rate as non-smokers.

These results suggest people who quit smoking lower their risk of recurrent congestive heart failure within two years. The research also showed the benefit from quitting smoking was just as great as the benefit from taking drugs for heart failure.
September 2001 Update

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Flu Vaccine and Recurrent Heart Attack Risk

Late each fall, the call goes out to remind people to get their flu vaccinations. Most healthy people equate the flu with a week of being miserable. However for the elderly or people with chronic illnesses, the complications of influenza, such as pneumonia, can be life threatening. Good enough reason to get the shot, but now research suggests the vaccination may also lower heart attack risk.

The study, conducted by researchers at the University of Texas-Houston, questioned whether getting a flu shot could reduce the risk of a second heart attack in people with coronary artery disease. Scientists have been studying a potential link between cardiovascular disease and infection, and some of their work suggests upper respiratory infections, such as the flu, might be a risk factor for heart attack.

The investigators evaluated 218 individuals with previous heart attacks who were seen in the university's cardiology outpatient clinic during the 1997-98 flu season. Of the patients who met the study criteria, 109 experienced a heart attack during the study period. These volunteers were matched with 109 controls with coronary artery disease, but had not experienced a second heart attack during the same period.

Of those who had had new myocardial infarctions, the rate of flu vaccination during the current season was 47%, versus 71% among those who did not have new heart attacks. After adjusting for differences between these groups, the researchers found the risk of heart attack was reduced by two-thirds among patients who had gotten a flu shot that season. This study showed no evidence that use of multivitamins or physical exercise changed risk for recurrent heart attack.

No one knows how flu vaccination might reduce a person's risk of heart attack. Perhaps exposure to the flu might cause atherosclerotic plaques to become less stable or the stress of this illness might dangerously increase the heart's workload for people with cardiovascular disease. Other theories include an increased tendency for blood clots during the flu or that the flu may contribute to poor blood vessel function. Whatever the cause and effect, people with coronary artery disease (and who are not allergic to the vaccine) should strongly consider getting a flu shot this season.
September 2001 Update

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More Encouraging Data on Alcohol and the Heart

Having a drink or two per day lowers your risk heart disease and stroke. Little surprise then that two new studies report people who drink alcohol also have lower risk of developing heart failure and better outcomes if they have heart attacks. The studies were reported in a recent issue of the Journal of the American Medical Association.

The first study involved 1913 adults who were admitted to 45 different U.S. hospitals between August 1989 and September 1994 for heart attacks. The researchers, who were based at Harvard Medical School and Harvard School of Public Health, interviewed the patients an average of 4 days after their heart attacks, inquiring about a range of issues including their alcohol consumption.

About half (47%) reported they didn't drink alcohol during the year before their heart attacks. Another 36% said they drank fewer than 7 drinks per week. The remainder (17%) said they had 7 or more drinks per week. Those who drank the most were younger, and more likely to be male, current or former cigarette smokers, and have physically active life styles.

Survival rates were lowest for those who did not drink at all before their heart attacks and best for those who drank 7 or more drinks per week. For every 100 people, 6.3 of the abstainers died each year, compared with 3.4 of those who drink 1-6 drinks per week and 2.4 of those drank 7 or more drinks.

Heart failure

The second study was based on 2,235 elderly people (average age 74 years) who participated in a long-term epidemiological survey in New Haven, CT. None of the subjects had heart failure at the time of enrollment in the study in 1982. And the researchers excluded heavy drinkers (those drinking more than four drinks per day).

Half of the subjects reported no alcohol consumption in the month before enrollment, while 40% reported consumption of 1-20 ounces (up to 1 or 1.5 drinks per day), and 10% reported drinking 21 to 70 ounces (about 1.5 to 4 drinks per day).

During the next 14 years, 281 people developed heart failure, including 28 fatalities. The rates of heart failure for every 1000 people per year were 16.1 for abstainers; 12.2 for those who drank 1-1.5 drinks per day; and 9.2 for those who drank more heavily. Statistical analyses that adjusted for other differences among these groups concluded that light drinking reduced one's risk for heart failure by 19%, and moderate or heavy drinking reduced the risk by 53%.

Because moderate drinking can easily progress to problem drinking, no experts feel comfortable in encouraging nondrinkers to take up alcohol for medical reasons. However, researchers are debating whether some people who have given up alcohol might be encouraged to resume it. Future research may also define certain subgroups who can benefit most from alcohol, perhaps by raising their HDL cholesterol.
September 2001 Update

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A Popular Cholesterol-Lowering Drug Recalled

Bayer Pharmaceutical Division is voluntarily withdrawing Baycol, a popular cholesterol-lowering drug, because of reports of sometimes fatal rhabdomyolysis, a severe muscle reaction.

Baycol (cerivastatin), approved in 1997, is a member of a class of cholesterol-lowering drugs commonly referred to as statins. Statins lower cholesterol levels by blocking a specific enzyme in the body that's involved in the synthesis of cholesterol. While all statins have been associated with very rare reports of rhabdomyolysis, cases of fatal rhabdomyolysis associated Baycol have been reported significantly more frequently than the others.

Rhabdomyolysis is a condition that results in muscle cell breakdown and release of the contents of muscle cells into the bloodstream. Symptoms of rhabdomyolysis include muscle pain, weakness, tenderness, malaise, fever, dark urine, nausea, and vomiting. The pain may involve specific groups of muscles or may be generalized throughout the body. However, some patients report no symptoms of muscle injury. In rare cases, the muscle injury is so severe that patients develop renal failure and other organ failure, which can be fatal.

Fatal rhabdomyolysis reports with Baycol have been reported most frequently when used at higher doses, when used in elderly patients, and particularly, when used in combination with gemfibrozil, another lipid-lowering drug. The FDA has received reports of 31 U.S. deaths due to severe rhabdomyolysis associated with use of Baycol, 12 of which involved concomitant gemfibrozil use.

People taking Baycol should consult with their physicians about switching to alternate medications to control their cholesterol levels. If you're experiencing muscle pain or are also taking gemfibrozil you should discontinue Baycol immediately and contact your physician.
August 2001 Update

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Take Low-Dose Aspirin and Skip Vitamin E to Prevent Cardiovascular Disease

For more than 100 years aspirin has helped relieve headaches and other pain, and now new evidence from the Primary Prevention Project backs the claim it also helps prevent heart attacks and other cardiovascular events. The same study also found the antioxidant vitamin E didn't help.

The theory that anti-platelet/anti-inflammatory drugs like aspirin and antioxidant nutrients like vitamin E might interfere with atherosclerosis and prevent cardiovascular disease is not new. But previous research on both possibilities has come up with mixed results. In an attempt to resolve the debates, Italian researchers randomized 4,495 people (2583 females and 1912 men) with an average age of 64.4 to receive low-dose aspirin (100mg/day) or no aspirin and vitamin E supplements (300mg/day) or no vitamin E. They limited their investigation to people over 50 with one or more of the major cardiovascular risk factors: hypertension, high blood cholesterol, diabetes, obesity, family history of early heart attacks or individuals who were elderly.

Aspirin proved to be beneficial with respect to all of the criteria measured. It reduced the risk of a cardiovascular death by 44% and the risk of cardiovascular events or disease by 23%. However, severe gastrointestinal bleeding was more frequent in the aspirin group than in the non-aspirin group (1.1% vs 0.3%). Consistent with the negative results of other large published trials, vitamin E provided no significant improvements in any of the criteria.

The study was stopped prematurely after a mean follow-up of 3.6 years because evidence from two other studies involving a total of 24,289 patients concurred that aspirin is beneficial in primary prevention.
August 2001 Update

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High Blood Pressure Drug Performs No Better Than Standard Treatment

An FDA advisory panel has decided to inform doctors about the results of a government study that found Cardura (doxazosin), a popular blood pressure medication sold by Pfizer, was less effective than a generic diuretic (chlorthalidone) in reducing some forms of cardiovascular disease. But the panel also concluded the agency didn't need to extend this warning to patients.

Cardura, which has been on the market for 10 years, is an alpha-adrenergic receptor blocker that relaxes smooth muscle throughout the peripheral parts of the body, including the blood vessels. It's often used for the management of hypertension, a condition involving persistently high arterial blood pressure. Hypertension is a major risk factor for the development of coronary heart disease, heart attacks and strokes.
Cardura's role in managing hypertension was investigated as part of the National Institute of Health's Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), the first large-scale blood pressure treatment study to compare several newer drug treatments with a cheaper generic diuretic.

The first part of ALLHAT was stopped early because users of Cardura had 25% more cardiovascular events and were twice as likely to be hospitalized for congestive heart failure as users of the diuretic. But the study didn't find Cardura users were any more likely to die than those using the diuretic. As a result, the NIH advised high blood pressure patients who now take Cardura consult with their doctors about a possible alternative. They also suggested the drug may not be the best choice for new patients. The American College of Cardiology followed with a clinical alert that advised physicians to stop prescribing Cardura and reassess its treatment value.

Last year, a group of patients filed a lawsuit with a U.S. District court claiming Pfizer did little to inform doctors and patients about the results of ALLHAT, but the petition was handed over to the FDA. The FDA advisory panel concluded that while it appeared the diuretic was more effective than Cardura in preventing congestive heart failure, there was not enough data to prove Cardura was harmful. The FDA often follows the recommendations of its advisory panels. Pfizer continues to maintain that Cardura is safe.
July 2001 Update

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Statins Reduce C-reactive Protein

Half of all heart attack victims have normal cholesterol levels. Consequently, doctors are looking for new methods to improve heart disease prevention. One promising new approach involves testing for high levels of the inflammation marker C-reactive protein to identify people who might benefit from drug therapy.

C-reactive protein (CRP) is secreted from the liver in response to inflammation in the body. Because atherosclerosis is partly an inflammatory process, high levels of CRP have been shown to predict the risk of heart disease. A new study has found that statins can reduce the risk of coronary events in people who have high levels CRP. These drugs are already used to lower LDL cholesterol, but the researchers found its anti-inflammatory effect was independent of its cholesterol-lowering abilities.

The five-year randomized trial done at Brigham and Women's Hospital and Harvard Medical School involved 5,742 participants. The researchers found that Lovastatin decreased both CRP levels by an average of 14.8% and the rates of coronary events. Other statins has also previously been shown to reduce CRP levels.

This study suggests statins may be an effective preventive therapy for people with high CRP levels — even if they have low or normal LDL cholesterol. Though everyone is encouraged to make healthy lifestyle changes to reduce their heart disease risk, only those at high-risk are candidates for these costly drugs. And measuring CRP levels in conjunction with cholesterol testing should better identify these high-risk individuals.
July 2001 Update

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Walk, Don't Run for Weight Loss

People often disrupt their sedentary lifestyles with bouts of high-intensity exercise, like running or aerobics, to avoid gaining weight or developing heart disease. But a new study shows spending some of your day engaged in moderate activity, like biking, walking, or even taking the stairs at work, may be more a successful method for boosting daily calorie expenditure and losing weight.

The study, published in Nature, involved 30 healthy, non-obese women and men. For two weeks, the participants’ energy expenditure was measured, while their activity levels were tracked using portable motion sensors and activity diaries. The investigator found the amount of moderate activity, not vigorous exercise, was a significant predictor of total energy expenditure. He hypothesized that moderate activity usually occupies a larger portion of the day compared to more vigorous exercise. For instance, studies on obese subjects have found adding intense exercise to diet didn’t enhance weight loss because the extra energy expenditure didn’t offset the reduced time spent on other physical activities.

This small, but informative study provides strong evidence that exchanging some of time you sit in front of a TV for moderate activity increases total daily energy expenditure and metabolic rate. Short bursts of vigorous activity in an otherwise inactive and unhealthy lifestyle is not enough. So take the stairs, not the elevator, and go for a walk at lunch. But don’t be discouraged from going for a run. Aerobic activities, like jogging, swimming and brisk walking, help make your heart stronger and more efficient, which can lower your heart disease risk still further.
June 2001 Update

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Garlic’s Effects on Cholesterol Are Modest

Garlic preparations, available in most health food stores, are sold with the promise of numerous health benefits. Lower cholesterol levels are among the most touted of these benefits. Unfortunately, data from only a few small research trials support the claim that garlic preparations can lower LDL cholesterol.

A "meta-analysis" of rigorous published trials involving garlic preparations offers a better gauge of garlic’s value in reducing cholesterol. A meta-analysis mathematically pools data from several studies to better estimate the effects of an intervention — for example, a drug, dietary supplement, operation, or lifestyle change — than one could do with the data from a single, smaller study. This report, published in the Annals of Internal Medicine, reviewed 45 controlled studies involving 796 subjects (In contrast, most studies of cholesterol-reducing medications involve much larger numbers of patients). Overall, the researchers found that, on average, garlic supplements decreased total cholesterol by 16 mg/dL. But the six most rigorous studies, which also controlled for the volunteers’ diets, failed to show a significant difference in cholesterol reductions between garlic and placebo groups. (Annals of Internal Medicine, Vol. 133, No. 6, pp. 420–29.)

These results are all the more disappointing because, in general, studies that show a positive effect are most likely to be published. Thus, meta-analyses may offer an overly optimistic assessment of a drug or other intervention. In other words, "negative" studies may have simply never been published (and thus could not be included in this meta-analysis) because researchers found no difference between garlic and a placebo. If so, the value of garlic would be even less than that described here.

If you’re taking a garlic supplement, the good news is that the meta-analysis found no evidence of dangerous side effects. It simply suggests the benefits are small. But for those of you only considering these preparations, the study doesn’t offer much encouragement. Perhaps its central message is that garlic is no substitute for the highly effective, safe medications that are proven to control cholesterol and lower heart disease risk. Garlic may or may not belong in your medicine cabinet, but it has proven itself to be a vital component to any well-stocked pantry.
June 2001 Update

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FDA Approves First Automatic and Non-Invasive Blood Glucose Monitor

People with diabetes who regularly monitor their blood glucose levels are less likely to develop the disease’s complications such as heart disease, blindness and kidney disease. Unfortunately, traditional blood glucose monitoring is time-consuming and requires sticking the finger for blood. So many diabetics test themselves less frequently than recommended.

A new bloodless glucose-monitoring device recently approved by the FDA could make monitoring easier. Made by Cygnus Inc., GlucoWatch Biographer is a prescription wristwatch-like device with sensors on its underside that monitor glucose levels. By a process called reverse iontophoresis, it applies a very low electric current to extract glucose samples from the skin’s interstitial fluid every 20 min for 12 hours, even during sleep. The device, which must be first calibrated using a finger-prick reading, stores the readings and sounds an alarm if the glucose reaches a pre-selected level.

The FDA approved the device on the basis of clinical trials done on both type I and type II adult diabetics. No research has been conducted on children. The studies compared GlucoWatch readings with traditional finger-prick blood glucose tests and found measurements were fairly consistent. However, up to 25% of the time, the results differed by more than 30% and sometimes GlucoWatch gave completely erroneous readings. The device was less effective at detecting very low glucose levels than very high levels. Also, it was not accurate if the patient’s arm was too sweaty and perspiration is common with hypoglycemia, or low blood sugar. GlucoWatch caused skin irritation in up to 50% of users.

GlucoWatch should not be used as a replacement for finger-prick blood tests. Any treatment decisions and all alarm values should be confirmed with blood glucose tests. But as the first automatic and non-invasive device, GlucoWatch may help patients better manage their diabetes.
June 2001 Update

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National Cholesterol Education Program Releases New Guidelines for Treating and Preventing High Cholesterol

On May 15, 2001, the National Cholesterol Education Program (NCEP) — coordinated by the National Heart, Lung, and Blood Institute (NHLBI) — released the first major revision of its recommendations for detecting and lowering high cholesterol in adults since 1993.

One of the fundamental features of the new guidelines is the accurate assessment of heart disease risk using a new "global risk assessment tool" that combines multiple risk factors into a measure of a person's absolute risk of developing coronary heart disease within the next 10 years. According to the guidelines, patients who have a risk of 20% or higher should receive aggressive therapy to control cholesterol levels. In addition to aggressive treatment of high LDL cholesterol, as laid out in the 1993 report, the revised guidelines also recommend a more assertive treatment approach for diabetes, low HDL levels, and high triglyceride levels.

Specific changes include:

  • Treating high cholesterol more aggressively for those with diabetes, even if they do not have heart disease.
  • A full lipid profile (which measures total cholesterol, LDL, HDL, and triglycerides) as the first test for high cholesterol (rather than simply testing total cholesterol and HDL and performing a full lipid profile only if total cholesterol is high).
  • A new level at which low HDL becomes a major risk factor for heart disease. The 1993 guidelines defined a low HDL as less than 35 mg/dL; now it is less than 40 mg/dL.
  • More aggressive treatment of high triglyceride levels.
  • Advising against the hormone replacement therapy (HRT) as an alternative to cholesterol-lowering drugs for post-menopausal women.

Another key change in the guidelines is intensified lifestyle recommendations regarding nutrition, exercise, and weight control to treat high cholesterol. The updated diet advises that less than 7% of daily calories come from saturated fat and limits dietary cholesterol to less than 200 mg per day. It also allows up to 35% of daily calories from total fat, provided most come from unsaturated or monounsaturated fat, which doesn't raise cholesterol levels. Additionally, the guidelines strongly underscore the need for weight control and physical activity, both of which improve various heart disease risk factors.

The revised recommendations also emphasize careful attention to the metabolic syndrome, a particular cluster of cardiovascular risk factors that is becoming increasingly common in the United States. Characteristics of metabolic syndrome include too much abdominal fat, high blood pressure, high blood sugar, elevated triglycerides, and low HDL.

For more information, see the "Live Healthier, Live Longer" Web site by going to the NHLBI home page at www.nhlbi.nih.gov and clicking on ATP III Cholesterol Guidelines under Highlights.

2001 Cholesterol Guidelines
Total Cholesterol Level Total Cholesterol Category
Less than 200 mg/dL Desirable
200-239 mg/dL Borderline High
240 mg/dL and above High
LDL Cholesterol Level LDL Cholesterol Category
Less than 100 mg/dL
Optimal
100-129 mg/dL Near optimal/above optimal
130-159 mg/dL Borderline high
160-189 mg/dL High
190 mg/dL and above Very high
Trigylceride Level
Triglyceride Category
Less than 150 mg/dL Normal
150-199 mg/dL Borderline high
200-499 High
Greater than or equal to 500 Very high
HDL Cholesterol Level HDL Cholesterol Category
Less than 40 mg/dL Low (representing increased risk)
60 mg/dL and above High (heart protective)

 

Three Categories of Risk that Modify
LDL Cholesterol Goals
Risk Category LDL Goal (mg/dL)
Coronary Heart Disease (CHD) and CHD equivalents Less than 100
Multiple (2+) risk factors Less than 130
0-1 risk factor Less than 160
Risk factors (exclusive of LDL cholesterol): cigarette smoking; blood pressure greater than or equal to 140/90 mm Hg or on antihypertensive medication; HDL cholesterol less than 40 mg/dL; a family history of coronary heart disease before age 55 in a father or brother or age 65 in a mother or sister; age above 45 for men and 55 for women

May 2001 Update

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Killing H. Pylori Helps Prevent Gastrointestinal Bleeding in Patients Taking Low-Dose Aspirin

Many people take low-dose aspirin on a daily basis to help prevent heart attacks. Others take larger doses of stronger nonsteroidal antiinflammatory drugs (NSAIDs), such as naproxen (Anaprox, Aleve, others), to relieve musculoskeletal pain such as that caused by arthritis. When taken on a regular basis, however, NSAIDs often cause ulcers and gastrointestinal (GI) bleeding. Ulcers, which are raw, crater-like breaks in the mucosal lining of the digestive tract, may also be caused by excess acid production and a bacterium known as Helicobacter pylori (H. pylori).

In a study published in the New England Journal of Medicine, researchers enrolled 400 patients with a history of GI bleeding who were taking aspirin or other NSAIDs to prevent heart disease or to control musculoskeletal pain. They set out to find whether eradicating H. pylori infection reduces the risk of recurrent GI bleeding in these patients. For six months, 250 patients were given an 80 mg "baby" aspirin once per day, while the remaining 150 patients received 500 mg of naproxen twice per day. Within each of the two groups, patients were randomly assigned to take either a daily dose of omeprazole (Prilosec), an acid-suppressing medication, or a one-week antibiotic treatment to eradicate H. pylori infection, followed by placebo for the remainder of the trial.

The researchers found that in patients taking aspirin, those who were treated for H. pylori had a 1.9% risk of GI bleeding while the risk for those taking omeprazole was 0.9%. In other words, for patients on low-dose aspirin, the treatments were almost equal.

The results were very different for patients taking naproxen. 19% of the naproxen patients who had H. pylori treatment suffered from recurrent bleeding. In contrast, only 4% of the omeprazole group did.

The study suggests that patients with a history of GI bleeding who take low-dose aspirin to prevent heart attacks should be tested for H. pylori infection and treated if the infection is found to be present. Patients taking non-aspirin NSAIDs and who have experienced GI bleeding are more likely to benefit from acid-suppressing therapy.
April 2001 Update

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Early Cognitive Impairment Following Coronary Bypass May Predict Lasting Cognitive Impairment

More than 500,000 coronary-artery bypass grafting (CABG) surgical procedures are performed in the United States each year to bypass blood around clogged arteries and improve the flow of blood and oxygen to the heart. Advances in anesthesia, surgical procedure, and other areas have made CABG a relatively safe procedure for an expanding group of heart disease patients including older and other high-risk patients. But while the risk of death after CABG has decreased, the risk of cognitive impairment has not. Growing evidence suggests that many patients experience short-term cognitive impairment after CABG.

A recent study in the New England Journal of Medicine confirmed not only the high incidence but also the persistence of cognitive decline following the procedure. It also showed that patients who exhibit signs of cognitive decline immediately following surgery are more likely to continue to suffer from cognitive decline at up to five years after surgery. Researchers from Duke University Medical Center tested the cognitive function of 261 patients before they underwent CABG surgery, and then again before discharge from the hospital and at six weeks, six months, and five years after the CABG procedure. 172 patients, whose average age was 61, completed all of the follow-up.

The researchers found that the incidence of cognitive decline was 53% at discharge, 36% at six weeks, 24% at six months, and 42% at five years. The pattern demonstrated improvement of cognitive functioning within the first six months, and then a decline between six months and five years after surgery.

Even after controlling for age, education level, and baseline test score, patients who experienced cognitive decline immediately following surgery were at a significantly increased risk for long-term cognitive decline and a reduced level of overall cognitive functioning.

It remains unclear why early, postsurgical cognitive decline is associated with a greater risk of long-term cognitive decline.
April 2001 Update

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Warfarin and Vaginal Cream Drug Interaction Warning

The Food and Drug Administration (FDA) has issued a warning stating that women taking the prescription blood thinner warfarin (Coumadin) should consult their doctor or pharmacist before using over-the-counter vaginal creams containing the antifungal drug miconazole because of an increased risk of bleeding or bruising. Miconazole is an active ingredient in many over-the-counter creams and suppositories used to treat vaginal yeast infections.

Doctors were already aware of adverse reactions between warfarin and systemically administered miconazole. This warning urges women to beware of creams and suppositories as well.

The warning was issued in response to two reports of abnormal blood clotting tests in women taking the anticoagulant warfarin who used vaginal miconazole. In addition to the abnormal blood-clotting test, one of the two women also developed bruises, bleeding gums, and a nosebleed. Two journal articles also warned of a possible interaction between warfarin and vaginal miconazole.

The FDA warning will appear on miconazole-containing product labels and consumer brochures.
April 2001 Update

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Cholesterol-Lowing Drugs for . . . Osteoporosis?

As we age, our bones tend to become less dense (that is, more porous and prone tofracture) — a condition known as osteoporosis. Typically thought of as a problem for post-menopausal women, men also suffer fractures due to osteoporosis. As a result, roughly 1.5 million Americans each year will have to endure the pain and inconvenience of a broken bone — often the hip, the wrist, or vertebra. It is hopeful news then, that the class of cholesterol-lowering drugs called "statins" may also provide some protection against the weakening of bones.

By analyzing data on 6,110 women in New Jersey, most of whom were over age 75, researchers discovered that those patients who had used a statin were 50% less likely to experience a hip fracture — even when investigators adjusted for the presence of other diseases or conditions (including diabetes, cancer, high blood pressure, and congestive heart failure). The chances of breaking a hip were lower still when statin use was current. Use of non-statin drugs to lower cholesterol was not associated with a similar protective effect on the bones. Another study, conducted in Britain, showed that statins seem to help the body increase bone mineral density at the hip, which in turn lowers a person's risk for hip fracture, and that this benefit accrues even after only a few weeks or months of statin use.

The likely reason that statins benefit bones as well as cholesterol levels is that these drugs act upon a series of chemical reactions called the "mevalonate pathway." Mevalonate is necessary for the body to produce cholesterol, but it is also involved in bone formation and resorption. Right now researchers think that this discovery may lead the way to additional (and possibly better) medications to treat or prevent osteoporosis. While people who do not need to take medication for high cholesterol should not rush to the doctor to ask for a statin, those who already take these medications should take comfort in knowing that they may be getting double benefits from their daily dose.

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More Questions on Estrogens

For years, the standard understanding of hormone-replacement therapy (HRT) was that it clearly reduced the risk of heart disease and osteoporosis in postmenopausal women. The tough part about deciding whether or not to take hormones lay in balancing the risks (a potential increased risk of breast cancer) and side effects against the advantages. Over time, research has discovered additional possible side effects from HRT. For example, nearly two years ago surprising findings were released from the Heart and Estrogen/Progestin Replacement Study (HERS). The findings were unexpected. Although the women taking hormone-replacement therapy (HRT) had improved blood lipid profiles, they did not have fewer heart attacks when compared with women not taking hormones. Doctors and researchers have been waiting for results of larger, longer-term studies to help clarify the many questions surrounding the potential risks and benefits of HRT. The Women's Health Initiative (WHI) is one of those trials. Recently, it too delivered a blow to the belief that estrogen replacement after menopause helped protect women against heart disease.

In early April 2000 WHI study investigators sent a letter to the women in the study taking estrogen. It explained that researchers had found a slightly higher rate of heart attacks, strokes, and blood clots in the legs and lungs among the study participants on HRT. While the number of women who had problems was very small (less than 1%), researchers felt it was right to inform study volunteers of this early assessment of the data. It is difficult to say whether or not this information helps women (or their doctors) in sizing up the benefits of HRT, but it certainly does give one pause. No one would suggest this data should make a woman taking HRT stop immediately, particularly if her goal in doing so is to relieve the short-term discomforts of menopause. However, she should consider revisiting the issue with her doctor. HRT is but one way to protect the heart. A healthy lifestyle and careful attention to other risk factors (such as high blood pressure and diabetes) has always been crucial. What's more, statins are proving to be so effective in women (and the questions on estrogen sufficiently disarming) that a consensus panel statement from the American Heart Association and the American College of Cardiology suggest statins as the first line drug for prevention of heart disease in women with high blood lipids.

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Disappointing Look at Vitamin E and Heart Disease

Over the years, observational and experimental studies have suggested that regular intake of vitamin E (from supplements and food sources) can help reduce heart disease risk. The scientific theory is that the antioxidant properties of this vitamin interfere with the oxidation of low-density lipoproteins, which slow the progression of atherosclerosis. The problem with experimental studies is that these data cannot tell us exactly how a given treatment or medication will act in real human beings. And the problem with observational, or prospective studies, (which follow a group of people over time to see which among them may develop a disease or condition) is that they are not really helpful in pinpointing the reasons those people develop that disease or condition.

Randomized controlled trials are considered the gold standard for evaluating a medical or preventive treatment. Here, study subjects are matched for a set of characteristics to "level the playing field." Then researchers randomly assign some patients to get the treatment or medication and another group to get a "fake" treatment or medication. Even when applying this research method to assess the value of vitamin E in preventing heart disease, results have been mixed. One study conducted in China showed that study volunteers taking a vitamin cocktail of vitamin E, beta carotene, and selenium had a lower rate of death from heart disease, although these supplements didn't seem to lower the rate of cardiovascular incidents (heart attack or stroke). Another study looked at 29,000 older, male smokers. These volunteers took 50 mg of vitamin E per day, plus beta-carotene for five to eight years, yet the death rate from coronary heart disease remained unaffected. Men in the study who had a history of heart attack were actually more at risk for death due to heart disease. The Cambridge Heart Study was far more encouraging. This research looked at roughly 2,000 patients assigned either to vitamin E or placebo. After less than two years of follow-up, the number of non-fatal heart attacks fell significantly, but deaths due to cardiovascular problems remained the same. Some problems in the study design suggest that these results could have occurred as easily due to chance as to the vitamin E. Yet another study conducted in Italy showed that 300 mg of vitamin E per day slightly increased the number of non-fatal heart attacks, but slightly lowered the death rate due to heart disease.

The most recent study was published in the New England Journal of Medicine. As part of the Heart Outcomes Prevention Evaluation (HOPE) study, investigators assigned 772 patients to take 400 IU of vitamin E each day, and 739 patients to placebo. All the study volunteers were at high risk for cardiovascular problems because they either already had evidence of heart disease or had diabetes plus one additional risk factor. After 4.5 years, there was no hint that the vitamin E helped reduce heart problems. The death rate due to cardiovascular disease was about the same in both groups, as were the rates for heart failure, unstable angina, and bypass or angioplasty. The vitamin E hypothesis is not completely dead, however. For example, some researchers believe vitamin E might be helpful in preventing new atherosclerotic plaques or that it may be effective only if used with other antioxidant vitamins. The researchers from this study will continue monitoring patients to determine whether vitamin E helps reduce risk for cancer.

So what to do? All these studies show that vitamin E is safe and very low in side effects, so it may not be time just yet to toss it from your health regimen. But right now, the chances are low that vitamin E offers major health benefits.

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Low Cholesterol Doesn't Make Smoking Safer

The incidence and toll of heart disease is increasing throughout the world, including in places you might not expect. For example, in the 1990s atherosclerotic heart disease became the leading cause of death in the Republic of Korea (South Korea). This may seem surprising because in East Asia, people tend to be leaner and have lower blood cholesterol levels. But in these countries, another potent risk factor for heart disease, cigarette smoking, is rampant. Seventy-two percent of Korean men, 50% of Chinese men, and 58% of Japanese men smoke.

In a recent study, researchers analyzed the interaction among heart disease risk factors in 106,675 Korean men who underwent insurance evaluations between 1990 and 1992. Most of these men (58%) were current cigarette smokers, and 60% had "healthy" total cholesterol levels below 200 mg/dL. During a six-year follow-up period, 3% of the men were either admitted to the hospital for a cardiovascular problem or died of heart disease. When compared to men who never smoked cigarettes, current and former smokers were roughly 1.5 times more likely to suffer from atherosclerotic cardiovascular disease — even those smokers with the lowest cholesterol level (below 171 mg/dL) were at greatly increased risk.

Clearly, the message is that smoking is a significant and dangerous factor for heart disease. But the logical extension is that a good cholesterol level doesn't cancel out the effects of other heart disease risk factors, smoking included.

For more information on the dangers of smoking see page 58 of the Family Health Guide.

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Is It Butter . . . or Medicine?

Not only can you find this product in the grocery store, but in television advertisements as well — a margarine-like spread that can help reduce cholesterol levels? Not as crazy as it sounds, Benecol is a margarine-like spread made with compounds called plant stanol esters, which have been shown to help lower cholesterol levels.

Plant stanol esters are a type of phytochemical (a chemical compound derived from plants, such as pine trees, soy, corn, and wheat) which block the LDL "bad" cholesterol from entering the micelles, the cellular structures that transfer cholesterol from the small intestine into the bloodstream. Sitostanol is particularly good at blocking intestinal absorption of cholesterol, and in its soluble form, it has an even more effective cholesterol-lowering effect.

Benecol has been available in Finland for four years, and studies there show that substituting Benecol for margarine or butter reduced cholesterol levels. In 1995, the New England Journal of Medicine published a study that evaluated the cholesterol-lowering effect of this butter substitute. This research found regular use of Benecol resulted in a 14% reduction in serum cholesterol levels (for example, a person with a cholesterol level of 240 mg/dl could get that level down to 207 mg/dl).

While this is a promising product, particularly for people who enjoy a pat of margarine on their toast or baked potato, consumers need to realize that this item is merely a supplement and no more. It is not a "magic bullet" but rather can be a useful addition to a heart-healthy diet — one that is low in saturated fats, trans fats, cholesterol and refined carbohydrates and rich in fruits, vegetables, and whole grains. For more information on high cholesterol levels and how to reduce them, see page 669 of the Family Health Guide.

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ACE Inhibitor Protects High-Risk Patients from Cardiovascular Complications

Results from an international study suggest patients at high-risk for cardiovascular events may benefit from taking 10 mg of ramipril (Altace) daily. Canadian researchers involved in the HOPE (Heart Outcomes Prevention Evaluation) study determined ramipril, a type of ACE inhibitor, significantly reduces the death rate of people with cardiovascular disease but without congestive heart failure. The results were so clear early on, in fact, that the trial ended ahead of schedule so that all participants could benefit.

The HOPE study began in 1994 and includes 267 health centers in 19 countries around the world. The participants, nearly 10,000 men and women, are all at high risk for cardiovascular events. The researchers randomly assigned 9,297 patients age 55 or older to take either 10 mg of ramipril once per day or a placebo. After nearly five years, they found treatment with ramipril reduced the rate of death from cardiovascular causes, as well as the rate of heart attack, heart failure, and stroke. The number of new diabetes cases, as well as the risk of complications related to diabetes, also declined. The effects were present regardless of age, gender, or the presence of coronary artery disease.

Whether other ACE inhibitors have the same beneficial effects is unknown. Ramipril is used to treat high blood pressure and received FDA approval in 1991. It enhances blood flow and prevents angiotensin from converting into a more potent substance that increases salt and water retention. Its side effects include cough, headache, and dizziness.

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Statins Better Than Estrogen to Reduce a Woman’s Chances of Second Heart Attack?

Results from the Heart and Estrogen/progestin Replacement Study (HERS) turned on its ear the conventional wisdom that estrogen-replacement therapy helps prevent coronary heart disease in postmenopausal women. The HERS data showed that women who had been given estrogen-plus progestin-replacement therapy after their first heart attack were just as likely to have a second heart attack as those women who were given a placebo after their first heart attack.

The findings are especially puzzling because over the course of the study (roughly four years), the women who took the hormone-replacement therapy experienced an 11% drop in LDL ("bad") cholesterol and a 10% gain in HDL ("good") cholesterol, compared to the women on a placebo. Because beneficial effects on cholesterol levels were believed to be partly responsible for the protective effects of hormone-replacement therapy, the HERS study casts doubt on whether it should be used to prevent heart attack in postmenopausal women with risk factors for CHD.

At the same time, series of research trials over the past few years have indicated that statins significantly reduce the chances of a second heart attack in women with average cholesterol levels. Results from the Cholesterol and Recurrent Events (CARE) trial found that women with a mean total cholesterol of 209 mg/dL and a mean LDL cholesterol of 139 mg/dL, who were given 40 mg of pravastatin per day, were 46% less likely to have a second major heart attack than patients given a placebo.

Based on this data, other statin study data, and results of the HERS trial, a 1999 consensus panel statement by the American Heart Association (AHA) and the American College of Cardiology (ACC) recommended that women with heart disease use statins, rather than estrogen-replacement therapy, as a first-line lipid-lowering treatment.

Because the participants in the HERS trial were women who had already had heart attacks, it is difficult to draw a definitive conclusion about potential benefits of hormone-replacement therapy in reducing the risk of heart disease in healthy women. Every woman should talk with her doctor about her particular risk factors for heart disease, the potential risks and benefits of both hormone-replacement therapy and statins, and her personal preferences in choosing an approach.

Journal of the American Medical Association, Vol. 280, No. 7, pp. 605–13.
New England Journal of Medicine, Vol. 335, No. 14, pp. 1001–9.

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Walking for Women: A Great Step Toward Fitness

Ask any doctor for his or her advice for healthy living and you'll find exercise a part of the prescription. However, it is one that patients must "fill" themselves and that can be tough. The most recent guidelines from the Centers for Disease Control and Prevention, the American College of Sports Medicine, and the Surgeon General's report recommend that individuals get at least 30 minutes of moderate-intensity activity on most (ideally all) days of the week. Yet 60% of Americans don't regularly engage in physical exercise at all.

Harvard Medical School researchers recently compared the effects of brisk walking with more vigorous forms of exercise, specifically in women. For this report, study investigators followed 72,488 women participating in the Nurses' Health Study for 11 years. At the start of the study in 1986, these women were all between the ages of 40 and 65 and had no known heart disease or cancer. They completed regular, detailed questionnaires about their physical activity.

Researchers found that vigorous exercise and brisk walking reduces the risk of heart attack for women by roughly the same amount. The bottom line is that brisk walking for three or more hours per week can reduce a woman's risk of cardiovascular disease by 30%-40%. Women who walk for a longer time or combine walking with other vigorous physical activity can expect to reduce their risk of heart disease even more. So women don't have to sign up for aerobics or train for a marathon to substantially reduce their heart disease risk. A good start is putting one foot in front of the other at a good pace. For more information on exercise and fitness, see page 51 of the Family Health Guide.

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Vitamin C: How Much Is Enough?

Vitamin C is touted as a potential weapon in combating a range of illnesses, from the common cold to cancer and heart disease.

No one believes that taking vitamin C supplements in moderate doses presents any danger, and foods rich in vitamin C (fruits and vegetables) offer real health benefits. But could consuming large amounts of vitamin C supplements be too much of a good thing?

Despite some theoretical dangers, vitamin C appears to have very few toxic effects. However, at very high doses, vitamin C can indeed cause problems. Diarrhea and abdominal bloating can result from taking several grams at once — a tactic that has been advocated by some for preventing and treating the common cold.

Studies show that high doses of vitamin C could lead to over-absorption of iron, which could potentially damage the heart, liver, and other organs. Too much vitamin C may also contribute to kidney stones or give false-positive readings on blood-stool tests. Such events occur rarely if ever, so these really are minor concerns. But, even if people are not endangering themselves much by taking large amounts of vitamin C, research suggests that they are not helping themselves either. Studies of dietary patterns show that people who get an average of 200 mg of vitamin C per day from fruits and vegetables have a lower risk of cancer — especially cancers of the mouth, esophagus, stomach, colon, and lung. Five servings of fruits and vegetables a day are enough to provide this much vitamin C. In research trials, consuming more vitamin C has not led to a detectable increase in health benefits. As for heart disease, there is evidence that marked vitamin C deficiency is associated with an increased risk of cardiovascular problems, but there is no proof that taking supplements offers additional benefits over those offered by a diet that includes the recommended amounts of fruits and vegetables.

Experts from the National Institutes of Health recently reviewed the evidence on this topic and concluded that, ideally, people should try to get their vitamin C from eating five servings of fruits and vegetables daily. Taking more than one gram (1,000 milligrams) of vitamin C per day should be discouraged because of the small, yet real, possibility of adverse effects. These recommendations do not mean that people who are taking vitamin C supplements or a multivitamin pill should stop, particularly if they just can't manage to eat enough fruits and vegetables. However, there is no reason to take high doses of vitamin C, and there may even be a small possibility of harm. For more information on vitamins and minerals, see page 43 of the Family Health Guide.

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Fish Oil Supplements Valuable for Heart Disease Sufferers

Eating like an Eskimo is believed to prevent cardiovascular disease. Now, a new Italian study has found that polyunsaturated fatty acid (fish oil) supplements significantly reduced the risk of recurrent heart troubles and related mortality in patients who had a history of heart disease.

The study involved 11,000 subjects who had survived heart attacks in the preceding three months. Researchers then monitored their progress for three-and-a-half years as they took daily doses of polyunsaturated fatty acid and vitamin E. Vitamin E, prevalent in leafy greens, is also touted for its antioxidant properties. Subjects received one of four treatments: polyunsaturated fat supplements, vitamin E supplements, both, or neither. Polyunsaturated fat supplements reduced patient mortality by nearly 20% and decreased chances of another heart attack by 10%-15%. Vitamin E, however, failed to improve survival significantly nor was there any additive effect when the two supplements were taken together. Neither supplement caused side effects.

The study might even underestimate the potential of polyunsaturated fatty acids, according to an accompanying editorial. Italians are already thought more resistant to coronary disease because of their Mediterranean diet. Results in less healthy populations might be amplified, and this could also explain vitamin E's lackluster performance. For more information on dietary fats and oils, see page 40 of the Family Health Guide.

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The Importance of Controlling Diabetes in Preventing Heart Disease

Cardiovascular disease is the number one killer of adults in the United States. In early November 1999, diabetes joined the ranks of high cholesterol and high blood pressure as one of the key, official, modifiable risk factors for cardiovascular disease.

Diabetes has long been recognized as an important contributor to many types of cardiovascular disease. Individuals with this condition are three times as likely to die of a stroke or to develop heart failure when compared with people who do not have diabetes. People with diabetes are also more prone to atherosclerosis, the leading cause of heart attacks. Part of the reason diabetes is such a heavy hitter is that it often comes along with other significant risk factors. For example, people with diabetes often also have other conditions that add to heart disease risk, for example, high LDL (low-density lipoprotein, or "bad") cholesterol, low levels of HDL (high-density lipoprotein, or "good") cholesterol, high blood pressure, high triglycerides, and insulin resistance.

Major health organizations, including the National Heart, Lung, and Blood Institute and the American Heart Association, are particularly concerned because the incidence of type 2 diabetes is on the rise. Why? Because Americans are becoming more overweight, less active, and older. While it is true that some of the predisposing factors for diabetes cannot be controlled, such as genetics and advancing age, individuals can take steps to reduce their chances of developing this illness (and its complications). To prevent developing type 2 diabetes, people need to exercise regularly and maintain a healthy weight. Regular checks of blood pressure, cholesterol, and glucose are also important.

If you do have diabetes, remember there is no such thing as a mild form of this disease. Work with your doctor to implement lifestyle changes that can help control this condition. And if lifestyle changes don't help enough, don't shy away from the medications your doctor may recommend. Taking control of diabetes can translate into myriad health benefits. For more information on risk factors for heart disease, including diabetes, see page 654 in the Family Health Guide.

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Cereal Fiber Reduces Heart Disease Risk for Women Too

Several studies have demonstrated that, for men, a high-fiber diet reduces the risk of coronary heart disease. Recently, data from the Nurses' Health Study suggests that the same is true for women.

Study investigators looked at the typical daily diet of 68,782 women. None of these women had known cardiovascular disease, cancer, high cholesterol, or diabetes at the time the study began. Researchers followed the women to see how many experienced a heart attack or died of heart disease. After adjusting for age differences among the groups, the women who ate the most fiber had a 59% lower risk of dying from coronary disease over the next 10 years when compared with women who ate the least amount of fiber. Statistical analysis indicated that each 10-gram per day increment in long-term total fiber intake was associated with a 19% reduction in coronary heart disease risk.

Researchers also found that the women with the highest long-term intake of cereal fiber had a 34% lower risk of coronary heart disease when compared with the women with the lowest consumption of cereal. Yet, the amount of fruit and vegetable fiber had little effect on heart disease risk. In fact, the benefits of cereal fiber appear to be particularly potent. An increase of five grams per day of cereal fiber was associated with a 37% reduction in heart disease risk.

The information from this report presents a particularly strong case for eating more whole grain products as a way to add fiber to your diet. You can do this by eating whole wheat bread, brown rice, and whole grain pastas, instead of the refined versions, and opting for a high-fiber breakfast cereal. Although the fiber in fruits and vegetables does not appear to lower heart disease risk, eating plenty of fruits and vegetables offers other health benefits, so these food groups should not get short shrift in anyone's diet. For more information on diet and nutrition, see page 39 of the Family Health Guide.

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Aspirin for Preventing Stroke and Other Vascular Problems

An aspirin a day keeps a stroke away in patients with a history of heart disease, but a recent review in Archives of Neurology reveals the drug’s stroke-preventing properties may not extend to healthy people.

Researchers from the University of Texas Health Science Center and three other institutions have concluded aspirin does not reduce the risk of stroke in people without heart disease. Indeed, their results suggest regular aspirin use might even slightly increase the risk in people at low risk for vascular problems. These conclusions were reached after the investigators performed a meta-analysis on five existing studies examining the preventive effects of aspirin. (A meta-analysis is a mathematical method used to compare the results of similar studies.) The researchers also reviewed four large observational studies that looked at regular aspirin use and stroke risk in low-risk individuals.

The five trials used in the meta-analysis involved a total of 52,251 participants with a mean age of 57 years. Three of the studies excluded women, though women accounted for roughly 20% of the total number of patients. Three studies used people at high risk for vascular disease, such as those with high blood pressure or diabetes, while the other two used healthy males at low risk. Dosage varied from 75 mg to 650 mg per day. The mean rate of stroke was 0.3% per year during an average study period of five years.

The meta-analysis found no significant risk reduction for patients taking aspirin compared with those taking a placebo. In contrast, the participants still enjoyed a 26% decrease in heart attack risk.

The researchers' review of four observational studies found aspirin modestly increases the risk of bleeding into the brain in low-risk patients — such bleeding can cause hemorrhagic stroke. However, hemorrhagic stroke accounts for only 10-15% of all strokes. Most strokes are ischemic, meaning they are caused by a temporary interruption in the blood flow to brain. When the four studies were pooled, no significant increase in risk of ischemic stroke was apparent.

The researchers stress that more information is needed before guidelines regarding stroke risk and aspirin use can be generalized. Certainly, people with a history of heart disease or whose risk of a heart attack eclipses their risk of stroke can benefit from aspirin. However, the majority of the subjects in the reviewed studies were middle-aged males. Men in this age group are more likely to suffer heart attacks, not strokes. Women and the healthy elderly were underrepresented, yet they are more prone to strokes rather than heart attacks. As a result, it’s still unclear whether anyone with a low risk of heart problems should be regularly taking aspirin.

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Ramipril for Diabetics with Heart Disease

The incidence of heart disease in the general population has been dropping. This is good news of course, but for individuals with diabetes, the statistics are not so promising. In fact, men with type 2 diabetes have experienced only a modest decline in heart disease rates, while women with diabetes have actually experienced an increase.

Heart disease accounts for 70% of deaths in people with diabetes. So, the outcome of a recent study, which demonstrated that the angiotensin-converting enzyme (ACE) inhibitor, ramipril, significantly lowered the incidence of heart disease, stroke, and death in people with diabetes who had a history of heart disease and hypertension, should be welcome news.

The Heart Outcomes Prevention Evaluation (HOPE) study included people with and without diabetes. More than one-third of the participants had diabetes. Of the participants with diabetes, the average age was a little over 65 years old, and one-third were women. All had a history of heart disease and half had a history of high blood pressure as well. All study volunteers were randomly assigned to either ramipril or a placebo. While ramipril did not lower the blood pressure of participants much — as it was originally intended to do — it did lower their risk for heart attack by 22%, their risk for heart disease by 37%, and their risk for stroke by 33%. Other studies conducted to evaluate the effects of ACE inhibitors on blood pressure in people with diabetes have had similar outcomes. (10.30.00)

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