The results of a paper published in the journal Chest (129(5):1219-25) show that alcoholic and ex-alcoholic individuals have a higher risk of suffering from community acquired pneumonia.

Although mortality did not differ significantly, an increase of the severeness of the disease was shown, and consequently, an increase of the morbidity and the complications was revealed. This study was conducted by the Pneumonia Multidiscipline Group of Hospital Clínic de Barcelona, led by Dr. Antoni Torres, from the Institut Clínic del Tórax, and leader of the IDIBAPS Group Management and Prevention of the Pulmonary Disease.

The increase of the risk of suffering from pneumonia in alcoholic patients exists due to the fact that the activity of their immune system decreases. This decrease not only is observed in alcoholic, but also in ex alcoholic patients. The daily quantity of alcohol consumption in order to include patients in the group of alcohol abuse was of 80 g in man and 60 g in women, the equivalent of 2 or 3 beers and 3 or 4 cups of wine.

Results are especially relevant since alcohol is the more abused drug in Spain, and causes a total of 12,000 deaths every year. In addition, pneumonia is a very frequent disease, with 10 patients every 1,000 inhabitants in Catalonia. This number is much higher if we take into account in the population over 65. This is the reason why the consequences of this study, and the possible vaccination of alcoholic of ex-alcoholic individuals against Pneumococcus, would affect a very high number of people. Alcohol consumption could turn into a new risk factor or a worsening factor to take into account in cases of community acquired pneumonia.

Until now, women had to rely on prevention and treatment guidelines for coronary heart disease based on research on men.

This month, the American Heart Association outlined measures for women to combat and prevent cardiovascular disease, the first evidence-based guidelines for women.

Coronary heart disease (CHD) is often fatal, and because nearly two thirds of women who die suddenly have no previously recognized symptoms, it is thus essential to prevent CHD. AHA figures show that about half a million women die of heart disease and strokes each year, killing more than the next seven causes of death combined, including cancer.

In comparisons between the genders, WomenHeart, the National Coalition for Women with Heart Disease, says that women are more likely than men to die within one year of a heart attack; women are twice as likely as men to die after a bypass; and 35 percent of female and 18 percent of male heart attack survivors will have a recurrent heart attack within six years.

Risk factors for cardiovascular disease in both men and women include high cholesterol and blood pressure, smoking, not exercising, obesity, stress and a family history of heart disease and stroke.

A small-molecule drug may be capable of preventing arrhythmias according to a team of researchers at Columbia University Medical Center. The new drug called JTV519 has been developed and tested in mice. It targets leaky calcium channels. Heart arrhythmias, which are characterized by fast and erratic beating of the heart, can cause sudden death. This is particularly more common in people with heart failure or otherwise weakened hearts.
The Role of Calcium Channels

In the normal heart cell, the membrane surrounding a heart cell contains a small calcium channel that is stimulated by the electrical impulses that drive heart rhythm. When stimulated, this calcium channel triggers another, larger calcium channel within the cell, called the ryanodine receptor (RyR2), to release calcium ions. The rush of calcium ions then signals the heart muscle to contract powerfully. The ryanodine receptor sits at the surface of the sarcoplasmic reticulum, a sac containing calcium ions, and is the major gatekeeper for calcium ion release. The more calcium released through the ryanodine receptor, the stronger the contraction of the heart.

In a previous study, the same research team found that the calcium channels from patients with heart failure have defective function that, in addition to making them unresponsive to further stimulation by catecholamines, also causes a calcium leak that can weaken heart muscle contraction and possibly trigger fatal heart arrhythmias. These arrhythmias, known as ventricular fibrillation, are the cause of death in about 50 percent of patients with heart failure.

RyR2, is normally held closed by the interaction of another protein called calstabin2. When calstabin binds it, the channel does not open, and no calcium is released. But when the interaction of RyR2 and calstabin2 is disrupted, the channel begins to leak Ca2+, triggering arrhythmia.

Study details

The research, led by Andrew Marks, MD, Director of the Center for Molecular Cardiology at Columbia University Medical Center, was set to investigate whether a drug known to enhance calstabin2 - ryanodine receptor binding could prevent the development of arrhythmias.

The experimental drug JTV519, a 1,4-benzothiazepine derivative, has recently been shown to reduce diastolic sarcoplasmic reticulum Ca2 leak in an animal model of heart failure. JTV519 was shown to increase binding of the protein calstabin2 to the ryanodine receptor hence the potential for blocking arrhythmias.

The study was conducted using mice which either had defective calstabin2 or had no calstabin2. Some of the mice were given the experimental drug. Both groups were then exercised to induce arrhythmias. The 10 mice that received the drug did not develop an arrhythmia, whereas 8 of 9 untreated mice died after arrhythmic events. The experimental drug had no effect on knockout animals that had no calstabin2 suggesting that calstabin2 presence is essential for drug to function. The drug blocked potentially fatal arrhythmias in these mice by stabilizing the crucial protein-protein interaction between RyR2 and calstabin and preventing Ca2+ leakage, Marks� team reports.

References

Xander H. T. Wehrens, Stephan E. Lehnart, Steven R. Reiken, Shi-Xian Deng, John A. Vest, Daniel Cervantes,3 James Coromilas,3 Donald W. Landry, Andrew R. Marks. Protection from Cardiac Arrhythmia Through Ryanodine Receptor�Stabilizing Protein Calstabin2. Science:304 April, 2004.

Altace was found to lower the risk of sudden cardiac death and nonfatal cardiac arrest in people at high risk of heart attacks and stroke.

Altace (Rimipril) belongs to a class of drugs known as Angiotensin-converting enzyme (ACE) inhibitors. ACE inhibitors are widely prescribed to patients following heart attacks and for those with heart failure. They are also recommended for people with high blood pressure, diabetes, and others at risk for ACE inhibitors and stroke.

Altace blocks ACE from converting angiotensin I to angiotensin II, a powerful vasoconstrictor, leading to decreased blood pressure, decreased aldosterone secretion, a small increase in serum potassium levels, and sodium and fluid loss; increased prostaglandin synthesis also may be involved in the antihypertensive action.

Past studies have shown that these medications reduce the risk of heart attack and stroke in people with heart disease.
The HOPE Trial

The Heart Outcomes Prevention Evaluation (HOPE) study followed a total of 9,297 high-risk patients who were aged 55+ either with a history of coronary artery disease (CAD), stroke, or peripheral vascular disease (PVD) or with diabetes plus at least one other cardiovascular risk factor (hypertension, elevated total cholesterol level, low high-density lipoprotein cholesterol level, cigarette smoking, or documented microalbuminuria.

The double blind, randomized study compared Altace with vitamin E or placebo treatment. Researchers now report that after an average of 4.5 years of treatment, 3% of the patients taking the ACE inhibitor had died from sudden cardiac death or experienced a nonfatal cardiac arrest, compared with 4% taking placebo. This translates into a 21% reduction in unexpected deaths, deaths due to cardiac arrest, or nonfatal cardiac arrest for those taking Altace.

In the HOPE study, roughly three out of four patients were also taking a blood thinner, a third were taking cholesterol-lowering statins, half were taking calcium channel blockers (another type of high blood pressure medication), and two out of five were taking beta-blockers. Thus showing that even when people were on other medications, they benefited from being on an ACE inhibitor.

These results stressed the importance in prescribing ACE inhibitors to patients at high risk of developing heart disease and stroke.

A few weeks after the withdrawal of the popular pain killer, Vioxx from the market, Bextra is also found to increase the risk of heart disease.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a large group of drugs that include aspirin, ibuprofen, Vioxx, Bextra and Celebrex. However, Vioxx, Bextra and Celebrex belong to a class of NSAIDs known as Cox-2 inhibitors, aslo known as second generation NSAIDs. All these drugs are effective in relieving arthritis pain.

They work by reducing substances that cause inflammation, pain, and fever in the body and is used to treat arthritis, acute pain in adults, and pain that accompanies menstrual cycles.
Vioxx and the risk of heart disease

Recently Merck, the company that manufactures Vioxx, voluntarily withdrew Vioxx from the market after a clinical trial confirmed that Vioxx increased patients' risk of heart attack and stroke. Merck made this decision independent of input from the FDA.

Merck's decision to withdraw Vioxx from the market is based on new data from a trial called the APPROVe trial. In the APPROVe trial, Vioxx was compared with placebo. The purpose of the trial was to see if Vioxx at 25mg was effective in preventing the recurrence of colon polyps. But the trial was also designed to look at the drug's long-term safety. This trial was stopped early because after 18 months on Vioxx, patients' heart attack and stroke risks doubled from 7.5 out of 1,000 for patients on placebo to 15 out of 1,000 for patients on Vioxx. The threat posed by this finding is very serious when one considers that when patients get into their 60s and 70s, arthritis and heart disease run together.

The safety of other Cox-2 inhibitors

Since then, there has been increased attention on Vioxx's sister drugs, Bextra and Celebrex. Because they have the same mechanism of action, it was feared that these drugs might also increase heart risk.

Now Pfizer, which produces the other two drugs, Celebrex and Bextra, has issued a warning that Bextra may cause rare skin and heart side effects. To date, there is no evidence that Bextra increases heart risk in arthritis patients without heart disease. But studies of Bextra alone or in combination with parecoxib, together with a study published in 2003, show an increase in "cardiovascular events" in patients undergoing heart bypass surgery. Pfizer also warns that Bextra may cause rare but serious skin reactions more often than other Cox-2 inhibitors. The risk of these skin reactions, Pfizer says, is greatest during the first two weeks of Bextra treatment.

So far, there is no hard evidence that Celebrex increases heart risk. On the contrary with Celebrex there is some evidence that it is more heart-friendly than Vioxx or Bextra. Celebrex doesn't raise blood pressure at high doses and there seems to be no increase in heart disease events from the many studies conducted.

European regulators said they were launching a safety investigation into the entire class of Cox-2 inhibitors. Also, an editorial in the New England Journal of Medicine raised questions about the safety of these drugs.

Pfizer is currently considering initiating clinical trials to test the safety of these drugs when used in the long term. In the mean time, patients currently taking these drugs should consult their physicians about whether to switch to a different drug and what the risks of taking these drugs have on them. If the only thing that works for a particular patient is a Cox-2 drug, it is probably a good idea for that patient to keep other risk factors for stroke or heart disease low.

UPDATE: In December, 2004 the NIH suspended the APC colon cancer prevention trial when findings suggested Celebrex more than doubled heart deaths, heart attacks, and strokes in people enrolled in the study (Full Story).

Results of a study in this week's issue of THE LANCET suggest that Atenolol (Tenormin�)--one of the most widely prescribed beta-blockers for reducing blood pressure--may not be effective in reducing heart attacks or death from cardiovascular causes.

Atenolol (Tenormin�) is one of the most commonly used beta-blockers clinically, and has often been used as a reference drug in randomized controlled trials of high blood pressure.

Beta-blockers work by competitively blocking beta-adrenergic receptors in the heart and juxtaglomerular apparatus. They lead to decreased heart rate, decreasing the work load by the heart. They do not produce coronary vasodilatation, but lead to a shift and redistribution of coronary circulation to the ischemic areas. It decreases the release of renin from the kidney, thus lowering blood pressure.
Study details

Concerns that Atenolol (Tenormin�) may not be the best reference drug for comparison with other antihypertensive drugs led Bo Carlberg (Umea University Hospital, Sweden) and colleagues to systematically review the effect of Atenolol (Tenormin�) on cardiovascular illness and death among patients with high blood pressure.

The investigators identified four studies that compared Atenolol (Tenormin�) with placebo or no treatment, and five studies that compared Atenolol (Tenormin�) with other antihypertensive drugs. The studies included some 24,000 patients followed for more than 4.5 years.

Atenolol (Tenormin�) was no different to placebo in terms of death from all causes, cardiovascular causes, or incidence of heart attack; a trend in reduced stroke incidence was the only favorable outcome. Atenolol (Tenormin�) slightly increased all-cause mortality compared with other antihypertensive drugs, in addition to showing a trend to increased cardiovascular death and increased stroke incidence.

In an interview with The Doctors Lounge, Carlberg said "We have not been able to show that Atenolol prevents cardiovascular disease in the same magnitude as many other antihypertensive drugs."

When we asked Dr. Carlberg whether his findings suggested that Atenolol use is dangerous, he replied: "No. Our study showed that Atenolol did not increase the risk of death compared with placebo." Co-author Lars H Lindholm comments: "We have some doubts about the suitability of Atenolol (Tenormin�) as a first-line antihypertensive drug and as a reference drug in outcome trials of hypertension." It should be noted that this is a retrospective analysis which needs to be confirmed by prospective randomized trial.

DALLAS � Nov. 8, 2004 � A new medication has dramatically reduced mortality among African-American patients suffering from heart disease, according to results of a study including UT Southwestern Medical Center at Dallas researchers.

The results were so favorable that investigators halted the multi-center trial so that all the 1,050 study participants suffering from advanced heart failure, including those on a placebo, could be given the combined drug treatment, said Dr. Clyde Yancy, a study author and director of the Congestive Heart Failure/Transplant Program at UT Southwestern/St. Paul University Medical Center.

"We discovered that patients were indeed living longer and that their incidence of death was dramatically less," said Dr. Yancy, professor of internal medicine.

A 43 percent decrease in the one-year mortality rates among African-Americans in the study receiving the combined treatment was observed by Dr. Yancy and his UT Southwestern colleagues, working in conjunction with University of Minnesota researchers. Participants, which included patients 18 years of age and older who had a heart failure diagnosis for at least three months, were recruited from 161 medical centers.

Dr. Yancy said the findings, published in the Nov. 11 edition of The New England Journal of Medicine, will have a substantial impact on the treatment of cardiovascular disease for African-Americans.

"Heart disease is the leading cause of death in the African-American community," Dr. Yancy said. "We were trying to find the best treatment for a disease that happens to be in a specific population."

The clinical trial, called the African-American Heart Failure Trial, or A-HeFT, used a combination of hydralazine and isosorbide dinitrate, two older drugs that had been used in the past to treat various heart conditions and are now being used in a new combination called BiDil.

In addition, study participants must have received standard therapy for their heart disease including beta blockers and diuretics.

The study began in June of 2001 and was discontinued on July 19, 2004, because the results were markedly favorable in decreasing mortality in the group taking BiDil as opposed to the group taking placebos.

By narrowing the focus of the study to a specific group of patients, Dr. Yancy said, the researchers could better assess the medicine's efficacy within that group. The findings, he added, provide strong evidence BiDil can slow the progression of heart failure in addition to decreasing death rates among African-American patients. Earlier heart drug studies have shown a marked difference in the drugs' effects in African-Americans and other ethnic population groups.

"Heart disease affects so many people and adds such a tremendous burden on the quality of life," Dr. Yancy said. "It is our hope that this treatment will allow patients with heart disease to enjoy a higher quality of life."

The National Institutes of Health (NIH) announced today that it has suspended the use of COX-2 inhibitor celecoxib (Celebrex� Pfizer, Inc.) for all participants in a large colorectal cancer prevention clinical trial conducted by the National Cancer Institute (NCI).

The study, called the Adenoma Prevention with Celecoxib (APC) trial, was stopped because analysis by an independent Data Safety and Monitoring Board (DSMB) showed a 2.5-fold increased risk of major fatal and non-fatal cardiovascular events for participants taking the drug compared to those on a placebo.

Additional cardiovascular expertise was added to the safety monitoring committees at the request of the Steering Committees for this trial after a September 2004 report that the COX-2 inhibitor rofecoxib (Vioxx�) caused a two-fold increased risk of cardiovascular toxicities in a trial to prevent adenomas. The APC is a study of more than 2,000 people who have had a precancerous growth (adenomatous polyp) removed. They were randomized to take either 200 mg of celecoxib twice a day, 400 mg of celecoxib twice a day, or a placebo for three years. The trial began in early 2000 and is scheduled to have been completed by Spring 2005.

Investigators at the 100 sites in the APC trial located primarily in the United States, with a few additional sites in the United Kingdom, Australia, and Canada, have been instructed to immediately suspend study drug use for all participants on the trial, although the participants will remain under observation for the planned remainder of the study.

"Data from the report on rofecoxib (Vioxx�) informed us of the need to focus on specific cardiovascular issues, and our Institutes brought in the experts to do so, said Elias A. Zerhouni, M.D., NIH Director. "Our overwhelming commitment is to advance the health and to protect the safety of participants in clinical trials. We are examining the use of these agents in all NIH-sponsored clinical studies. In addition, we are working closely with our colleagues at FDA to ensure that the public has the information they need to make informed decisions about the use of this class of drug."

"The rigor of our clinical trials system has allowed us to find this problem," said NCI Director Andrew C. von Eschenbach, M.D. "We have a strong system that provides us with the opportunity to both find ways to effectively treat and prevent disease and to do so in a way that protects the lives and safety of the participants."

However, another ongoing study looking at whether Celebrex can prevent colon cancer has not found any increased risk of heart attacks in patients taking the drug. This trial, the PreSAP trial, used the same heart measures and the same safety monitoring board as the APC trial.

"Pfizer is taking immediate steps to fully understand the [APC study] results and rapidly communicate new information to regulators, physicians, and patients around the world," Pfizer CEO Hank McKinnell says in a news release.

Because the two studies came up with opposite findings -- and because earlier studies showed no obvious sign of heart problems linked to Celebrex -- the FDA has not yet decided whether to ban Celebrex, to add additional warnings to the drug's label, or to wait for more information. But Acting FDA Commissioner Lester Crawford, MD, says the agency won't drag its feet.

"We will evaluate this information and may make statements very soon with regard to Cox-2 drugs in general and this product in specific," Crawford said today in a joint FDA/National Institutes of Health news conference.

NIH sponsors over 40 studies using celecoxib for the prevention and treatment of cancer, dementia and other diseases. In light of these new findings, NIH Director Zerhouni requested:

* a full review of all NIH-supported studies involving this class of drug.
* NIH Institutes to inform the principal investigators for all of these studies and will ask them to communicate directly with their study participants and explain the risks and benefits
* NIH to ask each investigator to inform us of the their plan to analyze their data in light of the information
* the Institutional Review Boards (IRBs) for all related trials to assess the new information and to conduct a safety review as well

UCLA researchers for the first time showed that advanced heart failure patients with diabetes who are treated with insulin faced a mortality rate four times higher than heart failure patients with diabetes treated with oral medications.

The new study may help raise awareness among physicians and patients of this previously unknown relationship between insulin use and increased mortality in advanced heart failure patients. More research is needed to explore the mechanisms of how insulin use may be contributing to the higher mortality rate.

The research appears in the January issue of the peer reviewed American Heart Journal.

Previous studies have shown a connection between type 2 diabetes, heart failure and insulin. The UCLA study is the first to identify a high mortality rate for advanced heart failure patients who use insulin to manage diabetes. "Further studies into what is the best strategy to control blood sugar levels in patients with diabetes and heart failure are urgently needed," said Fonarow. Dr. Gregg Fonarow, senior study author; professor of cardiology, David Geffen School of Medicine at UCLA; and director, Ahmanson-UCLA Cardiomyopathy Center.

Researchers assessed the history of diabetes and insulin treatment in 554 patients with advanced heart failure after adjusting for various risk factors. One year survival rates were 89.7 percent for non-diabetic patients, 85.8 percent for non-insulin-treated diabetic patients, and only 62.1 percent for insulin-treated diabetic patients.

Heart failure affects 5 million in the United States and is the most common cause of hospitalization for those 65 years and older. Between 25 to 44 percent of heart failure patients also have diabetes.

The study is funded by the Ahmanson Foundation and was conducted at UCLA. Fonarow is a research consultant and speaker for GlaxoSmithKline, Bristol-Myers Squibb, Pfizer and Merck.

DALLAS � Jan. 20, 2005 � Heart patients with gastrointestinal complications should use low doses of aspirin combined with drugs that treat stomach ulcers rather than taking the anti-platelet drug Plavix, which has been thought to reduce bleeding ulcers, according to a gastroenterologist at UT Southwestern Medical Center and the Dallas Veterans Affairs Medical Center.

Physicians are challenged in treating heart patients who may be at high-risk for gastrointestinal bleeding from aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). Factors that place patients at high-risk include a history of ulcers or gastrointestinal complications such as bleeding, increased age and congestive heart failure.

Low-dose aspirin (325 milligrams or less daily) has been shown to lower the risk of cardiovascular and cerebrovascular blood clots. It can, however, cause gastrointestinal ulceration and major bleeding, thereby limiting its overall usefulness even at the lowest effective amount. In an editorial in the current issue of The New England Journal of Medicine, Dr. Byron Cryer, associate professor of internal medicine at UT Southwestern, said current cardiology guidelines suggest patients who cannot take aspirin because of previous bleeding ulcers be given the drug clopidogrel (Plavix), which has been found to be marginally better than low-dose aspirin in preventing heart attacks and reducing bleeding ulcers. But, Plavix's effectiveness has not been proven in heart patients at greatest risk due to their history of gastrointestinal bleeding, and recent research indicates it actually may impair ulcer healing and markedly increase rates of bleeding.

"Clopidogrel inhibits new growth of small blood vessels in ulcers � which is important for ulcer healing," said Dr. Cryer, a VA physician. "Although Plavix may not primarily cause gastrointestinal ulcers, through inhibition of new blood vessel growth, it may impair healing of background ulcers. When combined with the propensity to increase bleeding, these agents may convert small, silent ulcers into large ulcers that bleed profoundly."

Consequently, Dr. Cryer recommends that patients at high-risk for gastrointestinal complications who require blood clot-preventing therapy should consume the lowest effective dose of aspirin combined with drugs used to treat stomach ulcers (such as Aciphex, Nexium, Prevacid, Prilosec or Protonix) rather than take clopidogrel.

The New England Journal of Medicine editorial accompanies a study in the same issue of the journal by researchers from Hong Kong. The study evaluates the use of antiplatelet therapies in patients with a history of aspirin-induced upper gastrointestinal bleeding and found those who took clopidogrel had a 900 percent increase in recurrent bleeding from ulcers when compared to patients who took aspirin with esomeprazole (Nexium).

ORLANDO, Feb. 18 � Women with diabetes have a significantly greater risk of dying from coronary heart disease (CHD) than men with diabetes, researchers reported today at the Second International Conference on Women, Heart Disease and Stroke.

Diabetes is a well-established CHD risk factor known to double a person's chance of dying from heart disease. There has been much debate, but no large studies of whether diabetes carries different heart risks for women than for men, said Mark Woodward, Ph.D., professor of biostatistics at The George Institute for International Health at the University of Sydney, Australia.

Using data on more than 450,000 people, which included participants in the Asia Pacific Cohort Studies Collaboration, researchers found that men with diabetes had about 90 percent higher risk of dying from CHD as men without diabetes. Women with diabetes had more than two and a half times the risk of women without diabetes. That translates to a greater than 50 percent excess relative risk for women than for men, he said.

The data came from two previous meta-analyses of 16 studies and a collaborative overview of 44 studies in nine countries in the Asia-Pacific Region (China, Japan, South Korea, Taiwan, Hong Kong, Singapore, Thailand, New Zealand and Australia).

About 5 percent of all the participants had diabetes. Diabetes was defined according to self-reported history with or without fasting glucose evidence as an alternative. The researchers were able to adjust for age, systolic blood pressure, total cholesterol and cigarette smoking in most of the data sets, he said.

Perhaps better monitoring and control of blood glucose levels in women with diabetes would reduce their CHD risk compared with men with diabetes, Woodward said.

"There is some evidence to suggest that people with diabetes benefit from treatment with aspirin, cholesterol-lowering drugs and blood pressure-lowering agents," he said.

This meta-analysis has similar drawbacks to most overviews including the possibility of publication bias (in this case the exclusion of studies that did not report sex-specific results), misdiagnosis of diabetes, lack of information on an individuals' medical treatment, no information on menopause status or on whether subjects had Type 1 diabetes, due to the body's inability to produce insulin, or Type 2 diabetes, initially caused by the inability to use the insulin produced. Data from randomized trials of individuals with diabetes would clarify these issues.

Besides continuing to seek data on the sex-specific relative risk for CHD related to diabetes, researchers at the George Institute are leading a large scale randomized trial Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) on 11,140 people. They are trying to ascertain whether more intensive glucose control combined with blood pressure lowering reduces cardiovascular mortality in people with Type 2 diabetes. The trial, which will follow participants for 4 ½ years on average, will end in 2006.

ORLANDO, Feb. 18 � Women with diabetes have a significantly greater risk of dying from coronary heart disease (CHD) than men with diabetes, researchers reported today at the Second International Conference on Women, Heart Disease and Stroke.

Diabetes is a well-established CHD risk factor known to double a person's chance of dying from heart disease. There has been much debate, but no large studies of whether diabetes carries different heart risks for women than for men, said Mark Woodward, Ph.D., professor of biostatistics at The George Institute for International Health at the University of Sydney, Australia.

Using data on more than 450,000 people, which included participants in the Asia Pacific Cohort Studies Collaboration, researchers found that men with diabetes had about 90 percent higher risk of dying from CHD as men without diabetes. Women with diabetes had more than two and a half times the risk of women without diabetes. That translates to a greater than 50 percent excess relative risk for women than for men, he said.

The data came from two previous meta-analyses of 16 studies and a collaborative overview of 44 studies in nine countries in the Asia-Pacific Region (China, Japan, South Korea, Taiwan, Hong Kong, Singapore, Thailand, New Zealand and Australia).

About 5 percent of all the participants had diabetes. Diabetes was defined according to self-reported history with or without fasting glucose evidence as an alternative. The researchers were able to adjust for age, systolic blood pressure, total cholesterol and cigarette smoking in most of the data sets, he said.

Perhaps better monitoring and control of blood glucose levels in women with diabetes would reduce their CHD risk compared with men with diabetes, Woodward said.

"There is some evidence to suggest that people with diabetes benefit from treatment with aspirin, cholesterol-lowering drugs and blood pressure-lowering agents," he said.

This meta-analysis has similar drawbacks to most overviews including the possibility of publication bias (in this case the exclusion of studies that did not report sex-specific results), misdiagnosis of diabetes, lack of information on an individuals' medical treatment, no information on menopause status or on whether subjects had Type 1 diabetes, due to the body's inability to produce insulin, or Type 2 diabetes, initially caused by the inability to use the insulin produced. Data from randomized trials of individuals with diabetes would clarify these issues.

Besides continuing to seek data on the sex-specific relative risk for CHD related to diabetes, researchers at the George Institute are leading a large scale randomized trial Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) on 11,140 people. They are trying to ascertain whether more intensive glucose control combined with blood pressure lowering reduces cardiovascular mortality in people with Type 2 diabetes. The trial, which will follow participants for 4 ½ years on average, will end in 2006.

DALLAS. Female heart attack patients undergoing angioplasty have a higher risk of death than men, but stenting may improve their outcomes, according to a study reported in Circulation: Journal of the American Heart Association.

A new analysis of the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) trial examined gender differences in outcomes after treatment with angioplasty compared to stenting, with and without the antiplatelet agent abciximab, when women and men arrive at the hospital after a heart attack. The trial investigated the safety and efficacy of stents compared to angioplasty alone in heart attack patients.

In angioplasty, a small balloon-tipped catheter is inserted into a blocked artery, and then the balloon is inflated to open the artery. Stenting is performed in conjunction with angioplasty, wherein a mesh tube � called a stent � is positioned to help keep the unblocked artery open.

�Angioplasty is known to save lives in the setting of a heart attack and saves more lives of women than men,� said lead author Alexandra J. Lansky, M.D. �For every 1,000 patients treated with percutaneous coronary interventions, an estimated 56 deaths are prevented for women compared to 42 deaths prevented for men. There is a larger absolute benefit for women because of their higher risk profile.�

Lansky is director of clinical services for interventional cardiology at New York-Presbyterian Hospital/Columbia and associate professor of clinical medicine at Columbia University Medical Center in New York City and director of the Women�s Health Initiative at the Cardiovascular Research Foundation.

Based on the CADILLAC findings, Lansky suggested that stenting may be the preferred treatment choice for women with heart attack.

�Stenting is the best alternative among excellent treatment options for women,� she said. �There is no difference in the death rates between stenting and angioplasty, but stenting offers a substantial benefit by decreasing the recurrence rate of new blockages.�

The study involved 2,082 heart attack patients who arrived at the hospital within 12 hours after symptoms began. Patients were randomized into four treatment groups: 518 received balloon angioplasty, 528 received balloon angioplasty plus abciximab, 512 received stenting alone, while 524 received stenting plus abciximab. Women represented 27 percent of the study population, and their average age was 66. The average age for men in the study was 57.

Lansky said that more than 1 million Americans undergo angioplasty each year, but only 35 percent of these procedures are performed on women.

In this analysis, death rates were higher for women: 7.6 percent of women had died one year later compared to 3 percent of men. Also, rates of major adverse cardiac events were also higher for women at one year: 23.9 percent for women compared to 15.4 percent for men.

For the first time in a randomized, controlled clinical trial, stent use was found to significantly reduce major adverse cardiac events in women at one year, 19.1 percent for stents compared to 28.1 percent for balloon angioplasty. The need to re-intervene was reduced from 20.4 percent with balloon angioplasty to 10.8 percent with stents, a significant reduction.

Women in the study had more diabetes, hypertension and high cholesterol than men and were older than men.

The women represented a high-risk population with higher short and long-term death rates compared to men. This was explained by their older age, smaller body surface area, increased frequency of other diseases and risk factors, and the greater occurrence of in-hospital complications. Major adverse cardiac events remained greater in women than men.

The fact that the women had a smaller body size and smaller vessels �appears to be a critical factor that confers higher mortality risk in women,� Lansky said.

The study also noted that women waited longer by an average of 22 minutes to go to the hospital than men, and women had as much as a 15-minute longer delay once they arrived at the hospital until the time treatment was started.

Lansky called on women to go to the hospital as soon as they suspect the symptoms of heart attack. She urged the medical profession to speed evaluations and the time to treatment from the emergency room to the catheterization lab. This will help optimize treatment for women, she said.

Co-authors are Cody Pietras, BSc; Ricardo A. Costa, M.D.; Yoshihiro Tsuchiya, M.D.; Bruce R. Brodie, M.D.; David A. Cox, M.D.; Eve D. Aymong, M.D.; Thomas D. Stuckey, M.D.; Eulogio Garcia, M.D.; James E. Tcheng, M.D.; Roxana Mehran, M.D.; Manuela Negoita, M.D.; Martin Fahy, M.S.; Ecaterina Cristea, M.D.; Mark Turco, M.D.; Martin B. Leon, M.D.; Cindy L. Grines, M.D. and Gregg W. Stone, M.D.

The study was supported in part by Guidant Corporation and the Cardiovascular Research Foundation.

Editor�s note: The American Heart Association�s Go Red For Women program offers information and educational tools for women about heart disease. For more information, visit the Go Red For Women Web site or call 1-888-MY-HEART.

Statements and conclusions of study authors that are published in the American Heart Association scientific journals are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.

(NORTHBROOK, IL, August 8, 2005) - The American College of Chest Physicians (ACCP) released today the first evidence-based clinical practice guidelines for the prevention and management of postoperative atrial fibrillation (AF) after cardiac surgery. Published in the August issue of CHEST, the peer-reviewed journal of the ACCP, the guidelines offer specific recommendations on cardiac pacing, anticoagulation therapy, pharmaceutical prophylaxis, intraoperative interventions, and pharmacologic control of ventricular rate and rhythm. Atrial fibrillation, or irregular heartbeat, is a common condition that occurs increasingly with age and is one of the most frequent complications of cardiac surgery.

"Over one third of patients suffer from AF after cardiac surgery, which is associated with a higher risk of operative morbidity, increased hospital stay, and increased hospital cost," said Guidelines Co-Chair Peter P. McKeown, MBBS, MPH, MPA, FCCP, Veterans Affairs Medical Center, Asheville, NC. "Although previous guidelines have focused on the management of chronic AF, our guidelines are the first to address AF associated with cardiac surgery."

Through the Health and Science Policy Committee of the ACCP, the guidelines were developed by a multidisciplinary panel of experts in the fields of cardiothoracic surgery, cardiology, anesthesiology, and epidemiology. The panel included representatives from the ACCP, the American College of Cardiology, the Society of Thoracic Surgeons, and the American College of Surgeons. Based on a systematic review of randomized, controlled trials, panel members made graded recommendations based on the quality of evidence available and the net benefit of the intervention.

Recommendations center on the main issues that arise in managing patients with postoperative AF, including overall prevention; control of ventricular response rate; restoration of normal sinus rhythm; and prevention of thromboembolism and the role of anticoagulation. Overall, guidelines recommend the use of beta-blockers over calcium channel blockers, a standard therapy for chronic AF, for general prevention of postoperative AF and control of ventricular rate. Guidelines also recommend against the routine use of magnesium and digitalis for the prevention of postoperative AF. Amidarone may be considered for patients in whom beta-blockers are contraindicated and as therapy for postoperative sinus rhythm control. Atrial pacing, the use of a pacemaker to control arrhythmia, was found to reduce the incidence of AF after cardiac surgery; however, biatrial pacing is recommended over single atrial pacing. Additionally, mild hypothermia and heparin-coated circuits are recommended to reduce the occurrence of AF during intraoperative procedures. In regard to the prevention of thromboembolism, the guidelines recommend cautious anticoagulation therapy for patients in whom AF has persisted for more than 48 hours.

"Atrial fibrillation that develops after cardiac surgery places the patient at risk for thromboembolism and stroke, both which may require anticoagulants or blood-thinning agents to treat. Yet, cardiac surgery may increase a patient's tendency to bleed," said Guidelines Co-Chair David D. Gutterman, MD, FCCP, Medical College of Wisconsin, Milwaukee, WI. "Therefore, anticoagulation therapy should be carefully considered in the treatment of postoperative AF, with the risks of bleeding balanced with the risk of embolic stroke."

"The development and implementation of clinical practice guidelines allow clinicians to practice medicine based on the highest quality of data available," said Paul A. Kvale, MD, FCCP, President of the American College of Chest Physicians. "Although recommendations for the prevention and management of postoperative atrial fibrillation are intended to guide clinicians in their health-care decisions, they can be adapted to address issues of individual patient circumstance."
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To order a copy of American College of Chest Physicians Guidelines for the Prevention and Management of Postoperative Atrial Fibrillation After Cardiac Surgery, or for more information, contact the ACCP at (800) 343-ACCP (2227).

CHEST is a peer-reviewed journal published by the ACCP.
Article reviewed by:

Dr. Tamer Fouad, M.D.

Early diagnosis and new treatments can help battle heart failure -- a growing national problem that causes 1 million hospital admissions each year, according to new guidelines released today by the American College of Cardiology (ACC) and the American Heart Association (AHA).

The document is available today on the Web sites of the ACC (www.acc.org) and the AHA (www.americanheart.org) and will be published in the Sept. 20, 2005, issues of the Journal of the American College of Cardiology, and Circulation: Journal of the American Heart Association along with the ACC/AHA Clinical Performance Measures for Adults with Chronic Heart Failure and the ACC/AHA Key Data Elements and Definitions for Measuring Clinical Measurements and Outcomes of Patients with Chronic Heart Failure.

Noting that new treatment approaches may also improve the quality of life for patients, the authors classified heart failure on a scale from risk factors to end-stage disease:

* Stages A and B are when patients lack early signs or symptoms of heart failure, but are at risk because of risk factors or heart abnormalities, which could include a change in the shape or structure of the heart.
* Stage C denotes patients with current or past heart failure symptoms such as shortness of breath.
* Stage D designates patients with refractory heart failure who might be eligible for specialized advanced treatment -- including cardiac transplantation -- or compassionate end-of-life care such as hospice.

Nearly any form of heart disease may ultimately lead to heart failure. The guidelines stress that early recognition and proper treatment of high blood pressure, diabetes, coronary artery disease and other cardiovascular risk factors can help patients delay or avoid heart failure.

The key to prevention is to get the risk factors under control. For instance, studies have shown controlling hypertension can reduce the incidence of heart failure by 50 percent.

"More treatments have made our decision-making far more complex since the last ACC/AHA heart failure guidelines only four years ago," said Sharon Ann Hunt, M.D., F.A.C.C., professor of cardiovascular medicine at Stanford University Medical Center and chair of the writing group.

From 1990-99, the number of people hospitalized with a primary diagnosis of heart failure increased from 810,000 to more than 1 million. This was due to the population aging and to more people surviving heart attacks. Heart failure mostly affects the elderly, and more Medicare dollars are spent for heart failure diagnosis and treatment than for any other disease.

About 5 million U.S. residents are living with heart failure, and more than 550,000 people are diagnosed with the condition each year. In 2005 the disease will cost an estimated $27.9 billion in direct and indirect health care expenses, the authors write.

Some people may not realize one of the main symptoms of heart failure is becoming easily exhausted.

"We know there are many people walking around who think they are just out of shape or that they are just getting older, or that their ankles are swelling because it's hot," said co-author Mariell Jessup, M.D., F.A.C.C., medical director of the heart failure and cardiac transplantation program and professor of medicine at the University of Pennsylvania Medical Center in Philadelphia. "They don't appreciate that this may be due to heart failure."

The guidelines also change the name of the condition from congestive heart failure (CHF) to heart failure (HF) to reflect the broad spectrum of the disease. Congestion occurs when the heart cannot efficiently pump or eject blood from its chambers. This causes fluid build-up in the lungs and heart, resulting in stiff, fluid-filled lungs and shortness of breath. The panel dropped the word 'congestive' because people can have few or no symptoms of congestion, and still have a severely abnormal heart with symptoms of fatigue and exercise intolerance caused by poor cardiac output, Jessup said.

FITS for fun - create spectacular pictures in minute. In recent years, doctors have recognized that many people with normal ejection fraction have heart failure. This often occurs because the heart pumps properly, but fails to fill adequately with blood, a condition called diastolic heart failure. These patients rarely have been included in clinical trials of new drugs and devices in the past, but they are the subjects of several new, ongoing trials. These trials should help settle the issue of whether their treatment should be the same as that for patients with reduced ejection fraction.

"The second major point is that heart failure does not go away," Jessup said. "There are drugs that need to be used and medical care that needs to be done on a regular basis."

The committee also recommended left ventricular assist devices (LVADs) be considered as permanent or "destination" therapy in selected patients.

LVADs are implanted mechanical devices that help pump blood through the heart and can be used as a reasonable permanent therapy in some end-stage heart failure patients who are not candidates for transplants, don't respond to standard treatment and have a one-year survival outlook of less than 50 percent. The devices, which recently received U.S. Food and Drug Administration approval as permanent or "destination" therapy, were first used as a temporary measure to keep patients alive while awaiting a heart transplant. "It's going to be a whole new era in treating heart failure," Jessup said. "Eventually, we'll have portable artificial pumps that can take over the action of the heart."

Other recommendations:

* Expand the number of patients eligible for implantable cardioverter-defibrillators (ICDs), devices implanted under the skin that save lives by shocking chaotic heart rhythms back into a healthy pattern. ***
* Provide information on end-of-life issues. Although treatment advances can extend lives, heart failure is often fatal. The guidelines recommend that cardiologists broach the subject of hospice care -- support and comfort for dying patients and their families.

"There is a failure to recognize that end-stage heart failure patients frequently come in and out of the hospital over and over again and suffer a lot with really no impact on their ultimate survival," Jessup said. "I think using hospice is a way of improving the remaining days that these patients have. Hospice can be a very positive experience for patients and their families."

She acknowledged that this represents a new role for many cardiologists.

"Cardiologists aren't used to talking about hospice. They are more used to doing interventions. So it is a big shift," she said.

The guidelines also suggest that a new perspective on treating end-stage heart failure could result in a smoother, less stressful transition for patients and their families.
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Co-authors and members of the Heart Failure Guidelines Writing Committee: William T. Abraham, M.D., F.A.C.C.; Marshall H. Chin, M.D., M.P.H.; Arthur M. Feldman, M.D., Ph.D. F.A.C.C.; Gary S. Francis, M.D., F.A.C.C.; Theodore G. Ganiats, M.D.; Marvin A. Konstam, M.D., F.A.C.C.; Donna M. Mancini, M.D.; Keith Michl, M.D.; John A. Oates, M.D.; Peter S. Rahko, M.D., F.A.C.C.; Marc A. Silver, M.D., F.A.C.C.; Lynne Warner Stevenson, M.D., F.A.C.C; and Clyde W. Yancy, M.D., F.A.C.C.

Other organizations that participated in the development of the guidelines were the American Academy of Family Physicians, the American College of Physicians, the American College of Chest Physicians, the Heart Failure Society of America and the International Society for Heart and Lung Transplantation.

*** Editor's note: The final version of these guidelines have further expanded the number of patients who should be considered for ICDs, by adding the recommendation that patients with ishemic cardiomyopathy, functional class 1 with low ejection fraction be considered for ICD placement (MADIT II trial).
Article reviewed by:

Dr. Tamer Fouad, M.D.

Hospitalized patients with severe congestive heart failure did not experience a benefit from use of pulmonary artery catheterization, but had more adverse events, according to a study in the October 5 issue of JAMA.

Advances in medical therapy have improved outcomes for many ambulatory patients with heart failure and low ejection fraction (EF; a measure of how much blood the left ventricle of the heart pumps out with each contraction), according to background information in the article. However, each year an estimated 250,000 to 300,000 patients are hospitalized for heart failure with low EF, and the 1-year survival rate after hospitalization may be as low as 50 percent, even with recommended medical therapies. Recent studies have indicated that pulmonary artery catheters (PAC), a device used to monitor hemodynamic status and guide therapy, may increase the risk of death for hospitalized patients.

Lynne W. Stevenson, M.D., of Brigham and Women's Hospital, Boston, and colleagues with the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial, tested the hypothesis that for patients with severe heart failure, therapy guided by PAC monitoring and clinical assessment would lead to more days alive and fewer days hospitalized during 6 months compared with therapy guided by clinical assessment alone. The randomized controlled trial included 433 patients at 26 sites and was conducted from January 18, 2000, to November 17, 2003. Patients were assigned to receive clinical assessment and a PAC or clinical assessment alone. The primary goal in both groups was resolution of clinical congestion, with other targets based on levels of pulmonary artery and right atrial pressures.

The researchers found that therapy in both groups led to substantial reduction in symptoms, jugular venous pressure, and edema (swelling from fluid buildup). Use of the PAC did not significantly affect the primary end point of days alive and out of the hospital during the first 6 months (133 days vs. 135 days), death (43 patients [10 percent] vs. 38 patients [9 percent]), or the number of days hospitalized (8.7 vs. 8.3). In-hospital adverse events were more common among patients in the PAC group (47 [21.9 percent] vs. 25 [11.5 percent]). There were no deaths related to PAC use, and no difference for in-hospital plus 30-day mortality (10 [4.7 percent] vs. 11 [5.0 percent]). Exercise and quality of life end points improved in both groups with a trend toward greater improvement with the PAC, which reached significance for the time trade-off at all time points after randomization.

"Based on ESCAPE, there is no indication for routine use of PACs to adjust therapy during hospitalization for decompensation of long-term heart failure. It seems probable that there are some patients and some therapies that yield improved outcome with PAC monitoring and others with counterbalancing deleterious effects," the authors write. "For patients in whom signs and symptoms of congestion do not resolve with initial therapy, consideration of PAC monitoring at experienced sites appears reasonable if the information may guide further choices of therapy.

"The ESCAPE trial defined the most compromised patient population to be studied in an National Heart Lung Blood Institute heart failure trial with medical therapy, with 19 percent (83 patients) mortality at 6 months. No diagnostic test by itself will improve outcomes. New strategies should be developed to test both the interventions and the targets to which they should be tailored. Although most trials in a high-event population have focused on reducing mortality, patients with advanced heart failure express willingness to trade survival time for better health during the time remaining. How patients value their daily lives should help guide both the design and evaluation of new therapies," the authors conclude.

(JAMA.2005; 294:1625-1633).

Editor's Note: This research was supported by a contract from the National Heart, Lung, and Blood Institute to Duke University Medical Center.
Use of Pulmonary Artery Catheter in Critically Ill Patients Has Neutral Effect

A meta-analysis of previous studies indicates that use of a pulmonary artery catheter in critically ill patients neither increases risk of death or hospital stay or adds benefit, according to another article in this issue of JAMA.

The PAC is used to diagnose various diseases and physiological states, monitor the progress of critically ill patients, and guide the selection and adjustment of medical therapy, according to background information in the article. The PAC is often considered a cornerstone of critical care and a hallmark of the intensive care unit (ICU). Approximately 1 million PACs are used annually in the United States. However, despite widespread use of these devices, there is conflicting data about their effectiveness, and whether they increase risk of illness and death. Since the mid-1980s, randomized clinical trials (RCTs) have been conducted to evaluate the efficacy of the PAC. However, none of these trials have been persuasive individually, because they are limited by small sample sizes in heterogeneous populations. Despite the overwhelmingly negative outcomes of the literature, clinicians continue to use the PAC in ICUs based on personal experience and the belief that careful monitoring will improve decision making and clinical outcomes.

Monica R. Shah, M.D., M.H.S., of Columbia University Medical Center, New York, and colleagues performed a meta-analysis of recently published clinical trials testing the safety and efficacy of the PAC. The researchers located the RCTs, in which patients were randomly assigned to PAC or no PAC, from several databases. Eligible studies included patients who were undergoing surgery, in the ICU, admitted with advanced heart failure, or diagnosed with acute respiratory distress syndrome and/or sepsis; and studies that reported death and the number of days hospitalized or the number of days in the ICU as outcome measures. The researchers found 13 RCTs that included 5,051 patients.

"Our meta-analysis of 13 RCTs evaluating the safety and efficacy of the PAC demonstrates that use of the catheter neither improves outcomes in critically ill patients nor increases mortality or days in hospital. This provides a broader confirmation of the recent results of the ESCAPE trial, which showed that the routine use of the PAC in patients with advanced heart failure did not reduce or increase death or days in hospital," the authors write.

"During the past 60 years, the PAC has evolved from a simple diagnostic tool to a device that is used for monitoring and determining goal-directed therapy. Our meta-analysis shows that despite the widespread acceptance of the PAC, use of this device across a variety of clinical circumstances in critically ill patients does not improve survival or decrease the number of days hospitalized. � These results suggest that the PAC should not be used for the routine treatment of patients in the ICU, patients with decompensated heart failure, or patients undergoing surgery until or unless effective therapies can be found that improve outcomes when coupled with this diagnostic tool," the authors conclude.

(JAMA.2005; 294:1664-1670).

Editor's Note: This meta-analysis was funded by the Duke Clinical Research Institute.

Editorial: Searching for Evidence to Support Pulmonary Artery Catheter Use in Critically Ill Patients

In an accompanying editorial, Jesse B. Hall, M.D., of the University of Chicago, comments on the articles in this week's JAMA on PAC.

"What is the evidence for the broader issue of PAC use in the ICU and perioperative setting? The data collected to date certainly do not support routine use of the catheter in any patient group, and the currently available information could be viewed as justifying 'pulling the pulmonary artery catheter' from routine use, a suggestion made almost 10 years ago. One important additional trial is nearing completion and evaluates the use of PAC in patients with adult respiratory distress syndrome."

"Should there be a positive result attributable to PAC in this trial, a specific niche for this technology may remain in critical care. If the results of this soon-to-be-completed trial show no benefit of PAC monitoring, it is likely that the available data will indicate that it is time to remove the catheter from widespread use, or at the very least relegate this former common monitoring tool to salvage therapy of an extremely small and select number of patients. The need to question the routine use of this monitoring modality was quite real and the results of the last 5 years of study most valuable. Once again the community of critical care physicians has been edified by the approach of 'Don't just do something, stand there! And then think about it. �'" Dr. Hall concludes.

(JAMA.2005; 294:1694-1695.

Use of the amino acid supplement L-arginine following a heart attack does not improve certain cardiac functions and measurements and may be associated with an increased risk of death, according to a study in the January 4 issue of JAMA.

L-arginine is a widely available dietary supplement and is publicized as having benefits for patients with hypertension, angina, heart failure and sexual dysfunction, according to background information in the article. Prior studies suggest that L-arginine has the potential to reduce vascular (blood vessel) stiffness.

Steven P. Schulman, M.D., of Johns Hopkins Medical Institutions, Baltimore, and colleagues conducted the Vascular Interaction with Age in Myocardial Infarction (VINTAGE MI) clinical trial to test whether administering L-arginine to patients following a first ST-segment elevation myocardial infarction (STEMI; a certain pattern on an electrocardiogram following a heart attack) over a 6-month period would decrease vascular stiffness and improve ejection fraction (a measure of how much blood the left ventricle of the heart pumps out with each contraction).

The randomized, double-blind, placebo-controlled trial included 153 STEMI patients; 77 were 60 years or older. Participants were enrolled from February 2002 to June 2004. Patients were randomly assigned to receive L-arginine (goal dose of 3 g three times a day) or matching placebo for six months.

The researchers found: "The VINTAGE MI study demonstrated that 6 months of L-arginine added to standard postinfarct medications did not reduce noninvasive measures of vascular stiffness, improve ejection fraction, or improve clinical outcomes. To the contrary, we noted a possible increased risk of death in older patients after infarction while taking L-arginine compared with those taking a placebo, leading to the early termination of the study. These findings have broad public health implications given the increasing availability and use of L-arginine in patients with and without established cardiovascular diseases."
Death occurred in 6 patients (8.6 percent) in the L-arginine group died during the 6-month study period vs. none in the placebo group.

"In conclusion, L-arginine therapy should not be given to patients following a myocardial infarction. It neither alters noninvasive measures of vascular stiffness nor improves left ventricular function. L-arginine therapy in older patients with diffuse atherosclerosis may worsen clinical outcomes," the authors write.
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JAMA.2005; 295:58-64

Studies examining the association between coffee consumption and risk of myocardial infarction (MI � heart attack) have been inconclusive. Coffee is a major source of caffeine, which is the most widely consumed stimulant in the world and has been implicated in the development of cardiovascular diseases such as heart attack, according to background information in the article. However, coffee contains a number of other chemicals that have variable effects on the cardiovascular system. It is not clear whether caffeine alone affects the risk of heart attack or whether other chemicals found in coffee may be responsible. Caffeine is metabolized primarily by the enzyme cytochrome P450 1A2 (CYP1A2) in the liver. Variations of the gene for this enzyme can slow or quicken caffeine metabolism. Carriers of the gene variant CYP1A2*1F allele are "slow" caffeine metabolizers, while individuals with the gene variant CYP1A2*1A allele are "rapid" caffeine metabolizers.

Ahmed El-Sohemy, Ph.D., of the University of Toronto, and colleagues conducted a study to determine whether gene variations of CYP1A2 modifies the association between consumption of caffeinated coffee and risk of nonfatal heart attack. The study included 2,014 case patients with a first acute nonfatal heart attack and 2,014 controls, living in Costa Rica between 1994 and 2004. The genotypes of the participants were determined. A food frequency questionnaire was used to assess the intake of caffeinated coffee.

Fifty-five percent of cases (n = 1,114) and 54 percent of controls (n = 1,082) were carriers of the slow *1F allele. For carriers of the slow *1F allele, those who drank 2 to 3 cups of coffee a day had a 36 percent increased odds of heart attack; those who drank 4 or more cups per day had a 64 percent increased odds of heart attack. Corresponding consumption for individuals with the rapid *1A/*1A genotype resulted in the reduced odds of heart attack by 22 percent and 1 percent, respectively.

Among the slow metabolizers, younger individuals showed an increased risk. The risk associated with drinking 4 cups/d or more compared with less than 1 cup/d increased from 2-fold for individuals younger than 59 years to more than 4-fold for those younger than 50 years. Among the fast metabolizers who were younger than 59 years of age, those who drank 1 cup/d or 2 to 3 cups per day had a reduced odds of a heart attack by 52 percent and 43 percent, respectively.

"In summary, consistent with most case-control studies, we found that increased coffee intake is associated with an increased risk of nonfatal MI. The association between coffee and MI was found only among individuals with the slow CYP1A2*1F allele, which impairs caffeine metabolism, suggesting that caffeine plays a role in the association," the authors conclude.
Source

JAMA. 2006;295:1135-1141.

If you're middle age and sleep five hours or less a night, you may be increasing your risk of developing high blood pressure, according to research reported in Hypertension: Journal of the American Heart Association.

"Sleep allows the heart to slow down and blood pressure to drop for a significant part of the day," said James E. Gangwisch, Ph.D., lead author of the study and post-doctoral fellow at Columbia University's Mailman School of Public Health.

"However, people who sleep for only short durations raise their average 24-hour blood pressure and heart rate. This may set up the cardiovascular system to operate at an elevated pressure."

Gangwisch said that 24 percent of people ages 32 to 59 who slept for five or fewer hours a night developed hypertension versus 12 percent of those who got seven or eight hours of sleep. Subjects who slept five or fewer hours per night continued to be significantly more likely to be diagnosed with hypertension after controlling for factors such as obesity, diabetes, physical activity, salt and alcohol consumption, smoking, depression, age, education, gender, and ethnicity.

The researchers conducted a longitudinal analysis of data from the Epidemiologic Follow-up Studies of the first National Health and Nutrition Examination Study (NHANES I). The analysis is based on NHANES I data from 4,810 people ages 32 to 86 who did not have high blood pressure at baseline. The 1982-84 follow-up survey asked participants how many hours they slept at night. During eight to 10 years of follow-up, 647 of the 4,810 participants were diagnosed with hypertension.

Compared to people who slept seven or eight hours a night, people who slept five or fewer hours a night also exercised less and were more likely to have a higher body mass index. (BMI is a measurement used to assess body fatness). They were also more likely to have diabetes and depression, and to report daytime sleepiness.

"We had hypothesized that both BMI and a history of diabetes would mediate the relationship between sleep and blood pressure, and the results were consistent with this," Gangwisch said.

Sleep deprivation has been shown previously to increase appetite and compromise insulin sensitivity

Short sleep duration was linked to a new diagnosis of high blood pressure among middle-aged participants, but the association was not observed among people age 60 or older, he said. Gangwisch said the differences between the younger and older subjects might be explained by the fact that advanced age is associated with difficulties falling and staying asleep. Another factor could be that subjects suffering from hypertension, diabetes, and obesity would be less likely to survive into their later years.

Among study limitations, researchers found that high blood pressure often goes undetected. An analysis of NHANES III data showed that over 30 percent of people who had high blood pressure didn't know they had it.

Since the study is based on observational data, Gangwisch said more research is needed to confirm the association between short sleep duration and high blood pressure. "We need to investigate the biological mechanisms and, if confirmed, design interventions that will help people modify sleep behavior," he said.

Gangwisch said the study's main message is clear: "A good night's sleep is very important for good health."

Chest pain is one of the common complaints heard in medical OPDs as well as at the GP�s clinic. Chest pain causes a lot of anxiety in the patient as it is many a time related to �heart attack� or angina and people are quite aware of the serious consequences of the symptom. Anyone having a chest pain would first think of the heart and would like to know if he/she is having a �heart attack�.

However not all times is a chest pain necessarily originating from or caused by diseases of the heart. There are plenty of other structures in the thoracic cavity and a systematic approach is needed to arrive at the correct diagnosis or in other words to find out the �real culprit� causing the chest pain.

Of special importance is the issue of chest pain in women, as this group is less liable to get heart disease till menopause. Estrogen is said to confer a protective effect and prevents the development of atherosclerosis. Myocardial infarction or Coronary artery disease (CAD) is very rare in menstruating women. As menopause approaches and estrogen levels go down, the probability of development of CAD catches up with those in men.

Even then, there are lots of young to middle aged, menstruating women complaining of chest pain and quite distressed about it. Before I highlight the special features of this particular issue lets first review the differential diagnosis of chest pain.

Differential Diagnosis of Chest Pain

1. Angina Pectoris/Myocardial Infarction

2. Other Cardiovascular Causes

a. Possibly Ischemic Pain

1) Aortic Stenosis
2) Hypertrophic Cardiomyopathy
3) Severe Systemic Hypertension
4) Severe Right Ventricular Hypertension
5) Aortic Regurgitation
6) Severe Anemia/hypoxia

b. Non Ischemic in Origin

1) Aortic Dissection
2) Pericarditis
3) Mitral Valve Prolapse

3. Gastrointestinal

a. Esophageal Spasm
b. Esophageal Reflux
c. Esophageal Rupture
d. Peptic Ulcer Disease

4. Psychogenic

a. Anxiety
b. Depression
c. Cardiac Psychosis
d. Self Gain

5. Neuromusculoskeletal

a. Thoracic Outlet syndrome
b. Lesions of Cervical/Thoracic Spine
c. Costochondritis[Tietze�s Syndrome]
d. Herpes Zoster
e. Chest wall pain

6. Pulmonary

a. Pulmonary Embolus/Infarction
b. Pneumothorax
c. Pneumonia with pleural involvement

7. Pleurisy

As most patients are anxious of their chest pain being that of Heart origin, we shall first have a look at the features of Cardiac Pain.

Clinical features of Angina Pectoris and Myocardial Infarction

Cardiac Pain or Angina Pectoris ( reversible loss of blood supply to the heart muscle) is retrosternal, vague, poorly localized, heavy, compressive, squeezy feeling. It rarely lasts less than 1 minute or more than 20 minutes, unless it is a heart attack. Patients get prompt relief in less than 5 minutes on cessation of all activities or use of sublingual nitrates. Angina pain can also be in the left shoulder, left arm, neck or the jaws.

Pain of a Myocardial Infarction ( total sudden blockage of an artery supplying blood to the heart muscle) would be similar to this but more severe and can last longer, will not be relieved by rest or sublingual nitrate and associated with palpitation, perspiration, nausea/vomiting, dizziness, blackout or even collapse.

Pain that is unlikely to be of cardiac origin is typically well localized, sharp, pricky, lancinating type sometimes lasting less than 15 seconds. It can be aching type too but mostly will be aggravated on deep inspiration and coughing. Patient will be able to localize it with the tip of her finger.

Pain that is localized just below left nipple is almost NEVER of cardiac origin.

Common causes of chest pain in young females

1. Valvular Heart Disease

Mitral Prolapse: This is a common and benign condition. Leaflets of the Mitral valve are long, bulky and redundant. They prolapse into the left atrium during systole. It is unknown how this causes chest pain. Suffice to say that the pain occurs at rest, is sharp, non- radiating and prolonged in duration.

Rheumatic Valve Disease: Mitral stenosis is a common rheumatic valve condition in females and can cause chest pain and dyspnea. The patient will have associated cough, expectoration, there would be a low pitched rumbling diastolic murmur which will clinch the diagnosis. A 2D echocardiography will be confirmatory.

2. Anxiety/Depression

There are a lot of personal/social causes for a young female to get into a vicious cycle of anxiety causing various physical symptoms, and those symptoms in turn causing more anxiety. Depression also causes �somatization� and produces various symptoms, chest pain being one of them. This chest pain can take any form; it can even mimic Anginal pain accurately. One needs to rule out organic causes before stamping the diagnosis of anxiety/depression.

3. Neuromusculoskeletal

The pain is very well localized, tender on touch, aggravated on deep inspiration, and not aggravated on exertion. Underlying cause can be pinpointed by suitable investigations like X ray of cervical spine, chest (thoracic outlet syndrome) etc. Pain of herpes Zoster sometimes defies diagnosis until the rash develops.

4. Gastrointestinal

Esophageal reflux is one of the most common causes of retrosternal pain. The pain is mostly burning in nature, occurs more often in reclining posture, and is relieved by assuming upright position. It is more frequent after an oily, heavy meal. Esophageal spasm is a variety of the same disease. Sometimes peptic ulcer disease can also cause pain in lower chest.

5. Pulmonary

Pulmonary cause of chest pain in young female could be a pulmonary embolism/infarct caused by deep vein thromboembolism resulting from oral contraception usage. The pain is acute, severe and patient generally is in a critical condition.

Pneumonia can also cause chest pain if there is pleural involvement with it, which usually is the case.

Pneumothorax, which is rupture of a lung alveolus into the pleural cavity will cause sudden acute filling up of air pressure in pleura and will cause severe acute chest pain if it is Tension Pneumothorax and moderate dull aching pain if it is simple Pneumothorax.

6. Pleurisy

Tubercular involvement of the pleura is called pleurisy. The pain is sharp stab like, occurring on slightest act of breathing. Associated features are low grade fever, cough, and malaise, loss of appetite and loss of weight.

Chest pain in a young female has lots of reasons as we have seen. Most of the time they are not of cardiac origin. A thorough clinical examination, appropriate investigations, and reassurance will go a long way in resolving this issue.

Dr. Apurva Madia

References

1. Hurst�s The Heart. 11th Edition, Mcgrow Hill. P 219

2. Sullivan J I: Are menstruating women protected from heart disease because of or in spite of Estrogen? Relevance to the iron hypothesis. Am Heart J 145:190, 2003

3. Mikkola B, Clarkson TB: Estrogen replacement therapy, atherosclerosis and vascular function. Cardiovasc Res 53: 605, 2002

4. Douglas PS, Ginsberg GS: The evaluation of chest pain in women. N Eng J Med 334: 1311, 1996.

5. Marroquin OC, Hloubkov R, Edmindowocz D et al: Heterogenity of microvascular dysfunction in women with chest pain not attributable to coronary artery disease: Implication for clinical practice. Am Heart J 145: 628, 2003.

6. D�Anton B, Dupis G, Fleet R et al: Sex differences in chest pain & predilection of exercise induces ischemia. Can J Cardiol 19:515, 2003

Source : http://www.doctorslounge.com/cardiology/articles/ischemic_heart/women_chest_pain/index.htm