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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 Related
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
years on average, will end in 2006.

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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 Related
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.

Back to Infectious Disease Articles

Oral sex may be a risk factor for

nongonococcal urethritis (NGU),
one of the most common sexually
transmitted diseases affecting both
Related
men and women, according to a
 new study in the February 1 issue of the Journal of Infectious
Diseases, now available online.

The study, by Australian researchers Catriona Bradshaw, MD, and colleagues at the
Melbourne Sexual Health Centre, is the first major case-control study to simultaneously
address all currently hypothesized causes of NGU. The findings help to identify areas for
future research on the causes of NGU, and suggest that treatment decisions should be
based on clinical features of the disease--not just microscopic assessment. The study also
is the first to demonstrate that the causes of NGU in men who have sex with other men
are similar to those found in heterosexual men.

NGU is caused by a number of different organisms (most notably, Chlamydia

trachomatis) and may lead to pelvic inflammatory disease, infertility, and chronic pelvic
pain. Though the cause of NGU is sometimes known, and antibiotics (azithromycin or
tetracycline) are generally effective, about half of all cases have no identifiable cause
a fact that makes treatment frustrating and uncertain for physicians and patients. Results
of previous studies show that Chlamydia trachomatis causes between 30 percent to 50
percent of cases of NGU and Mycoplasma genitalium, 10 percent to 30 percent.

From March 2004 to March 2005, the Melbourne team studied 329 men with NGU and
307 men without symptoms of urethritis. All subjects were given a sexual practice
questionnaire. The men in the study underwent a urethral smear, and provided a first-
stream urine specimen, which was tested for pathogens that may have caused NGU.

Chlamydial infection was common in both heterosexual and homosexual men with NGU
(22 percent and 15 percent, respectively) and was far more common than in control
groups. C. trachomatis and M. genitalium were associated with unprotected vaginal sex.
M. genitalium (9 percent), adenoviruses (4 percent), and herpes simplex type 1 (2
percent) were more common in NGU patients than in controls, after adjusting for age and
risk, which suggests that these organisms may be causes of NGU.

Adenoviruses and herpes simplex type 1 were associated with oral sex and sex between
male partners, suggesting that oral-genital contact may be an important mechanism of
NGU pathogen transmission. Additionally, NGU was associated with history of oral sex
with new partners. Together, these findings suggest that fellatio plays a significant role as
a cause of the syndrome.

In an accompanying editorial, H. Hunter Handsfield, MD, of the Battelle Center for

Public Health Research and Evaluation and the University of Washington, called the
landmark Melbourne study "a good interim step" whose findings "significantly advance
the field," but points out that many important questions remain yet to be answered.

The study provides important insight for both heterosexual and homosexual men, as it
indicates that NGU may be caused by otherwise harmless organisms shared by
monogamous partners. According to Handsfield, this finding may influence clinical
management of partners and counseling of couples. In addition, oral sex was associated
with NGU in which no pathogen was detected, indicating that there are causes of NGU
that have yet to be identified. The study also found that type 1 herpes simplex virus
(HSV-1), the usual cause of oral herpes (cold sores), accounted for more NGU cases than
did HSV-2; that herpetic NGU was most commonly associated with fellatio; and that up
to a third of NGU cases associated with known pathogens were not associated with
increased numbers of white blood cells in urethral secretions.

Back to Hematology Articles

CHICAGO Elderly people with the

lowest and highest hemoglobin
concentrations (the component of
red blood cells that carries oxygen)
are at increased risk of death,
according to a study in the October Related
24 issue of Archives of Internal
Medicine, one of the
JAMA/Archives journals.

Increasing evidence indicates that anemia is common in the elderly population, but few
studies have assessed the association of anemia with clinical outcomes, such as illness
and death, according to background information in the article. Anemia is defined by the
World Health Organization (WHO) as a hemoglobin concentration of less than 12 g/dL
(grams per one tenth liter) for women and less than 13 g/dL for men.

Neil A. Zakai, M.D., of the University of Vermont College of Medicine, Burlington,

compared the association of hemoglobin concentration and anemia status with subsequent
death over the course of eleven years in elderly adults living in four U.S. communities.
Hemoglobin concentrations were determined for participants recruited between 1989 and
1993. Participants were contacted biannually; telephone and clinic examinations were
conducted alternately. Deaths were reviewed and classified as cardiovascular or
noncardiovascular. Complete follow-up was available through June 2001 for this
analysis.

Hemoglobin concentration was analyzed in two ways: by dividing the participants'

baseline hemoglobin into five equal levels and by the WHO criteria for anemia. Based on
the WHO criteria for anemia, 498 individuals were anemic on enrollment (8.5 percent of
the 5,797 included in the analysis), the researchers report. The hemoglobin concentration
for the 1,205 individuals in the lowest fifth was higher than the WHO criteria for anemia,
and 41.3 percent of these 1,205 people did qualify as anemic by WHO standards.

"In this elderly cohort, the prevalence of anemia was 7.0 percent among white and 17.6
percent among black individuals," the authors write. "After 11.2 years of follow-up,
lower hemoglobin concentrations were associated with increased mortality risk,
independent of many potentially confounding factors. The magnitude of this association
was similar whether the lowest quintile [fifth] of hemoglobin or the WHO criteria for
anemia was used; however, the number of participants was much larger when considering
the lowest quintile of hemoglobin concentration." Another finding of the study was that
there was also elevated mortality among those in the highest hemoglobin quintile, even
after extensive adjustment for other factors.

"In conclusion, a lower hemoglobin concentration was independently associated with

mortality in this elderly cohort," the authors write. "The bottom hemoglobin quintile
defined a larger group at risk than anemia status based on WHO criteria. Future areas of
investigation should determine the optimal hemoglobin value that defines an abnormal
concentration in elderly individuals, study the causes of low hemoglobin concentrations
in elderly individuals and how these relate differentially to outcomes, evaluate the causes
of increased mortality in individuals with low and high hemoglobin concentrations, and
assess whether treatment of low hemoglobin in the general population reduces mortality."

###

(Arch Intern Med. 2005; 165: 2214-2220).

Editor's Note: This research was supported by contracts from the National Heart, Lung,
and Blood Institute, Bethesda, Md. Dr. Cushman has received research funding in the
form of a subcontract with the University of Alabama funded by Amgen; the project is
not related to this article.

Editorial: Anemia in the Elderly

Time for New Blood in Old Vessels?

In an accompanying editorial, Jerry L. Spivak, M.D., of The Johns Hopkins University

School of Medicine, Baltimore, Md., writes, "The four articles in this issue of the
Archives usefully highlight and advance our conceptions of the cause of anemia in the
elderly and anemia's health-related impact. Anemia, of course, is always the consequence
of another disorder, and correction of the underlying disorder is the most effective means
of alleviating the anemia. However, anemia in the majority of the elderly is caused by
conditions such as chronic renal insufficiency, chronic inflammation, cancer, or bone
marrow failure, some of which are actually an aftermath of the aging process and most of
which defy correction. It is now also well established that anemia frequently exacerbates
the illness causing it, while having its own independent adverse effects."

"What remains to be determined is whether pharmacologic correction of anemia can

slow disease progression, reduce morbidity [illness], improve quality of life, and prolong
survival, and whether there is a favorable cost-benefit ratio to society for such
improvements," Dr. Spivak continues. "Recent failed attempts to answer these questions
in the setting of renal failure or cancer indicate that this will not be an easy task, but the
prospect of a doubling in the number of elderly persons over the next 25 years indicates
that it is a task that cannot be ignored or deferred."

(Arch Intern Med. 2005; 165: 2187-2189).

Back to Surgery Articles

Obesity surgery translates to cardiac benefit

Saturday 8th April, 2006

ATLANTA, GA -- As rates of obesity in

America continue to soar, surgery
has become an increasingly popular Bariatric surgery is now an approved
solution when diet and exercise for class II-III obesity and may
regimens fail. Bariatric surgery is decrease risk of heart disease.
now an approved therapeutic
intervention for class II-III obesity,
and may correlate to improved risk Related
for heart disease.

In a study presented at the American College of

Cardiology's 55th Annual Scientific Session, a team of researchers from the Mayo Clinic
in Minnesota evaluated the effect of bariatric surgery on longterm cardiovascular risk and
estimated prevented outcomes. ACC.06 is the premier cardiovascular medical meeting,
bringing together over 30,000 cardiologists to further breakthroughs in cardiovascular
medicine.

The team completed a historical study between 1990 and 2003 of 197 patients with class
II-III obesity who undertook Roux-en-Y gastric bypass surgery (sometimes referred to as
"stomach stapling"), compared to 163 control patients enrolled in a weight reduction
program. With an average follow-up time of 3.3 years, the team recorded changes in
cardiovascular risk factors such as cholesterol levels, body mass index (BMI) and
diabetes criteria.

Though the team originally estimated a higher 10-year risk for cardiac events in the
surgical group at the start of the study due to their associated conditions, researchers
found at follow-up that the patients had a much lower risk than the control group for
having a heart complication (18.3 vs. 30 percent). Using the study parameters and risk
models based on previously published data, the team estimated that for every 100
patients, the surgery would prevent 16.2 cardiovascular events and 4.1 overall deaths, as
compared to the control group. However, should the number of deaths during surgery
approach 4 percent, the protective effect is limited, as may be in the case in centers with
very low volumes of weight loss surgeries.

In reviewing the cardiovascular risk factors calculated during the study, the team found
that at follow-up, the percentage of the surgery population meeting criteria for diabetes
was reduced from 30 percent (59 pts) to 11 percent (19 pts), and also showed reductions
in blood pressure, LDL cholesterol and BMI.

"With an understanding of the very close link between obesity and cardiovascular risk,
we feel confident that a procedure like bariatric surgery is an effective alternative to
current therapies, which can have a considerable and lasting improvement in cardiac
health," said John Batsis, M.D., of the Mayo Clinic, and lead author of the study. "For the
patients who are eligible for surgery, this suggests a reduced risk of cardiac events or
death."

Sources