Beta blockers may be of benefit in patients with advanced heart
failure and preserved left ventricular ejection fraction (LVEF), say
researchers in the Netherlands.

"This prospective observational study is the first to indicate that
treatment with beta blockers reduces mortality in patients with
advanced HF and preserved LVEF," say Dr Daniela Dobre (Northern
Centre for Healthcare Research, University Medical Centre Groningen,
the Netherlands) and colleagues in their paper in the European
Journal of Heart Failure.

However, they warn that the favorable effects of beta blockers in
this population of heart failure patients needs to be confirmed in
prospective, randomized clinical trials. Dobre told heartwire that a
number of studies of this nature are underway, including the
Japanese Diastolic Heart Failure Study.

Mortality almost halved by beta blockers

Dobre explained to heartwire that most patients who have heart
failure with preserved LVEF also have diastolic dysfunction, but
that this is not always the case and therefore the term "diastolic"
heart failure is disputed. In general, patients who have heart
failure with preserved LVEF are older, more likely to be female and
have hypertension than patients with heart failure and reduced EF.

There is clear evidence that beta blockers increase survival in HF
patients with reduced EF, she notes, but only two prior studies have
looked at beta blockers in HF with preserved EF, including the
EuroHeart Failure Survey, an observational study with only short-
term results (3 months), and a small randomized controlled trial of
propranolol, published in 1997.

"No large randomized trial or cohort study addressing the role of
beta blocker therapy in HF with preserved LVEF has yet been
completed. Such information is particularly important given the high
percentage of patients with [this type of] HF ?and the lack of
evidence-based recommendations for its management," she and her
colleagues observe.

Despite the paucity of guidance on the treatment of patients with HF
and preserved EF, Dobre said that in practice many of these patients
are on a beta blocker anyway because of hypertension.

They prospectively studied a cohort of 443 patients with advanced HF
and preserved LVEF (mean age 78 years, 56% female) who were admitted
to Rijnland General Hospital, Leiderdrop, the Netherlands between
January 2000 and June 2005. Overall 227 patients had a beta blocker
prescribed at discharge ?including carvedilol (up to a dose of
50mg/day), metoprolol (up to 200mg), bisoprolol (up to 10mg) or
nebivolol (up to 10mg). Follow-up was calculated from the day of
discharge until July 2005. Deaths were obtained from hospital
records, next-of-kin review or by telephone.

They note that their study population was "real life" ?for example,
they included patients with renal failure ?and so the results "may
be extrapolated to daily practice in patients with advanced HF and
preserved LVEF."

Results of a study provide more evidence that elderly patients with
acute coronary syndromes (ACS) derive as much, if not greater,
benefit from intensive lipid lowering as their younger counterparts.

Dr. Kausik K. Ray from the TIMI Study Group, Boston, Massachusetts,
and colleagues assessed the impact of achieving the National
Cholesterol Expert Panel (NCEP) optional LDL-C goal of < 1.8 mmol/L
(70 mg/dL) in ACS patients aged 70 or older who participated in the
PROVE IT-TIMI 22 statin treatment trial. Their findings appear in
the European Heart Journal for October.

In the post hoc analysis, among 634 elderly patients prescribed a
statin at hospital discharge for ACS, reaching the NCEP optional LDL-
C goal was associated with a significant 8% absolute reduction and a
40% relative reduction in risk of death, MI, or unstable angina,
compared with not reaching this low target.

Among 3,150 ACS patients younger than 70 years, the respective
reductions in risk associated with reaching the NCEP optional goal
were 2.3% and 26%.

Because the risk of events after ACS is much higher in the elderly
relative to younger patients, achievement of the NCEP optional LDL-C
target translated into greater benefits, comparatively, the team
notes.

The researchers estimate that achievement of the NCEP optional LDL-C
goal could prevent 80 acute events (death, MI or unstable angina)
over 2 years for every 1,000 elderly ACS patients treated compared
with 23 events per 1,000 younger patients.

"The incidence of major side effects among the elderly was similar
to that in younger patients and did not differ with the intensity of
the statin regimen," Dr. Ray and colleagues note.

"Routine use of statin therapy at hospital discharge after ACS and
achieving the NCEP LDL-C optional goal could be a simple and
effective secondary prevention strategy among the elderly," they
conclude.

Euro Heart J 2006;27:2310-2316

The average daily risk range (ADRR), a measure computed from an
individual's self-monitored blood glucose readings, is useful in
predicting both hypoglycemia and hyperglycemia, according to a
report in the November issue of Diabetes Care.

Maintaining well controlled blood glucose levels is important, and
there is a need for measures that accurately predict both high and
low blood glucose levels, the authors note.

Dr. Boris P. Kovatchev, from the University of Virginia Health
System in Charlottesville, and colleagues created the ADRR after
analyzing blood glucose data from 39 type 1 and 31 type 2 diabetics.

In their paper, the team gives the formulas for computing the ADRR
from 2-4 weeks of self-monitored blood glucose data, with readings
obtained at least 3 times daily.

The development measure was then tested in a validation cohort of
254 type 1 and 81 type 2 diabetics. In the validation cohort, the
ADRR and standard predictive measures, such as the daily blood
glucose range, were tested for their ability to predict blood
glucose variability in the next 3 months.

The authors found that the ADRR was better than the other measures
in predicting both high and low blood glucose levels. Across the
ADRR risk categories (low, moderate, and high), the likelihood of
hypoglycemia and hyperglycemia rose by 6-fold and 3.5-fold,
respectively.

"As a measure of glycemic variability that could be calculated
frequently and tracked over time, the ADRR has promise in
facilitating the provision of clinical relevant information to
patients and clinicians," the authors state. Additional research is
needed to determine if ADRR determination and feedback actually
translates into improved glycemic control, they add.

Diabetes Care 2006;29:2433-2438

Intervention studies employing counseling or education for the
primary prevention of coronary heart disease have no impact on
mortality and little effect in terms of clinical events, according
to a new updated review.


Dr Shah Ebrahim (London School of Tropical Medicine, UK) and
colleagues report their findings in the October 18, 2006 Cochrane
Database of Systematic Reviews. "The use of 'health-promotion'
techniques of one-to-one or family-oriented information and advice
on a range of lifestyles given to people at relatively low risk of
cardiovascular disease is not particularly effective in terms of
reducing the risk of clinical events," they comment.


"What our study shows is that we should be targeting health-
promotion activities to those at high risk, which might be of more
value than general health promotion for everyone," Ebrahim told
heartwire. "We need a rethink about how we do health promotion."


Drug therapies benefited those at greatest risk most
Ebrahim explained that his team first conducted a review of studies
in this field up to 1995 and for this update they further searched
to 2001. But he was disappointed to find that there had been "no
really big health-promotion trials with clinical end-point outcomes
conducted recently. This review really represents trials done in the
1960s, 1970s, and 1980s," he said.


Ten intervention trials with clinical end points that used
counseling or education to modify more than one cardiovascular risk
factor in adults from general populations, occupational groups, or
high-risk groups were included.


The pooled odds ratios for total and CHD mortality were 0.96 and
0.96 respectively. Net changes in systolic and diastolic blood
pressure and blood cholesterol were -3.6 mm Hg, -2.8 mm Hg, and -
0.07 mmol/L respectively. Odds of reduction in smoking prevalence
was 20%.

Some of the studies did include drug treatment, and in these the
clearest benefits seen were with use of antihypertensives and
cholesterol-lowering agents, with those participants at greatest
risk benefiting most.

Cardiologists must take note of prevention
However, Ebrahim stressed to heartwire that taking drugs to prevent
cardiovascular events "is a lifelong occupation, and these drugs are
not without hazard; in fact, many of them have quite unpleasant side
effects, and people just don't take them long term. In addition,
they cost money, and drug-based solutions for the whole population
are eye-wateringly expensive."

He also points out that the findings stand in contrast to those from
secondary-prevention studies, which show around a 20% reduction in
deaths when people change their lifestyles. "People who have had an
MI are highly motivated," he observes.


Ebrahim believes that cardiologists are not particularly interested
in prevention, but they should be. "This is not just the preserve of
public-health officials or primary-care doctors, it's everybody's
business.

"We need to try and change people's mind-set. Those in their 20s,
30s, and 40s need to stop smoking and exercise regularly or they are
building up problems for the future. And the whole environment in
which we live is wrong. We are too sedentary, and our diet is
wrong."

Noninvasive assessment of coronary artery disease by coronary 64-
slice multidetector computed tomography (MDCT) can be used for
ruling out ACS in subjects presenting with chest pain to the
emergency department and may be useful for improving early triage, a
new study suggests.


The study, published online in Circulation on October 30, 2006, was
conducted by a team led by Dr Udo Hoffman (Massachusetts General
Hospital, Boston, MA). They explain that accurate triage of patients
presenting with acute chest pain to the emergency department remains
difficult because chest-pain history, a single set of biochemical
markers for myocardial necrosis, and the initial 12-lead ECG, alone
or in combination, cannot identify a group of patients who can be
safely discharged without further diagnostic testing. As a
consequence, more than 60% of patients with chest pain who are
admitted to the hospital turn out not to have ACS. In addition, the
rate of missed diagnosis of ACS remains unacceptably high (2% to 8%).


They point out that as coronary artery disease is the major
underlying cause of ACS, a noninvasive method that quickly and
accurately excludes the presence of CAD could substantially improve
the ability to triage patients with chest pain and that MDCT could
be the answer. This scan requires patients to be injected
intravenously with a contrast agent and to hold their breath during
the 15-second exam.


CT results matched eventual clinical diagnosis

In the current study, patients presenting with chest pain to the
emergency department underwent MDCT for the assessment of coronary
atherosclerotic plaque and significant coronary artery stenosis. An
expert panel, blinded to the CT data, determined the presence or
absence of ACS on the basis of all data accrued during the index
hospitalization and five-month follow-up. Among 103 patients, only
14 patients were found to have ACS. The MDCT results correlated well
with other methods of diagnosis. Both the absence of significant
coronary artery stenosis and nonsignificant coronary atherosclerotic
plaque on the CT scan accurately predicted the absence of ACS, with
a negative predictive value of 100%. Multivariate logistic
regression analyses demonstrated that adding the extent of plaque
from a MDCT scan significantly improved the initial models
containing only traditional risk factors or clinical estimates of
the probability of ACS.


Hoffman commented to heartwire that this is the first study that
has "very rigorously" looked at the role of MDCT in a cardiology
clinical application. "MDCT is an emerging technology and is not
used routinely yet, but it is probably used most in patients with
stable angina to help decide whether to send them to angiography. We
may do about 10 a day, and many private practices will offer this,
but there is a reimbursement issue at the moment as it is not an
established diagnostic modality yet," he explained.


"Great potential"

But Hoffman believes that MDCT has great potential as a diagnostic
aid in chest-pain patients presenting in the emergency room. "At
present, just acting on the traditional risk factors and tests
conducted in the emergency department, it can still be difficult to
differentiate those patients with an ACS from those whose chest pain
is not cardiac related. Many patients are admitted to the hospital
for stress tests and angiography, but fewer than 40% of patients
admitted after initially normal blood tests and ECG turn out to have
symptoms related to heart disease. But if we add the CT information
to those tests conducted in the emergency department, things become
a lot clearer," he said.


Hoffman believes MDCT will be used to exclude ACS rather than to
confirm it. "I am not suggesting that MDCT be used at present to
decide whether patients need a stent or not¡X it's not ready for
that yet¡Xbut it probably does have a role in helping to decide who
needs to be sent to angiography and who can be sent home. MDCT does
not give the level of knowledge necessary to know whether a stent is
required¡Xyou need angiography for that¡Xbut it can tell you whether
there is significant stenosis or not. The beauty of MDCT is that it
is much easier to perform than angiography. It takes less time,
requires less physician time, it is less invasive, has fewer
complications, and is much less expensive. It's not going to replace
angiography but it may enable fewer patients to be sent to
angiography by ruling out ACS beforehand," he told heartwire.


Hoffman said that it would probably not be needed for all patients
presenting with chest pain, as those who are thought to be very
likely to be having an ACS are referred straight to angiography
anyway and those who have a very low likelihood of having an ACS are
also quite easy to identify and so doing MDCT in these patients
would probably not be cost-effective. But there is a large group of
patients in the middle in whom doctors are not sure what is going
on, and it is these patients in whom MDCT would be useful. "The
challenge now is to make emergency department doctors familiar with
this new technology," he added.


Larger trial planned

Hoffman hopes to have data on around 400 patients by early next
year. "Although the current study lays the groundwork for using MDCT
and identifies the patients who may benefit most, we need
observational studies and randomized clinical trials to determine
whether this technology improves the ability to quickly assess
patients with chest pain and whether its use results in fewer
hospitalizations and invasive tests," he said. He is planning a
larger multicenter trial to start later next year that will
randomize 1800 to 2000 chest-pain patients to either MDCT or not,
with physicians using the test results in their decision-making.


A large trial of MDCT is also under way in stable-angina patients,
the Prospective Investigation Of Coronary Artery Disease (PIOCAD),
in which 1000 patients with stable disease will receive a CT and a
cath, and the cost-effectiveness of each of these modalities will be
compared.


Hoffmann U, Nagurney JT, Moselewski F, et al. Coronary multidetector
computed tomography in the assessment of patients with acute chest
pain. Circulation 2006; DOI: 10.1161/CIRCULATIONAHA.106.634808.
Available at: http://circ.ahajournals.org.

AstraZeneca has announced that it will not pursue further
development of an investigational drug, NXY-059, known as Cerovive,
after results of a phase 3 trial showed no significant reduction in
stroke-related disability with treatment vs placebo.

In a statement, the company notes that full results from the Stroke
Acute Ischemic NXY-059 Trial (SAINT II) will be reported at the
upcoming International Stroke Conference in February 2007 in San
Francisco.

SAINT II was a randomized, double-blind, placebo-controlled trial of
the drug in 3200 patients with ischemic stroke, enrolled from 350
participating centers in 31 countries. Principal investigator was
Ashfaq Shuaib, MBBS, from the University of Alberta, Edmonton. The
primary outcome was reduction in stroke-related disability assessed
by the modified Rankin scale.

However, the trial ultimately fell short of achieving statistical
significance with NXY-059 compared with placebo on this primary end
point, with an odds ratio of 0.94 (P = .33), the company release
said.

Trapping Free Radicals

NXY-059 is a free-radical trapping agent that had been shown to be
neuroprotective in animal models of stroke. The results of SAINT II
are disappointing in light of positive results seen with the agent
in SAINT I, published earlier this year in the New England Journal
of Medicine (2006;354:588-600), showing that treatment with NXY-059
within 6 hours of ischemic stroke significantly improved the primary
outcome of reduced disability at 90 days, although treatment did not
have a significant effect on other outcomes, including neurologic
function on the National Institutes of Health Stroke Scale (NIHSS).

An intriguing finding from a post hoc analysis of SAINT I was that,
in patients who received tPA, treatment with NXY-059 was associated
with a lower incidence of hemorrhagic transformation (P = .001) and
of symptomatic intracranial hemorrhage (P = .036).

The SAINT I trial marked the first time that a neuroprotective
strategy had shown benefit in a large clinical trial, despite
excellent results with many such agents in animal models of stroke.
After SAINT I, the enrollment in SAINT II was increased to 3200 from
1700 to increase its statistical power.

"AstraZeneca plans no further development of NXY-059 in acute
ischemic stroke," Tomas Odergren, vice president and global product
director for the agent, said in the company statement. However, it
does plan a pooled analysis of SAINT I and SAINT II data to see what
further information might be gleaned, the release notes.

Underlines Need for Confirmation

The result from SAINT II "is obviously disappointing but not
entirely unexpected," Larry B. Goldstein, MD, director of the Duke
Center for Cerebrovascular Disease at Duke University Medical
Center, in Durham, North Carolina, and current chair of the American
Heart Association Stroke Council, told Medscape. "It also points out
that post hoc subgroup analyses ¡X ie, reduction of tPA-related
hemorrhages in the prior study ¡X can be misleading, and findings
from a single trial of a putative new therapy need to be confirmed
in a second trial."

Ralph L. Sacco, MD, from Columbia University, in New York, also
characterized the news as disappointing, both for the field of acute
stroke therapy and in particular the concept of neuroprotection. "We
were cautiously optimistic after SAINT I but knew that a larger
trial was required to substantiate the findings," he told
Medscape. "I still remain optimistic that the right drug, in the
right stroke patient, using a sensitive outcome, will show benefits
in a neuroprotection trial, but the stakes remain high."

Dow Jones Newswires reported yesterday that AstraZeneca's share
price dipped on the news. "AstraZeneca is now left with a very thin
pipeline after the recent expensive failures in late-stage testing
of drugs such as blood-thinner Exanta (ximelagatran), lung cancer
drug Iressa, and Galida for diabetes," the newswire report notes.

It adds that analysts at Deutsche Bank AG had previously forecast
sales of around $750 million for NXY-059 and quotes Deutsche Bank
analysts as saying in a note to investors that "the setback is
likely to prompt investors to question the breadth and risk profile
of the late-stage pipeline" at the company.

Third-quarter results, though, also released yesterday by
AstraZeneca, showed sales up 11% and earnings per share up 34%.

Less than 1% of patients who present to the ER with isolated
dizziness symptoms, including vertigo and imbalance, have a stroke
or TIA, according to a report in the October issue of Stroke.

However, because so many people present with these symptoms, the
absolute number of stroke cases presenting in this fashion may be
high, the authors note.

Findings from case reports and small series have shown that
dizziness may be the principal or only complaint in stroke patients,
but until now no large population-based study has investigated the
frequency of stroke among patients seen in the ER for dizziness
symptoms.

The current study involved all patients, older than 44 years of age,
with dizziness symptoms who presented to an ER or were directly
admitted to a hospital in Neuces County, Texas between January 1,
2000 and June 30, 2003.

Of the 1666 patients who had dizziness symptoms, 53 (3.2%) had a
final diagnosis of stroke or TIA, senior author Dr. Lewis B.
Morgenstern, from the University of Michigan Medical School in Ann
Arbor, and colleagues report. Moreover, just 0.7% of patients with
dizziness symptoms as the only presenting complaint had a stroke or
TIA.

The average age of stroke/TIA patients was 69.3 years, significantly
older than the 65.3 years noted in non-stroke/TIA patients, the
report indicates. Male gender was linked to stroke/TIA, whereas
isolated dizziness symptoms tended to support a non-stroke diagnosis.

Among the various dizziness symptoms, imbalance was a predictor of
stroke/TIA, the report indicates.

"This study suggests that of the patients presenting with dizziness
symptoms, those with other neurologic symptoms, who are older and
male, are at the highest risk for a cerebrovascular etiology," the
authors conclude. "More detailed population-based studies and
prospective clinical studies on the relationship of stroke and
dizziness symptoms are critically needed so that stroke can be
rapidly identified."

Stroke 2006;37:2484-2487

Dehydroepiandrosterone (DHEA) is widely marketed as an anti-aging
compound, but findings from a new study suggest that this claim is
unfounded. Combined treatment with the aromatase inhibitor
atamestane offered no benefit as well.

The new results are in agreement with a report released early this
month in The New England Journal of Medicine, which showed no
benefit of DHEA on physical functioning or quality of life in
elderly men and women.

In the present study, reported in The Journal of Clinical
Endocrinology and Metabolism for October, Dr. Majon Muller, from
University Medical Center Utrecht in the Netherlands, and colleagues
note that age-related decline in androgens has been linked to some
aspects of frailty. Therefore, this might be improved by hormone
replacement with DHEA or treatment with atamestane, "which in
elderly men results in 30-50% increase in testosterone."

The investigators assessed changes in physical frailty in 100
elderly men who were randomized to receive DHEA, atamestane, both
agents, or neither agent for 36 weeks.

The subjects, mean age 78 years, were healthy and living on their
own, but had low strength scores at baseline. Physical frailty was
determined by isometric grip strength, leg extensor power, and
physical performance, according to the report.

Eight-three men completed the study, the investigators report. No
significant differences in any of the frailty outcomes were noted
between the treatment groups and the placebo group.

While the current findings do not support an anti-aging effect for
these compounds, it is possible that with a longer treatment period
or higher dose some benefits might be seen, Dr. Muller and
colleagues conclude.

J Clin Endocrinol Metab 2006;91:3988-3991

Analysis of two-year data from the Alberta Provincial Project for
Outcome Assessment in Coronary Heart Disease (APPROACH) study
revealed that among "real-world" patients who underwent angioplasty,
those who were implanted with drug-eluting stents (DES), as opposed
to bare-metal stents, had significantly fewer deaths, CABG, and
repeat PCI. These observational-study findings were presented in an
oral session at the Canadian Cardiovascular Congress 2006 [1].


Diane Galbraith (APPROACH Project Office, Calgary, AB) explained
that while rates of DES use in some centers in the US are above 80%,
they are lower in Canada; in Alberta, the rate of DES use is about
60%.

Dr Todd Anderson (University of Calgary, AB), the meeting's
scientific program chair, told heartwire that concerns about the
risk of late stent thrombosis prompted the group to examine the
APPROACH database. "We are reducing the number of procedures that
individuals will have to have again--from a one in 10 chance of a
second procedure to a less than 5% chance. But are we trading off
the risk of that patient dying suddenly down the road?" he asked.

"Our own personal experience, which prompted this evaluation of the
APPROACH database, was several cases of individuals late out after
their stents who presented with subacute stent thrombosis and
horrible outcomes--emergency bypass surgery and death in a couple of
individuals," said Anderson.

The APPROACH registry consists of data from all patients in the
province of Alberta who underwent cardiac catheterization since
1995. The team compared mortality, CABG, and repeat PCI rates in
6975 consecutive patients who received angioplasties in Alberta
between April 2003 and March 2005. A total of 1131 patients (16%)
received DES, 5455 patients (78.2%) received bare-metal stents, and
389 patients received balloon angioplasty. The patients had a mean
age of 62.5 years. The DES patients were more likely to be female
and had more comorbidities than the bare-metal-stent patients.


DES performed well; prudent use is key

Kaplan-Meir curves showed that two-year event-free survival in
these "real-world" patients, using the combined end points of
revascularization procedures (PCI, CABG) and death of patients
undergoing PCI, were significantly better among patients who
received DES than among those who received bare-metal stents (log
rank p = 0.001).

Mortality was very similar in the two groups; overall, during a
follow-up of two years, DES tended to perform very well, despite a
small (less than 0.5%) "blip" at one year, Anderson summarized. He
noted that the results do not completely alleviate concerns about
DES; rather, they reinforce the need for groups to be particularly
careful about why they are putting in a DES as opposed to a bare-
metal stent. "Use it when you need to, but do not use it
nonjudiciously; optimize the technique; . . . and make sure that
there is no current reason that the antiplatelet therapy would have
to be discontinued. If we follow those rules, I think that drug-
eluting stents are still very safe and very efficacious for reducing
event rates."


The four key advantages of APPROACH is that it included two types of
stents (there was a 50/50 split between Cypher and Taxus stents), it
was geographically inclusive, it included a longer follow-up, and it
comprised "all comers" (as opposed to a specific group of patients),
Galbraith said. "Databases like APPROACH offer us the opportunity
for postmarketing surveillance, and we think that is critical to
provide more insight into long-term DES efficacy and safety
benefits."


Galbraith PD, et al. Evidence of late events after PCI with drug-
eluting stents: Is there cause for concern? Canadian Cardiovascular
Congress; October 21-25, 2005; Vancouver, BC. Abstract 268.

The biggest randomized trial to date comparing Taxus and Cypher
stents has found no difference in clinical events between the two
groups. Results from the Danish SORT-OUT II study, which was 50%
larger than the pivotal REALITY trial and looked only at clinically
driven major adverse cardiac events (MACE), was presented earlier
this week at the TCT 2006 meeting.

Also showcased at the conference was an expert panel, convened
to "restore the balance" in the media coverage of drug-eluting
stents (DES), who told the press that there has been a "hysterical
over-reaction" to stent thrombosis and death/MI data in DES meta-
analyses and registry studies.

Sorting through SORT-OUT II
The SORT-OUT-II study, partly supported by contributions from Cordis
and Boston Scientific, was conducted throughout Denmark, where all
five Danish university medical centers randomized 2098 patients out
of a total of 11 749 undergoing PCI between August 2004 and January
2006. As Dr Anders M Gall?/b>e (Gentofte Hospital, Copenhagen,
Denmark) noted during his presentation, the randomized cohort is a
cross-section of real-world patients from across the whole country.
In all, the randomized population included roughly 17% STEMI
patients, 33% unstable-angina/non-STEMI patients, and 44% stable-
angina patients. Roughly 15% of the patients were diabetic.

At nine months, the curves for MACE-free survival for the Cypher and
Taxus stents were identical, at approximately 92%, Galløe showed.
There were no significant differences for any of the end points
alone or in combination.

"We can conclude that there are no significant differences in nine-
month clinically or patient-driven MACE," Galløe concluded. He also
noted that in addition to the randomized cohort, all other PCI
patients in Denmark are also being tracked in a registry, with cause-
of-death in any patient being confirmed by death certificate and/or
autopsy report. Ultimately, results in the randomized group will be
compared with outcomes in the registry patients, providing a true
picture of DES use and impact in Denmark.

Discussing the findings, Dr Patrick Serruys (Erasmus Medical Center,
Rotterdam, the Netherlands) said there were many things he liked
about the SORT-OUT II trial, including the fact that the events
occurring during follow-up truly mimicked a real-world scenario,
with patients seeking help from their physicians for true symptoms
rather than angiographic evidence of restenosis.

Less "real-world" was the low percentage of STEMI patients and
diabetics in the randomized groups, suggesting that some selection
bias was occurring, Serruys noted.

Still, Serruys concluded, the investigators are to be congratulated
for their study: "There's nothing rotten in the state of Denmark."

Experts mull over DES safety
The TCT program committee went to some lengths this year to have
some of the most respected names in interventional cardiology speak
with the press about the relative risks/benefits of DES in the wake
of studies presented at the ESC/WCC 2006. "This is an effort to
restore the balance," Dr Martin Leon (Columbia University, New York,
NY), said to explain the rationale for the press
conference. "Unfortunately the results that were reported at the ESC
represented an incomplete dataset," and triggered "hype and
hysteria" in the lay press and general public. "It's important for
the press to understand that we are not in any way suggesting that
this signal of late thrombosis isn't there," Leon stated. "We're
simply arguing that the consequences from these events have not
harmed our patients, and a reduction in restenosis more than
counterbalances those concerns."

heartwire has compiled a sample of some of the key points made to
the press.

Dr Stephen G Ellis (Cleveland Clinic, OH): "The process of
restenosis itself is not benign. Sometimes it presents with a heart
attack and sometimes the treatment of the restenosis leads to a
heart attack, such that there appears to be a balancing out, at
least during the time-period studied, of the excess risk of a heart
attack engendered by stent thrombosis per se, and that related to
restenosis."

Dr Marty Leon (Columbia University): "We've spent a billion dollars
over the past 20 years to eradicate restenosis. I don't think we did
that because we thought it was a benign process."

Dr Jeffrey Moses (Columbia University): "This debate about medical
therapy vs PCI has been going on since the advent of angioplasty,
and the up-tick in interventions was not due to the advent of
DES. . . . The rapid adoption of DES was an indication of how
profound the problem [of restenosis] was in the first place."

Dr Spencer King (Fuqua Heart Center, Emory University, Atlanta,
GA): "My position has always been that perhaps we should be a bit
more selective and perhaps not use drug-eluting stents universally,
but rather use them where we think they are most critically needed
to reduce restenosis. In the final analysis, it's a balance between
risk and benefit. . . . We have lost a little bit of the risk-
benefit cognitive discussion over this [because of] such excitement
about the new technology."

Dr Barry F Utretsky (University of Texas Medical Branch,
Galveston): "I'm quite confused about the real risk. The number of
patients studied in these trials was not very large, because the
percentage of risk was low in both arms. . . . I think we need more
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Dr Bill O'Neill: "I wish [the media] could get the word out to the
public that this is a problem, but the scope of the problem is very
small. We're all getting these calls from patients saying, am I
going to die? Can I get this thing taken out? Can I get bypass
surgery? It's a real phenomenon, but the risk of it is 0.5% to 0.6%:
it's very uncommon, much lower than the risk from their native
coronary disease. The magnitude of the problem has been lost, and
I'm really concerned that it's creating an inordinate, unnecessary
degree of stress in our patients."

The Science of Juice Plus+ Clinical Research
Researchers at leading hospitals and universities around the world
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University of Arizona –1999 • In 80 days, immune system
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Brigham Young Univ. –1999 • After 80 days, 66% decrease in DNA
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Univ. of Maryland – 2003 • 28 day study showed oxidative stress was
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Univ. of Sydney – 2003 • 6 week study lowered homocysteine levels by
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Dept. of Health, Italy - 2003 • In 4 weeks, lowered homocysteine
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Univ. of Vienna – 2004 • 14 week study, showed significant increase
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Univ. of Wurzburg, Germany • the effect of JP+ on the outcome of
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Wake Forest University, • the effect of JP+ on nutritional status
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Tokyo Women's Med Univ. • the bioavailability of Juice Plus+ in an
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There is no substitute for eating a wide variety of fresh, raw
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"The news isn't that fruits and vegetables are good for you, it's
that they are so good for you they could save your life."  TIME
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         g.      Infectious Disease


         h.      International Health and Development By Region


         i.        Global Eye Care


         j.        Glaucoma Symposium



[Non-text portions of this message have been removed]

This trial was completed in Israel in July 2006.  Can anyone advise
how the general trial results (positive or negative) can be accessed
or will they be kept secret until published?

http://www.clinicaltrials.gov/ct/show/NCT00272571

Assays for the fibrin-degradation product d-dimer could potentially
be used to identify patients on oral anticoagulants to treat venous
thromboembolism (VTE) who are at high risk for recurrence, report
investigators in the October 26, 2006 issue of the New England
Journal of Medicine [1].



The finding in patients who had experienced a first episode of deep-
venous thrombosis or pulmonary embolism suggests that the d-dimer
test "may be useful in guiding the duration of anticoagulation by
helping clinicians select patients who may benefit the most from the
prolongation of this demanding and risky treatment," write the
authors, Dr Gualtiero Palareti (S Orsola-Malpighi University
Hospital, Bologna, Italy) and colleagues.



D-dimer testing was performed in 608 such patients about a month
after they went off at least three months of therapy with warfarin
or acenocoumarol. The treated first VTE episode was required to have
been "unprovoked," defined as not being associated conditions that
might promote VTE, including pregnancy, a recent leg fracture or
plaster casting, hospital-bed confinement, and cancer.



Those in whom the qualitative d-dimer assay yielded normal results
remained off anticoagulation therapy, while patients with abnormal d-
dimer readings were randomized either to resume or stay off oral
anticoagulants.



The patients with abnormal d-dimer results who remained off
anticoagulation showed a higher rate of the composite primary end
point, confirmed recurrent VTE or major bleeding event, than either
of the two other groups over a follow-up that lasted at least nine
months and averaged 1.4 years.
The adjusted primary end-point hazard ratio (95% CI) for patients
with abnormal d-dimer results who stayed off anticoagulants was 4.26
(1.23-14.6) compared with those with an abnormal test who resumed
anticoagulation and 2.27 (1.15-4.46) compared with those with normal
d-dimer results (p=0.02 for both differences). The hazard increases
were independent of age, sex, preenrollment duration of
anticoagulation therapy, type of VTE event that earned study
eligibility, and the presence or absence of congenital
thrombophilia.



The primary end-point risk was about the same for patients who had
tested normal for d-dimer and those who tested abnormal and went
back on oral anticoagulation, according to Palareti et al.



The authors note several limitations of their study that could be
addressed in future trials, including its unblinded nature, its
inability to clarify the role of role of d-dimer testing when it is
performed either before patients go off anticoagulation or
repeatedly during follow-up, its inability to define the associated
bleeding risk as a sole end point, and its limitation to patients
with unprovoked VTE, "since the optimal duration of anticoagulation
is most uncertain in this category of patients. However, a
management strategy for all groups of patients, regardless of the
nature and number of their previous events, would be of great
practical use."

Two new studies examine the problematic disorders of impulse
control ¡X including repetitive behaviors, pathological gambling,
and hypersexuality ¡X seen in patients with Parkinson's disease
(PD), particularly those on dopamine agonists.

In these reviews, the prevalence of these behaviors was between 6%
and 13%, depending on which drug the patients were taking, "so it's
not uncommon," Kevin J. Black, MD, from the Washington University
School of Medicine, in St. Louis, Missouri, coauthor of an editorial
accompanying the papers, told Medscape. "There's very little real
scientific data about it ¡V including which patients are more
susceptible ¡X so this is really the beginning of the research in a
way."

The reports appeared in the October 10 issue of Neurology.

Establishing Prevalence

While hypersexuality has been described in relation to levodopa
therapy since the 1970s, when the drug was first introduced, in the
past 10 to 15 years other complex, repetitive behaviors have been
described, particularly in relation to newer dopamine agonist drugs,
Dr. Black noted. These fall into 2 categories: disinhibited
behaviors, things that patients "have had some interest in but
suddenly [it] becomes a passion or addiction, like gambling,
Internet card-playing, or various kinds of sexual activity ¡X even
shopping." The other type of behavior has been called punding, a
specific repetitive behavior such as, for example, emptying a
dresser drawer, then replacing all the items, and emptying it again.

"It's been interesting in the past several years, because it's been
recognized to be maybe a bit more frequent than we previously
expected, particularly because it's associated with significant
psychosocial dysfunction and can be quite hidden as behaviors,"
Valerie Voon, MD, from the National Institute of Neurological
Disorders and Stroke, in Bethesda, Maryland, first author on 1 of
the current reports, told Medscape. "The reason we got interested in
these behaviors is there weren¡¦t any good studies that
systematically assessed the prevalence rates."

In their study, Dr. Voon and colleagues at the Toronto Western
Hospital, in Toronto, Ontario, surveyed 297 patients with PD using
systematic screens and rigorous definitional criteria with the aim
of establishing the prevalence of hypersexuality and compulsive
gambling specifically, as well as any association with medication in
a case-control design.

They found that the lifetime prevalence of pathologic hypersexuality
was 2.4%. Compulsive shopping prevalence was 0.7%. Combined with
their previously reported data on pathologic gambling, where the
lifetime prevalence was 3.4% (Neurology. 2006;66:1750-1752), the
lifetime prevalence of any of these behaviors was 6.1%.

This increased to 13.7% among patients who were on any type of
dopamine agonist, a relationship that has been reported previously
by this and other groups. For example, in their own previous paper
on pathologic gambling, gambling was associated with dopamine
agonists as a class effect, without any association with dose or
agonist type, Dr. Voon noted.

She added that in that previous paper, they'd found patients who
were gambling had lost a mean of $100,000, and 40% of patients with
this disorder had experienced threatened or actual marital
dissolution, "so these are very disruptive behaviors," she said.

"We are now generally warning anyone in whom we're about to start a
dopamine agonist about these behaviors as a potential side effect,
along with other side effects such as fatigue and sleep disorder,
and will also screen for these disorders on routine follow-up," Dr.
Voon told Medscape.

Establishing risk factors for these behaviors could be potentially
useful, allowing more vigilant follow-up or consideration of
alternative therapies to dopamine agonists in susceptible
individuals, she added.

Clinical Features and Impulse Control Disorders

In a second paper in the same issue of Neurology, Gregory Pontone,
MD, from Johns Hopkins University School of Medicine, in Baltimore,
Maryland, and colleagues looked at clinical features associated with
impulse control disorders, including hypersexuality and pathologic
gambling or shopping, in a group of PD patients.

The hope, the authors noted, was that delineating these factors
might improve detection of these "devastating complications of
antiparkinsonian treatment."

They studied 66 men and 34 women with idiopathic PD who had been
recruited for a longitudinal study looking at work- and social-
related disability in PD. Subjects were 65 years of age or younger,
were nondemented, and had no history of current substance abuse or
psychotic disorder.

Of 66 men and 34 women who underwent psychiatric interview, 6 men
and 3 women were found to have 1 of several impulse control
disorders, including pathological gambling or shopping or
hypersexuality, for an overall prevalence of 9%.

The presence of these disorders was associated again with the use
dopamine agonists, but also with depressed mood, disinhibition,
irritability, and appetite disturbance.

A Silver Lining?

In their editorial, Dr. Black and coauthor Joseph H. Friedman, MD,
from Brown University Medical School in Providence, Rhode Island,
write that the 2 new papers by Voon and colleagues and Pontone and
colleagues "add important clinical information" about these
disorders, but questions remain.

Among these is whether dopamine agonists are associated with these
behaviors in other disorders where they are used, such as restless
legs syndrome, they point out. Further, it's not clear why other
impulsive behaviors such as pyromania are not seen or at least have
not yet been recognized in patients with PD.

Finally, they note, "These observations provide a dramatic
illustration that problem behaviors, often linked to moral
turpitude, may be biochemical in origin and not the result of poor
upbringing or deficiencies in moral fiber."

If dopamine agonists cause de novo problem gambling, for example, it
may be possible to devise treatments for the more common variety of
gambler, they speculate. However, already, a trial using a dopamine
antagonist in patients with non-PD related pathologic gambling
showed no effect of treatment.

"Time will tell what we learn from these unfortunate experiences,
but it is hard to imagine that there will not be a silver lining, at
some point, to this cloud of problematic side effects," Drs. Black
and Friedman conclude.

Neurol. 2006;67:1254-1257, 1258-1261, 1118-1119

New lipid targets set out by the Canadian Diabetes Association (CDA)
reflect more recent evidence from clinical trials and will affect
the rates of cardiovascular disease in diabetic patients, according
to one of the members of a committee that devised the new targets.

In a key change, the CDA recommends that patients with diabetes be
treated to achieve a low-density lipoprotein cholesterol (LDL-C)
level of 2.0 mmol/L or less, a decrease from the previous
recommendation of 2.5 mmol/L.

Presented here recently at the annual meeting of the CDA and the
Canadian Society for Endocrinology and Metabolism and published in
the September 15 issue of the Canadian Journal of Diabetes, the new
targets are part of the larger set of clinical practice guidelines
that are under revision and will be published in their entirety in
2008. The Canadian Cardiovascular Society is also releasing revised
lipid targets, largely harmonized with the CDA's guidelines.

The CDA opted to make the revision to the cholesterol level targets
prior to the complete revision of the 2003 CDA clinical practice
guidelines because of the growing incidence of diabetes as a public
health issue, explained Stewart Harris, MD, MPH, FCFP, a professor
at the Schulich School of Medicine in the departments of family
medicine/division of endocrinology and biostatistics and
epidemiology at the University of Western Ontario in London, Canada.

¡§Since 2003, there have been a number of significant major
intervention trials that have also demonstrated that LDL cholesterol
is the most important cholesterol in terms of overall benefit in
reducing risk of morbidity and mortality by obtaining lower levels
for cardiovascular disease even from the previously established
levels, which were 2.5 mmol/L for LDL and a ratio of total
cholesterol to high-density lipoprotein cholesterol (TC/HDL) of 4.0
[or less],¡¨ said Dr. Harris, in an interview here at the annual
meeting and professional conference of the CDA and the Canadian
Society of Endocrinology and Metabolism.

Dr. Harris cited the Collaborative Atorvastatin Diabetes Study
(CARDS) and the Treating to New Targets (TNT) trial as supplying
conclusive evidence of the benefit of a decreased LDL-C level.

¡§Even in patients with modestly elevated cholesterol on entry into
the trial, investigators saw substantial benefit continuously as you
approached 2.0 mmol/L in reduction of cardiovascular morbidity and
mortality,¡¨ Dr. Harris said.

The TNT trial found that both the relative and absolute risk of
current coronary or cerebrovascular events in patients with
established coronary heart disease were significantly reduced with
increased dosage of lipid-lowering drugs, suggesting more aggressive
cholesterol reduction is justified in patients with established
coronary disease.

¡§This [data from the trials] is grade A, level 1 evidence that will
make an impact on reducing morbidity and mortality,¡¨ said Dr.
Harris. ¡§We know that up to 80% of patients with diabetes will die
prematurely of cardiovascular disease. This is an opportunity to
reduce the impact of morbidity and mortality in the face of a
diabetic epidemic. There was some sense of urgency that we need to
redefine the target levels.¡¨

The new CDA lipid targets have also placed less importance on the
TC/HDL ratio, which was suggested to be 4 or lower in the 2003 CDA
guidelines.

Dr. Harris pointed to data from the Fenofibrate Intervention &
Events Lowering in Diabetes (FIELD) trial as support for the CDA¡¦s
decision. The study did not demonstrate a significant reduction in
major coronary events taken alone that was the study's primary end
point.

¡§In the previous set of guidelines, the [TC/HDL] ratio was a co-
primary target,¡¨ said Dr. Harris. ¡§The recommended ratio has not
changed, but it has now dropped to a secondary outcome.¡¨

The threshold for initiating treatment of hypertriglyceridemia has
also been modified, with the CDA suggesting that a fibrate be
prescribed if serum triglycerides exceed 10.0 mmol/L to decrease the
risk of pancreatitis. The previous guidelines indicated 4.5 mmol/L
as the threshold.

Additionally, the revised targets suggest moderate
hypertriglyceridemia, ranging from 4.5 mmol/L to 10.0 mmol/L, be
treated with a statin or fibrate as a first-line choice. If targets
are not achieved after 4 to 6 months, a second lipid-lowering
medication of a different drug class should be added to the regimen.

¡§The 4.5 mmol/L was not supported by any specific evidence,¡¨ said
Dr. Harris. ¡§It was just a general suggestion.¡¨

Amir Hanna, MD, MB, BCh, FRCPC, FACP, a professor emeritus in the
department of medicine at the University of Toronto and director of
the diabetes clinic at St. Michael¡¦s Hospital in Toronto, Ontario,
Canada, described the new lipid targets as evidence-based.

¡§The lower level of LDL [2.0 mmol/L] cuts down on [cardiovascular]
events and is very reasonable,¡¨ said Dr. Hanna, noting that data
from trials such as CARDS showed that irrespective of baseline LDL-C
levels, patients benefited from taking a statin in terms of
experiencing fewer cardiovascular events.

He added that patients would have to adhere to lipid-lowering
therapy to maintain LDL-C levels of 2.0 mmol/L or lower.

Dr. Harris is a consultant and/or has received funding from Pfizer
Canada Inc, Merck Frosst Canada Ltd, AztraZeneca Canada Inc,
GlaxoSmithKline, Eli Lilly, Novo Nordisk, and Sanofi-Aventis. Dr.
Hanna reports no relevant financial relationships.


Can J Diabetes. 2006;30:230-240

Two new studies have shown that there is no benefit to treating
coronary angiography or PCI patients with an iso-osmolar contrast
agent. In these latest studies, there was no difference in the
incidence of contrast-induced nephropathy in patients treated with
iodixanol, an iso-osmolar, nonionic contrast agent, or those treated
a low-molecular contrast agent.



The studies, Cardiac Angiography in Renally Impaired Patients
(CARE), led by Dr Richard Solomon (University of Vermont College of
Medicine, Burlington), and Ionic Versus Nonionic Contrast to Obviate
Worsening of Nephropathy After Angioplasty in Chronic Renal Failure
Patients (ICON), led by Dr Roxanna Mehran (Columbia University, New
York, NY), were both presented here during the late-breaking
clinical-trials session at the TCT 2006 annual meeting.



"Based on the data that we now have, including the data that were
presented by Dr Mehran, low-osmolar contrast agents, which are
generally less expensive than iso-osmolar contrast agents, can be
safely used in high-risk patients when those patients receive some
volume and possibly some antioxidant therapy," concluded
Solomon. "As long as you give a patient volume and use a low-osmolar
agent, you are just as safe as when you use an iso-osmolar agent."



Results from the ICON trial



Presenting the ICON results first to the media, Mehran noted that
contrast-induced nephropathy continues to be a significant concern
for radiologists and cardiologists. It usually occurs 24 to 48 hours
after contrast exposure, with creatinine levels peaking five to
seven days later and normalizing within seven to 10 days. While
levels often return to normal, elevated contrast-induced nephropathy
is a leading cause of iatrogenic renal failure, morbidity, and
mortality after coronary angiography, particularly in those with
preexisting renal disease, said Mehran.



"There is no question that patients with heart disease have renal
disease, and vice versa, and we need to look at this overlap of
disease processes and be able to deal with the complications," said
Mehran.



For this reason, investigators sought to determine the nephrotoxic
potential of iodixanol, an iso-osmolar, nonionic contrast media, and
ioxaglate, an ionic contrast agent with low osmolality that is less
viscous than iodixanol, in complex patients with comorbid disease.
Previous studies have suggested that iso-osmolar agents might be
beneficial in reducing the risk of nephropathy, while others have
hypothesized that a less viscous agent, such as ioxaglate, might
also reduce the risk. In the ICON study, contrast-induced
nephropathy was defined as new-onset or exacerbation of renal
dysfunction following contrast administration in the absence of
other causes, resulting in a relative 25% increase or an absolute
0.5-mg/dL increase in serum creatinine levels from baseline.



Overall, 74 patients with renal insufficiency undergoing angiography
were randomized to ioxaglate, and 71 patients were randomized to
iodixanol. Patients were quite sick, said Mehran, with 45% having
diabetes mellitus and 87% having hypertension. All patients had
stable renal function, defined as two consecutive serum creatinine
measurements within 15% of each other and within 1.5 to 3.0 mg/dL.
All subjects were well hydrated, said Mehran, receiving
approximately 3.7 L of fluid. The use of N-acetyl-cysteine was left
to the discretion of the investigator. The primary end point was the
peak increase in serum creatinine out to day three.



Compared with ioxaglate, iodixanol did not significantly reduce the
increase in serum creatinine levels after coronary catheterization
or PCI, said Mehran. There was no significant difference between the
two agents at any time, nor was there any difference between the two
agents when other definitions of contrast nephropathy were used.
Also, in-hospital and 30-day outcomes did not differ between the two
agents. The rate of contrast nephropathy in this population with
either contrast media was 18% to 20%, despite excellent hydration,
noted Mehran.



"I think that this is such an important problem, because no matter
how hard we try to treat patients, this risk continues to stay,"
said Mehran. "It's important because 20% of our patients [in this
study] were exposed to this complication. Hydration is a must, and
right now there are some trials ongoing that look at local drug
delivery into the renal artery to try to prevent this
complication . . . but there are no real good answers right now."



CARE also attempts to tackle the issue



In the second study presented during the late-breaking clinical-
trials session, the CARE investigators randomized 414 high-risk
patients with an estimated glomerular filtration rate <60 mL/min and
undergoing coronary angiography to iodixanol, the iso-osmolar agent,
or iopamidol, a low-osmolar contrast agent. Using multiple
definitions of chronic induced nephropathy, Solomon and colleagues
sought to determine, like Mehran, whether the low-osmolar agent was
as effective as the more expensive iso-osmolar contrast media.



All patients underwent complementary preventive strategies,
including volume expansion with sodium bicarbonate and the use of a
double dose of N-acetyl-cysteine that was left to the discretion of
the operators. The contrast agents were administered intra-
arterially, noted Solomon, as delivery via this route is thought to
be associated with a lower incidence of nephropathy.



Investigators found that there was no difference in the incidence of
contrast-induced nephropathy in patients treated with iopamidol or
iodixanol. Looking only at patients who underwent PCI or those with
diabetes mellitus, investigators also found no difference in the
incidence of nephropathy among those treated with the different
agents, although there were trends favoring the low-osmolality
agent. In addition, there was no difference in contrast-induced
nephropathy among those who received N-acetyl-cysteine. Iopamidol
was associated with a significantly smaller mean increase in serum
creatinine levels when compared with iodixanol.

In 2003, the NEPHRIC trial showed that iodixanol was superior to
iohexol in patients with chronic kidney disease and diabetes
mellitus. This led many to believe that the newer iso-osmolar agents
were superior to those with low osmolality. Solomon noted that the
study included only patients with diabetes mellitus, and none had
volume expansion before treatment, possibly affecting the results.
These early trials included many different patient populations and
tested different agents against each other, leading to disparate
results across various trials. The implications from CARE, as well
as ICON, are clear, however.



"Osmolality is not the sole determinant of contrast-induced
nephropathy, no matter how it was defined," Solomon concluded.



Many confusing studies to date



Commenting on the results of the studies, discussant Dr Cindy Grines
(William Beaumont Hospital, Royal Oak, MI) noted that clinicians
remain interested in serum creatinine increases as even small
increases trend toward higher mortality that is more significant
over time. Moreover, the data haven't always been clear, despite
previous head-to-head comparisons.



"It's been very difficult to sort through all of these trials
because of differences in design, different patient populations,
different volumes of contrast agents administered, and totally
different types of procedures," said Grines. "There were also huge
differences in hydration protocols that would make comparisons
difficult. And most of the studies have been negative to date."



With the presentation of both studies, Grines said the data suggest
that any low-osmolar contrast agent is acceptable in patients
undergoing catheterization or PCI as long as they're adequately
hydrated. However, Grines questioned whether the surrogate end
point, the transient change in serum creatinine levels, is an
acceptable end point or whether larger trials are needed to make
this conclusion about the equivalence of both agents.

Bivalirudin alone can safely replace heparin and GP IIb/IIIa
inhibitors in ACS patients undergoing contemporary PCI, with similar
rates of ischemia and less bleeding at 30 days, results from the
ACUITY-PCI substudy suggest. The findings largely mirror those of
the broader ACUITY study, as previously reported by heartwire, but
also hint at particular subsets in whom the choice of thrombin
inhibitor may prove more complicated.



Dr Gregg Stone (Columbia University, New York, NY) presented the
results of ACUITY-PCI here at the TCT 2006 meeting earlier this
week, emphasizing their congruence with the overall ACUITY findings,
as well as those of REPLACE-2 in low- to moderate-risk patients
undergoing PCI.



"The conclusions and clinical implications from the ACUITY-PCI trial
are clear," Stone said. "In patients with moderate- and high-risk
ACS undergoing PCI, replacing upstream heparin with bivalirudin in
patients treated with GP IIb/IIIa inhibitors provides similar
clinical and angiographic outcomes; however, replacing heparin and
GP IIb/IIIa blockers with bivalirudin alone with provisional GP
IIb/IIIa inhibitor use in less than 10% of patients results in
similar rates of ischemia, with markedly reduced hemorrhagic
complication, thereby improving overall event-free survival."



ACUITY-PCI was made up of the 7789 patients from the ACUITY trial
who underwent PCI during the trial. Drug-eluting-stent use in these
patients was roughly 60% in all three groups: heparin plus GP
IIb/IIIa inhibitors, bivalirudin plus GP IIb/IIIa inhibitors, and
bivalirudin alone, with randomization roughly equal between the
three groups. At 30 days, the primary end point of ACUITY-PCI, non-
CABG major bleeding, was significantly lower in the bivalirudin-only
group at 30 days, with no significant differences in ischemic
events, in composite or analyzed independently. Unlike the main
ACUITY trial, the net clinical benefit--combining ischemic and
bleeding events--was no different between the heparin-plus-GP
IIb/IIIa-inhibitor group and the bivalirudin-only group.

An expert panel discussing the results following the presentation
appeared on the whole to agree with Stone's conclusions, but several
pointed to the two subgroups, both identified in a post hoc
analysis, in whom lingering concerns of a bleeding/ischemia trade-
off with bivalirudin have dogged this drug since the beginning. In
troponin-positive patients--a group also singled out in the main
trial--ischemic complications were not significantly different
between the heparin-plus-GP IIb/IIIa-inhibitor and bivalirudin-only
groups, but there was a 1% absolute increase in ischemic composite
events. At the same time, however, the incidence of major bleeding
was significantly reduced in this subgroup.



In a press conference, Dr Harvey White (Auckland City Hospital, New
Zealand), a member of the ACUITY trial steering committee,
emphasized that the increase in the ischemic composite was
nonsignificant and made up of "enzyme leaks."



"An enzyme leak is associated with a 2.5 times mortality increase at
12 months, whereas the risk from bleeding is 3.6 times for mortality
at one year . . . so the risk from bleeding is three and a half
times higher," White said. "Interventionalists are certainly going
to look at this [increase in ischemic events], but I think the most
important thing is that this wasn't statistically significant, and
bleeding was."

Patients without clopidogrel on board: Increased ischemic risk?



Also attracting attention in ACUITY-PCI, as in the main ACUITY
trial, were patients not on clopidogrel, roughly one third of the
ACUITY-PCI population. Among patients not on clopidogrel, bleeding
was significantly reduced, as in the PCI cohort as a whole, but
ischemic events were significantly increased, by almost 3%.

The clopidogrel observations "make physiological sense," Dr James
Ferguson (Texas Heart Institute, Houston) told heartwire. "The
simple reason is that bivalirudin has a relatively short half-life,
and in higher-risk individuals you need more antiplatelet therapy
for a longer period of time. . . . So if you are not pretreated and
you get your thienopyradine in the procedure, it's going to take a
while for it to kick in. What you see in the times when the
bivalirudin is wearing off and the patient may not yet be covered by
the thienopyradine already on board, that's when there would be
difficulties."



Ferguson cautioned that the clopidogrel results should be taken with
a grain of salt, since the analysis was not specified in the trial
protocol. "Does this mean that you have to load with clopidogrel and
if someone has not been loaded with clopidogrel that you shouldn't
use bivalirudin alone? I would not go to that conclusion right now,
but it's a concern, and it's something you need to think about."



One-year data will offer direction



Also commenting on the study for heartwire, Dr Eric Topol (Case
Western Reserve University, Cleveland, OH) said the substudy results
were "interesting."



It looks like certain subgroups, including troponin-negative
patients and patients who have taken prior clopidogrel, do well on
bivalirudin monotherapy, he said. "But of course this is post hoc
type of analysis, and nothing is definitive here."



One-year data will be even more informative, he suggested, and will
likely have a greater impact on the question of whether a
bivalirudin strategy could replace standard practice in ACS patients
undergoing PCI. "In the meantime, a case can be made that there is
no 'trade-off' in certain groups of patients--just pronounced less
bleeding and no numerical excess in MI."



Another ACUITY paper focusing on the diabetic subset, also presented
at TCT 2006, suggests that diabetics might also be well suited to
bivalirudin monotherapy, Topol noted.



Influence on practice



Other experts tried to predict if and how the ACUITY-PCI results
might influence their practice. White stated that he believed
bivalirudin should be "the drug of choice," although for cost
reasons it currently is used in only 15% of cases in his hospital,
primarily in patients believed to be at higher bleeding risk.



But Dr David Faxon (Brigham and Women's Hospital, Boston, MA)
pointed to the wide range of patients included in ACUITY PCI,
ranging from moderate- to high-risk ACS patients. "There's unstable
angina and there's unstable angina," he said. For very high-risk
patients, "I must say, I'm hanging on to the GP IIb/IIIas."



Likewise, Dr Deepak Bhatt (Cleveland Clinic, OH) pointed out that
ACUITY-PCI speaks to non-ST-elevation ACS patients and specifically
applies to patients treated in the same way as those in the trial,
with relatively quick door-to-balloon times. Questions remain,
however, regarding the STEMI population. "Intuitively I think that
GP IIb/IIIa inhibitors would add value there, in patients with STEMI
and visible thrombus, and there are ongoing studies addressing the
use of bivalirudin in those settings," Bhatt said.



Ferguson made the point that noninferiority studies like ACUITY tend
to reinforce practice patterns, not change them. "If you were a
believer in bivalirudin before ACUITY, then the glass is half full;
if you were a skeptic before, then the glass is half empty. But what
this trial does is reinforce that bivalirudin is an option once you
make a decision to go to the cath lab."



Ferguson does not believe bivalirudin will eliminate a role for GP
IIb/IIIa inhibition. "I'm not sure that the results of ACUITY mean
that we should be using less GP IIb/IIIa blockers, but it solidified
the position of bivalirudin in the invasively managed patients. Now
we have more data for people who choose to pursue that option: there
are concerns that one has to consider in high-risk individuals,
including troponin-positive patients and those who do not have
thienopyradine pretreatment, but one size doesn't fit all, and you
need to use the therapies that fit best within your institution."

Drug-eluting stents may be safely used to treat stenoses in the
intracranial and extracranial circulation and may be less likely to
develop restenoses than bare metal stents, according to a report in
the October issue of Stroke.

There has been a reluctance to use bare metal stents for symptomatic
intracranial and extracranial stenoses because of the high
restenosis rates, the authors explain.

Dr. Tudor G. Jovin from the University of Pittsburgh Medical Center,
Pennsylvania and colleagues evaluated the safety, technical
feasibility, and short-term restenosis rate of drug-eluting stents
(DES) in the extracranial and intracranial cerebral circulation in
59 patients with symptomatic atherosclerotic lesions.

Sixty-two of 65 vessels were successfully treated with DES, the team
reports, with a reduction of mean stenosis from 83% before treatment
to 12% after the procedure.

There were only two periprocedural complications, the results
indicate, including one non-flow-limiting dissection and one
disabling stroke 12 hours after the procedure.

A median of 4 months after the procedure, three of 50 stents (6%)
were found to have restenosis of at least 50%, the researchers
report, but only one of the 48 patients presented with symptoms of a
stroke or TIA at follow-up.

"This report shows that delivery of a DES to the extracranial and
intracranial vessels is feasible with a high technical success rate
and low complication rate," the authors conclude. "The rates of
restenosis at short-term follow-up are encouraging but require
further investigation with longer-term follow-up."

Stroke 2006;37:2562-2566

Placement of multiple overlapping drug-eluting stents is a safe and
effective treatment for long coronary lesions, Korean researchers
report.

Trials investigating the use of drug-eluting stents have typically
only enrolled patients with simple coronary lesions, according to
the report in the American Journal of Cardiology for October 1.
However, in real-world settings, diffuse coronary lesions are
sometimes encountered and are often treated with multiple
overlapping stents. Still, the safety and efficacy of this approach
is unclear.

In the present study, Dr. Seung-Jung Park and colleagues, from the
University of Ulsan in Seoul, assessed the outcomes of 347
consecutive patients with long coronary lesions who were treated
with the "full metal jacket" approach, defined as the use of
overlapping stents for a total length of at least 60 mm with no gaps
between stents.

The mean patient age was 61.0 years and the average stented length
was 71.9 mm, the report indicates. Stent placement was deemed a
technical success in 97.7% of cases.

While hospitalized, two patients developed acute stent thrombosis
and one patient died, yielding a major complication rate of 0.7%.

The angiographic restenosis rate was 13.7%. On multivariate
analysis, a small reference artery diameter and use of Taxus
(paclitaxel-eluting) stents were predictive of restenosis. The only
predictor of stent thrombosis and cardiac death/Q-wave MI was left
ventricular dysfunction (ejection fraction <45%).

During an average follow-up period of 16.6 months, 9 patients died,
1 patient had a nonfatal MI, and 13 target vessel revascularizations
were required, the report shows. The likelihood of not having a
major adverse cardiac event at 1 and 2 years was 95.4% and 91.4%,
respectively.

"These findings suggest that multiple overlapping drug-eluting
stents may be an effective treatment option for complex long
lesions," the researchers conclude. Still, this approach should be
used carefully, particularly in patients with left ventricular
dysfunction, they advise.

Am J Cardiol 2006;98:918-922

New lipid targets set out by the Canadian Diabetes Association (CDA)
reflect more recent evidence from clinical trials and will affect
the rates of cardiovascular disease in diabetic patients, according
to one of the members of a committee that devised the new targets.

In a key change, the CDA recommends that patients with diabetes be
treated to achieve a low-density lipoprotein cholesterol (LDL-C)
level of 2.0 mmol/L or less, a decrease from the previous
recommendation of 2.5 mmol/L.

Presented here recently at the annual meeting of the CDA and the
Canadian Society for Endocrinology and Metabolism and published in
the September 15 issue of the Canadian Journal of Diabetes, the new
targets are part of the larger set of clinical practice guidelines
that are under revision and will be published in their entirety in
2008. The Canadian Cardiovascular Society is also releasing revised
lipid targets, largely harmonized with the CDA's guidelines.

The CDA opted to make the revision to the cholesterol level targets
prior to the complete revision of the 2003 CDA clinical practice
guidelines because of the growing incidence of diabetes as a public
health issue, explained Stewart Harris, MD, MPH, FCFP, a professor
at the Schulich School of Medicine in the departments of family
medicine/division of endocrinology and biostatistics and
epidemiology at the University of Western Ontario in London, Canada.

¡§Since 2003, there have been a number of significant major
intervention trials that have also demonstrated that LDL cholesterol
is the most important cholesterol in terms of overall benefit in
reducing risk of morbidity and mortality by obtaining lower levels
for cardiovascular disease even from the previously established
levels, which were 2.5 mmol/L for LDL and a ratio of total
cholesterol to high-density lipoprotein cholesterol (TC/HDL) of 4.0
[or less],¡¨ said Dr. Harris, in an interview here at the annual
meeting and professional conference of the CDA and the Canadian
Society of Endocrinology and Metabolism.

Dr. Harris cited the Collaborative Atorvastatin Diabetes Study
(CARDS) and the Treating to New Targets (TNT) trial as supplying
conclusive evidence of the benefit of a decreased LDL-C level.

¡§Even in patients with modestly elevated cholesterol on entry into
the trial, investigators saw substantial benefit continuously as you
approached 2.0 mmol/L in reduction of cardiovascular morbidity and
mortality,¡¨ Dr. Harris said.

The TNT trial found that both the relative and absolute risk of
current coronary or cerebrovascular events in patients with
established coronary heart disease were significantly reduced with
increased dosage of lipid-lowering drugs, suggesting more aggressive
cholesterol reduction is justified in patients with established
coronary disease.

¡§This [data from the trials] is grade A, level 1 evidence that will
make an impact on reducing morbidity and mortality,¡¨ said Dr.
Harris. ¡§We know that up to 80% of patients with diabetes will die
prematurely of cardiovascular disease. This is an opportunity to
reduce the impact of morbidity and mortality in the face of a
diabetic epidemic. There was some sense of urgency that we need to
redefine the target levels.¡¨

The new CDA lipid targets have also placed less importance on the
TC/HDL ratio, which was suggested to be 4 or lower in the 2003 CDA
guidelines.

Dr. Harris pointed to data from the Fenofibrate Intervention &
Events Lowering in Diabetes (FIELD) trial as support for the CDA¡¦s
decision. The study did not demonstrate a significant reduction in
major coronary events taken alone that was the study's primary end
point.

¡§In the previous set of guidelines, the [TC/HDL] ratio was a co-
primary target,¡¨ said Dr. Harris. ¡§The recommended ratio has not
changed, but it has now dropped to a secondary outcome.¡¨

The threshold for initiating treatment of hypertriglyceridemia has
also been modified, with the CDA suggesting that a fibrate be
prescribed if serum triglycerides exceed 10.0 mmol/L to decrease the
risk of pancreatitis. The previous guidelines indicated 4.5 mmol/L
as the threshold.

Additionally, the revised targets suggest moderate
hypertriglyceridemia, ranging from 4.5 mmol/L to 10.0 mmol/L, be
treated with a statin or fibrate as a first-line choice. If targets
are not achieved after 4 to 6 months, a second lipid-lowering
medication of a different drug class should be added to the regimen.

¡§The 4.5 mmol/L was not supported by any specific evidence,¡¨ said
Dr. Harris. ¡§It was just a general suggestion.¡¨

Amir Hanna, MD, MB, BCh, FRCPC, FACP, a professor emeritus in the
department of medicine at the University of Toronto and director of
the diabetes clinic at St. Michael¡¦s Hospital in Toronto, Ontario,
Canada, described the new lipid targets as evidence-based.

¡§The lower level of LDL [2.0 mmol/L] cuts down on [cardiovascular]
events and is very reasonable,¡¨ said Dr. Hanna, noting that data
from trials such as CARDS showed that irrespective of baseline LDL-C
levels, patients benefited from taking a statin in terms of
experiencing fewer cardiovascular events.

He added that patients would have to adhere to lipid-lowering
therapy to maintain LDL-C levels of 2.0 mmol/L or lower.

Dr. Harris is a consultant and/or has received funding from Pfizer
Canada Inc, Merck Frosst Canada Ltd, AztraZeneca Canada Inc,
GlaxoSmithKline, Eli Lilly, Novo Nordisk, and Sanofi-Aventis. Dr.
Hanna reports no relevant financial relationships.


Can J Diabetes. 2006;30:230-240

A molecular genetic autopsy performed on the tissue of a 21-year-old
woman who died suddenly of unexplained causes identified a novel
mutation in the KCNH2 gene at a region that is known to give rise to
long-QT syndrome [1]. This novel molecular autopsy identification of
a hidden cause of sudden cardiac death was presented in a poster
here at the Canadian Cardiovascular Congress 2006.


Dr Michael Gollob (University of Ottawa Heart Institute, ON) told
heartwire that sudden cardiac death in an otherwise healthy
individual is always a tragedy, and in up to 40% of cases, routine
autopsy fails to identify a specific pathologic diagnosis. He added
that it is very likely, however, that a significant proportion of
these young victims die from a genetic arrhythmia¡Xthat is, from a
purely electrical disease of the heart in which there is no
associated structural disease for pathologists to view.


In this case, a 21-year-old woman was found dead in her bed some
hours after studying for university exams. She had been taking
a "cold medicine" for upper-respiratory-tract symptoms, and she had
a previous history of recurrent syncope with no specific etiology. A
standard autopsy revealed a myxomatous mitral valve and "septum at
origin of left main coronary." Her mother had a previous diagnosis
of "epilepsy" that was based on frequent episodes of passing out and
observed seizurelike activity.


Gollob explained that following genetic counseling, the woman's
parents consented to genetic analysis of tissue from their daughter.
Genomic DNA was extracted from liver tissue using standard
techniques and was analyzed for genetic mutations in genes that are
known to cause sudden cardiac death: genes known to give rise to the
long-QT syndrome, Brugada syndrome, or catecholaminergic polymorphic
ventricular tachycardia.


Direct DNA sequencing identified a novel mutation in the HERG gene,
otherwise known as KCNH2, at a "mutation hot spot" region of the
gene that is known to give rise to long-QT syndrome.


In an ongoing process, the researchers assessed surviving family
members to see whether they were carriers for this genetic mutation.
They were able to reassure the woman's surviving sister that she
does not carry this genetic mutation and is not at risk for long-QT
syndrome. The victim's mother, however, had an inappropriate
diagnosis of epilepsy. She actually had long-QT syndrome and carried
the same genetic mutation as her deceased daughter. The mother is
now being appropriately treated. "We have in our experience seven
cases of young individuals who were diagnosed with epilepsy but who
actually had long-QT syndrome," Gollob added.


Genetic testing might prevent similar tragedies

"We propose that genetic testing should be part of the standard
autopsy in autopsy-negative sudden cardiac death in previously
healthy young individuals," said Gollob. "We feel this is important,
because not only will it provide closure to the family and to the
community, it also provides an opportunity to definitively screen
surviving family members to see whether they also harbor the same
genetic disease and are at risk of sudden death."


Rutberg J et al. Molecular autopsy in the sudden cardiac death of a
young female: First Canadian report. Canadian Cardiovascular
Congress 2006; October 21-25, 2006; Vancouver, BC. Abstract 099.

Elevated levels of mannose-binding lectin either alone or in
combination with increased levels of C-reactive protein (CRP) are
predictive of death in patients with type 2 diabetes, new research
suggests. Increased levels of both proteins are associated with the
development of albuminuria.

As reported in the Archives of Internal Medicine for October 9,
patients with mannose-binding lectin levels greater than or equal to
1000 g/L were 50% more likely to die than those with lower levels.

Mannose-binding lectin is known to play an important role in
inflammation and complement activation, both of which may contribute
to the development of diabetic vascular complications. While prior
studies have linked elevated mannose-binding lectin levels with
adverse outcomes in type 1 diabetics, the prognostic significance of
this finding in type 2 diabetics was unknown.

To investigate, Dr. Troels Krarup Hansen, from Aarhus University
Hospital in Denmark, and colleagues analyzed data from 326 patients
with type 2 diabetes who had mannose-binding lectin and CRP levels
measured at baseline and then were followed for more than 15 years.
Urinary albumin excretion was determined each year.

As noted, the presence of elevated mannose-binding lectin levels
increased the risk of death by 50%. Moreover, this risk was largely
unchanged after adjusting for known confounding factors.

Mannose-binding lectin added to the prognostic power of CRP, the
authors note. With high levels of mannose-binding lectin and CRP, a
2.7-fold increased risk of death was noted compared with low levels
of both proteins.

Patients who were initially normoalbuminuric with high levels of
both CRP and mannose-binding lectin were 2.6-times more likely to
develop albuminuria than those with low levels of both. By contrast,
elevated CRP or mannose-binding lectin levels alone did not
significantly increase the risk of albuminuria.

While the findings suggest a role for mannose-binding lectin testing
in predicting diabetes outcomes, they also suggest a new therapeutic
approach, the authors note. Namely, the targeted down-regulation of
complement factors may have a beneficial effect on diabetes outcomes.

Arch Intern Med 2006;166:2007-2013

Statins are highly effective in preventing new stroke or MI in
patients with severe carotid arterial disease, a new study shows
[1].



The results indicate that all patients with this disease at high
risk of another event should be treated with statins, regardless of
whether or not they have hypercholesterolemia, lead investigator Dr
Gautham Ravipati (New York Medical College, Valhalla) told
heartwire.



He presented the findings of the study today at the CHEST 2006
meeting (annual meeting of the American College of Chest
Physicians).



Many with high cholesterol still not on statins



From January 2001 to December 2005, Ravipati and his colleagues
analyzed the charts of 449 patients with carotid arterial disease,
all of whom had experienced a narrowing of one or two carotid
arteries but had either refused revascularization or were deemed
unsuitable candidates.



Of the 449 patients, 298 (66%) were treated with statins and 151
were not. Follow-up occurred within a mean of 26 months for the
statin group and 21 months for the control group.



The researchers identified hypercholesterolemia in all 298 (100%)
patients treated with statins and in 145 of 151 (96%) of those not
treated with statins.



"We were shocked at how many patients with high cholesterol were
still not treated with statins," Ravipati commented.



The incidence of new stroke, new MI, or death in patients on statins
in the study was 15% compared with 68% in those not treated with
statins (p<0.001).



Independent predictors for the time to development of new stroke,
new MI, or death included use of statins, diabetes, and prior
events, but interestingly not hypercholesterolemia. "We were very
surprised that cholesterol was not an independent risk factor,"
Ravipati noted.
Treat high-risk patients, even if cholesterol is normal



"This indicates that we should aggressively treat these patients
even if their cholesterol is normal," says Ravipati. "Of course,
statins will never take away from good risk-factor modification," he
stressed, adding that those particularly at risk include diabetics
and people who have already had a TIA, stroke, or MI.

"But there is an underutilization of statins. The message should
be: 'Don't start a statin based on the cholesterol. Start it
independently.' If a patient has had an event but his cholesterol
seems 'normal,' his level is probably not 'normal' for him."



Reassuringly, none of the patients taking statins had hemorrhagic
strokes, Ravipati said.



He believes some of the benefits of statins in this population are
likely independent of their cholesterol-lowering effects. So-called
pleiotropic effects such as anti-inflammatory, antioxidant, and
possibly antithrombotic effects of statins, as well as a beneficial
effect of the drugs on endothelial function, could play a role, he
noted.

Ravipati G, Aronow WS, Ahn C, et al. Reduction of myocardial
infarction or stroke or all-cause mortality in patients with carotid
arterial disease treated with statins. CHEST 2006; October 21-26,
2006; Salt Lake City, UT. Abstract 3651.

Severely obese patients who undergo gastric bypass surgery exhibit
significantly greater weight loss and have higher quality of life at
2 years after surgery than obese patients who were denied the
surgery or obese study participants who did not want surgery.

These findings were reported here at the 2006 annual scientific
meeting of NAASO, The Obesity Society.

"This prospective study demonstrates significant reduction in
morbidity for the surgical group," lead investigator Ted Adams, PhD,
MPH, from the University of Utah School of Medicine in Salt Lake
City, told attendees. A 5-year follow-up study is planned.

Dr. Adams and colleagues compared changes in body weight, body mass
index (BMI), metabolic rate, sleep quality, and a host of other
parameters in severely obese (SO) patients (n = 422) who underwent
Roux-en-Y gastric bypass (GBP) surgery with 2 SO control groups
after 2 years. One control group included SO participants who wanted
the surgery but were denied by their health insurance companies (n =
413), and the other group consisted of 321 SO randomly-selected
participants who did not want the surgery (n = 321).

Participants' average weights were comparable at baseline: 295 lb
(BMI, 47) for the surgery group, 286 lb (BMI, 47) for the denied
group, and 273 lb (BMI, 45) for the group that did not want surgery.

All participants underwent exhaustive clinical tests and surveys,
including resting metabolic rate, sleep study, echocardiogram,
exercise treadmill tests, blood pressure, blood chemistries,
anthropometrics, and Impact of Weight on Quality of Life (IWQOL)
questionnaires. To assess the difference in mean 2-year changes
between groups, the researchers treated clinical variables as
dependent variables, while the study group served as the independent
variable.

The researchers reported that by all measures, GBP patients showed
significant improvement (P < .001) compared with the other 2
grops. "Short-term at least ¡X that's 2 years ¡X most comorbidities
were significantly reduced compared to significantly obese
individuals not seeking weight loss surgery and individuals who are
seeking surgery but did not have it," Dr. Adams told attendees
during the oral presentation.

After 2 years, the surgery group lost an average of 100 lb compared
with a 12-pound loss for the denied group, and 0.5-lb weight gain
for the group not seeking surgery. The surgery group's average
treadmill time increased by 4.3 minutes compared with a 0.9-minute
increase for the denied group, and no change for the group not
seeking surgery. The GBP patients had significantly improved left
ventricular mass after 2 years, while left ventricular mass
increased in both control groups.

Overall, the surgery group showed a 59-point increase in their IWQOL
scores vs a 13-point increase for the denied group and a 6-point
increase for the group that did not want surgery. "So there was a
marked improvement in perceived QOL," Dr. Adams told Medscape.

The risk for comorbidities also decreased in the surgery group
compared with the 2 control groups. The odds ratio for diabetes
resolution in the surgery group compared with the control group that
did not seek surgery was 0.035 (95% confidence interval [CI], 0.012 -
  0.099; P < .0001). The odds ratio for diabetes resolution for the
surgery group vs the denied group was 0.067 (95% CI, 0.03 - 0.154; P
< .0001).

"At two-years post GBP, significant comorbid improvements were seen
in GBP cases when compared to control groups," write Dr. Adams and
colleagues in the abstract. "The demonstrated benefits of surgery
occurred despite significant improvements in denied SO controls when
compared to random SO controls. These groups are being followed for
6 years to test whether or not short-term improvements continue long-
term."

"It's an excellent study," James Early, MD, from the University of
Kansas in Wichita, told Medscape. "The problem is what happens in 5
years. Especially with gastric bypass, after 2 years, the stomach
accommodates greater intake, the intestine accommodates to a larger
amount of food, and people learn to 'eat around the surgery.' So it
will be interesting to see what happens in 5 years." Dr. Early, who
attended the presentation, was not involved in the study.

The study was funded by the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDIC). Dr. Adams reports no
relevant financial relationships.

NAASO: The Obesity Society 2006 Annual Scientific Meeting: Abstract
16-OR. Presented October 21, 2006.

Stress single photon emission computed tomography (SPECT) is useful
in assessing dyspnea and can detect undiagnosed coronary artery
disease, according to a report in the September American Heart
Journal.

"This study and other studies suggest that patients who present with
dyspnea and undergo stress imaging have a fairly high yield of
abnormal results, indicating that dyspnea in many of these patients
represents an 'anginal equivalent,'" Dr. Todd D. Miller from Mayo
Clinic, Rochester, Minnesota told Reuters Health.

Dr. Miller and colleagues evaluated the prevalence, severity, and
prognostic value of perfusion defects detected by stress SPECT in
1864 patients without known coronary artery disease referred for
evaluation of dyspnea. The mean age was 65.8 years and 89% were
overweight or obese.

Forty-five percent of patients had an abnormal SPECT image, the
authors report, and 11% had a high-risk scan.

Male sex and diabetes were the two strongest independent variables
for predicting an abnormal or high-risk SPECT scan, the
investigators report.

Annual mortality rates varied by SPECT outcomes, the results
indicate, ranging from 4.7% among patients with a high-risk scan to
3.2% for intermediate-risk scans and 2.5% for low-risk scans.

Summed stress scores and left ventricular enlargement provided
incremental prognostic information, the researchers note, but
including left ventricular ejection fraction did not improve the
model.

The likelihood of undergoing angiography within 6 months increased
with increasing severity of the SPECT abnormality, the report
indicates, and 85% of patients who underwent angiography had at
least one reversible defect.

"In general, patients with high-risk SPECT scans (11% of our
population) should undergo coronary angiography," Dr. Miller
said. "The value of performing serial testing in other patients to
track disease is completely uncertain, as there are no data on
serial testing."

"However, it would seem reasonable to follow the higher risk
patients (older men and patients with diabetes) more closely,
although the interval at which follow-up testing might be performed
is uncertain," Dr. Miller continued.

"Dyspnea is not currently a Medicare-approved indication for stress
testing," Dr. Miller added. "Results of these studies suggest that
this issue should be re-assessed."

Am Heart J 2006;152:551-557

Thrombolysis during the first 3 hours after stroke symptom onset may
be inadvisable if MRI reveals leukoaraiosis, which suggests the
patient may have an increased risk of intracerebral hemorrhage,
report researchers with the MR Stroke Study, an international
research effort to standardize the use of MRI in acute stroke.

Leukoaraiosis is a marker visible on MRI indicating chronic ischemic
damage of the cerebral microcirculation, possibly due to cerebral
angiopathy, according to Dr. Tobias Neumann-Haefelin of Goethe
Universitat in Frankfurt, Germany and colleagues. Leukoaraiosis on
MRI may therefore signal increased intracerebral hemorrhage risk,
contraindicating thrombolysis in these patients, the stroke team
hypothesized.

The investigators retrospectively studied 449 patients with an acute
anterior circulation stroke, evaluating data collected within 6
hours of stroke onset. Their findings are reported in the October
issue of Stroke.

All patients received standard MRI, including a high-quality T2-
weighted sequence, before receiving thrombolysis. Moderate-to-severe
leukoaraiosis was visible on MRI in 114 patients and absent or mild
in 335 patients.

Symptomatic intracerebral hemorrhage occurred in 10.5% of patients
with severe leukoaraiosis compared with 3.8% of those without
leukoaraiosis. The risk of intracerebral hemorrhage was 2.9-fold
higher when leukoaraiosis was visible on MRI, Dr. Neumann-Haefelin's
group reports.

CT is used for most patients presenting with stroke symptoms.
Although leukoaraiosis is better assessed using MRI, CT can show
moderate-to-severe cases of leukoaraiosis, which is "in our opinion,
easier to identify than early infarct signs," the authors write. As
such, its presence or absence on MRI or CT "may be included
cautiously in the decision-making process for or against
thrombolysis."

Stroke 2006;37:2463-2466

Compared with other patients who underwent coronary artery bypass
grafting (CABG), those with severe chronic kidney disease (CKD) had
worse postsurgery physical function but experienced similar
improvements in mental health. These findings come from what is
believed to be the first study to quantify the changes in quality of
life in patients with varying degrees of CKD who underwent CABG
surgery.

Chirag R. Parikh, MD, PhD, from Yale University in New Haven,
Connecticut, told Medscape: "It appears that patients with CKD have
quite a bit of pathophysiologic disease compared with other cardiac
patients, and they may not derive as much improvement in quality of
life."

The article is published in the October 9 issue of the Archives of
Internal Medicine.

25% of CABG Patients Have CKD

The authors explain that of the more than 500,000 patients who
undergo CABG each year in the United States, certain subgroups ¡X
women, the elderly, or obese patients ¡X derive less benefit.
Patients with CKD have higher in-hospital complication rates as well
as other problems, such as anemia, altered mineral metabolism, etc,
and comorbidities such as diabetes, which might affect their
postsurgery benefits. Understanding potential postoperative quality-
of-life benefits is very important for patients with CKD who are
contemplating CABG, but information was lacking for this subgroup,
the authors write. They aimed to shed light on this topic by
examining changes in physical function and mental health scores over
a 6-month period in a cohort of patients with varying degrees of CKD
who underwent CABG.

The study population was drawn from the Approaches to Recovery after
Coronary Surgery cohort. From 1999 to 2001, all patients age 30 and
older who were admitted for CABG surgery at Yale-New Haven Hospital
in New Haven, Connecticut were eligible for the study. A total of
1055 patients were included in the study sample.

The patients were stratified based on the National Kidney Foundation
classification system:

66% had stages 0 to 2 CKD (GFR, > 60 mL/min/1.73 m2).
29% had stage 3 CKD (GFR, 30 ¡V 59 mL/min/1.73 m2).
5% had stages 4 to 5 CKD (GFR, < 30 mL/min/1.73 m2).

While the patients were in the hospital recovering from CABG, they
completed a baseline interview by answering questions from the
Medical Outcomes Trust Short Form 36-Item Health Survey. For the
physical-function component of the interview, patients indicated
their degree of limitation over the past month in activities such as
walking, running, lifting groceries, or climbing stairs. For the
mental-health portion of the interview, they were asked to rank how
often within the past month they experienced anxious moments, calm
and peaceful moments, and cheerful or depressed moods. Patients were
surveyed by phone 6 months later and classed as improved, worse, or
unchanged.

Severe CKD Patients: Worse Fitness, Better Mood

For the physical-fitness component of quality-of-life survey, 21% of
patients with severe CKD who underwent CABG had worse scores at 6
months than at baseline, whereas no patient in the rest of the
cohort had worse scores. On the other hand, patients with the most
severe CKD had larger improvements in mood, probably because they
were the most depressed at baseline, the authors write, adding that
all groups were relieved to have less pain.

Study Points the Way for Future Research

The authors acknowledge several study limitations: the group with
severe CKD was small, this was not a randomized trial, and there was
no control group who did not undergo CABG. Dr. Parikh said that it
was hoped that future studies would address these issues. The
authors write that current American College of Cardiology and
American Heart Association guidelines indicate that improvement in
quality of life is a primary indication for CABG surgery, so it is
important to have good quality-of-life data for this subgroup. "The
results from this study and future studies in this area with an
appropriate control group (those without CABG) may assist in the
decision process of whether to pursue CABG in patients with coronary
artery disease in those with advanced CKD," they conclude.

Arch Intern Med. 2006;166:2014-2019.

Results of a study provide more evidence for an association between
use of second-generation antipsychotic drugs -- in this case
olanzapine, quetiapine, and risperidone -- and the onset of diabetes.

"There is growing evidence of metabolic side effects, such as
hyperglycemia and weight gain, following the use of certain second-
generation antipsychotic agents," Dr. Bruce L. Lambert of the
University of Illinois at Chicago and colleagues note in a report in
the October 1st issue of the American Journal of Epidemiology.

"Prescribers should be mindful of diabetes risks when treating
patients with schizophrenia," they advise. .

Dr. Lambert and colleagues studied 15,767 patients with
schizophrenia who started treatment with olanzapine, risperidone,
quetiapine, or the conventional antipsychotic haloperidol, between
1999 and 2001.

In adjusted analyses, with patients initiating haloperidol serving
as the reference group, diabetes risk was increased equally with new
use of olanzapine, risperidone, or quetiapine. Each appeared to
increase the risk by 60% to 70%, relative to haloperidol, the team
reports.

"What this means," Dr. Lambert told Reuters Health, "is that about 2
of every 100 patients on the old drug would be expected to develop
diabetes every year, but roughly 3 out of every 100 patients on the
new drugs develop diabetes."

The risk of diabetes with the second-generation antipsychotics was
higher in patients younger than age 50 years.

"When deciding whether to take one of these new antipsychotic drugs
(e.g., olanzapine, risperidone, and quetiapine)," Dr. Lambert
commented, "doctors and patients need to consider the risk of
developing diabetes. Older drugs (e.g., haloperidol, perphenazine)
may be equally effective without the increased risk of diabetes,
although all antipsychotic drugs have side effects and risks of
their own."

He said it's also important to note that the current study did not
investigate diabetes risk associated with aripirazole and
ziprasidone -- the newest drugs in this class.

Am J Epidemiol 2006;164:672-681