High-risk patients who have survived a first MI can reduce their
risk of subsequent cardiovascular events by eating either a
Mediterranean-style diet or the low-fat diet recommended by the AHA,
with no differences in risk reduction between the two diets, new
research suggests.

The findings run counter to other recent diet studies that have
suggested that the Mediterranean diet, with an emphasis on foods and
oils rich in omega-3 fatty acids, may improve risk-factor profiles
and be superior to an approach that indiscriminately reduces fat
and, in tandem, increases carbohydrate consumption. Dr Katherine E
Tuttle (Providence Medical Research Center, Spokane, WA) presented
the results of the late-breaking study earlier this week at the
American College of Cardiology 2007 Scientific Sessions. She says
the findings should provide more options for people who simply don't
like to eat the signature foods of the Mediterranean diet, namely
lots of fish and plant-based proteins.

"The good news is there is more than one heart-healthy diet. You can
offer choices for different groups of people in the community," she
told heartwire.

Tuttle et al's study randomized 101 patients to either the AHA's
step II diet (n=50) or a Mediterranean-style diet (n=51), with
randomization occurring within six weeks of patients' index MIs. In
both dietary interventions, patients received individual counseling
sessions with a dietician--two sessions within the first month, then
again at months 3, 6, 18, and 24--as well as six or more group
counseling sessions. Both diets recommended limiting cholesterol
consumption to <200 mg/day and saturated fats to <7% total calories;
the Mediterranean diet, however, recommended much higher percentages
of monounsaturated fats and omega-3 fatty acids and a reduced
consumption of carbohydrates. Outcomes in the two intervention arms
were then compared with 101 patients in a matched "usual-care" group
who had received standard advice, when first hospitalized for their
MI, on the benefits of a low-fat diet.



Both diets better than usual care

After a median of 46 months of follow-up (ranging from 18 to 72
months), Tuttle and colleagues found no differences in rates of
death, MI, unstable angina, stroke, or hospital admission for
congestive heart failure (CHF) between the AHA- and Mediterranean-
diet groups. Strikingly, however, people randomized to either diet
were significantly more likely than people in the usual-care group
to avoid these events over the follow-up period. A total of eight
events occurred in each of the dietary-intervention groups, none of
them deaths; by contrast, 40 events occurred in the usual-care
group, of which seven were deaths. Strokes also occurred
significantly more often in the usual-care group.

The AHA and Mediterranean diets also produced significant
improvements in HDL and triglyceride levels over 24 months of follow-
up, although with trends toward increased LDL-cholesterol, as
compared with baseline levels; changes, however, were no different
between the two groups.

"AHA step II and Mediterranean-style dietary interventions had
similar benefits on cardiovascular outcomes and risk factors after
MI," Tuttle concluded.

Intensity of intervention, not type, may be key

The equivalent findings were well received by trial participants,
Tuttle noted during the discussion following her formal presentation
of the trial results. "One of the things that our dieticians
regularly reported was that for the people in this study--these were
American, older, white patients in the Northwest--a lot of these
patients . . . actually had trouble increasing their intake of olive
oil and fish. They did it, but they were relieved by these results,
because they preferred the low-fat diet," she said.

One of the session moderators, Dr Paul Ridker (Brigham and Women's
Hospital, Boston, MA), pointed out that the most "compelling"
finding may not be the equivalent findings between the two
intervention groups but the difference between the intervention and
usual-care groups, underscoring the importance of healthcare
provider support for dietary interventions.

It's a point echoed by Tuttle, who told heartwire that the study,
more than anything, shows the value of providing more intensive
support for people who are trying to make significant dietary and
lifestyle changes, regardless of the type of diet. In this study,
participants were only required to attend the group counseling
sessions six times over the 24 months but were encouraged to attend
monthly classes if desired. Many took advantage of these extra
classes, said Tuttle, not only to have the support of the dieticians
and counselors but also for the encouragement of fellow study
participants.

Commenting on the study for heartwire, Dr Sidney Smith (University
of North Carolina, Chapel Hill) said, "I think the most important
message from this study is that diets based on a reduced intake of
cholesterol and saturated fats can have an impact on top of optimal
medical therapy."

But Smith, too, singled out the value of intensive, ongoing support
for dietary changes. "This study points to the importance of
including counseling for diet as part of patient-discharge routines.
This is one of the things we've fought for, reimbursement for diet,
smoking-cessation, and exercise counseling, and this story really
speaks to the impact of that kind of counseling."

First-in-human testing of a novel protein kinase C inhibitor, KAI-
9803, used in the treatment of patients with ST-segment-elevation MI
(STEMI) undergoing PCI has shown the compound to be safe, as well as
having a favorable impact on multiple biomarkers of reperfusion
success.

"We saw consistent trends in some of the biomarkers, like CK-MB area
under the curve (AUC) and ST-segment-recovery AUC, which looks at
how the EKG recovers and how the injury pattern recovers, as well as
some important findings with some of the dose groups," lead
investigator Dr Matthew Roe (Duke Clinical Research Institute,
Durham, NC) told heartwire. "We certainly saw signs of drug
activity, but we can't theorize, for sure, the degree of that or the
significance of that in this small study, as we primarily set out to
show that it was safe. It was certainly safe, and so we think this
paves the way for future studies."

The study, known as Direct Inhibition of {:delta:} Protein Kinase C
Enzyme to Limit Total Infarct Size in Acute Myocardial Infarction
(Delta-MI), was presented this week at the American College of
Cardiology 2007 Scientific Sessions.

Inhibitor of protein kinase C

Speaking with heartwire, Roe explained that protein kinase C, when
subjected to ischemia and reperfusion, will move from the cell
membrane to the mitochondria. In turn, this stimulates a number of
intercellular processes deleterious to the cells, eventually causing
cell death and the destruction of cellular metabolism. To inhibit
protein kinase C during PCI, KAI-9803 is first administered via the
lumen of the balloon to the distal vessel after the guidewire is
removed and before flow is reestablished. After flow is
reestablished, a second dose is administered down the guide catheter
to bathe the whole area with the drug.


"This drug goes into the cell, blocks the receptor that protein
kinase C would move to from the membrane to the mitochondria, and
prevents all those destructive processes from occurring," he
said. "So it's really a novel compound in that it targets this one
specific mechanism of cellular activity. We gave the drug before
reperfusion occurred so that we knew the drug would be in the
myocardial cells before blood flow was restored and before all these
activities tended to be upregulated and happen in a dramatic
cascade."

In total, 150 patients with anterior STEMI undergoing planned PCI
were randomized in a 2:1 manner to intracoronary KAI-9803 or
placebo. Investigators tested four doses--0.05 mg, 0.5 mg, 1.25 mg,
and 5.0 mg--and measured various biomarkers, including continuous ST-
monitoring and infarct size by CK-MB.

Results showed that KAI-9803 might be associated with less
myocardial necrosis and with lower CK-MB AUC values at all dose
levels. Furthermore, improved tissue perfusion, measured during
coronary angiography after stent implantation and by continuous
electrocardiogram recordings, and reduced infarct size 14 days after
MI were observed at the 0.5-mg and 1.25-mg dose levels. No serious
adverse events required termination of KAI-9803, and there were no
significant differences in safety parameters in the two study arms.

Asked about the need for adjunctive therapy during PCI of STEMI
patients, Roe said better results are still needed in the real world
as well as in patients with comorbidities like heart and renal
failure.

"In reality, the clinical outcomes could be very much improved with
this type of compound," he said. "The impact might not be present at
30 days, but a year or two later, when we see if the patient
develops heart failure or has arrhythmia."

Until a large, randomized controlled trial that's still in the works
sheds a brighter light on the question, concerns that nesiritide may
be renotoxic or life-threatening when used in patients with acute
decompensated heart failure (ADHF) are based on hindsight
observations from separate, often very different studies [1,2]. With
prospectively gained insights in short supply, a small randomized,
placebo-controlled trial suggested that the drug neither worsens nor
improves kidney function in an especially high-risk population that
presented with ADHF and moderate to severe renal insufficiency [3].

Although it randomized only 75 patients, "the results of our study
don't show even a hint of a trend, positive or negative, on renal
function," Dr Ronald M Witteles (Stanford University, CA) told
heartwire. "So the likelihood of [our] missing a large adverse renal
effect from this treatment is small."

As the first ADHF trial to prospectively evaluate the drug's effects
on renal function, Witteles said, finding "no indication of benefit
or harm," it should "alleviate some concerns" about the use of
nesiritide. He presented the findings here at the American College
of Cardiology 2007 Scientific Sessions.

The patients, required at randomization to have a glomerular
filtration rate (GFR) of 15 to 60 mL/min, received either nesiritide
as a 0.01-µg/kg/min infusion for 48 hours or matching placebo.
Patients also received an initial 2-µg/kg bolus at the treating
physicians' discretion; more often than not, the bolus was omitted
as a caution in patients with preexisting hypotension, which
occurred in about 35% of patients in each group, Witteles said.

The mean admission serum creatinine was about the same in both
groups, 1.82 and 1.86 mg/dL for nesiritide recipients and controls,
respectively. Also comparable were the admission GFR and systolic
blood pressure.

There were no significant differences in either primary end point,
prevention of worsened renal function (defined as >20% increase in
serum creatinine compared with admission) and change in serum
creatinine from admission to discharge or the seventh hospital day,
whichever came first, Witteles reported. Nor were there differences
in a range of secondary end points, including weight loss,
furosemide intake, hypotension prompting withdrawal of the
continuous infusion, and hospital length of stay.

Thirty-day mortality and rate of death or rehospitalization were
statistically similar, although there were "small trends favoring
placebo," Witteles said. But he noted the trial was underpowered to
show any such differences authoritatively.

The findings "should make people more comfortable" about using
nesiritide in ADHF, agreed Dr Barry M Massie (University of
California and Veterans Affairs Medical Center, San Francisco), who
wasn't involved in the trial. Any evidence for nesiritide's kidney
effects should be kept in perspective, he observed for heartwire: in
the previous trials that led to concerns that the drug may be
renotoxic, serum creatinine levels were seen to be increased often
later than one week after the nesiritide infusion, inconsistently,
and in presumably sicker patients who had subsequently come back to
the hospital. The current study's results may be more reliable,
according to Massie. "Common sense tells me, if a drug is going to
affect renal function, you should see it by seven days."

He also said the findings dispute the idea that nesiritide protects
the kidneys when given with diuretics, which had been the drug's
reputation and a key reason for its previous popularity in ADHF. "My
concern all along was that there was no evidence that it improved
renal function, and yet physicians believed it."

Scios funded the current study, which Witteles said, nonetheless,
was "investigator-initiated." Massie is a member of the steering
committee for the Scios-backed FUSION-2 and ASCEND-HF trials and
reports having consulted for Scios. Coauthor Dr Donald Schreiber
(Stanford University) reports being on the speakers' bureau for
Sanofi-Aventis and Schering and receiving research support from
Abbott Point of Care, Scios, and AstraZeneca. Coauthor Dr Michael
Fowler (Stanford University) reports receiving consulting fees or
honoraria from AstraZeneca, Scios, Medtronic, Merck, and
GlaxoSmithKline and research support from Scios.

Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K. Short-term risk
of death after treatment with nesiritide for decompensated heart
failure: A pooled analysis of randomized controlled trials. JAMA
2005; 293:1900-1905.
Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of worsening
renal function with nesiritide in patients with acutely
decompensated heart failure. Circulation 2005; 111:1487-1491.
Witteles RM, Kao D, Vagelos R, et al. Nesiritide does not cause
renal dysfunction in acute decompensated heart failure: A
randomized, double-blind, placebo-controlled study. American College
of Cardiology 2007 Scientific Sessions; March 26, 2007; New Orleans,
LA. Abstract 808-4.

Dehydroepiandrosterone (DHEA) supplementation does not improve
insulin secretion, insulin action, or postprandial glucose turnover
in the elderly, researchers report in the March issue of Diabetes.

"While it is clear that both DHEA and glucose tolerance decrease
with age, the former does not appear to cause the latter," senior
investigator Dr. Robert A. Rizza told Reuters Health. "Treatment of
elderly subjects with DHEA in amounts sufficient to restore their
concentrations present in young healthy subjects does not improve
glucose tolerance."

Dr. Rizza, of the Mayo Clinic, Rochester, Minnesota, and colleagues
note that in a previous study, they found that DHEA replacement had
no beneficial effects on quality of life, body composition, or
physical performance in such patients.

To investigate a possible influence on insulin action, the
researchers randomized 112 elderly men and women with relative DHEA
deficiency to receive DHEA or placebo for a period of 2 years.

Despite restoring DHEA sulfate concentrations to values observed in
young men and women, the investigators observe that "the changes
over time in fasting and postprandial glucose concentrations, meal
appearance, glucose disposal, and endogenous glucose production were
identical to those observed after 2 years of placebo."

"These data strongly argue against a role of DHEA deficiency in the
pathogenesis of age-related deterioration in glucose tolerance,"
they conclude. "They also provide further evidence that DHEA has
little or no value as an anti-aging drug in elderly subjects and
therefore should not be used for this purpose."

Diabetes 2007;56:753-766.

Full data from the Aggressive Reduction of Inflammation Stops Events
(ARISE) study, a phase 3, double-blind, placebo-controlled trial
with succinobucol (AGI-1067, AtheroGenics Inc), were presented today
at the American College of Cardiology 2007 Scientific Sessions, and
although the study missed its primary end point, investigators say
they remain "bullish" on the compound.

The study, designed to assess the incremental benefits of
succinobucol over current standard of care in coronary-artery-
disease (CAD) patients, showed that the novel compound did not
reduce the length of time to the first occurrence of cardiovascular
mortality, resuscitated cardiac arrest, nonfatal MI, nonfatal
stroke, hospitalization for angina pectoris, or use of coronary
revascularization, findings that were previously reported by
heartwire. There was, however, a significant 19% reduction in
cardiovascular death, cardiac arrest, MI, and stroke, a prespecified
secondary end point, as well as a significant reduction in new-onset
diabetes.

Dr Jean-Claude Tardif, the coprincipal investigator who presented
the ARISE findings during the late-breaking clinical-trials session,
told the press he was cautiously optimistic about the results and
that the positive secondary findings could be used to direct future
research.

"Reductions in heart attacks and strokes are certainly something
that is very clinically relevant," Tardif said. "Yes, we have to
confirm these findings because our primary end point was not
achieved, but if you have a drug, irrespective of things you can
measure in the blood, that is reducing MI, stroke, and new-onset
diabetes, on top of standard of care, and we can confirm that in the
next trial, I think this is a very promising therapy.

During the clinical-trials session, however, Dr Robert Harrington
(Duke Clinical Research Institute, Durham, NC) expressed concern
about interpreting the results too positively, especially in light
of the fact that succinobucol increased LDL-cholesterol levels,
decreased HDL-cholesterol levels, and was associated with a trend
toward more heart-failure hospitalizations.

"Perhaps we should be a little more cautious here," said
Harrington. "You have some good things going in one direction, some
bad things going in another, some good metabolic parameters with
glucose control, some bad metabolic parameters with LDL and HDL, so
I'm really not sure what to make of this other than things going in
both directions. Overall, I'd say it's probably pretty neutral."

Some signals going in strange directions

AGI-1067 was the first in a new class of drugs, known as vascular
protectants, that aimed to reduce inflammation in blood-vessel walls
and to provide antioxidant protection. Investigators sought to test
whether the agent would provide additional protection on top of
standard care in patients with CAD. In total, 6144 patients with
acute coronary syndrome were randomized to succinobucol or placebo,
and all patients were well treated, with 90% of patients taking
statins and aspirin, as well as ACE inhibitors, beta blockers, or
other lipid-lowering therapies.

Results showed no difference in the primary end point, with the
Kaplan-Meier curves for placebo and succinobucol virtually
identical. Regarding the prespecified secondary end points, there
was no significant difference in the composite of cardiovascular
death, cardiac arrest, MI, stroke, or unstable angina. However, when
unstable angina was removed, there was a significant 19% reduction
in cardiovascular death, cardiac arrest, MI, or stroke. In addition,
investigators also reported a significant 64% reduction in new-onset
diabetes mellitus.

Tardif said that he did not believe this to be chance finding and
that he remains "pretty upbeat" about the drug.

However, as noted by Harrington, the agent moved lipid levels in an
atherogenic fashion, increasing LDL cholesterol and decreasing HDL
cholesterol. Although the drug was safe and well tolerated, there
was an increase in heart-failure hospitalizations observed with the
drug. Addressing the lipid findings, Tardif pointed to the late-
breaking torcetrapib studies, in which he participated, that showed
significant decreases in LDL cholesterol and dramatic increases in
HDL cholesterol but also an increased risk of cardiovascular
mortality and clinical events. Reducing hard cardiovascular events,
as observed in ARISE, is "more important than an LDL number," he
said.

Results hopeful

Commenting on the study, Dr E Murat Tuzcu (Cleveland Clinic, OH),
who chaired the media briefing, said he believed that further study
of the drug is warranted.

"The results do not tell us to give credence to these therapies,"
said Tuzcu. "But they also tell us that we shouldn't lose hope with
this because there are positive signals. Now, this is an arduous and
slow process but it will allow us to go forward more intelligently
and with more information."

AtheroGenics has previously said it would continue to develop the
drug, based on these positive secondary end points, and prepare for
discussions with the US Food and Drug Administration (FDA) on how to
proceed further. In December 2005, AstraZeneca agreed to pay
AtheroGenics up to $1 billion for exclusive rights to the drug,
although payment was contingent upon the drug's approval by the FDA.
AstraZeneca currently has a limited time window to decide if it
wishes continue its involvement with the drug program.

The new antianginal drug ranolazine (CV Therapeutics) has no role in
ACS patients, according to the results of the MERLIN TIMI-36 trial.
But the study has provided reassurance about the drug¡¦s safety
profile in stable angina patients.

Ranolazine was approved in 2006 for use in treating angina pain, but
because the drug increases the QT interval, there has been some
concern that it might have proarrhythmic effects, and its indication
has therefore been limited to second-line therapy in patients who
continue to experience angina despite treatment with another class
of antianginal medication. Following the reassuring safety data from
this trial, it is expected that the drug will gain a first-line
indication for the treatment of stable angina.

Lead investigator Dr David Morrow (Brigham and Women¡¦s Hospital,
Boston, MA) explained that the MERLIN trial was conducted to
investigate three issues: whether ranolazine had a role in the new
indication of ACS; whether the drug had disease-modifying effects in
stable patients; and to gain more data on its long-term safety
profile. Although the first two objectives were not met, the trial
did successfully address safety concerns with the drug, showing no
adverse trend in death or arrhythmia and suggesting that, if
anything, it might have antiarrhythmic effects.

The trial enrolled 6560 non-ST-elevation ACS patients who were all
treated with standard of care and randomized to ranolazine or
placebo. Ranolazine was administered as a 200-mg IV infusion given
over one hour, followed by an 80-mg/h infusion for up to 96 hours.
Oral treatment (1000 mg twice daily) was then given for
approximately 12 months. Results showed no difference between the
two groups in the primary end point of cardiovascular
death/MI/recurrent ischemia. On further analysis, it was found that
the drug had no effect on cardiovascular death or MI, so did not
have disease-modifying effects, but its antianginal effect was
confirmed, with a significant reduction in recurrent ischemia.

The new antianginal drug ranolazine (CV Therapeutics) has no role in
ACS patients, according to the results of the MERLIN TIMI-36 trial.
But the study has provided reassurance about the drug¡¦s safety
profile in stable angina patients.

Ranolazine was approved in 2006 for use in treating angina pain, but
because the drug increases the QT interval, there has been some
concern that it might have proarrhythmic effects, and its indication
has therefore been limited to second-line therapy in patients who
continue to experience angina despite treatment with another class
of antianginal medication. Following the reassuring safety data from
this trial, it is expected that the drug will gain a first-line
indication for the treatment of stable angina.

Lead investigator Dr David Morrow (Brigham and Women¡¦s Hospital,
Boston, MA) explained that the MERLIN trial was conducted to
investigate three issues: whether ranolazine had a role in the new
indication of ACS; whether the drug had disease-modifying effects in
stable patients; and to gain more data on its long-term safety
profile. Although the first two objectives were not met, the trial
did successfully address safety concerns with the drug, showing no
adverse trend in death or arrhythmia and suggesting that, if
anything, it might have antiarrhythmic effects.

The trial enrolled 6560 non-ST-elevation ACS patients who were all
treated with standard of care and randomized to ranolazine or
placebo. Ranolazine was administered as a 200-mg IV infusion given
over one hour, followed by an 80-mg/h infusion for up to 96 hours.
Oral treatment (1000 mg twice daily) was then given for
approximately 12 months. Results showed no difference between the
two groups in the primary end point of cardiovascular
death/MI/recurrent ischemia. On further analysis, it was found that
the drug had no effect on cardiovascular death or MI, so did not
have disease-modifying effects, but its antianginal effect was
confirmed, with a significant reduction in recurrent ischemia.

Safety results showed no difference between the two groups in death
from any cause or sudden cardiovascular death. In addition, there
was a reduction in clinically significant arrhythmia on Holter
monitoring.

Morrow commented: ¡§These results support the safety of ranolazine
in a much larger population than previously studied. There were
concerns that this drug may have been proarrhythmic, but our results
actually suggest the opposite--that it could be antiarrhythmic. This
has also been suggested in experimental studies, and it warrants
additional investigation in further clinical trials.¡¨

Cochair of the late-breaking clinical-trial session at which the
MERLIN study was presented, Dr Salim Yusuf (McMaster University,
Hamilton, ON), agreed that the results supported the use of
ranolazine in stable disease. Continuing his campaign against the
use of angioplasty in stable coronary disease patients, he quipped:
¡§Ranolazine actually looks as good as PCI in this indication.¡¨

In recent years, young patients with type 1 diabetes appear to be
benefiting from more intensive management than was previously the
case, researchers report in the March issue of the Journal of
Pediatrics

"We have witnessed significant improvement in diabetes control in
children and adolescents with type 1 diabetes over the past decade,"
senior investigator Dr. Lori M. B. Laffel told Reuters Health.

"This improvement follows the routine use of intensive treatment
tools such as frequent blood glucose monitoring, new insulin
analogs, and more frequent insulin injections or insulin pump
therapy for youth with diabetes," she added.

Dr. Laffel, of Harvard Medical School, Boston, and colleagues came
to this conclusion after following 299 diabetic children for 2
years. Findings in this group, who were enrolled in 1997, were then
compared with those in a group of 152 children who were enrolled in
2002 and also followed for 2 years.

As well as showing improved control, children in the more recent
group had an incidence of severe hypoglycemic events that was almost
50% lower than those in the patients studied earlier. They also had
25% fewer emergency room visits.

Moreover, although a trial conducted in the 1990s had indicated that
the use of intensive insulin therapy was associated with significant
weight gain, said Dr. Laffel, "there has been no excessive weight
gain in association with these newer treatment approaches."

"We are encouraged by these improvements, although we need to
continue to find new and improved ways to normalize the blood
sugars," she added.

J Pediatr 2007;150:279-285.

Insulin pump users with type 1 diabetes who actively participate in
self-care, have realistic expectations of pump use, and have
emotional recall of diabetes diagnosis are more likely to have
better glycemic control, according to results of a study published
in the March issue of Diabetes Care.

Dr. Katie Weinger, of Harvard Medical School, Boston, and colleagues
had adult insulin pump users take part in focus groups that were
loosely formed on the basis of the subjects' A1C level. Five
reviewers used NVivo2 qualitative software to code transcripts of
the focus group meetings into themes.

A total of 30 long-term diabetics participated in five focus groups.
Two of the groups had low mean A1C (6.8%), one had mild A1C (7.8%),
and two had high A1C (9.1%). The authors report that three major
themes were identified: impact on diabetes self-care, emotional
reactions to the insulin pump, and body image and social acceptance.

Subjects in the low A1C group described the pump as a tool to meet
glycemic goals. These patients had a more active approach to
diabetes. Patients who described the pump as a panacea had a more
passive approach to self-care and had poorer glycemic control.

Patients in the low A1C groups reported emotional reactions to
starting the insulin pump that reminded them of feelings they
experienced when they were initially diagnosed with diabetes.
Subjects in the high A1C groups did not report experiencing these
feelings.

"Participants in the low A1C groups stated that the pump helped them
feel more accepting of their diabetes, less ashamed of it, and able
to speak about it to others for the first time," Dr. Weinger and
colleagues write.

"In contrast, high A1C group participants spoke of being 'tired' of
the pump," they note. "They described feeling discouraged
and 'frustrated' that the pump did not 'fix everything' and
that 'it's still a lot of work.'"

The researchers report that women were more concerned than men about
body image and social acceptance with insulin pump use.

"Interventions to improve diabetes management with pump use should
include evaluation and discussion of active versus passive
approaches to self-care, recall of diabetes diagnosis, expectations
of the pump, and pump-related self-consciousness and body image
concerns," they conclude.

Diabetes Care 2007;30:549-554.

In recent years, young patients with type 1 diabetes appear to be
benefiting from more intensive management than was previously the
case, researchers report in the March issue of the Journal of
Pediatrics

"We have witnessed significant improvement in diabetes control in
children and adolescents with type 1 diabetes over the past decade,"
senior investigator Dr. Lori M. B. Laffel told Reuters Health.

"This improvement follows the routine use of intensive treatment
tools such as frequent blood glucose monitoring, new insulin
analogs, and more frequent insulin injections or insulin pump
therapy for youth with diabetes," she added.

Dr. Laffel, of Harvard Medical School, Boston, and colleagues came
to this conclusion after following 299 diabetic children for 2
years. Findings in this group, who were enrolled in 1997, were then
compared with those in a group of 152 children who were enrolled in
2002 and also followed for 2 years.

As well as showing improved control, children in the more recent
group had an incidence of severe hypoglycemic events that was almost
50% lower than those in the patients studied earlier. They also had
25% fewer emergency room visits.

Moreover, although a trial conducted in the 1990s had indicated that
the use of intensive insulin therapy was associated with significant
weight gain, said Dr. Laffel, "there has been no excessive weight
gain in association with these newer treatment approaches."

"We are encouraged by these improvements, although we need to
continue to find new and improved ways to normalize the blood
sugars," she added.

J Pediatr 2007;150:279-285.

Lowering blood pressure can improve diastolic dysfunction even in
patients with mild hypertension, a new study has shown.

The Valsartan in Diastolic Dysfunction (VALIDD) trial, presented
today at the American College of Cardiology 2007 Scientific
Sessions, is the first large-scale randomized trial to assess a
therapeutic intervention for improvement of diastolic function using
new noninvasive Doppler technology. The study¡¦s primary objective
was to compare the effect on diastolic dysfunction of two
antihypertensive regimens--one based on an inhibitor of the renin
angiotensin system (RAS) and one based on other medications--in
patients with mild hypertension. While there was no difference
between these two groups, both groups showed a substantial reduction
in blood pressure that was itself associated with a significant
improvement in diastolic dysfunction.

Lead investigator Dr Scott Solomon (Brigham and Women¡¦s Hospital,
Boston, MA) said: ¡§Our study has shown an important result.
Diastolic dysfunction is an important pathophysiology between
hypertension and heart failure, affecting around half of
hypertension patients. Patients with diastolic dysfunction have an
increased risk of developing heart failure, but there is no targeted
therapy for this condition. This study suggests that lowering blood
pressure is the most important thing we can do for patients with
hypertension and diastolic dysfunction and shows that we need to be
more aggressive in this regard even in patients with only mildly
elevated blood pressure."

Dr Randall C Starling (Cleveland Clinic, OH), cochair of the late-
breaking clinical-trial session at which these results were
presented, agreed. ¡§Although this trial did not show a difference
between the two regimens studied, there is still a very important
public-health message here," he commented.

Introducing the trial, Solomon noted that although many studies have
shown that treating hypertension can regress left ventricular
hypertrophy (LVH), the effect on diastolic dysfunction is not known.
¡§There is a tremendous amount of research focusing on systolic
function, but there is very little information on diastolic
function, which is also an important cause of heart failure," he
said. The recent availability of Doppler tissue-imaging technology
now allows diastolic dysfunction to be measured easily in a
noninvasive way and so should lead to more studies in this field. As
inhibition of the renin angiotensin system brings about other
benefits than just lowering blood pressure, such as better
regression of LVH and reduction of myocardial fibrosis, Solomon and
his colleagues tested the hypothesis that lowering blood pressure
with a RAS inhibitor would improve diastolic function to a greater
extent than blood-pressure lowering without inhibiting the RAS.

In the study, 482 patients older than age 45 with a history of or
untreated hypertension and without heart failure underwent screening
for diastolic dysfunction using tissue Doppler assessment of
myocardial relaxation velocities. The 384 patients with evidence of
diastolic dysfunction based on low lateral annular relaxation
velocities (<10 cm/s if age 45-55; <9 cm/s if age 55-65; <8 cm/s if
age > 65) were randomized to blood-pressure lowering with the
angiotensin receptor blocker valsartan 320 mg daily vs blood-
pressure lowering without RAS inhibitors for 38 weeks. In addition
to study medication, patients were given standard blood-pressure-
lowering drugs, such as diuretics, beta blockers, or calcium-channel
blockers if needed, with the aim of achieving a target blood-
pressure rate of 135/80 mm Hg in both treatment groups. Change in
diastolic dysfunction (as measured by diastolic relaxation
velocities) between baseline and 38 weeks was compared.

Results showed that at baseline patients had only mildly elevated
blood pressure (an average of 144/86 mm Hg) and that after treatment
there was a greater than 10-mm-Hg reduction in blood pressure in
both treatment groups. Diastolic function was also improved
significantly in both groups, although the improvement observed in
the valsartan group was similar to that in the other
antihypertensive group.

Solomon pointed out that despite the fact all patients included in
this study had hypertension, there was a very low incidence of LVH
(less than 4%) or myocardial structural changes. ¡§We thought we
would have seen a higher prevalence of LVH and myocardial fibrosis
and, if we had, we may have shown a more pronounced effect in the
valsartan group.

¡§We are seeing the effect of a hemodynamic benefit in this study,
but we may have seen a difference between the two groups if the
condition of the population had not been so benign," he speculated.
¡§We have shown that reducing blood pressure has a beneficial effect
on diastolic function, but the question of whether there is an
incremental effect of RAS inhibition will have to wait for further
studies," he added.

Solomon and his colleagues are now planning another study in
patients with more severe hypertension. This new study, known as
EXCEED, will test a slightly different concept--whether more
aggressive blood-pressure lowering improves diastolic dysfunction
more than less aggressive blood-pressure lowering. Both groups will
be treated with a combination of valsartan and amlodipine but at
different doses to correlate with aggressive or less aggressive
therapy.

Levels of CRP are predictive of future risk of cardiovascular events
in patients with stable coronary artery disease, and risk starts to
increase at lower levels of CRP than previously thought, a new study
has shown [1].

Lead author Dr Marc Sabatine (Brigham and Women¡¦s Hospital, Boston,
MA) explained to heartwire that many studies have shown CRP levels
to be a predictor of cardiovascular events in healthy individuals
and in patients with ACS, but there was not much information on the
population with stable coronary heart disease. ¡§We have data on
this from both ends of the spectrum, but until now there has been a
large gap in the middle that we have not known much about," he
commented. ¡§We have now filled that gap in our knowledge."

In their study, which will be published in the March 27, 2007 issue
of Circulation, Sabatine et al measured high-sensitivity (hs) CRP in
3771 patients with stable coronary artery disease enrolled in the
PEACE trial, a randomized placebo-controlled trial of the ACE
inhibitor trandolapril. Patients were followed up for a median of
4.8 years. Results showed that after adjustment for baseline
characteristics and treatments, levels of hs-CRP above 1 mg/L were
found to be associated with a significantly greater risk of
cardiovascular death, MI, or stroke compared with levels below 1
mg/L.

In addition, elevated hs-CRP levels were an independent predictor of
new heart failure and new diabetes but did not identify patients who
derived particular benefit from the ACE inhibitor.

Sabatine pointed out that in most other studies examining CRP levels
and future cardiovascular risk, increased risk has not been apparent
until CRP levels reached 3 or higher, but in the current study,
increased risk was observed at the much lower cutoff value of 1
mg/L. He explained that this study probably gave a more accurate
result, as it had greater power than some previous studies, with 400
major events in almost 4000 patients. ¡§The biology of CRP is no
different; it¡¦s just that prior studies have been unable to show
the increased risk down to this level," he said. Noting that the US
Centers for Disease Control and the American Heart Association
recommend categorizing patients using predefined CRP cut points of
<1, 1 to 3, and >3 mg/L into low-, average-, and high-risk
categories, respectively, Sabatine noted that this study suggests
people categorized as ¡§average¡¨ risk according to this definition
are actually at increased risk. ¡¥These CDC/AHA cutoff points are
not unreasonable, but we are saying that it would really be
desirable to have a CRP level less than 1," he told heartwire.

Not practice-changing at present

Sabatine noted that treatment of patients will not change because of
this information at present, as all such patients should be treated
with statins whatever their level of CRP and the effect of ACE
inhibition was not different according to CRP levels in this study.
¡§As yet, there is no clinical mandate to measure CRP, but higher
levels of CRP do tell us that these patients are at higher absolute
risk and therefore will gain a greater relative benefit from
interventions. This study also underscores the importance of
inflammation in CHD and suggests that if we ever do get an anti-
inflammatory therapy, this could be targeted to those patients with
increased levels of CRP."

In the paper, the researchers conclude: ¡§Data from studies of
statin therapy suggest that patients with CAD who have a
persistently elevated hs-CRP level remain at increased risk of
adverse cardiovascular events and that lower levels of hs-CRP are
achieved with more intensive statin therapy. However, we await the
results of prospective trials that target therapy based on CRP
levels. Depending on the data that emerge, CRP may then join the
other classic risk factors that we routinely measure and treat."

Sabatine MS, Morrow DA, Jablonski KA, et al. Prognostic significance
of the Centers for Disease Control/American Heart Association high-
sensitivity C-reactive protein cut points for cardiovascular and
other outcomes in patients with stable coronary artery disease.
Circulation 2007; 115:1528-1536.

PCI plus stenting and optimal medical therapy is no better at
preventing future events than optimal medical therapy alone in
patients with stable coronary disease, according to the results of
the Clinical Outcomes Utilizing Revascularization and Aggressive
Drug Evaluation (COURAGE) trial [1]. The much-anticipated results
add fat to the mounting fire over whether stents, including drug-
eluting stents, are being overused for the treatment of stable CAD
or for the prevention of future cardiac events.

After embargo break, COURAGE results released early

Originally slated for presentation on the final day of the American
College of Cardiology 2007 Scientific Sessions, COURAGE trial
results were published in the online edition of the Wall Street
Journal on Monday, prompting the ACC to permit early publication of
the results by other news organizations. According to the Journal,
results of the study were discussed at a Boston Scientific-sponsored
symposium Sunday night; perhaps not surprisingly, the Journal story
is largely dismissive of the trial results. The Journal story quotes
Dr Martin Leon as calling COURAGE a "critically flawed study." The
article also states that Leon "had reviewed the COURAGE study after
it was submitted to a medical journal."

Lead investigator Dr William E Boden (Buffalo General Hospital, NY)
will present the results Tuesday morning, with full results of the
study published simultaneously online March 27, 2007 in the New
England Journal of Medicine.

"Although the addition of PCI to optimal medical therapy reduced the
prevalence of angina, it did not reduce long-term rates of death,
nonfatal myocardial infarction, and hospitalization for acute
coronary syndromes," Boden et al conclude in the published paper.

In an editorial accompanying the study, Drs Judith S Hochman (New
York University School of Medicine, NY) and P Gabriel Steg (Universit
é Paris, France) say the study findings are practice-changing [2].

"The COURAGE trial should lead to changes in the treatment of
patients with stable coronary artery disease, with expected
substantial healthcare savings," they write. "PCI has an established
place in treating angina but is not superior to intensive medical
therapy to prevent myocardial infarction and death in symptomatic or
asymptomatic patients such as those in this study."

Other commentators suggested the findings are not unexpected. "PCI
has never been shown to reduce death or MI compared with medical
therapy," Dr Eric Topol (Scripps Translational Science Institute, La
Jolla, CA) told heartwire. "COURAGE really does not present anything
new but simply reinforces that the basis for revascularization is
for control of ischemia. There is no surprise with this trial."

Likewise, Dr Christopher Cannon (Brigham and Women's Hospital,
Boston, MA) called the trial confirmation of a "back-to-basics
approach."

"This is actually what many people would have expected, thinking
about the pathophysiology of stable CAD, but it runs a little bit
counter to the current sucking sound of patients being drawn to the
cath lab," he told heartwire. "Anyone with ACS ends up being cathed
appropriately, but many other people have ended up in the cath lab
as well."

But many cardiologists--interventionalists in particular--may not be
easily persuaded by the results. "The real question is whether
cardiologists will have the 'courage' to change the way they
practice, which in 2007 flies in the face of the evidence," said Dr
James Stein (University of Wisconsin, Madison). "We know PCI in the
setting of an acute coronary syndrome saves lives, but 85% of PCIs
in the US are done in stable patients, and of those I'd bet that at
least 25% are asymptomatic patients. This study clearly shows
something we all knew--but many did not want to believe--that
angioplasties don't save lives, except in acutely ill patients, and
don't prevent heart attacks. Cardiologists say yes, we know that, we
are relieving symptoms, but why are so many done on people who are
asymptomatic? And why all the 'screening' stress tests?"

Dr Eric Cohen (Sunnybrook Health Sciences Centre and Women's College
Hospital, Toronto, ON), who was a site investigator for COURAGE,
commented, "COURAGE does not tell us that there is no role for PCI
in the management of stable CAD, but I think it is telling us to be
more selective in targeting only those patients with very
significant symptoms and to be more modest in our expectation of
what is achieved."

Cohen also pointed out that Canadian centers made
a "disproportionately large" contribution to the COURAGE
study, "perhaps because the momentum leading directly to PCI was
slightly less intense in Canada at the time and thus patients and
physicians were somewhat more amenable to randomization."

The implications from COURAGE are good news for Canada and other
countries where PCI is not available to large portions of the
population. "Utilization of PCI has grown substantially in Canada
during the [duration] of the COURAGE trial but remains below most of
the US.  The results of COURAGE suggest that despite a lower rate of
PCI in Canada, our patients with stable CAD are not being
disadvantaged in terms of hard outcomes. It also suggests that in
the US, particularly in some regions with very high rates of PCI,
utilization could likely be reduced without a detrimental impact on
clinical outcome."

Summoning COURAGE

Between 1999 and 2004, the COURAGE trial enrolled and randomized
2287 patients either to PCI plus optimal medical therapy or to
optimal medical therapy alone. Over a follow-up period ranging from
2.5 to 7.0 years, a total of 211 all-cause deaths or nonfatal MIs
(the primary outcome of COURAGE) occurred in the PCI group, compared
with 202 in the medical-therapy group, a statistically
nonsignificant difference. When stroke was added to the composite
end point, again there were no differences seen between the two
groups. When outcomes were analyzed individually, there were no
differences in rates of deaths, MI, stroke, or hospitalization for
acute coronary syndromes between the PCI and medical-therapy groups.

Over the median 4.6 years of follow-up, more medical-therapy
patients than PCI-treated patients underwent subsequent
revascularization, usually due to refractive angina or objective,
noninvasive evidence of worsening ischemia.

The only statistically significant difference between the two
treatment strategies was reduced prevalence of angina, which was
greater in the PCI group at one and three years. However, by five
years--in part a reflection of subsequent revascularization in the
medical-therapy group--there was no significant difference in
freedom from angina, with roughly 73% of both groups reporting no
angina at five years.

Boden and colleagues propose that their findings can be explained,
in part, by the fact that plaque morphology and vascular remodeling
are different in ACS--where stenting has proved superior to medical
therapy--than in stable coronary disease. Focal management of stable
lesions through PCI would not lead to a reduction of clinical events
if the lesions themselves were in no danger of triggering an acute
coronary event, they explain; by contrast, systemic medical therapy
and risk-factor management may have the effect of reducing plaque
vulnerability.

While the authors identify the low numbers of women and nonwhites in
COURAGE as limitations of the study, they reject the idea that the
lack of drug-eluting stents (DES) should restrict the
generalizability of their results to current-day PCI. "Published
data indicate no benefit (either short-term or long-term) with
respect to death and MI in patients with stable CAD who receive DES,
as compared with those who receive bare-metal stents," they write.

Shaking things up

Commenting on the study, Cannon predicted that COURAGE "is going to
shake things up in the cath labs," pointing out that the trial
addresses a very important segment of the population: the 30% to 40%
of patients undergoing catheterization and PCI for stable disease.

But the results will be viewed differently for patients with and
without manageable symptoms, Cannon emphasized. While freedom from
angina was similar in both groups in COURAGE at five years, a full
third of medically managed patients underwent PCI or CABG during the
follow-up period, he noted. As such, COURAGE specifically showed a
lack of benefit for PCI over medical therapy for preventing future
events but did not speak to the treatment of patients with
refractory symptoms.

"Many people undergo stenting for symptoms, and that's appropriate,"
says Cannon. "So of the stable 30% to 40% of patients undergoing
cath, many should continue to do so; it's perfectly valid for them
to undergo revascularization to improve their symptoms. If patients
have real angina, and if they're on one or two meds, or they're very
bothered by their symptoms, and if the goal is to relieve those
symptoms, not prevent future events, then that's okay."

Several experts emphasized to heartwire that the COURAGE results
will provide hard data for physicians concerned about the
medicolegal repercussions of not opting to revascularize on the
basis of screening results.

"The problem is fear of malpractice: docs are afraid of getting sued
if they don't do a stress test and if they don't do a cath in
response to an abnormality," Stein explained.

Cannon agreed: "Now we have something to fall back on," he told
heartwire.

Whether PCI rates take a dip based on COURAGE remains to be
seen. "Economic incentives favor procedures rather than medical
therapy with lifestyle and medications. PCIs are very lucrative for
hospitals and doctors; talking to patients and taking care of their
risk factors, unfortunately, is not," Stein said.

Patients, too, may not want to accept that drugs may be all they
need, Stein added. "Patients don't understand that minor blockages,
not seen on stress tests or opened by PCI, cause the vast majority
of heart attacks. Most docs know that, but many don't practice that
way. A major educational effort is needed."

Boden WE, O'Rourke RA, Teo KK, et al. Optimal medical therapy with
or without PCI for stable coronary disease. N Engl J Med 2007;
DOI:10.1056/NEJMe070829. Available at: http://www.nejm.org.
Hochman JS and Steg PG. Does preventive PCI work? N Engl J Med 2007;
DOI: 10.1056/NEJMe078036. Available at: http://www.nejm.org.

Avoiding meats and fatty foods and adhering to salads and cooked
vegetables appears to reduce the risk of developing type 2 diabetes,
according to study findings published in the March issue of the
American Journal of Epidemiology.

Dr. Allison Hodge, of the University of Melbourne, Australia, and
colleagues examined the association between dietary patterns and
type 2 diabetes in a 4-year prospective study of 36,787 adults in
the Melbourne Collaborative Cohort Study who provided dietary
information. During follow-up, 365 new cases of type 2 diabetes were
diagnosed.

The researchers defined four eating patterns, based on factor
analysis of 123 food and beverage items: Mediterranean,
characterized by olive oil, salad vegetables, legumes and avoidance
of sweet bakery items, margarine and tea (factor 1); salad and
vegetables (factor 2); meats including other fatty foods (factor 3);
and fruits (factor 4).

Factor 1 was associated with country of birth but not with diabetes,
according to the authors. There was an inverse association observed
between factor 2 and diabetes. Factor 3 was positively associated
with diabetes. No association was observed between factor 4 and
diabetes risk.

"Our results suggest that avoiding an eating pattern including meat
and fatty foods, and favoring a pattern high in salad and cooked
vegetables could reduce the risk of developing type 2 diabetes," Dr.
Hodge said in an interview with Reuters Health.

"What is important is that the focus is on eating patterns rather
than single foods," she explained. "It may be that these eating
patterns contribute to diabetes risk through an impact on body
weight; overweight and obesity are still the most important risk
factors for type 2 diabetes."

"One interesting thing about our results is that unlike most
researchers who have identified eating patterns using factor
analysis, we do not find a 'healthy' and an 'unhealthy' pattern,"
Dr. Hodge said. "This may relate to the inclusion of Greek and
Italian migrants to Australia to broaden the range of dietary
intakes in the cohort."

Am J Epidemiol 2007;165:603-610.

Results of a study published in the March issue of the Archives of
Neurology suggest that there is a general association between high
adiposity and an increased risk of dementia, particularly among
the "younger" elderly. In addition to age, other patient factors can
confound this association.

"The few studies exploring the association between adiposity,
measured by body mass index (BMI), and dementia in elderly persons
were conflicting," Dr. Jose A. Luchsinger and colleagues from
Columbia University College of Physicians and Surgeon in New York,
write.

The researchers hypothesized that higher adiposity is associated
with higher dementia risk, and that this relation is attenuated by
age. Their study included 893 subjects with BMI data, 907 with waist
circumference data, and 709 with a second weight measurement. At
baseline, all subjects were free of dementia.

At 5-year follow-up, evaluations revealed 181 incident dementia
cases, 112 Alzheimer's disease cases, and 53 dementia cases
associated with stroke. The mean patient age was 77.0 years.

Patients in the third BMI quartile had a lower dementia risk than
those in the first BMI quartile, after adjusting for demographics
and apolipoprotein E-epsilon-4 status. Patients in the third BMI
quartile also had a lower Alzheimer's disease risk. Those in the
second BMI quartile had a lower risk of dementia associated with
stroke.

"In persons younger than 76 years, the association between BMI
quartiles and dementia resembled a U shape," Dr. Luchsinger's team
explains. "The second (HR, 0.4) and third (HR, 0.3) quartiles were
related to lower risk, while the fourth (HR, 1.0) was similar to the
reference," they note.

"In older people (at least 76 years), dementia risk decreased with
increasing BMI; this association was almost statistically
significant (fourth quartile HR, 0.6; p = 0.07 for trend)."

For all of the subjects, an association was observed between those
in the fourth BMI quartile of waist circumference and a higher risk
of stroke-related dementia.

Subjects younger than 76 who were in the fourth quartile of waist
circumference had an increased risk of dementia (HR, 2.3; p = 0.03
for trend) and Alzheimer's disease (HR, 5.1; p = 0.04 for trend).

Weight loss was associated with a higher risk of dementia and
dementia associated with stroke. Weight gain was related to a higher
risk of dementia associated with stroke only.

Arch Neurol 2007;64:392-398.

Patients with high levels of apolipoprotein A1 and HDL cholesterol
and large HDL particles have a decreased risk of developing
recurrent venous thromboembolism (VTE), a new study has shown [1].
In consecutive patients with a single episode of unprovoked VTE, the
risk of recurrence was cut in half in subjects with apolipoprotein-
A1 levels exceeding 1.30 mg/mL when compared with subjects who had
lower levels.

"The present study is prospective in nature and provides strong
evidence for an association of protection against risk of recurrent
venous thrombosis with elevated levels of apolipoprotein A1, the
major protein component of HDL," write lead author Dr Sabine
Eichinger (Medical University of Vienna, Austria) and colleagues in
a paper published online March 19, 2007 in Circulation. "This
finding may justify further clinical studies to assess whether
strategies to elevate HDL using lifestyle changes will reduce risk
for venous thrombosis."

While dyslipidemia and dyslipoproteinemia are established risk
factors for arterial thrombosis, with lipid-lowering drugs used to
prevent ischemic events, the relevance of dyslipoproteinemia for the
occurrence of VTE is not clear, the authors write. There is
evidence, though, they add, that venous and arterial thrombotic
disease share similar risk factors, including age, male sex,
elevated body weight, lupus anticoagulant, and elevated homocysteine
levels.

With this in mind, investigators sought to examine the association
between HDL-cholesterol levels and recurrent VTE. Using data from
the ongoing Austrian Study of Recurrent Venous Thromboembolism
(AUREC), Eichinger and colleagues studied 772 patients with a first
spontaneous VTE. Average follow-up was 48 months, and recurrent VTE
developed in 100 of the 772 patients.

Overall, patients with a recurrent VTE had significantly lower
levels of apolipoprotein A1 than those without recurrence. When
investigators entered apolipoprotein A1 as a continuous variable in
a Cox proportional hazards model, the relative risk of VTE
recurrence was 0.87 (95% CI 0.80-0.94) for every 0.1-mg/mL increase
in plasma apolipoprotein-A1 levels.

Investigators did not predefine cutoff values for apolipoprotein A1,
due to the hypothesis-generating nature of the study, but instead
looked at the strength and linearity of the association between
apolipoprotein A1 and the risk of recurrence by calculating relative
risks for various apolipoprotein-A1 levels. The strongest
association between apolipoprotein A1 and recurrent VTE was observed
at levels >1.30 mg/mL, which corresponds to the lower limit of the
highest tertile in this cohort. In addition, there was a trend for
association between recurrence and low levels of HDL particles and
HDL cholesterol.

Eichinger and colleagues point out that male sex is an independent
risk factor for VTE recurrence, conveying a fourfold greater risk
than being female. In this study, apolipoprotein-A1 levels were
significantly lower among men than women, suggesting the protective
properties of HDL cholesterol might explain this difference between
the sexes. The authors write, however, that these results warrant
further study, including replication in other patient populations,
especially to determine whether one or more HDL parameters might be
useful to clinicians in assessing the risk of recurrent VTE

Eichinger S, Pecheniuk NM, Hron G, et al. High-density lipoprotein
and the risk of recurrent venous thromboembolism. Circulation 2007;
115:1609-1614.

Three new studies, published in the March 24, 2007 issue of BMJ,
have questioned the clinical and cost effectiveness of stenting and
suggest that surgery may be the better option for many patients.

In an accompanying editorial [1], cardiac surgeon Prof David Taggart
(University of Oxford, UK) says these studies "raise key issues not
only about the decision-making process for intervention in the
individual patient but also how to obtain maximum value from limited
health-service resources."

In an interview with heartwire, Taggart claimed that many patients
are never even informed about the possible benefits of surgery, as
the decision process is handled by an interventional cardiologist.
Taggart is calling for a change in the way these patients are
managed, with a multidisciplinary team being involved in the
decision as to whether to treat with stent or surgery.

Commenting on these papers for heartwire, interventionalist Dr
Robert Harrington (Duke University, Durham, NC) said these studies
and editorial demonstrate a growing concern among cardiac surgeons
that their livelihood is being threatened by PCI, which has evolved
over recent years to be the dominant form of CAD revascularization.
But he added that the call for interdisciplinary teams to evaluate
the revascularization options with patients was an interesting idea
and one that might be beneficial for patients.

LAD single-vessel-disease meta-analysis

The first two papers look at patients with single-vessel disease of
the left anterior descending (LAD) coronary artery [2,3]. The
authors, led by Dr Omer Aziz (Imperial College London, UK),
conducted a meta-analysis of 12 studies comparing the best
percutaneous intervention (transluminal coronary artery stenting)
with the least invasive surgical intervention (minimally invasive
direct coronary artery bypass with left internal thoracic artery) in
such patients.

Results showed that patients who received stents had a higher rate
of recurrence of angina, more major adverse coronary and cerebral
events, and more repeat revascularizations than those who underwent
surgery. But there was no significant difference in MI, stroke, or
mortality at maximum follow-up between interventions. The
researchers conclude that the findings suggest that minimally
invasive direct coronary artery bypass produces a more definitive
revascularization in the mid term in these patients.

Surgery cost-effective in long-term

The second paper, by the same group, looked at the cost-
effectiveness of these procedures, again in patients with single-
vessel disease of the LAD. Results showed that stenting was more
effective and less costly than bypass surgery in the first two
years, but in the third year, bypass surgery, while still more
expensive, became marginally more effective, although not cost-
effective at this point. However, by 10 years, the authors say,
surgery "is probably cost-effective," with a cost of £6274.02 per
quality-adjusted life year (QALY). They conclude that minimally
invasive left internal thoracic artery bypass is more effective than
stenting in the long term, justifying its initial additional cost,
but these findings do not take into account the effect of drug-
eluting stents, for which data on long-term effectiveness are awaited

The third paper deals with a different group of patients--those with
multivessel disease [4]. The authors, led by SC Griffin (University
of York, UK), conducted an observational study comparing cost-
effectiveness of CABG, stenting, or medical management in patients
rated as appropriate for revascularization. Results showed that CABG
seemed cost-effective but stenting did not. "Cost-effectiveness
analysis based on observational data suggests that the clinical
benefit of percutaneous coronary intervention may not be sufficient
to justify its cost," the researchers conclude.

An interventionalist responds

Responding to some of these issues for heartwire, interventional
cardiologist Dr David Moliterno (University of Kentucky, Lexington)
described the meta-analysis by Aziz and colleagues as "provocative,"
but he pointed out that even with data combined from several studies
their data set remains too small to provide new insight or
definitive guidance for clinical practice.

Moliterno said: "It is well established that percutaneous
revascularization and bypass surgery result in similar rates of
death and myocardial infarction at long-term follow-up. Yet if the
results of the present meta-analysis were extended to 1000
surgically treated patients, 17 more deaths and 10 more MIs would
occur at maximum follow-up than if the patients had undergone stent
placement. In contrast, 97 repeat revascularizations would be
avoided with bypass surgery. In this study, bare-metal stents were
used, but the new drug-eluting stents markedly reduce the rate of
repeat revascularizations and therefore could attenuate this benefit
of surgery." He added: "Fortunately, large-scale, prospective
studies are ongoing with the SYNTEX and FREEDOM trials, together
randomizing more than 4000 patients to multivessel bypass surgery vs
drug-eluting-stent placement."

A moving target?

But Taggart argues that this is simply moving the goalposts. "There
have been hosts of studies showing surgery gives better results than
stenting over the past 20 years, but interventional cardiologists
keep on moving the target. When surgery was shown to be better than
balloon angioplasty, they said, "Wait for the stent studies,' and
now they are saying, 'Wait for the drug-eluting-stent studies.' "

He also believes that the benefit of surgery has been underestimated
in most studies, as patients with more severe disease were
excluded. "Most studies comparing stents and surgery have enrolled
patients with minimal disease, and a survival benefit is not going
to show up in these patients. But these results have been rolled out
to justify using stents in all patients. This is a complete
distortion of the evidence," he commented to heartwire

Taggart admits that, conceptually, stenting is obviously a popular
option. "If you can achieve the same results without having to open
the chest, of course this will be appealing. But the result is often
not the same. And there is enormous pressure from the stent
industry, which inevitably influences the situation."

He points out that there is much more evidence in favor of surgery
in patients with multivessel disease, with a survival benefit having
been shown in this group, but there is still an increasing tendency
for these patients to get stents. Taggart believes the fact that
interventional cardiologists alone make the decision of whether
stents or surgery should be used is the stumbling block here. "A
significant number of patients don't even know that surgery is an
option. Patients need to be given all the information on the options
before the decision as to which way to go is made.

"Yes, there is the supermarket convenience of inserting a stent
while the patient is there in the cath lab rather than having to
schedule another procedure time, but this is not a trivial decision.
It is not reasonable for this decision to be made in a couple of
minutes when the patent is lying on the cath-lab table. The
different options need to be explained thoroughly, with input from
both interventionalists and surgeons."

Taggart says some lesions can be stented there and then in the cath
lab and no one will argue--for example, single-vessel disease that
is not proximal and for which stenting will not block a side
branch. "But for more complicated single-vessel lesions and all
multivessel disease, the treatment procedure should be separated
from the diagnostic procedure and not undertaken until the patient
has been informed of all the options," he concludes.

Stop the "mine-is-better-than-yours" mentality

Harrington comments that Taggart has some interesting ideas but that
too much effort (and marketing money) is spent on the "mine-is-
better-than-yours" mentality and that instead all parties should
work together to address the questions that will truly allow better
healthcare. "Care for patients with obstructive CAD should be
evidence based, and PCI and CABG should be thought of as
complementary procedures with benefits (and risks) for different
categories of patients based on CAD anatomy, LV function, other
comorbid conditions, and patient values and preferences," he
concludes.

Taggart DP. Coronary revascularization surgery is effective on
clinical and economic grounds, but stenting does not seem to be cost
effective. BMJ 2007; 334:593-594.
Aziz O, Rao C, Panesar SS et al. Meta-analysis of minimally invasive
internal thoracic artery bypass versus percutaneous
revascularisation for isolated lesions of the left anterior
descending artery. BMJ 2007; 334:617-621.
Rao C, Aziz O, Panesar SS et al. Cost effectiveness analysis of
minimally invasive internal thoracic artery bypass versus
percutaneous revascularisation for isolated lesions of the left
anterior descending artery. BMJ 2007; 334:621-624.
Griffin SC, Barber JA, Manca A. Cost effectiveness of clinically
appropriate decisions on alternative treatments for angina pectoris:
prospective observational study. BMJ 2007; 334:624-628.

Boosting support for the use of multislice computed tomography
(MSCT) in patients presenting to emergency departments with chest
pain, a new study has found that MSCT has a high sensitivity and
specificity for diagnosing or ruling out ACS in these patients [1].

In a study published online March 19, 2007 in Circulation, Dr Ronen
Rubinshtein (Technion-Israel Institute of Technology, Haifa, Israel)
and colleagues say the test could have a "major impact" on emergency-
department decision-making.

Rubinshtein et al's findings add to those of other recent studies
supporting the use of MSCT for emergency-department triage of
patients with chest pain, but as senior author Dr Basil Lewis
(Technion-Israel Institute of Technology) pointed out to heartwire,
this latest research takes the additional step of tracking patients
after hospital discharge to check for late events.

"We showed that . . . multislice CT had high sensitivity and
specificity for diagnosing ACS, confirmed by regular standard tests
during hospitalization, and excellent negative predictive value to
rule out ACS," he said. "Patients with a negative emergency-
department MDCT scan could safely be sent home, and none developed
ACS during a 15-month follow-up period."

High sensitivity, specificity

In the study, 58 patients presenting to the emergency department
with chest pain but with no new ECG changes or elevated biomarkers
underwent 64-slice CT. In all, MSCT identified 15 patients as having
no or minimal atheroma, 20 with nonobstructive plaque, and 23 with
obstructive coronary disease (>50% luminal narrowing). These results
were verified by additional testing for elevated cardiac biomarkers
or through myocardial perfusion scintigraphy and/or invasive
angiography, which diagnosed 20 of 23 MSCT-positive patients with
ACS. Over 15 months of follow-up, no deaths or MIs occurred in any
of the 35 patients discharged from the emergency department on the
basis of MSCT findings; one of these patients underwent late PCI.

"Although not all emergency-department patients with chest pain
require CT imaging for risk stratification, the present study
demonstrates applicability of the technique to selected patients in
the population with intermediate risk in whom the incremental value
of noninvasive imaging may have a significant impact on patient
management," the authors conclude.

A challenge for ED physicians

To heartwire, Lewis emphasized that the number of patients falling
into the intermediate category is not insignificant. The paper, he
said, provides insights into "a real-world cohort of patients
presenting to the ED with chest pain of uncertain origin, which
clearly could be an acute coronary syndrome that we cannot afford to
miss. We are talking about some 20% to 25% of the patients who
present to the emergency department with chest pain. They are
patients with intermediate risk and no definite new ECG changes and
no elevated biomarkers."

He continued: "This intermediate group presents the greatest
challenge to the emergency-department physician and the cardiologist
on call, because high-risk patients are hospitalized in any event
and low-risk patients--often with very atypical symptoms--can be
discharged."

Discussing some of the shortcomings of current-generation MSCT
scanners, Lewis said he believes the issue of radiation exposure
is "grossly overrated." He points out that current management of
chest-pain patients often entails "lots of radionuclide tests and
often with a lot of radiation," and many patients also undergo
repeat angiography, which, while carrying a lower radiation
exposure, offers much less information than an MSCT scan.

For Lewis, the larger problems for MSCT are contrast dose,
particularly in patients with renal dysfunction, and coronary
calcification, predominantly in elderly patients, which limits the
ability to interpret a CT scan.

"Hopefully rapidly evolving CT technology will take care of these
issues," he commented.

Rubinshtein R, Halon DA, Gaspar T, et al. Usefulness of 64-slice
cardiac computed tomographic angiography for diagnosing acute
coronary syndromes and predicting clinical outcome in emergency
department patients with chest pain of uncertain origin. Circulation
2007; DOI: 10.1161/CIRCULATIONAHA.106.618389. Available at:
http://www.circulationaha.org.

Boosting support for the use of multislice computed tomography
(MSCT) in patients presenting to emergency departments with chest
pain, a new study has found that MSCT has a high sensitivity and
specificity for diagnosing or ruling out ACS in these patients [1].

In a study published online March 19, 2007 in Circulation, Dr Ronen
Rubinshtein (Technion-Israel Institute of Technology, Haifa, Israel)
and colleagues say the test could have a "major impact" on emergency-
department decision-making.

Rubinshtein et al's findings add to those of other recent studies
supporting the use of MSCT for emergency-department triage of
patients with chest pain, but as senior author Dr Basil Lewis
(Technion-Israel Institute of Technology) pointed out to heartwire,
this latest research takes the additional step of tracking patients
after hospital discharge to check for late events.

"We showed that . . . multislice CT had high sensitivity and
specificity for diagnosing ACS, confirmed by regular standard tests
during hospitalization, and excellent negative predictive value to
rule out ACS," he said. "Patients with a negative emergency-
department MDCT scan could safely be sent home, and none developed
ACS during a 15-month follow-up period."

High sensitivity, specificity

In the study, 58 patients presenting to the emergency department
with chest pain but with no new ECG changes or elevated biomarkers
underwent 64-slice CT. In all, MSCT identified 15 patients as having
no or minimal atheroma, 20 with nonobstructive plaque, and 23 with
obstructive coronary disease (>50% luminal narrowing). These results
were verified by additional testing for elevated cardiac biomarkers
or through myocardial perfusion scintigraphy and/or invasive
angiography, which diagnosed 20 of 23 MSCT-positive patients with
ACS. Over 15 months of follow-up, no deaths or MIs occurred in any
of the 35 patients discharged from the emergency department on the
basis of MSCT findings; one of these patients underwent late PCI.

"Although not all emergency-department patients with chest pain
require CT imaging for risk stratification, the present study
demonstrates applicability of the technique to selected patients in
the population with intermediate risk in whom the incremental value
of noninvasive imaging may have a significant impact on patient
management," the authors conclude.

A challenge for ED physicians

To heartwire, Lewis emphasized that the number of patients falling
into the intermediate category is not insignificant. The paper, he
said, provides insights into "a real-world cohort of patients
presenting to the ED with chest pain of uncertain origin, which
clearly could be an acute coronary syndrome that we cannot afford to
miss. We are talking about some 20% to 25% of the patients who
present to the emergency department with chest pain. They are
patients with intermediate risk and no definite new ECG changes and
no elevated biomarkers."

He continued: "This intermediate group presents the greatest
challenge to the emergency-department physician and the cardiologist
on call, because high-risk patients are hospitalized in any event
and low-risk patients--often with very atypical symptoms--can be
discharged."

Discussing some of the shortcomings of current-generation MSCT
scanners, Lewis said he believes the issue of radiation exposure
is "grossly overrated." He points out that current management of
chest-pain patients often entails "lots of radionuclide tests and
often with a lot of radiation," and many patients also undergo
repeat angiography, which, while carrying a lower radiation
exposure, offers much less information than an MSCT scan.

For Lewis, the larger problems for MSCT are contrast dose,
particularly in patients with renal dysfunction, and coronary
calcification, predominantly in elderly patients, which limits the
ability to interpret a CT scan.

"Hopefully rapidly evolving CT technology will take care of these
issues," he commented.

Rubinshtein R, Halon DA, Gaspar T, et al. Usefulness of 64-slice
cardiac computed tomographic angiography for diagnosing acute
coronary syndromes and predicting clinical outcome in emergency
department patients with chest pain of uncertain origin. Circulation
2007; DOI: 10.1161/CIRCULATIONAHA.106.618389. Available at:
http://www.circulationaha.org.

While burns and smoke inhalation are well-known occupational hazards
of fighting fires, less appreciated is the risk of heart disease
among men and women working in this dangerous occupation. Now, the
results of a new study have helped highlight the specific risk of
coronary heart disease that firefighters face in various tasks, with
fighting fires and responding to alarms associated with a higher
risk of death from coronary heart disease than various nonemergent
duties. [1]

"What makes this study unique is not that we described the number of
deaths that were due to heart disease or even exactly what duties
they occurred in," Dr Stefanos Kales (Harvard Medical School,
Boston, MA) told heartwire. "Instead, this is a statistical analysis
with several different models that allowed us to estimate duty-
specific risks. We think we've provided the strongest evidence to
date that specific firefighting activities can indeed trigger heart
events in susceptible firefighters."

The results of the study are published in the March 22, 2007 issue
of the New England Journal of Medicine.

Heart disease accounts for 45% of death among US firefighters

Speaking with heartwire, Kales said that the most frequent cause of
death among firefighters is heart disease, a finding that is often
underappreciated, especially in light of the risks these men and
women undertake with their firefighting duties. Cardiovascular
events, largely due to coronary heart disease, have previously been
shown to account for 45% of deaths among firefighters on duty, which
is significantly higher than the cardiovascular mortality of police
officers, emergency workers, or those in the general workforce.

Kales said that while various biologically plausible explanations
have been proposed, including smoke and chemical exposure, irregular
physical exertion, handling heavy equipment, heat stress, shift
work, a high prevalence of cardiovascular risk factors, and
emotional stress, previous data from his group suggested that
coronary events may be triggered by specific firefighting duties,
including putting out fires, responding to an alarm, and physical
training. As would be expected, these events usually occur in
firefighters with underlying coronary heart disease, he noted.

To confirm the findings from an earlier case-control study [2],
which showed that coronary events may be triggered by specific
firefighting duties, and to further explore duty-specific risks of
firefighting, Kales and colleagues performed a study of all deaths
of US firefighters between 1994 and 2004, excluding deaths
associated with the September 11, 2001 terrorist attacks. Estimates
of the proportion of time firefighters spent performing various
duties were obtained from a municipal fire department, from 17 large
metropolitan fire departments, and from a national database.

Among the most active large metropolitan fire departments, the risk
of death from coronary heart disease was 12 times higher for
firefighters suppressing fires than the risk of death in performing
nonemergent duties. If investigators looked at the national activity
levels, the risk of death from coronary disease while putting out
fires was more than 100 times that of nonemergent duties. Similarly,
responding to alarms, returning from alarms, and physical training
were all associated with an increased risk of coronary heart disease
death compared with nonemergent duties in all three models.

"Nobody is really sure how much time is spent in certain duties,
these are just estimates, and every firefighter is different in
terms of how he or she spends his time, and every fire department is
probably going to have a wide range," said Kales. "While we can't
say what the exact risk is, we presented a fairly wide range of
estimates so that we can be quite confident that the risk is
increased. . . . Although we can't say that we were surprised by the
results, we were struck by how consistent the evidence is."

Kales told heartwire that the promotion of fitness programs and
wellness activities, as well as regular physicals aimed at the early
treatment of risk factors before cardiovascular-disease onset,
should be mandatory. In addition, physicians who care for
firefighters should be cognizant of how dangerous certain
firefighting activities can be and use that information to be
aggressive in risk-factor reduction, he said.

When heart disease is diagnosed in a firefighter, he added, extreme
caution should be exercised when returning them to the most
strenuous of emergency duties. Kales' group has previously shown
that 25% of deaths and 20% of nonfatal retirements were linked to
firefighters with underlying disease. "I wouldn't want to say that
none of them should ever go back, but a lot of caution of should be
exercised and, obviously, every case should be looked at on an
individual basis," he said.

Firefighters might begin their careers healthy, but . . .

In an audio supplement to the published study [3], Dr Linda
Rosenstock (University of California, Los Angeles), who wrote an
accompanying editorial with Dr Jorn Olsen (University of California,
Los Angeles) [4], praised the authors for identifying periods of
firefighting where coronary heart disease deaths are clustering.

"To the degree that we understand that and put in prevention
programs, we may be able to reduce these deaths to some degree,"
said Rosenstock. "But we know that most of the people dying from
cardiovascular deaths, including firefighters in this study, are
dying with underlying cardiovascular disease."

The implications of the findings, she said, are clear. Modifiable
risk factors, whether or not they are related to their occupation,
should be aggressively treated.

"Firefighters are like others," said Rosenstock. "They might enter
the workforce healthy, but they may, because they are not keeping up
with an active physical-fitness regimen or because they have other
risk-taking behaviors, such as cigarette smoking or being
overweight, increase the likelihood that they're going to develop
coronary disease. With that increased likelihood comes the setting,
the background, to which they are more likely to have a fatal
cardiac event triggered by and associated with extreme exertion."

The goal, she added, is to keep firefighters, who usually enter the
workforce very healthy, as healthy as possible throughout their
working life. Preplacement and annual medical examinations,
including clearance for firefighters to wear self-contained
breathing apparatuses, the implementation of fitness programs, and
annual physical-performance evaluations should be mandatory, said
Rosenstock.

Kales SN, Soteriades ES, Christophi CA, Christiani DC. Emergency
duties and deaths from heart disease among firefighters in the
United States. New Engl J Med 2007; 356:1207-15.
Kales SN, Soteriades ES, Christoudias SG, Christiani DC.
Firefighters and on-duty deaths from coronary heart disease: a case
control study. Environ Health 2003; 2:14.
Interview with Linda Rosenstock on firefighter's risk of death from
cardiovascular causes. Supplement to: Kales SN et al. Emergency
duties and deaths from heart disease among firefighters in the
United States. New Engl J Med 2007; 356:1207-15.
Rosenstock L, Olsen J. Firefighting and death from cardiovascular
causes. New Engl J Med 2007; 356:1261-63.

Patients with high levels of apolipoprotein A1 and HDL cholesterol
and large HDL particles have a decreased risk of developing
recurrent venous thromboembolism (VTE), a new study has shown [1].
In consecutive patients with a single episode of unprovoked VTE, the
risk of recurrence was cut in half in subjects with apolipoprotein-
A1 levels exceeding 1.30 mg/mL when compared with subjects who had
lower levels.

"The present study is prospective in nature and provides strong
evidence for an association of protection against risk of recurrent
venous thrombosis with elevated levels of apolipoprotein A1, the
major protein component of HDL," write lead author Dr Sabine
Eichinger (Medical University of Vienna, Austria) and colleagues in
a paper published online March 19, 2007 in Circulation. "This
finding may justify further clinical studies to assess whether
strategies to elevate HDL using lifestyle changes will reduce risk
for venous thrombosis."

While dyslipidemia and dyslipoproteinemia are established risk
factors for arterial thrombosis, with lipid-lowering drugs used to
prevent ischemic events, the relevance of dyslipoproteinemia for the
occurrence of VTE is not clear, the authors write. There is
evidence, though, they add, that venous and arterial thrombotic
disease share similar risk factors, including age, male sex,
elevated body weight, lupus anticoagulant, and elevated homocysteine
levels.

With this in mind, investigators sought to examine the association
between HDL-cholesterol levels and recurrent VTE. Using data from
the ongoing Austrian Study of Recurrent Venous Thromboembolism
(AUREC), Eichinger and colleagues studied 772 patients with a first
spontaneous VTE. Average follow-up was 48 months, and recurrent VTE
developed in 100 of the 772 patients.

Overall, patients with a recurrent VTE had significantly lower
levels of apolipoprotein A1 than those without recurrence. When
investigators entered apolipoprotein A1 as a continuous variable in
a Cox proportional hazards model, the relative risk of VTE
recurrence was 0.87 (95% CI 0.80-0.94) for every 0.1-mg/mL increase
in plasma apolipoprotein-A1 levels.

Investigators did not predefine cutoff values for apolipoprotein A1,
due to the hypothesis-generating nature of the study, but instead
looked at the strength and linearity of the association between
apolipoprotein A1 and the risk of recurrence by calculating relative
risks for various apolipoprotein-A1 levels. The strongest
association between apolipoprotein A1 and recurrent VTE was observed
at levels >1.30 mg/mL, which corresponds to the lower limit of the
highest tertile in this cohort. In addition, there was a trend for
association between recurrence and low levels of HDL particles and
HDL cholesterol.

Eichinger and colleagues point out that male sex is an independent
risk factor for VTE recurrence, conveying a fourfold greater risk
than being female. In this study, apolipoprotein-A1 levels were
significantly lower among men than women, suggesting the protective
properties of HDL cholesterol might explain this difference between
the sexes. The authors write, however, that these results warrant
further study, including replication in other patient populations,
especially to determine whether one or more HDL parameters might be
useful to clinicians in assessing the risk of recurrent VTE

Eichinger S, Pecheniuk NM, Hron G, et al. High-density lipoprotein
and the risk of recurrent venous thromboembolism. Circulation 2007;
115:1609-1614.

ACC Scientific Sessions - New Orleans, Louisiana March 24-27, 2007 
   
Vasomedical is pleased to announce that it will participate in the ACC
Scientific
Sessions to be conducted this year in New Orleans, Louisiana March 24-27, 2007.
The company will demonstrate its Lumenair Model EECP® therapy system and
provide information on the therapy as well as its products and services in its
booth
(#1756) during the exhibit hours on Saturday evening (4:00 PM - 6:30 PM), Sunday
(9:00 AM to 5:00 PM), Monday (9:00 AM to 5:00 PM) and Tuesday (9:00 AM - 1:30
PM). 
   
  We look forward to meeting with our current customers, prospective future
customers, distributors and sales agents to discuss the positive opportunities
and
benefits that EECP® therapy provides for patients in the physician practice,
clinic
and hospital market.  
     
  We are very pleased to announce that four EECP® therapy presentations have
been
accepted and scheduled at the ACC 
   
  1. Symposium Presentation: 
  Session Title: Advanced Coronary Artery Disease: Options When There Are No
Options* 
  Track ACC.Myocardial Ischemia and Infarction 
  Type ACC.Symposium 
  Date/Time 3/26/2007 11:00 AM - 12:30 PM 
  Room Room 217 
  Speaker: 11:15AM - 11:30AM  
   
  Enhanced External Counterpulsation   
  George A. Beller  
  Univ of VA 
  Charlottesville, VA  
   
  Learning Objectives understand the potential mechanisms of benefit of EECP
therapy
in patients with refractory angina, be knowledgeable of the clinical trials and
registry
data showing benefit of EECP in patients with angina pectoris. learn about the
potential role of EECP in the management of patients with heart failure based on
the
PEECH trial. 
   
  2. Oral Presentation: 
  Title: Exercise Testing  
  Track ACC.Imaging and Diagnostic Testing 
  Type ACC.Oral Contributions 
  Date/Time 3/27/2007 11:00 AM - 12:30 PM 
  Room Room 271 
  Number of Credits 1.50 
  Speaker/Moderator 11:15AM - 11:30AM  
   
  Enhanced External Counterpulsation Treatment Decreases Arterial Stiffness and
Myocardial Oxygen Demand in Patients With Refractory Angina 
  Darren P. Casey, C. Richard Conti, Wilmer W. Nichols, Matheen A. Khuddus,
Calvin Y.
Choi, Randy W. Braith, University of Florida, Gainesville, FL  
  Speaker Company University of Florida 
   
  Learning Objectives Interpret pressure waveforms generated by applanation
tonometry., Describe both central and peripheral benefits of EECP therapy in
symptomatic patients with CAD. 
   
  3. Poster Presentation: 
  Title: Myocardial Ischemia and Infarction  
  Track ACC.Myocardial Ischemia and Infarction 
  Type ACC.Poster Session 
  Abstract Category Unstable Ischemic Syndrome - Clinical 
  Date/Time 3/25/2007 9:00 AM - 12:30 PM 
  Room Hall H 
  Speaker/Moderator 10:00AM - 11:00AM  
   
  Enhanced External Counterpulsation Inhibits Intimal Hyperplasia by
Downregulating
Proliferative Signaling Proteins 
  Yan Zhang, Hong Ma, Gui-Fu Wu, Xiao-Hong He, Xiao-Lin Chen, Dong-Hong Liu,
Zhi-Min Du, Yu-Gan Dong, Ya-Fei Jin, Dian-Qiu Fang, Jin-Yun Luo, Yan Xiong, Kui-
Jian Wang, William E. Lawson, John CK Hui, Zhen-Sheng Zheng, The Key Laboratory
on
Assisted Circulation, The First Affiliated Hospital, Sun Yat-sen University,
Guangzhou,
People's Republic of China, State University of New York at Stony Brook, Stony
Brook,
NY --  
   
  Speaker: The Key Laboratory on Assisted Circulation, The First Affiliated
Hospital,
Sun Yat-sen University 
   
  Learning Objectives Describe the role of shear stress in lessening intimal
hyperplasia
in hypercholesterolemia, Describe how shear stress affects the signaling pathway
for
the cellular proliferation, growth, and migration of VSMCs 
   
   
  4. Moderated Poster Presentation: 
  Abstract Category Vascular Biology/Atherosclerosis/Thrombosis/Endothelium 
  Date/Time 3/25/2007 9:00 AM - 1:00 PM 
  Room Hall H 
  12:00PM - 1:00PM - 276 
   
  The Effect of External Counterpulsation Therapy on Circulating Endothelial
Progenitor
Cells in Patients With Angina Pectoris 
   
  Alon Barsheshet, Hanoch Hod, Michael Shechter, Orna Sharabani-Yosef, Eti
Rosenthal, Israel M. Barbash, Shlomi Matetzky, Reshef Tal, Ariel G. Bentancur,
Ben-
Ami Sela, Arnon Nagler, Jonathan Leor, Neufeld Cardiac Research Institute, Heart
Institute, Sheba Medical Center, Ramat Gan, Israel

First-trimester exposure to agricultural pesticides increases the
risk of gestational diabetes mellitus, according to a report in the
March issue of Diabetes Care.

Previous studies have examined the relationship between pesticides
and diabetes, the authors explain, but none have focused on
gestational diabetes.

Dr. Tina M. Saldana from the National Institute of Environmental
Health Sciences, Research Triangle Park, North Carolina and
colleagues assessed the risk of developing gestational diabetes
mellitus following pesticide exposures among wives of farmers
enrolled in the Agricultural Health Study.

Of 11,273 women who became pregnant within 25 years after enrollment
in the study, 506 (4.5%) reported having gestational diabetes.

Overall, 57% of women reported having mixed or applied pesticides at
some time in their life, and the proportion was similar for those
with and without gestational diabetes mellitus, the authors report.

However, women who mixed or applied pesticides or repaired pesticide-
related equipment during the first trimester of pregnancy had a more
than twofold increased risk of developing gestational diabetes
mellitus, the report indicates.

In contrast, there was no increased gestational diabetes mellitus
risk among women with residential exposures to pesticides or
indirect exposures during the first trimester.

Similarly, the researchers note, women who had mixed or applied
pesticides at any time before enrollment in the study did not face
an increased risk of gestational diabetes mellitus compared with
those who did not.

Among 15 pesticides studied, the risk of gestational diabetes
mellitus was significantly associated with ever having used the
herbicides 2,4,5-T; 2,4,5-TP; atrazine; and butylate and the
insecticides diazinon, phorate, and carbofuran, the investigators
report.

"Although much is known about common risk factors for gestational
diabetes mellitus, our understanding of whether and how
environmental exposures may affect risk is still limited," the
authors conclude.

"Understanding any potential effect of environmental exposures on
glucose tolerance during pregnancy may have substantial public
health importance beyond the direct effects on gestational diabetes
mellitus."

Diabetes Care 2007;30:529-534

With 24 late-breaking clinical trials, 18 "smaller" late-breaking
trials, and half a dozen additional "late-breaking" emerging-
technology presentations, the American College of Cardiology (ACC)
2007 Scientific Sessions and concurrent i2 Summit will pose some
tough challenges for people hoping to catch all of the clinical-
trial results and still find time to eat, sleep, and schmooze. The
i2 Summit begins Saturday, while the ACC main arena gets going on
Sunday.

Some of the trial results, regardless of where the chips fall, will
be "practice-changing," outgoing ACC president Dr Steven Nissen
(Cleveland Clinic, OH) told heartwire.

One of the trials that has generated the most chatter in the run-up
to the meeting is the Clinical Outcomes Utilizing Revascularization
and Aggressive Drug Evaluation (COURAGE) trial, to be presented by
Dr William E Boden (University of Connecticut School of Medicine,
Farmington). The trial, testing whether PCI plus intensive,
guideline-driven medical therapy would be superior to intensive
medical therapy alone, enrolled more than 2000 patients with
documented myocardial ischemia and angiographically confirmed CAD.
The composite primary end point is all-cause mortality or acute MI
(time to first event) during a median five-year follow-up.

Nissen called COURAGE "a blockbuster either way."

"This will have a huge impact," he said. "About 40% of patients
undergoing coronary interventions today are undergoing them for
chronic stable angina. And the question is, how effective is
intervention in comparison with just medical therapy alone in those
patients?"

Likewise, Dr Salim Yusuf (McMaster University, Hamilton, ON), who
will be a discussant following Boden's presentation, recently told
heartwire, "If COURAGE shows a clear benefit of angioplasty, that's
interesting, but if it shows no benefit compared with medical
therapy, it's going to shake the foundation of interventional
cardiology."

Earlier in the meeting, Dr Jean-Claude Tardif (Montreal Heart
Institute, QC) is presenting results from another much-anticipated
study, the Effect of Reconstituted HDL on Atherosclerosis (ERASE)
trial. Nissen described ERASE as "a follow-on from the apo-A1 Milano
story, which was very important. This is now wild-type, regular HDL,
it's a larger study than the Apo-A1 study was, and it has the
potential for commercialization more quickly because it's not a
recombinant HDL, it's actually reconstituted from blood products. We
will want to look at those results very carefully," he said.

Failed trials also to attract attention

Proving that in any story, the plot can be as important as the dé
nouement, several failed studies are also expected to capture ACC
crowds. Three torcetrapib trials will be presented on Monday,
hopefully providing some insights into the increased rates of deaths
and CV events seen with the experimental HDL-raising drug. Pfizer
halted the major study of its novel cholesteryl-ester-transfer-
protein (CETP) inhibitor in December, as reported by heartwire.

"Even though we know the drug didn't work, it's so important to see
the detailed results in terms of understanding mechanism and how the
whole strategy of HDL raising will play out," Nissen said. "Many
other pharmaceutical companies have drugs in the CETP-inhibitor
class. So Wall Street is very interested and the companies are very
interested, because the question we're going to be trying to answer
through these imaging trials is whether this is a class effect or a
molecular toxicity of torcetrapib alone."

Sponsors of two other clinical trials slated for presentation during
the ACC late-breaking-trials session have released results in
advance of the meeting, citing Securities and Exchange Commission
regulations that require disclosure of any information that could
have a major impact on stock price. As reported by heartwire, CV
Therapeutics announced March 7, 2007 that its MERLIN TIMI-36 trial
of ranolazine had failed to reach its primary end point. Today,
AtheroGenics released preliminary results from its ARISE trial of
AGI-1067, showing that the study had failed to reach its primary end
point. For both ARISE and MERLIN, however, the companies--not
surprisingly--are arguing that secondary-end-point and/or safety
results that will be unveiled at the ACC meeting are compelling and
suggest the drugs still have a future.

New treatments for HF?

On the heart-failure front, Nissen singled out the EVEREST trial of
tolvaptan, a vasopressin receptor antagonist being tested for its
effects on clinical status, morbidity, and mortality in patients
hospitalized with acute decompensated heart failure. While tolvaptan
first showed promise in the phase 2 Acute and Chronic Therapeutic
Impact of a Vasopressin 2 Antagonist in Congestive Heart Failure
(ACTIV in CHF) trial, the drug had no beneficial effects on LV
remodeling and was not significantly different from placebo for the
primary or secondary end points in the METEOR trial. Dr Marvin A
Konstam (Tufts University, Boston, MA) is presenting the EVEREST
results on Sunday.

Nissen also pointed to the Follow-Up Serial Infusions of Nesiritide
for the Management of Patients With Heart Failure (FUSION II) trial.
The study, a follow-up on FUSION I, is evaluating once- or twice-
weekly treatment with nesiritide vs placebo as part of a
posthospitalization treatment strategy in patients with end-stage
heart failure. The primary end point for this study is mortality and
cardio-renal rehospitalization; the study aims to determine whether
the drug is safe for outpatient "tune-ups," a practice that was
widely in use, off-label, before safety questions were first raised
about the drug several years ago following its approval for use in
an inpatient setting for patients with acute decompensated CHF.

"FUSION II could hit a home run, potentially," Nissen told
heartwire. "I think it's an important trial."

New DES; old DES fears

In addition to COURAGE, several DES clinical-trial and registry
results are slated for presentation during the i2 Summit.

"There's going to be a lot more information on stent thrombosis from
DES, and there's going to be a lot of interesting new information on
the merits of bypass surgery vs stenting vs medical therapy," i2
program chair Dr William Knopf (Atlanta Cardiology Group, GA) told
heartwire. "Those will all be very exciting presentations."

The opening day of the i2 Summit will include nine-month clinical,
angiographic, and IVUS results from the pivotal US SPIRIT-III Trial
of Abbott's Xience V everolimus-eluting stent vs Boston Scientific's
Taxus stent in more than 1300 patients and six-month angiographic
and IVUS results from the ABSORB trial. ABSORB is a first-in-human,
nonrandomized study of Abbott's fully bioabsorbable stent in 60
patients in Europe. Also on the first day of the meeting, Dr Michael
Maeng (Aarhus University Hospital, Denmark) is presenting new
registry data examining stent-thrombosis rates following DES
implantation in western Denmark.

Knopf also highlighted presentations in the peripheral vascular
arena, in particular "some interesting debates in carotid stenting
vs carotid surgery, which is always a hot topic." Results from the
1500-patient EXACT carotid stenting registry is slated for
presentation on Monday.

Preliminary results of the Aggressive Reduction of Inflammation
Stops Events (ARISE) study, a phase 3, double-blind, placebo-
controlled trial with the novel anti-inflammatory agent AGI-1067
(AtheroGenics Inc, Alpharetta, GA) were announced ahead of schedule
today and showed that the drug did not result in a statistically
significant difference in the primary composite end point.

The ARISE study, designed to assess the incremental benefits of AGI-
1067 over current standard of care in coronary artery disease (CAD)
patients randomized to placebo or AGI-1067, in addition to statins
and other cholesterol-lowering medications, showed that the novel
compound did not reduce the length of time to the first occurrence
of cardiovascular mortality, resuscitated cardiac arrest, nonfatal
MI, nonfatal stroke, hospitalization for angina pectoris, or use of
coronary revascularization.

AGI-1067 was the first in a new class of drugs known as vascular
protectants that aimed to reduce inflammation in blood-vessel walls.
Full results of the study will be presented at the American College
of Cardiology 2007 Scientific Sessions in New Orleans next week.
ARISE investigator Dr Marc Pfeffer (Brigham and Women's Hospital,
Boston, MA) declined comment to heartwire until after the late-
breaking clinical-trials presentation on March 27, 2007.

Company still plans continued development

Although the 6000-patient study missed its primary end point, a
statement issued by AtheroGenics said that a number of secondary
predefined end points were reached. These end points included a
reduction in the composite of hard atherosclerotic clinical end
points, composed of cardiovascular death, MI, and stroke, as well as
an improvement in several key diabetes parameters, including
glycemic control.

The company said it would continue to develop the drug, based on
these positive secondary end points, and prepare for discussions
with the Food and Drug Administration (FDA) on how to proceed
further. In December 2005, AstraZeneca agreed to pay AtheroGenics up
to $1 billion for exclusive rights to the drug, although payment was
contingent upon the drug's approval by the FDA. When the data are
analyzed, AstraZeneca has 45 days to decide whether to continue its
involvement with the drug program.

AtheroGenics has had a rocky history with AGI-1067. In 2004, the
company released the final results of the Canadian Antioxidant
Restenosis Trial (CART-2), and while the data showed there was a
statistically significant plaque regression from baseline with the
new agent, it was not statistically significantly different when
compared with patients receiving the standard of care. The interim
CART-2 results were also regarded with skepticism when the study was
moved from the Montreal Heart Institute to the Cleveland Clinic
Foundation and when a large number of patients were excluded after
randomization due to inadequate baseline intravascular ultrasound
(IVUS) scans.

An embargo policy has been put in place by the ACC such that any
company issuing an unauthorized press release prior to the late-
breaking clinical-trials session will not be allowed to present the
final results. However, the press release issue by AtheroGenics was
officially cleared with the ACC and president Dr Steven Nissen.

A black-box warning has been added to the safety labeling for
erythropoiesis-stimulating agents (ESAs) to advise of the increased
risk for death and other serious adverse events associated with
their use in patients with cancer and renal failure, the US Food and
Drug Administration (FDA) said Friday.

Although the warning was based on data from 4 recently completed
cancer trials that evaluated new dosing regimens, use of ESAs in a
new patient population, and use of new unapproved ESAs, the warning
applies to all products in this drug class, including darbepoetin
alfa (Aranesp, Amgen, Inc) and epoetin alfa (Epogen and Procrit,
Amgen), according to an alert sent Friday from MedWatch, the FDA's
safety information and adverse event reporting program.

In a study of patients with chronic renal failure (CRF), adjustment
of ESA dose to maintain target hemoglobin levels higher than 12 g/dL
yielded an increased risk for mortality and nonfatal myocardial
infarction, stroke, heart failure, and thrombosis. Similar dose
modifications in head/neck cancer patients receiving radiation
therapy resulted in accelerated tumor growth.

Also, ESA therapy at recommended doses in cancer patients not
receiving chemotherapy was linked to an increased risk for mortality
with no reduction in transfusion requirements, and its use in the
orthopaedic surgical setting led to an increased incidence of
thrombosis.

¡§This new information is consistent with risks found in 2 clinical
studies in patients with chronic renal failure treated with an
unapproved regimen of an ESA that were reported in November 2006,¡¨
the FDA said.

When using ESAs for approved indications, healthcare professionals
are advised to maintain the lowest hemoglobin level consistent with
avoiding the need for transfusions; patients should be monitored to
ensure that levels do not exceed 12 g/dL.

Darbepoetin alfa and epoetin alfa are indicated for the treatment of
CRF-related anemia, and chemotherapy-related anemia in patients with
nonmyeloid malignancies. An intravenous route of administration is
recommended for patients on hemodialysis.

Epoetin alfa is also indicated for the treatment of anemia in
zidovudine-treated HIV patients and to reduce the risk of allogenic
blood transfusion in patients undergoing surgery (except cardiac
surgery).


Adverse events potentially related to use of ESAs should be reported
to the manufacturer and to the FDA's MedWatch reporting program by
phone at               1-800-FDA-1088        , by fax at 1-800-FDA-
0178, online at http://www.fda.gov/medwatch, or by mail to 5600
Fishers Lane, Rockville, MD 20852-9787.

Urine proteomic profiling can predict the development of diabetic
nephropathy in type 2 diabetic patients with normoalbuminuria well
before the condition arises, according to a report in the March
Diabetes Care.

"We have identified a set of urine proteins almost 10 years before
the onset of diabetic nephropathy that identify those who will go on
to get diabetic nephropathy, the most common cause of renal failure
in the U.S. and the world," Dr. Ravi Thadhani, from Massachusetts
General Hospital and Harvard Medical School in Boston, told Reuters
Health.

Dr. Thadhani and colleagues compared urinary proteomic profiles
among 62 Pima Indians with type 2 diabetes and normal urinary
albumin excretion, who were followed for 10 years for the
development of diabetic nephropathy.

The authors identified a 12-peak predictive signature that provided
a 93% sensitivity, 86% specificity, and 93% accuracy for predicting
the development of diabetic nephropathy.

When the signature was tested against all samples in the validation
set (17 case samples and 17 matched controls), the overall accuracy
was 74%, with a sensitivity of 71% and a specificity of 76%, the
report indicates.

The 12-peak signature was independently predictive of diabetic
nephropathy in a multivariate binary logistic regression model
adjusting for baseline hemoglobin A1c, the researchers note, whereas
hemoglobin A1c was no longer significantly associated with
subsequent diabetic nephropathy.

"While these findings require a significant amount of work to
identify and test the robustness of these markers, they offer the
potential for clinicians one day to be able to tell whether a
diabetic patient will get renal failure well before the development
of this devastating condition, and, hence, offer hope for early
intervention to prevent its onset," Dr. Thadhani said.

"First we need to confirm the identification of the proteins we
uncovered, then we need to test this profile in other populations
with type 2 diabetes to determine if the same predictive potential
remains," Dr. Thadhani explained. "Then we will carry out
prospective studies in larger populations."

Diabetes Care 2007;30:638-643.

The rate of kidney disease mortality in the United States has
increased by 52% in the past 16 years and continues to be higher in
blacks than whites, according to a study of Michigan data published
in the March 16 issue of the Morbidity and Mortality Weekly Report.

The findings underscore the need for developing additional measures
directed at preventing kidney disease, particularly in black
communities.

Analysis of Vital Statistics data revealed that the death rate per
100,000 population rose from 10.1% (95% confidence interval [CI],
9.4 - 10.8) in 1989 to 15.4% (95% CI, 14.7 - 16.1) in 2005.

Study investigators also reported that the age-adjusted mortality
rate was consistently at least twice as high in blacks vs whites in
both men (32.6 [95% CI, 27.1 - 38.1] for black men vs 16.5 [95% CI,
15.2 - 17.8] for white men) and women (27.3 [95% CI, 23.3 - 31.3]
for black women vs 11.8 [95% CI, 10.9 - 12.7] for white women).


As might be expected, study results also showed that the death rate
increased with age, from 1.1 per 100,000 population (95% CI, 0.9 -
1.3) for people younger than 50 years, to 19.0 (95% CI, 17.2 - 20.8)
in those aged 50 to 74 years, and to 173.6 (95% CI, 163.5 - 183.7)
for those aged 75 years or older.


The increasing kidney disease death rate in Michigan may be
explained in part by the increasing prevalence of kidney failure as
well as its risk factors, diabetes and hypertension, the authors
note.

Interventions aimed at educating black patients about kidney disease
and the need for implementing diet and exercise-oriented prevention
measures are available in community-based settings such as beauty
salons, barber shops, schools, preschools, and Head Start programs.

MMWR. 2007;56(10):225-227.

Paclitaxel-eluting stents reduce the late lumen loss and restenosis
rate in saphenous vein graft lesions, researchers in Germany report
in the March issue of Heart.

"Drug-eluting stents reduce angiographic restenosis in saphenous
vein grafts," Dr. Rainer Hoffmann, from University RWTH Aachen, told
Reuters Health. "However, the major adverse cardiac event rate
remains high."

Dr. Hoffmann and colleagues compared the efficacy of paclitaxel-
eluting stents and bare metal stents for treating obstructed
saphenous vein grafts in 60 consecutive patients.

Of the 51 patients in each group who underwent angiographic follow-
up at 6 months, patients in the paclitaxel group had larger in-stent
and in-lesion minimal lumen diameter than did patients in the bare
metal stent group, the authors report.

In-stent late lumen loss was significantly lower in the paclitaxel
group, the results indicate, and this translated into a
significantly lower binary in-stent restenosis rate. Target vessel
failure at 6 months was significantly less frequent in the
paclitaxel group (18%) than in the bare metal stent group (41%).

However, major adverse cardiac event rates at 6 months were high,
affecting 15% of the paclitaxel patients and 37% of the bare metal
stent patients.

"This study showed a significant advantage of using non-polymer-
based paclitaxel-eluting stents in the treatment of obstructed vein
grafts compared with bare metal stents with regard to late lumen
loss, restenosis rate, and clinical events," the authors
conclude. "Thus, the study supports the use of drug-eluting stents
for obstructed saphenous vein grafts."

Additional studies are needed to see if sirolimus-coated stents are
more effective in preventing restenosis and recurrent target lesion
revascularization in saphenous vein grafts, the investigators add.

Heart 2007;93:331-334.

Patients with MI who come to the hospital on weekends are less
likely to survive than patients who are admitted to the hospital
during the week, a new study has shown [1]. Likely mediating this
higher rate of mortality, say investigators, is the additional
finding that admission on the weekend is associated with lower use
of invasive cardiac procedures.

Publishing their findings in the March 15, 2007 issue of the New
England Journal of Medicine, lead author Dr William Kostis (Robert
Wood Johnson Medical School, Piscataway, NJ) and colleagues write
that this higher rate of mortality represents 9 to 10 additional
deaths per 1000 admissions per year and has important implications
for clinical care.

"The increase in mortality, which may persist for more than a year,
could account for several thousand deaths annually in the United
States," write the authors. "More appropriate hospital staffing or
regionalization of the care of patients with acute myocardial
infarction may prevent some of these deaths."

In an editorial accompanying the published study, Drs Donald
Redelmeier and Chaim Bell (University of Toronto, ON) note that
while clinicians strive to provide care to patients every day of
week, doing so is difficult, partly because many who work in
hospitals are not always compensated for taking the weekend shift
[2]. Even casual observations of the hospital parking lot on a
Saturday suggest that the intensity of care on the weekend does not
match the care provided on other days of the week, they write.

"The shortfall of weekend medical care is important because the
consequences of adverse events cannot always be offset by working
harder on subsequent days," write Redelmeier and Bell. "If the
patient dies on the weekend, no heroics on Monday will suffice."

Fewer procedures and higher mortality

Kostis and colleagues note that hospital staffing is typically
reduced on weekends, both in terms of the number of clinicians and
the available expertise on site. While the difference in staffing
might result in different outcomes for patients with acute
conditions--management of acute MI, specifically, requires urgent
diagnostic and therapeutic procedures--findings from previous
studies have been inconsistent.

To compare mortality rates among patients admitted with MI on
weekends and those admitted during the week, investigators obtained
data from the Myocardial Infarction Data Acquisition System (MIDAS),
a database that contains clinical data on patients discharged with
an acute MI diagnosis from nonfederal hospitals in New Jersey as
well as information on the use of invasive cardiac procedures such
as catheterization, PCI, or CABG. The study included 231 164
patients admitted to New Jersey hospitals between 1987 and 2002 with
acute MI as the primary reason for admission.

Overall, there were no significant differences in demographic
characteristics, coexisting conditions, or infarction site between
patients admitted on weekends and those admitted during the week.
Despite this, patients admitted on the weekend were less likely to
undergo invasive cardiac procedures, especially on the first and
second days of hospitalization.

Mortality 30 days after admission was also significantly higher for
patients admitted on a weekend than for those admitted during the
week. This difference became significant the day after admission and
persisted until one year. Mortality on the weekend remained
significantly higher after adjustment for clinical characteristics,
but became nonsignificant after the additional adjustment for
invasive cardiac procedures, the investigators report.

When the analysis was restricted to admissions to hospitals equipped
to perform PCI, the adjusted risk of death at 30 days was still
increased for weekend admission, the authors report.

Kostis and colleagues point out that unmeasured confounders might
have contributed to the reported differences in mortality between
patients admitted on weekends and those admitted on weekdays. For
example, the MIDAS database does not include data on the time from
the onset of symptoms to presentation, infarct size, hemodynamic
status at presentation, or medications administered during
hospitalization. None of these limitations, they contend, "detract
from the fact that mortality was higher and the rate of invasive
procedures was lower for weekend admissions."

"Overall," the authors conclude, "our study suggests that a hospital
workweek of Monday through Friday is not optimal for the care of
patients with acute myocardial infarction."

Higher threshold for activating catheterization lab on weekends

In an audio supplement to the published study, Dr Thomas Lee
(Partners Health Care System, Boston, MA), one of the associate
editors of the journal, said that most hospitals would reduce
overhead costs if labs could run full time, but staff shortages
preclude hospitals from operating 24 hours per day, seven days per
week [3]. While aware there are falloffs in how aggressive
physicians are with patients having an MI on the weekend, Lee said
he was surprised at how many fewer angioplasties were performed on
the weekend.

"When people are not in the hospital, and they are further away, the
threshold for calling somebody in is very different," commented
Lee. "On the weekend, at night, waking up your colleagues, calling
them, it's very inconvenient, and doctors will use a different
threshold [for calling the cath lab team in]. The result is that
fewer procedures are performed. A lot of times it doesn't make a
difference if you wait and do those procedures on Monday, but
myocardial infarction is one diagnosis where it does make a real
difference."

According to editorialists Redelmeier and Bell, an awareness of the
shortfalls in weekend hospital care has implications for patients.
If patients feel unwell during the week, they should not wait until
the weekend to see whether they feel better. Second, if unsure how
sick they might be, they should contact their doctor before the end
of workweek. And finally, if hit by a medical emergency on the
weekend, they should still proceed to the emergency department, as
they are still far safer there than at home.

To offset the disparity in weekend care, Lee said his hospital
attempts to schedule physicians who live close to the hospital for
on-call service. In addition, the emergency department is able to
directly activate the cath lab team without having to first call a
cardiologist.

"We run the risk that the cath lab team might come in and find that
it wasn't a myocardial infarction at all, but we feel it's a small
price to pay for reducing the delay," said Lee. If such solutions do
not work, Lee said some hospitals might have very little choice but
to pay to operate the cath lab at night and on weekends or else live
with the notion that they are providing second-rate care.

Kostis WJ, Demissie K, Marcella SW et al. Weekend versus weekday
admission and mortality from myocardial infarction. N Engl J Med
2007; 356:1099-1109.
Redelmeier DA, Bell CM. Weekend worriers. N Engl J Med 2007;
356:1164-1165.
Interview with Thomas Lee on increased mortality with weekend
hospital admissions. Supplement to: Kostis WJ et al. Weekend versus
weekday admission and mortality from myocardial infarction. N Engl J
Med 2007; 356:1099-1109.

How well patients hospitalized with acute heart failure fare after
discharge depends a lot on their age, their syndrome's severity at
presentation, and how sick they might be in other ways, according to
a community-based study published in the March 12, 2007 issue of the
Archives of Internal Medicine [1].

First author Dr Robert J Goldberg (Brown University, Providence, RI)
and associates say their findings reveal a generally poor long-term
prognosis after hospitalization for acute HF but also point out some
independent risk factors that could potentially guide the selection
of therapies in individual cases.

In the group's analysis of 2445 patients treated for acute HF as the
primary diagnosis at 11 hospitals in metropolitan Worcester, MA, all-
cause mortality after discharge was 37% after one year and 53% and
78% after two and five years, respectively.

The authors observe that long-term mortalities in several prior
population-based studies of patients hospitalized for acute HF were
considerably lower. The reason, they speculate, is that compared
with the earlier groups, their patients were older, on average, and
more likely to have a prior history of HF and had more comorbidities
such as chronic obstructive pulmonary disease (COPD) or diabetes.

"Our data suggest that HF in an older population remains a terminal
condition for most hospitalized patients," they write.

In a multivariate analysis, all-cause mortality within three months
of discharge was independently associated with older age, a history
of stroke, higher serum urea nitrogen, and lower blood pressure at
hospitalization. Predictors of one-year mortality were similar and
also included COPD at admission. For mortality at five years, the
list of apparent risk factors expanded to include peripheral
vascular disease, edema, and chronic HF. Hypertension at baseline
was protective over the short term but had little long-term effect
either way.

Chest pain was associated with reduced mortality risk at one year,
possibly, the authors speculate, because patients with underlying
ischemic heart disease may have often received coronary
revascularization.

There was an inverse association between body-mass index (BMI) and
mortality throughout the follow-up, consistent with a large body of
data suggesting that obesity is protective in acute HF, observe the
authors. The phenomenon is not well understood. "It remains unclear
if patients who are obese to begin with are protected from this
syndrome and the extent to which obesity affects subsequent HF-
associated mortality," Goldberg et al write.

Physicians should have a "realistic understanding" of the "guarded"
long-term prognosis of patients hospitalized with acute HF,
according to the authors. "Clinicians also need to be aware of
factors that adversely affect patients¡¦ long-term survival, which
may facilitate targeted treatment toward specific high-risk groups."
Decisions as to whether to use such "aggressive" interventions as
CABG, multivessel PCI, or implantable cardioverter-defibrillators,
they add, should consider the effect of comorbidities on long-term
outcomes.

Goldberg RJ, Ciampa J, Lessard D, et al. Long-term survival after
heart failure: A contemporary population-based perspective. Arch
Intern Med 2007; 167:490-496.