Is this spam?  In any event EECP is utter nonsense.  If it does any good at all,
it is certainly attributable to placebo effect.

   ----- Original Message -----
   From: Gerald Oros
   To: heart119@yahoogroups.com
   Sent: Wednesday, January 31, 2007 5:28 PM
   Subject: [Heart119] To Whom It Should Concern


   I received a copy of this thought provoking letter from another
   advocate of Enhanced External Counterpulsation (EECP_. I would like
   to share it with you today.

   Gerald Oros

   To Whom It Should Concern:

   The recent article by Doctor David Moskowitz, CEO of Geno Med, that
   appeared
   in the A.C.P. Observer, the monthly news magazine for Doctors of
   Internal Medicine,
   published by American College of Physicians, hit a nerve. Dr.
   Moskowitz actually
   had the audacity to challenge the Medical community's monetary based
   "status quo",
   that so obviously exists today in Western Medicine, when he said "In
   medical school,
   we were encouraged to find cures! I wouldn't have believed it if
   somebody had told
   me then, that there was no point in finding any cures, because news of
   the cure would
   be suppressed. Yet, that is exactly what has happened for the past
   four years"! And
   Dr. Moskowitz continued, "Medicine, like any human endeavor, thrives
   on the status
   quo and hates change. In the 1950s, nobody thought twice about putting
   polio wards
   and TB sanitaria out of business. But potentially eliminating 90% of a
   $25 billion/year
   industry, is another thing altogether. Nowadays, nobody wants their
   budget cut."

   And here I thought it was only EECP that was being stone-walled by the
   all-powerful
   Medical establishment! The parallels between the two are profound, and
   I'm sure
   there are many more worthwhile therapies that are being covered up and
   buried by
   the quest for "treatment options", that Western Medical practice
   currently finds itself
   "monetarily mired" in. God forbid a cure be found, for it would only
   cut into our
   "good doctor's" profit margins and precious revenue streams. The poor
   patient is
   made to suffer, for sake of profit. Can this be? It never should not
   be! I wonder, is
   there such a thing as a "Class Action, Medical Industry-wide,
   Malpractice Lawsuit"?
   I can't imagine how many Heart patients have been left to die after
   being told, "there
   is nothing more we can do"! Instead of being informed by a caring
   health professional
   or even a Cardiologist, about EECP, a proven, 100% safe and much more
   effective
   treatment than any of the currently available but far more expensive
   and invasive,
   procedures. Is our entire system of Medical care broken or just simply
   monetarily
   misguided?

   Doctor's continue to rip open chest cavities in a deadly and alarming
   rate, in a vain
   attempt to become some kind of amateur human plumbers, even while
   every single
   one of these currently common invasive procedures, have all recently
   been thrown
   under the bus! Study after study asks whether they even do more harm,
   than good!
   One must wonder how, and why, these expensive and overly invasive
   methods were
   ever approved in the first place, while much safer and more effective
   methods are
   put through years of jumping through an endless series of hoops? It
   very well may
   be, that our currently existing "Medical community" may indeed turn
   out to be a far
   "more effective killing machine" than any group, of terrorists!


   A Future Heart Patient





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

I received a copy of this thought provoking letter from another
advocate of Enhanced External Counterpulsation (EECP_.  I would like
to share it with you today.

Gerald Oros


To Whom It Should Concern:

The recent article by Doctor David Moskowitz, CEO of Geno Med, that
appeared
in the A.C.P. Observer, the monthly news magazine for Doctors of
Internal Medicine,
published by American College of Physicians, hit a nerve. Dr.
Moskowitz actually
had the audacity to challenge the Medical community's monetary based
"status quo",
that so obviously exists today in Western Medicine, when he said "In
medical school,
we were encouraged to find cures! I wouldn't have believed it if
somebody had told
me then, that there was no point in finding any cures, because news of
the cure would
be suppressed. Yet, that is exactly what has happened for the past
four years"!  And
Dr. Moskowitz continued, "Medicine, like any human endeavor, thrives
on the status
quo and hates change. In the 1950s, nobody thought twice about putting
polio wards
and TB sanitaria out of business. But potentially eliminating 90% of a
$25 billion/year
industry, is another thing altogether. Nowadays, nobody wants their
budget cut."

And here I thought it was only EECP that was being stone-walled by the
all-powerful
Medical establishment! The parallels between the two are profound, and
I'm sure
there are many more worthwhile therapies that are being covered up and
buried by
the quest for "treatment options", that Western Medical practice
currently finds itself
"monetarily mired" in. God forbid a cure be found, for it would only
cut into our
"good doctor's" profit margins and precious revenue streams. The poor
patient is
made to suffer, for sake of profit. Can this be? It never should not
be! I wonder, is
there such a thing as a "Class Action, Medical Industry-wide,
Malpractice Lawsuit"?
I can't imagine how many Heart patients have been left to die after
being told, "there
is nothing more we can do"! Instead of being informed by a caring
health professional
or even a Cardiologist, about EECP, a proven, 100% safe and much more
effective
treatment than any of the currently available but far more expensive
and invasive,
procedures. Is our entire system of Medical care broken or just simply
monetarily
misguided?

Doctor's continue to rip open chest cavities in a deadly and alarming
rate, in a vain
attempt to become some kind of amateur human plumbers, even while
every single
one of these currently common invasive procedures, have all recently
been thrown
under the bus! Study after study asks whether they even do more harm,
than good!
One must wonder how, and why, these expensive and overly invasive
methods were
ever approved in the first place, while much safer and more effective
methods are
put through years of jumping through an endless series of hoops? It
very well may
be, that our currently existing "Medical community" may indeed turn
out to be a far
"more effective killing machine" than any group, of terrorists!


                A Future Heart Patient

Be Careful When Looking For Work At Home No Fees
   Work at home no fees is a common way to scam people into a dead end
opportunity with expensive hidden costs and fees. There are many legitimate work
at home no fee offers, but careful examination is necessary before jumping into
something without doing your homework. http://parttimeworkathome.blogspot.com/




---------------------------------
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Try the Yahoo! Mail Beta.

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

Check out this report on Doctors...

http://www.freewebs.com/amareports/index.htm

All,

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The HMG-CoA reductase inhibitor rosuvastatin exerts rapid
immunomodulatory effects on the level of T-cell activation in
patients with acute coronary syndrome (ACS), according to German
researchers.

Dr. Andreas Link of Universitatsklinikum des Saarlandes, Homburg and
colleagues note in the December issue of the European Heart Journal
that it is unclear how quickly the beneficial effects of statins
occur in patients with ACS and whether these drug properties are
related to lipid lowering.

To investigate further, the researchers randomized 35 patients with
troponin-positive ACS to rosuvastatin 20 mg/day or to placebo.

Compared to placebo, at 72 hours, rosuvastatin treatment
significantly reduced plasma concentrations of the pro-inflammatory
cytokines tumor necrosis factor-alpha and interferon-gamma.

It also induced a rapid and significant reduction in these cytokines
in stimulated T-lymphocytes and inhibited the Th-1 immune response.

The investigators note that the magnitude of these anti-inflammatory
actions did not increase appreciably over the 6-week observation
period. They conclude that statins inhibit the activity of the Th-1
response independently of the present plasma lipid levels.

Co-author of an accompanying editorial, Dr. Kazunori Shimada of
Jutendo University School of Medicine, Tokyo pointed out in remarks
to Reuters Health that "acute coronary syndrome is an immune disease
and rosuvastatin is an immunomodulatory agent."

These results, he concluded, "extend our knowledge of the clinical
use of statins in patients with acute coronary syndrome."

Eur Heart J 2006;27:2945-2955

New research, reported in the December 15 issue of the American
Journal of Cardiology, suggests that ventricular premature complexes
(VPCs) on electrocardiograms in apparently healthy individuals are
associated with increased risk for cardiac events.

To assess the significance of VPCs, Dr. Ross J. Simpson, Jr., at the
University of North Carolina at Chapel Hill, and associates
evaluated data from the prospective Atherosclerosis Risk in
Communities (ARIC) study. Their cohort included 15,070 individuals
ages 45 to 64 years when they underwent baseline examinations
between 1987 and 1989. They were followed until the end of 2000.

VPCs were present on the baseline 2-minute electrocardiograms of 940
(6.2%) subjects, Dr. Simpson and his colleagues report in the
December 15th issue of the American Journal of Cardiology. Those
with VPCs were more likely to have CHD, hypertension and diabetes.
VPCs were also more common among those who were older, black, and
male.

The authors observed that 729 subjects at baseline already had CHD.
In this group, the risk of CHD mortality was more than 3-fold higher
in the presence of VPCs (7.8% versus 2.1%).

Among those free of CHD at baseline, the risk of fatal CHD doubled
when VPCs were present at baseline (3.4% versus 1.7%).

"Increased risk of CHD and death associated with VPCs persisted
after controlling for cardiovascular disease risk factors,
medication use, and other covariates in proportional hazards
regression models," Dr. Simpson and his team report.

They maintain that when VPCs show up on routine ECGs of apparently
healthy patients, more aggressive management of modifiable risk
factors -- including blood pressure, cholesterol, and smoking --
  "would seem to be a prudent clinical response."

Am J Cardiol 2006;98:1609-1612

Recent studies suggest that the incidence of nephrolithiasis is
increasing, both in the US and worldwide, and data compiled by
researchers at the Mayo Clinic in Rochester, Minnesota, suggest that
diabetes may be a predisposing factor for renal stones, particularly
for those composed of uric acid.

Dr. John C. Lieske and his associates used the Rochester
Epidemiology Project diagnostic index to identify all Olmsted County
residents diagnosed with nephrolithiasis between 1980 and 1999. The
3,561 cases were matched by age and gender with an equal number of
control subjects. They then searched the index for diagnoses of
diabetes, hypertension, and obesity.

After adjusting for age, calendar year of index, hypertension, and
obesity, diabetes was significantly associated with a diagnosis of
nephrolithiasis (odds ratio 1.22, p = 0.02), the team reports in the
American Journal of Kidney Disease for December.

For closer scrutiny of this issue, Dr. Lieske's group obtained a
random sample of 269 subjects with confirmed incident
nephrolithiasis and their 260 matched stone-free controls. The odds
ratio for diabetes was of a similar magnitude but was no longer
statistically significant due to the smaller sample size.

However, when they analyzed the cases according to stone type, the
prevalence of diabetes was 40% among the 10 individuals with uric
acid stones, versus 9% among the 112 with calcium stones and 7% in
the control group. After adjusting for BMI, the odds ratio for
diabetes associated with uric acid stones was 5.03 (p = 0.03).

Even so, the investigators say it's unlikely that diabetes is the
only factor driving the increased incidence of nephrolithiasis. It
may be partly attributed to "better detection, because of widespread
use of sensitive imaging modalities."

Am J Kidney Dis 2006;48:897-904

Confirmation that carotid intima-media thickness (IMT) is a reliable
predictor of future risk of cardiovascular events has come from a
new meta-analysis [1]. The meta-analysis, published online January
22, 2007 in Circulation, found that carotid IMT is a strong
predictor of both stroke and MI.

The authors, led by Dr Matthias Lorenz (Johann Wolfgang Goethe-
University, Frankfurt, Germany), explain that as carotid IMT can be
measured relatively simply and noninvasively, it is well-suited for
use in large-scale population studies and it is increasingly being
used for risk stratification in individuals and as an end point in
intervention studies. But an important precondition for this
application of IMT is that it can predict future risk of clinical
vascular events. They note that a number of longitudinal studies
have examined the relationship between IMT and future events, but
different studies have used different measurement methods and
studied different populations. Furthermore, some studies have
investigated relatively small populations, which resulted in large
confidence intervals for the risk estimates. To gain more robust
estimates of the predictive value of increased IMT for clinical
cardiovascular end points, they carried out a meta-analysis of these
studies.

They reviewed data from eight studies, with a total of 37 197
subjects who were followed up for a mean of 5.5 years. Results
showed that after adjustment for age and sex, increased carotid IMT
was associated with increased risk of both MI and stroke.

¡§With data of 200 000 person-years in eight studies, the results of
this meta-analysis improve the precision of estimating the risk that
is associated with IMT," the researchers write. ¡§For an absolute
carotid IMT difference of 0.1 mm, the future risk of MI increases by
10% to 15% and the stroke risk increases by 13% to 18%," they
report.

In an interview with heartwire, one of the authors, Dr Hugh Markus
(St George¡¦s University of London, UK), said this study should
increase confidence in carotid IMT as a measure of future risk of
cardiovascular events. ¡§With the large population included in this
meta-analysis, we can be much more certain exactly how carotid IMT
measurements relate to future risk. If you are going to use a marker
as an end point in clinical trials, you have to have robust data on
how it relates to risk, and now we have such data."

Markus said this study confirms that carotid IMT is a suitable end
point for studies of potential new antiatherosclerotic drugs, and it
can also be used to predict risk in health screening. ¡§The carotid
artery is simple to visualize with an ultrasound scan, as it is so
close to the skin surface, so that a clear measurement of IMT can be
seen very easily, and this study suggests that thickening of this
artery wall by atherosclerosis is a good indicator of what is going
on in the vasculature generally," he added.

Lorenz MW, Markus HS, Bots ML, et al. Prediction of clinical
cardiovascular events with carotid intima-media thickness a
systematic review and meta-analysis. Circulation 2007; 115:459-467.

A new study suggests that obstructive sleep apnea (OSA) and obesity,
while linked, are likely independent predictors of atrial
fibrillation/flutter (AF) in people younger than 65 years [1]. The
findings have important implications not only for understanding the
pathophysiology of AF, but also for the exploding incidence of
obesity, the authors write.

"Our study showed that obesity and OSA are each, in and of
themselves, related to new-onset AF, and that when they coexist, the
risk of AF increases even further," lead author on the study, Dr
Apoor S Gami (Mayo Clinic, Rochester, MN), told heartwire.

The paper appears online January 29, 2007 in the Journal of the
American College of Cardiology.

Previous studies have suggested that obesity is an independent
predictor of incident AF, while other work by the group at the Mayo
Clinic has explored the link between OSA and AF. How OSA and obesity
might interact or increase the risk of AF was unclear, the authors
note. "The studies in obesity could not address whether OSA was an
intermediate mechanism between obesity and AF," Gami commented. "We
thought this was highly likely, and we aimed to assess the
contributions of both conditions, obesity and OSA, on the
development of new AF."

Retrospective review of sleep-disorder patients

For their study, Gami et al retrospectively reviewed records for
3542 adults in Olmsted County, MN who had no AF but who were
referred for sleep evaluations, including a diagnostic
polysomnogram, between 1987 and 2003 at the Mayo Clinic Sleep
Disorders Center. Three quarters of the patients were diagnosed with
OSA, as defined by an apnea-hypopnea index >5.

Over an average of 4.7 years, incident AF occurred in 133 subjects.
Established risk factors for AF, including male gender, increasing
age, hypertension, CAD, heart failure, and smoking were found to
predict AF in patients under age 65, as did higher body-mass index
(BMI) and OSA. In age-stratified, multivariate analyses, the same
established risk factors predicted AF in subjects under age 65, as
did increasing BMI and decreasing nocturnal oxygen saturation (a
consequence of OSA).

"From a clinical perspective, the most important findings are, one,
that the presence of OSA strongly predicts the development of AF
over an average of five years, and, two, that the magnitude of
nocturnal oxygen desaturation is an independent predictor of future
AF," Gami told heartwire. "This should have an impact on our care of
patients, as the number of people with OSA in the US is estimated to
be over 25 million, and the vast majority of them are undiagnosed."

Physicians should be aware that people at risk of developing OSA, as
well as those already diagnosed with OSA, are at a higher risk for
cardiovascular complications, including--as the current study shows--
AF, Gami added. "For patients with AF, it would now be reasonable to
identify OSA and treat it if present, as an adjunct to AF
management."

That said, Gami clarified that his study was "not an interventional
trial": as such, it is not yet known whether OSA therapy could
decrease the risk of AF.

"The study's finding that hypoxemia was an independent predictor of
AF suggests that effective OSA treatment that relieves hypoxemia may
decrease the risk of AF. Whether OSA treatment joins the
armamentarium of AF management strategies will need to be answered
by a well-conducted randomized trial."

CPAP in AF prevention?

Of note, however, use of continuous positive airway pressure (CPAP)
did not reduce risk of AF in this study. Gami et al say this may be
explained by the fact that their method of classifying use of CPAP
was limited by the retrospective nature of the research; they also
point out that CPAP is typically used in more severe cases of sleep
apnea and as such this might have confounded the relationship
between its use and incident AF. To heartwire, Gami emphasized that
the study was not designed to identify a treatment effect of CPAP
and for most of the patient follow-up in this study, CPAP machines
that record compliance were not used. "Thus, we did not have
reliable data to answer the question of CPAP and the risk of AF," he
said.

The findings also apply solely to patients under age 65. In subjects
65 or older, heart failure was the only independent predictor of AF.

"It is possible that when obesity and/or OSA are diagnosed at age 65
years or older, both conditions would already have been present for
many years before diagnosis, and any effect on the incidence of AF
already would be manifest," Gami and colleagues
hypothesize. "Subjects with AF at the time of diagnosis of OSA were
excluded from our study--it is possible that if the effects of
obesity and OSA had not already led to AF by the age of 65, then
they were unlikely to do so as these older patients aged."

Gami AS, Hodge DO, Herges RM, et al. Obstructive sleep apnea,
obesity, and the risk of incident atrial fibrillation. J Am Coll
Cardiol 2007; DOI:10.1016/j.jacc.2006.08.060. Available at:
http://content.onlinejacc.org.

Compared with bare metal stents, sirolimus-eluting stents are not
cost-effective in preventing reinterventions after 1 and 2 years of
follow-up, according to a report in the December 2006 issue of the
European Heart Journal.

Sirolimus-eluting stents clearly decrease the incidence of cardiac
events, the authors explain, but they are also considerably more
expensive than bare metal stents.

Dr. Patrick W. Serruys and colleagues from Erasmus Medical Center,
Rotterdam, The Netherlands investigated the cost-effectiveness of
sirolimus-eluting stents (SES) compared with bare metal stents (BMS)
in reducing the need for target vessel revascularization.

During the first year, rates of reinterventions were lower in SES
patients (3.65%) than in BMS patients (10.4%), the authors report,
and the difference at 2 years was even greater (6.4% versus 14.7%,
respectively).

Procedural costs were 3036 higher in the SES group, the results
indicate, driven largely by the 2925 price premium of the SES. In
contrast, the report indicates, follow-up costs were somewhat lower
in the SES group due to fewer reinterventions.

The incremental cost-effectiveness for SES at 1 year was 29,373 per
repeat revascularization avoided, the researchers note. This
decreased to 22,627 per repeat revascularization avoided in the 2-
year analysis.

"Based on the price of 1929 per SES paid by our institution in April
2002, the unrestricted use of SES was not cost-effective to our
institution, at either 1 or 2 years, using the acceptable maximum
threshold of 10,000 per repeat revascularization avoided," the
authors conclude.

"Given a not unreasonable bare stent price of 400 today," the
investigators say, "a drug-eluting stent would have to fall to 779
to be cost-neutral within the framework of the model presented here."

Eur Heart J 2006;27:2996-3003

Adding pioglitazone to standard therapy does not improve glycemic
control and may cause weight gain in adolescents who have type 1
diabetes with evidence of insulin resistance, Canadian researchers
report in The Journal of Pediatrics for December.

In theory, note Dr. Jill Hamilton, from the Hospital of Sick
Children in Toronto, and colleagues, increasing the insulin dosage
to overcome insulin resistance should be enough to improve glycemic
control in adolescent type 1 diabetics. However, this often does not
occur, and there is a need for "adjunctive therapies to complement
the action of insulin."

While pioglitazone, an insulin-sensitizing agent, can improve
metabolic control in subjects with type 2 diabetes, the benefits of
adjunctive pioglitazone therapy in adolescents with type 1 diabetes
have not been studied.

In their study, Dr. Hamilton and colleagues randomized 35 teens with
type 1 diabetes to receive pioglitazone or placebo in addition to
standard insulin therapy for 6 months. All of the subjects required
> 0.9 U/kg/day of insulin and had suboptimal metabolic control with
HbA1c of 7.5% to 11%.

Participation in the trial was associated with a modest, but
significant improvement in metabolic control. However, pioglitazone
was no better than placebo in improving control, as determined by
changes in HbA1c as well as the required insulin dose.

With pioglitazone, the BMI standard deviation score increased by
0.3, on average, but no change was noted with placebo (p = 0.01).

The current findings contrast with a recent study involving adults
with type 1 diabetes, the researchers point out. In that study,
adjunctive use of rosiglitazone did help patients cut back on the
required insulin dose. Moreover, on subgroup analysis, use of
rosiglitazone produced a greater reduction in HbA1c. Dr. Hamilton's
team believes these differences may relate to the fact that patients
in the current study were leaner than those in the adult study.

J Pediatr 2006;149:845-849

Long-term statin therapy slowed the echocardiographic progression of
moderately advanced aortic stenosis in asymptomatic patients taking
the drug for elevated low-density lipoprotein (LDL) cholesterol,
report the authors of a prospective, open-label study appearing
online January 22, 2007 in the Journal of the American College of
Cardiology [1].

The finding supports a wealth of observational evidence that aortic
stenosis is a progressive atherosclerosislike disease that may be
amenable to statins, according to the investigators, who say their
results--when combined with earlier research--suggest that any
statin therapy aimed at aortic stenosis would have to catch the
process at an early enough stage to be effective.

"This is the first study to provide positive clinical evidence for
the potential of targeted therapy in patients with asymptomatic
aortic stenosis," write Dr Luis M Moura (Hospital Pedro Hispano,
Matosinhos, Portugal) and colleagues. Their results, which the group
cautions are only "hypothesis-generating," are scheduled to be
published in the journal's February 6, 2007 issue.

"There's a modest amount of evidence that starting someone with
moderate aortic stenosis on a statin would be good for them--it
might retard progression of the aortic stenosis and it might reduce
their risk of dying from a heart attack," according to Dr Blase A
Carabello (Baylor College of Medicine, Houston, TX). That evidence
isn't strong enough to support a formal recommendation to treat
aortic stenosis with a statin, he told heartwire, but the study from
Moura et al is "important" and "keeps the door open" for such an
approach in the future.

Carabello, who wasn't connected with the study, observed that most
patients with aortic stenosis "are going to have an indication for a
statin anyway. . . . The only question mark would be if you had a
patient with mild aortic stenosis who had perfectly normal lipids--
would you start a statin? We don't have any of those data." But such
patients are probably few, he added.

Of Moura et al's 121 asymptomatic patients with "moderate to severe"
aortic stenosis, the 61 with LDL cholesterol >130 mg/dL were started
on rosuvastatin per guidelines and, along with the remaining
patients, were followed for 18 months. To qualify for the study,
named Rosuvastatin Affecting Aortic Valve Endothelium (RAAVE), the
patients' aortic valve areas had to measure at least 1.0 cm2; the
average was 1.21 cm2. Over a mean of 73 weeks, those on rosuvastatin
showed significantly less stenosis progression by multiple
echocardiographic criteria, including change in aortic valve area,
compared with the group that didn't get the statin.

Patients with aortic stenosis who have dyslipidemia, CAD, or
diabetes "will be treated with statins anyway. The wealth of
evidence, including the present study, suggests that such patients
will also enjoy a beneficial effect in terms of slowing the
progression of aortic stenosis in addition to reduction in other
cardiovascular end points," observes Dr Brian P Griffin (Cleveland
Clinic, OH) in an accompanying editorial [2].

"Given the modest correlation between beneficial valve effect and
LDL reduction, the target LDL required for treatment of the primary
disease for which statins are being prescribed will likely be
adequate, at least until more evidence is available," he
writes. "Until further data are available, there does not seem to be
an indication for statin therapy just on the basis of aortic
stenosis alone if conventional guidelines for statin therapy are not
met."

Dr Nalini M Rajamannan (Northwestern University, Chicago, IL), a
RAAVE coauthor who explores the pathophysiology of aortic-valve
disease in the laboratory, commented to heartwire that the study--in
combination with another published in 2005--supports a role for
statin therapy in the treatment of mild to moderate aortic stenosis
but not advanced disease, which is characterized by a lot of
calcification.

That other study, the Scottish Aortic Stenosis and Lipid Lowering
Trial, Impact on Regression (SALTIRE) [3], saw no statin effect on
the disease process in 155 patients with a mean baseline aortic
valve area of 1.03 cm2 who were randomized to a statin or placebo.
Patients in the trial had a mean baseline LDL-cholesterol level of
134 mg/dL and, at least at the time, were not considered to have an
absolute indication for statin therapy.

As reported previously by heartwire, at least two years of
atorvastatin at 80 mg/day in SALTIRE caused LDL cholesterol to
plunge but had no significant effect on extent of aortic-valve
calcification or change in aortic-jet velocity. "We have clearly
shown that high-dose atorvastatin reduces serum LDL-cholesterol
concentrations by more than a factor of two, as anticipated, but it
does not halt the progression or induce regression of the valvular
disease process," the group's 2005 paper declared.

But the patients' aortic disease was, on average, substantially more
advanced than in RAAVE, according to observers; in that study, the
mean aortic valve area among rosuvastatin recipients was 1.23 cm2.
The average baseline aortic stenosis would be characterized in
SALTIRE as "severe" and in RAAVE as "moderate," according to
Carabello. "I think that SALTIRE was helpful. It tells us that
there's probably not much point in starting statins when disease is
far advanced."

In his editorial, Griffin appears to agree. "The SALTIRE study is a
relatively small one and the patients had relatively advanced aortic
stenosis, not just in terms of valve area but also in terms of the
calcification of the valve at the onset of the trial and may
therefore have been less amenable to a treatment effect of statins."

According to Rajamannan, "SALTIRE is a landmark trial" that, like
RAAVE, is a piece of a larger puzzle that "tells us when not to
start therapy." She agrees that the randomized study started the
statin probably too late to reverse calcification. The goal, she
said, "should be early interruption of the disease process, and
statins can probably achieve that."

Based on her laboratory work and other research, she said, early
aortic stenoses don't typically contain much calcification and
are "atherosclerosislike," similar to lipid-rich lesions in early
vascular disease. That's when statins are most likely to slow their
progression. If echocardiography discloses that kind of aortic
stenosis in a patient, Rajamannan said, and the LDL cholesterol is
over the 100-mg/dL threshold, she'd recommend a statin based on the
LDL and counsel the patient that it's unapproved for valve disease
but some evidence shows it might slow progression.

Below an LDL of 100 mg/dL, she said, she'd recommend a statin anyway
based on all the other evidence and recent insights from the
Treating to New Targets (TNT) study, for example, that lowering LDL
further than guideline-specified goals can reduce CV risk in some
groups.

Carabello said prescribing a statin for a patient with mild to
moderate aortic stenosis but no guidelines-based indication for
statin therapy isn't unreasonable--the drugs have important non-LDL-
related effects that could well influence aortic-disease
progression. "The physician who wants to do it isn't crazy. And the
physician who doesn't want to do it is more in line with the current
data," he said. "Either position is entirely defensible."

According to the RAAVE report, Rajamannan "is an inventor on the
patent for the use of statins in aortic valve disease. She does not
receive any financial royalties from this patent." According to the
editorial, Griffin "is an investigator of a trial of atorvastatin in
aortic stenosis that has been partly funded by Pfizer."

Moura LM, Ramos SF, Zamorano JL, et al. Rosuvastatin affecting
aortic valve endothelium to slow the progression of aortic stenosis.
J Am Coll Cardiol 2007; 49:554-561.
Griffin BP. Statins in aortic stenosis: New data from a prospective
clinical trial. J Am Coll Cardiol 2007; 49:562-564.
Cowell SJ, Newby DE, Prescott RJ, et al. A randomized trial of
intensive lipid-lowering therapy in calcific aortic stenosis. N Engl
J Med 2005; 352:2389-2397.

Long-term statin therapy slowed the echocardiographic progression of
moderately advanced aortic stenosis in asymptomatic patients taking
the drug for elevated low-density lipoprotein (LDL) cholesterol,
report the authors of a prospective, open-label study appearing
online January 22, 2007 in the Journal of the American College of
Cardiology [1].

The finding supports a wealth of observational evidence that aortic
stenosis is a progressive atherosclerosislike disease that may be
amenable to statins, according to the investigators, who say their
results--when combined with earlier research--suggest that any
statin therapy aimed at aortic stenosis would have to catch the
process at an early enough stage to be effective.

"This is the first study to provide positive clinical evidence for
the potential of targeted therapy in patients with asymptomatic
aortic stenosis," write Dr Luis M Moura (Hospital Pedro Hispano,
Matosinhos, Portugal) and colleagues. Their results, which the group
cautions are only "hypothesis-generating," are scheduled to be
published in the journal's February 6, 2007 issue.

"There's a modest amount of evidence that starting someone with
moderate aortic stenosis on a statin would be good for them--it
might retard progression of the aortic stenosis and it might reduce
their risk of dying from a heart attack," according to Dr Blase A
Carabello (Baylor College of Medicine, Houston, TX). That evidence
isn't strong enough to support a formal recommendation to treat
aortic stenosis with a statin, he told heartwire, but the study from
Moura et al is "important" and "keeps the door open" for such an
approach in the future.

Carabello, who wasn't connected with the study, observed that most
patients with aortic stenosis "are going to have an indication for a
statin anyway. . . . The only question mark would be if you had a
patient with mild aortic stenosis who had perfectly normal lipids--
would you start a statin? We don't have any of those data." But such
patients are probably few, he added.

Of Moura et al's 121 asymptomatic patients with "moderate to severe"
aortic stenosis, the 61 with LDL cholesterol >130 mg/dL were started
on rosuvastatin per guidelines and, along with the remaining
patients, were followed for 18 months. To qualify for the study,
named Rosuvastatin Affecting Aortic Valve Endothelium (RAAVE), the
patients' aortic valve areas had to measure at least 1.0 cm2; the
average was 1.21 cm2. Over a mean of 73 weeks, those on rosuvastatin
showed significantly less stenosis progression by multiple
echocardiographic criteria, including change in aortic valve area,
compared with the group that didn't get the statin.

A population-based study confirms that rofecoxib, but not celecoxib,
is associated with increased risk of a first-time MI. However,
patients with a prior MI may be at increased risk for experiencing
another if they use either COX-2-selective inhibitor, the research
indicates.

Further studies are needed to determine if traditional NSAIDs also
raise the risk of repeat MI, according to the report in the February
issue of Heart.

Previous studies looking at the cardiovascular side effects of COX-2-
selective inhibitors have largely excluded patients with a history
of MI, Dr. James M. Brophy, from the McGill University Health Centre
in Montreal, and colleagues note.

The current study involved data on 125,000 patients, mean age 75
years, who were treated with an NSAID between January 1999 and June
2002 and logged in a Quebec, Canada healthcare database. During the
mean follow-up of 2.3 years, 3423 patients had an MI, and were
matched to 68,456 controls. The cardiac outcomes of current NSAID
users were compared with those of subjects who had not used an NSAID
in the year prior to the index event.

The MI rate ratio with rofecoxib use was 1.59 in patients with a
prior MI and 1.23 in those without a previous MI. The rate ratio
with celecoxib was 1.40 for a repeat MI, but not significant (RR =
1.03) for first-time MI.

Due to insufficient statistical power, the researchers were unable
to determine the effect of traditional NSAIDs on repeat MI risk,
dose-response relationships, or whether an interaction with aspirin
occurred.

"Our study is the first to examine in detail the effect modification
of a previous MI on the cardiac risk associated with the use of COX-
2 inhibitors," the researchers conclude. "A large randomized trial
is required to more completely and reliably assess the
cardiovascular safety of celecoxib and traditional NSAIDs in this
population of high-risk patients."

Heart 2007;93:189-194

The findings of a new meta-analysis question the current practice of
combining aspirin and oral anticoagulant therapy except in patients
with a mechanical heart valve, because of uncertainty over the
benefits in reducing thromboembolic events and the increased risk of
major bleeding [1].

The meta-analysis, published in the January 22, 2007 issue of the
Archives of Internal Medicine, was conducted by a team led by Dr
Francesco Dentali (McMaster University, Hamilton, ON).

They explain that combination antithrombotic therapy consisting of
low-dose aspirin and an oral anticoagulant is recommended only for
patients with a mechanical prosthetic heart valve but is also taken
by a considerable number of patients with chronic atrial
fibrillation. Despite a lack of evidence for therapeutic efficacy,
some experts have suggested that adding aspirin to an oral
anticoagulant might be useful in these patients because they
frequently have concomitant coronary artery disease or are at high
risk for stroke.

To determine whether such combination treatment was actually safe
and effective, Dentali et al performed a systematic review and meta-
analysis of randomized trials comparing the combination of aspirin
plus an oral anticoagulant with oral anticoagulant therapy alone.

They included 10 such trials with a total of 4180 patients in which
oral anticoagulant therapy was administered to achieve the same
target international normalized ratio (INR) or was given at the same
fixed dose in both treatment arms.

Results showed that the risk for arterial thromboembolism was lower
in patients receiving the combination therapy, but these benefits
were limited to patients with a mechanical heart valve, and there
was no difference in the risk for arterial thromboembolism between
groups in patients with atrial fibrillation or coronary artery
disease.

There was no difference in all-cause mortality between the two
groups, but major bleeding was significantly higher in patients
receiving both aspirin and oral anticoagulation compared with those
receiving oral anticoagulation alone.

Dentali et al point out that these results suggest that, for
patients receiving oral anticoagulant therapy, the current practice
of adding aspirin to their treatment should be considered carefully,
and the benefits in reducing thromboembolic events should be weighed
against the increased risk of major bleeding.

They note that large randomized trials are needed to assess the
benefits and risks of these two treatment approaches in patients
with both atrial fibrillation and CAD and high-risk patients with
atrial fibrillation, but at the present time, there is little
support in the published literature for the common clinical practice
of adding aspirin to anticoagulant therapy, except in selected
patients with a mechanical heart valve.

The researchers conclude: ¡§Our findings question the current
practice of using combined aspirin-oral anticoagulant therapy in
patients with atrial fibrillation and concomitant CAD or in patients
at high risk for stroke. This issue is likely to affect a large
number of patients, since approximately 2.5 million people in North
America have chronic atrial fibrillation, of whom 30% to 40% have
concomitant CAD and 10% to 15% are considered at high risk for
stroke. Evidence for combined therapy in patients with a mechanical
prosthetic heart valve is more compelling. In these patients,
combination therapy is highly effective in reducing thromboembolic
events.¡¨

Dentali F, Douketis J D, Lim W, and Crowther M. Combined aspirin¡V
oral anticoagulant therapy compared with oral anticoagulant therapy
alone among patients at risk for cardiovascular disease. A Meta-
analysis of randomized trials. Arch Intern Med 2007; 167:117-124.

Certain non-diabetic patients with major depressive disorder show
improved insulin sensitivity following treatment with amitriptyline
or paroxetine, German researchers report.

In the December issue of the Journal of Clinical Psychiatry, Dr.
Bettina Weber-Hamann of the Central Institute of Mental Health,
Mannheim and colleagues note that there is substantial evidence that
depression is a risk factor for type 2 diabetes.

The hypothalamus pituitary-adrenal (HPA) system may be involved,
they suggest, and its activity could also be modified by
antidepressant treatment.

To investigate further, the researchers conducted a double-blind
study of 80 non-diabetic inpatients who had an episode of major
depression. They were randomized to treatment with the tricyclic
antidepressant amitriptyline, or the selective serotonin reuptake
inhibitor paroxetine for 5 weeks.

In the amitriptyline group, 16 showed remission, 11 had a response,
and 9 patients did not respond. The corresponding numbers in the
paroxetine group were 17, 7 and 20.

Before and at the end of treatment, all patients were given an oral
glucose tolerance test. After correction for body mass index,
insulin sensitivity was seen to improve only in patients who showed
remission with either drug.

In addition, following treatment, saliva cortisol concentrations
fell only in amitriptyline patients in remission or who responded,
suggesting, say the investigators, that the agent may reduce HPA
system activity.

However, as Dr. Weber-Hamann pointed out in remarks to Reuters
Health, "successful treatment with the serotonin reuptake inhibitor
paroxetine similarly improved glucose utilization without affecting
HPA system activity."

This, she concluded, underscores "the assumption that additional
factors may play a role in regulating the sensitivity to insulin in
patients with major depression."

J Clin Psychiatry 2006;67:1856-1861

The FreeStyle Navigator continuous glucose monitoring system is not
as accurate as the current-generation home glucose meters. However,
investigators believe that the device has the potential to become an
important addition to the treatment of children with type 1 diabetes.

"Direct reading, near-continuous, minimally invasive glucose sensors
hold great promise for improving the care of patients with diabetes
and other abnormalities of glucose metabolism," researchers point
out in the January issue of Diabetes Care. "These sensors can
provide both a measure of the current glucose concentration as well
as glucose trends, with alarms for high and low thresholds and
predicted hypo- and hyperglycemia."

Dr. Darrell M. Wilson and colleagues from the Jaeb Center for Health
Research, Tampa, Florida, assessed the accuracy and precision of the
FreeStyle Navigator continuous glucose monitoring system in 30
children with type 1 diabetes (mean age 11.2 years).

The Navigator glucose values were compared with reference serum
glucose values of blood samples collected in an inpatient clinical
research center and measured in a central laboratory using a
hexokinase enzymatic method, and in an outpatient setting with a
FreeStyle meter.

The team determined the median absolute difference and median
relative absolute difference for sensor-reference and sensor-sensor
pairs.

In a total of 1811 inpatient sensor-reference pairs, the median
absolute difference between these measurements was 17 mg/dL and the
median relative absolute difference was 12%.

For 8639 outpatient pairs, the median absolute difference and
relative absolute difference was 20 mg/dL and 14%, respectively.

During the inpatient stays, the subjects simultaneously used two
Navigator sensors resulting in 1971 Navigator-Navigator pairs. The
mean relative absolute difference between these simultaneous
measurements was 13%.

The researchers report that 91% and 81% of sensors in the inpatient
and outpatient settings, respectively, had a median relative
absolute difference no greater than 20%.

"After adjustment for glucose level, accuracy was significantly
better at night for both inpatient and outpatient settings," Dr.
Wilson and colleagues explain. "Accuracy was also significantly
better for children 14 to 18 years of age during home use, but was
not impacted by age during the inpatient visit."

Although the precision of the FreeStyle Navigator system does not
yet match that of existing systems, the researchers believe it may
eventually "become an important adjunct to treatment."

Diabetes Care 2007;30:59-64

Dietary guidelines for children have been updated by the American
Heart Association (AHA) and published in the Sept. 27 issue of
Circulation.

"Since the AHA last presented nutrition guidelines for children,
significant changes have occurred in the prevalence of
cardiovascular risk factors and nutrition behaviors in children,"
write Samuel S. Gidding, MD, and colleagues from the AHA. "This
scientific statement summarizes current available information on
cardiovascular nutrition in children and makes recommendations for
both primordial and primary prevention of cardiovascular disease
beginning at a young age."

Although saturated fat and cholesterol intake have decreased, in
terms of percentage of total caloric intake, overweight has
paradoxically increased. Recent advances in understanding overweight
and obesity in children include national survey data linking
children's cardiovascular risk status to current diet; new research
on the efficacy of diet intervention in children; and studies
focusing on the importance of prenatal and early life nutrition.

"It is estimated that 75% to 90% of the cardiovascular disease
epidemic is related to dyslipidemia, hypertension, diabetes
mellitus, tobacco use, physical inactivity, and obesity; the
principal causes of these risk factors are adverse behaviors,
including poor nutrition," the guidelines state. "The
atherosclerotic process begins in youth, culminating in the risk
factor–related development of vascular plaque in the third and
fourth decades of life. Good nutrition, a physically active
lifestyle, and absence of tobacco use contribute to lower risk
prevalence and either delay or prevent the onset of cardiovascular
disease."

On the basis of these observations, the panel recommends strategies
for primordial prevention, or preventing the development of
cardiovascular risk factors in the first place. These include
education, health policy, and environmental change to support
optimal nutrition and physical activity. The recommendations address
diet composition, total caloric intake, and physical activity.
Optimal implementation of the diet in the pediatric group requires
that children and all other members of their households actively
make the recommended changes.

The AHA statement offers medical practitioners dietary and physical
activity recommendations for healthy children; reviews the current
content of children's diets and the adverse health consequences of
increased intakes of calories (relative to energy expenditure),
saturated and trans fat, and cholesterol; and offers age-specific
guidelines for implementation of the recommended diet, including the
period from before birth to two years of age. It provides guidelines
to implement recommendations in clinical practice as well as public
health strategies to improve the quality of children's diets. It
revises the 1982 recommendations, while building on the recent
consensus statement on optimal nutrition for the prevention of many
chronic diseases of adulthood.

"This revision responds to the obesity epidemic that has emerged
since the publication of the last statement that addressed
children's nutrition from the AHA and has new focuses on both total
caloric intake and eating behaviors," the authors write. "This
revision strongly conveys the message that foods and beverages that
fulfill nutritional requirements are appropriate for growing and
developing infants, children, and adolescents. Calorie-dense foods
and beverages with minimal nutritional content must return to their
role as occasional discretionary items in an otherwise balanced
diet."

Although there is a strong scientific base for understanding the
potential harm and benefit of current dietary practices and the
relationship to risk factors, the scientific base for recommended
interventions is weakened by limited number, statistical power, and
scope of intervention studies; limited efficacy of attempted
interventions; and lack of generalizability of studies of feeding
behaviors at younger ages.

In contrast to previous guidelines, the revised recommendations
allow a more liberal intake of unsaturated fat, focus on ensuring
adequate intakes of omega-3 fatty acids, and emphasize foods that
are rich in nutrients and that provide increased amounts of dietary
fiber. Recommendations that are similar to those in previous
guidelines are for restriction of saturated and trans fats and
inclusion of fruits, vegetables, whole grains, legumes, low-fat
dairy products, fish, poultry, and lean meats. The guidelines note
that children and adolescents typically consume insufficient fruits,
vegetables, and fish, and that use of appropriate portions of low-
fat dairy products and lean cuts of meat will be critical in meeting
dietary needs and nutrient requirements. At present, the major
sources of saturated fat and cholesterol in children's diets are
full-fat milk and cheese and fatty meats.

For children older than two years and their families, the AHA
recommends balancing dietary calories with physical activity to
maintain normal growth, 60 minutes daily of moderate to vigorous
play or physical activity, daily intake of vegetables and fruits
(with limited juice intake), use of vegetable oils and soft
margarines low in saturated fat and trans fatty acids instead of
butter or most other animal fats, consumption of more whole grain
breads and cereals rather than refined-grain products, reduced
intake of sugar-sweetened beverages and foods, daily use of nonfat
(skim) or low-fat milk and dairy products, increased consumption of
fish (especially oily fish, broiled or baked), and reduced salt
intake, including salt from processed foods.

To meet these recommendations, the guidelines recommend that parents
reduce added sugars, including sugar-sweetened drinks and juices;
use canola, soybean, corn oil, safflower oil, or other unsaturated
oils instead of solid fats during food preparation; use recommended
portion sizes on food labels when preparing and serving food; use
fresh, frozen, and canned vegetables and fruits at every meal; limit
added sauces and sugar; regularly serve fish as an entrée; remove
the skin from poultry before eating; use only lean cuts of meat and
reduced-fat meat products; limit high-calorie sauces; eat whole
grain breads and cereals rather than refined products; replace meat
with legumes and tofu for some entrées; and replace breads,
breakfast cereals, and prepared foods that are high in salt and/or
sugar with high-fiber, low-salt, low-sugar alternatives.

Parent and caregiver responsibilities for children's nutrition are
choosing breast-feeding for first nutrition, maintaining it for 12
months if possible; controlling when food can be eaten; providing a
social context for eating behavior; teaching about food and
nutrition; counteracting inaccurate information from the media and
other influences; teaching other care providers about proper food
choices for children; serving as role models for healthy eating; and
promoting and participating in regular daily physical activity.

The guidelines recommend breast-feeding as the exclusive source of
nutrition for the first four to six months of life. To improve
nutritional quality after weaning, they recommend delaying
introduction of 100% juice until at least six months of age and
limiting it to no more than 4 to 6 oz. per day; responding to
satiety clues and not overfeeding; introducing healthy foods and
continuing to offer them if initially refused; and avoiding foods
without overall nutritional value.

Strategies to improving nutrition in young children are for parents,
not children, to choose meal times; provide a wide variety of
nutrient-dense foods, such as fruits and vegetables, instead of high-
energy-density/nutrient-poor "junk" foods; age-appropriate portion
size; use of nonfat or low-fat dairy products as sources of calcium
and protein; limiting snacking and use of juice or sweetened
beverages; limiting sedentary behaviors; allowing children with
normal body mass index to self-regulate total caloric intake; and
having regular family meals to promote social interaction and role
model food-related behavior.

The guidelines also provide nutritional strategies for schools and
discuss legislation being considered to improve children's nutrition.

Some of the guidelines authors report various financial arrangements
with the U.S. Department of Agriculture; National Institutes of
Health; Dairy Management Inc.; National Cattlemen's Beef
Association; Mars, Inc.; National Dairy Council Speakers Bureau;
Brands Global Advisory Council on Health, Nutrition and Fitness;
U.S. Potato Board; Cadbury; Grain Foods Foundation; and/or
International Food Information Council.

Circulation. 2005;112:2061-2075

The bile acid-binding resin colestimide effectively treats obesity,
insulin resistance, and type 2 diabetes in a mouse model, according
to a report in the January issue of Diabetes.

"Since dyslipidemia in patients with type 2 diabetes leads to high
mortality, this research provides a message on the beneficial effect
of this kind of drug on both diabetes and dyslipidemia, leading to
possible better outcomes for macro- and micro-vascular
complications, Dr. Misato Kobayashi from Osaka University Graduate
School of Medicine, Suita, Japan and Dr. Hiroshi Ikegami from Kinki
University School of Medicine, Osaka, told Reuters Health.

"Moreover, this study suggests the bile acid metabolism pathway as a
novel therapeutic target for the treatment of obesity, insulin
resistance, and type 2 diabetes," they added.

Dr. Kobayashi, Dr. Ikegami, and colleagues investigated the effects
of colestimide on glucose metabolism and the underlying mechanisms
in a mouse model of type 2 diabetes.

Colestimide treatment prevented diet-induced obesity and
hyperglycemia, and ameliorated established diet-induced obesity in
mice, the authors report.

Serum concentrations of total, VLDL, and LDL cholesterol decreased
significantly in the prevention part of the study and at least
marginally in the intervention portion without affecting HDL
cholesterol levels, the results indicate.

Treatment with colestimide improved fatty liver and fat
accumulation, the researchers note, while reducing insulin
resistance and improving insulin secretion.

Among the mechanisms involved in these improvements were an increase
in fecal lipid excretion and changes in the expression of genes
involved in the catabolism of cholesterol and synthesis of fatty
acids, the report indicates.

"Since bile acid-binding resins have been clinically used as
cholesterol-lowering agents, it is reasonable to try this therapy in
patients with type 2 diabetes and dyslipidemia," they researchers
suggest.

"To extend this therapy in type 2 diabetes without dyslipidemia, it
would be better to wait for results from controlled trials and/or
the long-term effect on glucose metabolism, as well as on chronic
complications."

Diabetes 2007;56:239-247

Understanding the latest research on the metabolic syndrome may
require a knowledge of funny math. Findings of a new meta-analysis
show that the syndrome is more than the sum of its risk factors--and
that it may pose a higher risk to women than to men [1].

Metabolic syndrome--a cluster of cardiac risk factors that includes
abnormal cholesterol, central obesity, high blood sugar, and high
blood pressure--nearly doubled a person¡¦s risk of developing CVD,
according to a pooling of new research.

¡§This study found a significantly increased risk of cardiovascular
events and death in people with the metabolic syndrome,¡¨ senior
author Dr Apoor Gami (Mayo Clinic, Rochester, MN) reported to
heartwire.

Furthermore, the study found CVD risk associated with metabolic
syndrome was higher in women than in men.

Researchers used a huge amount of data from more than 40 studies and
172 573 individuals. Eligible studies included patients who had
metabolic syndrome or a clustering of three or more coronary risk
factors. The end points were new heart-disease events or death, and
the studies varied in length, ranging from two to 16 years.

The study is reported in January 30, 2007 issue of the Journal of
the American College of Cardiology.

The syndrome is so named because it is a disorder characterized by
multiple metabolic abnormalities, some of which include
hyperglycemia, abdominal obesity, high triglycerides, low HDL
cholesterol, and hypertension. Other abnormalities also have been
used in various definitions of metabolic syndrome. Generally, anyone
with three of these abnormalities is considered to fit the diagnosis.

Metabolic syndrome has taken center stage recently. The controversy
emerged when major national health organizations questioned the
clinical use of the syndrome, with some suggesting that it simply
¡§added another label.¡¨

In 2005 the American Diabetes Association and the European
Association for the Study of Diabetes issued a statement that the
syndrome should not be considered a separate disease [2].

The World Health Organization (WHO) was the first to publish
criteria for metabolic syndrome in 1999.

But the National Cholesterol Education Program Adult Treatment Panel
III (NCEP ATP III) refined these in 2003, making them more practical
for doctors to apply when caring for patients.

NCEP ATP III provided thresholds for major risk factors:
central/abdominal obesity, elevated triglycerides, low HDL
cholesterol, high blood pressure, and elevated fasting glucose.
Using this definition, up to one third of the US adult population
may have the syndrome, said Gami.

Women have 33% higher risk compared with men

The overall relative risk for cardiovascular events and death for
people with the metabolic syndrome was 1.78 (95% CI 1.58-2.00), the
study found. Cardiovascular events were about 33% higher for women
than men, according to seven studies that provided separate risk
analyses for both sexes.

As part of the study, investigators did a separate meta-analysis of
studies that simultaneously adjusted for metabolic syndrome and its
components. The relative risk was 1.54 (95% CI 1.32-1.79).

¡§The metabolic syndrome may itself be a risk factor above and
beyond its recognized individual risk factors," Gami said.

¡§This finding highlights the possibility that there are yet unknown
mechanisms or risks associated with the metabolic syndrome that are
not captured by the traditional risk factors that we currently think
constitute the syndrome,¡¨ he told heartwire.

¡§Our findings are applicable to clinical practice: clinicians can
use this evidence to motivate patients when counseling them to
reduce risk factors,¡¨ he added.

Women should be aware that they are at higher risk. ¡§We generally
think of men having a higher risk of CVD, but with the metabolic
syndrome, it appears women have a higher risk relative to men,¡¨
Gami said.

As far as which criteria are better, the study found that the WHO
criteria predicted a higher risk for CVD, but the others were
predictive as well.

¡§In the end,¡¨ Gami said, ¡§regardless of how you diagnose it,
metabolic syndrome is associated with CVD risk.¡¨

Researchers noted that their meta-analysis supports other studies
that found no major limitations in estimating CVD risk if body-mass
index is substituted for abdominal obesity (eg, waist circumference)
when defining metabolic syndrome.

¡§Clinicians were getting a mixed message about the utility of
making the diagnosis, because there was still so much uncertainty
about the condition. That¡¦s why we wanted to get a full picture of
the cardiovascular risks and quantify it,¡¨ Gami said.

The findings should ¡§quiet the controversy¡¨ regarding whether or
not the syndrome exists or is a risk factor for the development of
CVD and death; however, he noted that there are still ¡§important
questions¡¨ about the causes of the syndrome and how to prevent it.

Dr Scott Grundy (University of Texas Southwestern Medical Center,
Dallas), chair of the panel of the American Heart Association and
the National Heart, Lung, and Blood Institute update report on
metabolic syndrome, commented that the meta-analysis packages the
research in an easy reference for physicians and provides added
impetus for patients to improve lifestyles.
Gami A, Witt BJ, Howard DE, et al. Metabolic syndrome and risk of
incident cardiovascular events and death: A systematic review and
meta-analysis of longitudinal studies. J Am Coll Cardiol 2007;
49:403-414.
Kahn R, Buse J, Ferrannini E, et al. The metabolic syndrome: time
for a critical appraisal: joint statement from the American Diabetes
Association and the European Association for the Study of Diabetes.
Diabetes Care 2005: 28:2289¡V2304

The choice of diclofenac as the comparator drug in the MEDAL trial
of Merck¡¦s new COX-2 inhibitor, etoricoxib (Arcoxia), has come
under scrutiny again, this time as the subject of a perspective in
the January 25, 2007 issue of the New England Journal of Medicine
[1].

The MEDAL trial was a large-scale phase 3 trial conducted primarily
to investigate the cardiovascular safety of etoricoxib, so that the
drug could gain approval in the US. In the study, which was reported
at the American Heart Association meeting last November, more than
30 000 arthritis patients were randomized to etoricoxib or
diclofenac and were followed for an average of 18 months. Results
showed similar pain-relief efficacy for the two drugs and a similar
rate of thrombotic cardiovascular events.

The authors of the current perspective, Drs Bruce Psaty and Noel
Weiss (University of Washington, Seattle) note that diclofenac,
though not the most frequently used nonsteroidal anti-inflammatory
drug (NSAID) in the US, was chosen as the comparator, according to
the MEDAL report, because it is ¡§the most widely prescribed NSAID
in the world.¡¨ But they point out that its relative COX-2
selectivity is similar to that of the COX-2 inhibitor celecoxib
(Celebrex, Pfizer), and as the potential for cardiovascular
complications associated with COX-2 inhibition was recognized as
early as 1999, it might have been hypothesized that diclofenac would
increase the risk of cardiovascular events even before the MEDAL
trial began.

Indeed, they report that in 26 trials that have compared diclofenac
and the new COX-2 inhibitors, the risk of cardiovascular events was,
if anything, slightly lower with the new drugs. In contrast, in 42
trials that used naproxen as the comparison treatment, COX-2
inhibitors were associated with an increased risk. ¡§These data
suggest that as compared with naproxen, diclofenac may increase the
risk of vascular events by about 70%," Psaty and Weiss write.

Naproxen should have been the comparator

They say that the comparison group in a clinical trial should
receive the best available active treatment, and the FDA¡¦s
Arthritis and Drug Safety and Risk Management Advisory committees
have recommended naproxen, not diclofenac, as the ¡§preferred
comparator¡¨ for large trials of COX-2 inhibitors.

They point out that as the MEDAL trial was so large, the FDA will
have ¡§an unusual abundance¡¨ of data available when reviewing the
approvability of etoricoxib, but many key clinical questions have
not been answered, such as what the gastrointestinal and
cardiovascular safety of etoricoxib is as compared with that of
traditional NSAIDs and whether the combination of naproxen and a
proton-pump inhibitor is as safe as or safer than etoricoxib for the
gastrointestinal tract. "The MEDAL program missed the opportunity to
address these important clinical and public-health questions," they
add.

They note that the selection of comparison drug has also been an
issue in several antihypertensive trials that have used atenolol as
the comparator, even though this is not the best antihypertensive to
prevent cardiovascular disease.

Public-private partnership: A better way

Psaty and Weiss point out that the Institute of Medicine recently
proposed a public-private partnership to help define key public-
health questions that merit investment in large, long-term phase 4
trials and to recommend the design of such trials. Noting that some
companies may not be keen to fund such trials, they suggest that
they may have to be publicly supported or, alternatively, the FDA
should be able to dictate their design.

They conclude: ¡§Sponsors need incentives to evaluate drugs in a
manner that highlights potential clinical value, not marketing
potential," and ¡§the identification, design, and prioritization of
large phase 4 drug trials of potential public-health importance
represent a major medical, social, and scientific effort that
currently lacks a champion in the US."

Califf: If companies fund the trial, they hold the cards

In an accompanying audio interview available on the journal's
website [2], Dr Robert Califf (Duke University, Durham, NC) says
that it was likely that by using diclofenac as the comparator
instead of naproxen, the MEDAL investigators and the company ¡§were
avoiding the comparison that had the highest probability of being
adverse to what they were trying to achieve in the marketplace." But
he added that the argument that diclofenac is the most widely
prescribed NSAID in the world does make it a reasonable choice as a
comparator. ¡§Today, if such a trial were designed in a public
forum, it would almost certainly have naproxen as a comparator; it
may also even have a placebo comparator. But there is no doubt that
if the steering committee wanted a study done that was adverse to
the interests of the company, it is unlikely that the company would
put hundreds of millions of dollars into it,¡¨ Califf said.

¡§I think it is fair to say that the design of the MEDAL trial is
about as good as it gets in the current system, but it is obvious
that if a company is paying for the entire study, then the company
holds the cards in terms of the final design. This is why many of us
have been calling for a public-private partnership to fund clinical
trials. Such a partnership would be allocated a small fraction of
the healthcare dollars as funding. The bottom line is that our
understanding of the science of the effects of drugs has far
outstripped the regulatory and clinical-trial mechanisms currently
available. We need a recalibration of the system to do much larger
studies over a much longer time. This will cost more money but will
undoubtedly save many more lives," Califf concluded.

Psaty BM and Weiss NS. NSAID trials and the choice of comparators--
questions of public health importance. N Engl J Med 2007; 356;328-
330.
Interview with Robert Califf on COX-2 inhibitors and study design.
Supplement to: Psaty BM and Weiss NS. NSAID trials and the choice of
comparators. N Engl J Med 2007; 356:328-30. Available at:
http://www.nejm.org.
Whalen J. Drug makers try to bring back COX-2 inhibitors. Wall
Street Journal, January 19, 2007. Available at: http://www.wsj.com.

The problem: Evidence-based guidelines tend to be broad and unable
to account for the unique characteristics of individual patients. A
possible solution: Equip electronic health-record systems with
programming that generates management "recommendations" tailored for
each case at hand.

In a simulation that randomized physicians to use either formal
guidelines or a computerized patient-specific ratings system for
help in deciding whether to use ECG stress testing or angiography in
fictional patients with suspected angina, the individualized
approach more often led to the "right" decision [1]. "Patient-
specific ratings substantially changed physician testing behavior,
but conventional guidelines did not," write Dr Cornelia Junghans
(University College London, UK) and associates in the January 22,
2007 issue of the Archives of Internal Medicine.

Coauthor Dr Harry Hemingway (University College London) told
heartwire that for now, the computerized ratings system is largely a
research tool, but one that could potentially bring the kind of
consistent care guidelines strive for to patients who don't easily
fit their typically broad recommendations. One of its advantages, he
said, is the ability to provide individualized clear-cut
recommendations supporting or against a procedure or test. "That
clarity of message is not always quite there in the guidelines."

The study's 145 cardiologists and general practitioners in the UK
were randomized to assess 48 fictional patients with the aid of
either guidelines or the computerized ratings system, to which they
added their own clinical judgment. The cases had been rated on their
appropriateness for either stress testing or angiography by two
expert panels using published methods, according to Junghans et al.

Physicians' decisions on whether to perform either test were
significantly more likely to agree with the expert panels when they
were assisted by the patient-specific ratings.

Likelihood that decisions based on patient-specific ratings,
compared with guidelines, agreed with expert panels Parameter
  Stress ECG
  Angiography

OR (95% CI)
  1.57 (1.36¡V1.82)
  2.24 (1.90¡V2.62)



Also compared were physicians' management decisions on separate
cases before and after access to the guidelines or patient-specific
ratings. In this analysis, the patient-specific ratings made a
significant impact on the decision process, by shifting physicians
toward the "correct" approach for both stress testing and
angiography. But the conventional guidelines had no such effect on
decisions involving either test, the authors write.

Should the patient-specific ratings system be widely adopted in
actual clinical practice, Hemingway speculated, it could be embedded
in electronic health-records systems for easy access and be based on
the views of an expert panel that convenes to revise the algorithms
on a regular basis. "It would be updated the same way guidelines are
updated," he said.

Junghans C, Feder G, Timmis AD, et al. Effect of patient-specific
ratings vs conventional guidelines on investigation decisions in
angina. Appropriateness of Referral and Investigation in Angina
(ARIA) trial. Arch Intern Med 2007; 167:195-202.

Treatment with the diabetes drug pioglitazone, a PPAR-gamma agonist,
may help prevent the cognitive impairment that often accompanies
radiotherapy to the brain, findings from an animal study suggest.

"These findings offer the promise of improving the quality of life
of these patients," Dr. Mike E. Robbins, from Wake Forest University
School of Medicine in Winston-Salem, North Carolina, said in a
statement. "The drug is already prescribed for diabetes and we know
the doses that patients can safely take."

Up to one half of brain tumor patients who receive radiotherapy will
develop progressive cognitive impairment, according to the report in
the International Journal of Radiation Oncology, Biology, and
Physics for January. Chronic inflammation is thought to play a key
role in this pathogenic process and recent reports have suggested
that PPAR-gamma agonists may have a beneficial effect in this regard.

The present study involved young adult rats that received sham or
real whole brain irradiation with or without pioglitazone before,
during, and after treatment. Object recognition testing was used to
assess cognitive function 1 year after completion of radiotherapy.

Compared with rats that received sham irradiation, irradiated rats
that did not receive pioglitazone displayed cognitive impairment. By
contrast, no drop in cognitive function was observed in irradiated
animals treated with pioglitazone. Further testing showed no
advantage for continuing the drug for 54 weeks after irradiation
compared with just 4 weeks.

"Translating these findings to the clinic offers the promise of not
only improving the quality of life for long-term brain tumor
survivors, but also increasing their therapeutic window," the
authors conclude.

Int J Radiat Oncol Biol Phys 2007;67:6-9

The US has better control of hypertension than a number of European
countries, probably because of its more aggressive stance on therapy
and lower treatment thresholds, a new study shows [1]. Dr Y Richard
Wang (Temple University, Philadelphia, PA) and colleagues report
their findings in the January 22, 2007 issue of the Archives of
Internal Medicine.

But coauthor Dr G Caleb Alexander (University of Chicago, IL)
cautions against reading too much into these differences. "The
comparison is interesting, but the differences are less important
than some of the similarities," he told heartwire. "One of our
concerns is that the differences will be focused on at the expense
of the similarities."

"There are a wealth of studies that indicate an epidemic of
hypertension in every country, with a substantial number of people
undiagnosed," Alexander says. And even in the US, nearly half of the
hypertensive patients did not achieve their BP goal set by the JNC 7
guidelines in this study, he notes. "Thus, better BP control in the
US should not be too quickly praised. Substantial potential for
better hypertension control . . . exists in both Europe and the US."

Use of drug combinations higher in the US

Wang and colleagues analyzed data from the CardioMonitor 2004 survey
of outpatients with hypertension visiting 291 cardiologists and 1284
primary-care physicians in the US and five Western European
countries: France, Germany, Italy, Spain, and the UK. The physicians
in the survey were randomly selected, and those who agreed to
participate completed two-page diaries for 15 cardiovascular
patients. Information collected included patient characteristics,
initial blood-pressure level before treatment, any comorbidities,
and the use of seven types of antihypertensive drugs (thiazides,
other diuretics, beta blockers, calcium-channel blockers, ACE
inhibitors, angiotensin receptor blockers, and other
antihypertensives).

Guidelines regarding the blood pressure at which treatment should
begin differ in various countries, as does the definition of high
risk; the recommendations tend to be more aggressive in the US, the
authors note.

They found that only 65% of US patients had an initial pretreatment
blood-pressure level of 160/100 mm Hg or higher, compared with 81%
to 90% of European patients.

Multivariate analysis controlling for age, sex, current smoking, and
physician specialty indicated that European patients had higher
latest systolic BP levels (by 5.3 to 10.2 mm Hg across countries
examined) and diastolic BP levels (by 1.9 to 5.3 mm Hg), a smaller
likelihood of hypertension control (odds ratio 0.27-0.50), and a
smaller likelihood of medication increase for inadequately
controlled hypertension (odds ratio 0.29-0.65).

While use of thiazides was quite similar across countries,
utilization of other antihypertensive drugs varied widely, with no
particular pattern. Use of combination therapy was highest in the US-
-64% vs 44% to 59% across European countries.

"The rate of hypertension control was highest in the US," the
authors write. "In addition, of the 11 969 patients with
inadequately controlled hypertension, the US had the highest
percentage of patients receiving any medication increase during the
visit."

"Together, our findings suggest that better hypertension control in
the US may be explained by lower treatment thresholds and more
intensive treatment, both of which are consistent with the more
aggressive treatment guidelines in the US compared with the other
countries examined," they note.

"Clinical inertia" a key barrier to care

But Alexander told heartwire there are some important limitations to
the study, such as the fact that the survey provided only
a "snapshot" of hypertension and treatment and does not allow a
proper assessment of how early diagnosis, early treatment, and
intensive treatment over time individually contribute to better
hypertension control in the US.

Also, factors such as diagnostic criteria, healthcare coverage,
financing, and delivery differ among countries, which may have had
an impact on the findings, he notes.

He suspects that "clinical inertia" plays a large part in the
undertreatment of hypertension everywhere. "Rather than responding
by starting or upping treatment, both patients and physicians alike
may rationalize as to why it is high. This is an important barrier
to care."

Yang YR, Alexander GC, Stafford RS, et al. Outpatient hypertension
treatment, treatment intensification, and control in Western Europe
and the United States. Arch Intern Med 2007; 167:141-147.

Blocking the autonomic nervous system that regulates the fight-or-
flight or noradrenaline reactions is effective in acutely
normalizing blood pressure in obese individuals, research shows.

This finding, Dr. Italo Biaggioni from Vanderbilt University,
Nashville, told Reuters Health, is "in agreement with the theory
that has been around for some time that the noradrenaline system is,
in large part, responsible for the hypertension of obesity. This
would suggest that lowering the noradrenaline system in obese
patients would be an effective way of controlling their high blood
pressure."

Dr. Biaggioni and colleagues assessed the role of the autonomic
nervous system in BP and thermogenesis control by measuring the
changes in 10 obese and 10 lean subjects in BP and resting energy
expenditure acutely induced by complete autonomic withdrawal
achieved by blocking ganglionic transmission with stepwise IV
trimethaphan.

They report in the January issue of Hypertension, that acute
autonomic withdrawal "reduced and even normalized" BP and peripheral
vascular resistance in obese subjects, which provides "strong
evidence for a causal relationship."

In contrast, the observed increase in resting energy expenditure in
obese subjects was not significantly lowered by autonomic
withdrawal, "suggesting resistance to the metabolic effects of
sympathetic activity in this condition," the investigators note.

Dr. Guido Grassi from University of Milan writes in a related
editorial that these "intriguing" results clearly indicate that the
sympathetic nervous system is mechanistically involved in obesity-
related hypertension.

Dr. Biaggioni's team notes that "commonly used antihypertensive
treatment is ineffective in reducing sympathetic activation. We
argue that increased sympathetic activity can be targeted in the
treatment of obesity-associated hypertension and that drug
development should be directed toward this end."

Hypertension 2007;49:5-6,27-3

Treatment with the diabetes drug pioglitazone, a PPAR-gamma agonist,
may help prevent the cognitive impairment that often accompanies
radiotherapy to the brain, findings from an animal study suggest.

"These findings offer the promise of improving the quality of life
of these patients," Dr. Mike E. Robbins, from Wake Forest University
School of Medicine in Winston-Salem, North Carolina, said in a
statement. "The drug is already prescribed for diabetes and we know
the doses that patients can safely take."

Up to one half of brain tumor patients who receive radiotherapy will
develop progressive cognitive impairment, according to the report in
the International Journal of Radiation Oncology, Biology, and
Physics for January. Chronic inflammation is thought to play a key
role in this pathogenic process and recent reports have suggested
that PPAR-gamma agonists may have a beneficial effect in this regard.

The present study involved young adult rats that received sham or
real whole brain irradiation with or without pioglitazone before,
during, and after treatment. Object recognition testing was used to
assess cognitive function 1 year after completion of radiotherapy.

Compared with rats that received sham irradiation, irradiated rats
that did not receive pioglitazone displayed cognitive impairment. By
contrast, no drop in cognitive function was observed in irradiated
animals treated with pioglitazone. Further testing showed no
advantage for continuing the drug for 54 weeks after irradiation
compared with just 4 weeks.

"Translating these findings to the clinic offers the promise of not
only improving the quality of life for long-term brain tumor
survivors, but also increasing their therapeutic window," the
authors conclude.

Int J Radiat Oncol Biol Phys 2007;67:6-9

Cortisol secretion is elevated in type 2 diabetics with chronic
complications, according to a report in the January Diabetes Care.

Some previous studies have shown elevations of ACTH in patients with
type 2 diabetes, the authors explain, whereas others have shown no
alteration in hypothalamic-pituitary-adrenal (HPA) axis activity.

Dr. Iacopo Chiodini from University of Milan, Italy and colleagues
evaluated the HPA activity in a sample of 170 type 2 diabetic
patients with or without chronic complications and in a sample of 71
nondiabetic controls matched for sex, age and BMI.

Overall, the patients with type 2 diabetes had higher levels of
urinary free cortisol; serum cortisol after a 1-mg overnight
dexamethasone suppression test; 12:00 p.m. serum cortisol; and
hypertension than did the control group, the authors report.

Among diabetic patients, those with chronic complications had higher
parameters of HPA axis function than did those without chronic
complications, the results indicate.

HPA axis function did not correlate with A1c, disease duration,
waist circumference, insulin resistance, or number of components of
the metabolic syndrome, the researchers note.

The number of diabetic complications, however, was significantly
associated with 12:00 p.m. serum cortisol level and with diabetes
duration, the report indicates.

Serum cortisol level at 12:00 p.m. was significantly related to
retinopathy and neuropathy, the investigators say, but other
parameters of the HPA axis were not individually associated with the
presence of any diabetes complication.

"Even if these findings have no immediate implications for the
clinical management of these patients, further studies are needed to
find out if HPA axis activity has a causative role in determining
chronic complications of type 2 diabetes," Dr. Chiodini told Reuters
Health.

"A good idea may be to evaluate the effects of rosiglitazone on
pituitary-adrenal activity in diabetic patients with and without
complications, given the role of this molecule in both adrenal
activity and insulin resistance," Dr. Chiodini added.

Diabetes Care 2007;30:83-88

Cynical distrust, depression, and chronic stress were linked with
elevated levels of inflammatory markers in a new large cross-
sectional study that looked at individuals aged 45 to 84 [1].

The study, on psychosocial factors and inflammation in the Multi-
Ethnic Study of Atherosclerosis (MESA), is reported in the January
22, 2007 issue of the Archives of Internal Medicine.

¡§Higher levels of cynical distrust were associated with
progressively higher levels of major inflammatory markers, and
similar patterns were seen for chronic stress, with no clear
evidence of a threshold effect,¡¨ Dr Nalini Ranjit (University of
Michigan, Ann Arbor) told heartwire.

The MESA cohort included 6814 men and women who were free of
clinical cardiovascular disease. The study included a racial mix of
white (38.5%), black (27.8 %), Hispanic (21.9%), and Chinese (11.8%)
subjects.

Researchers also assessed the impact of behavior (physical activity,
smoking, alcohol use) and other health factors (diabetes, body-mass
index [BMI], recent infection, use of medication) on the stress-
inflammation relationship. A large part of the association was
accounted for by BMI and diabetes.

Associations of psychosocial factors with inflammation were reduced
by about 45% to 100% after adjustment for BMI and diabetes and about
20% to 55% taking into account behavioral factors.

¡§It is possible that stress is associated with obesity and
diabetes, resulting in increases in inflammation; this in turn could
explain the relationship of stress to atherosclerosis,¡¨ Ranjit said.

¡§The take-home message is that problems of psychosocial stress and
lifestyle risk factors--particularly obesity--should be considered
together during management of CVD and other inflammation-related
chronic disorders,¡¨ she said.

Studies linking stress to heart disease are not new--many date back
to more than a quarter of a century. ¡§However, the mechanism is
unclear; the goal of this study was to find out whether inflammation
is the missing link,¡¨ she told heartwire.

Researchers also noted that while most psychosocial/CVD research
examines major depression, MESA included chronic stress and cynical
personality.

The study is also unique because it describes a mechanism, includes
a large database, and measures mediating factors in detail.

CRP, IL-6 higher in those with chronic stress, depression

In the cohort of the MESA study, three major inflammatory markers
were measured: C-reactive protein, IL-6, and fibrinogen. Cynical
distrust was scored on an 8-item scale of the Cook-Medley Hostility
Scale, depression was assessed using the Center for Epidemiologic
Studies-Depression Scale score, and chronic stress used a 0 to 4
scale based on work and relationship stress.

The strongest links to psychosocial factors were found for C-
reactive protein and IL-6. For cynical distrust, there was a 7% (95%
CI 3%-11%) difference in IL-6 level and a 9% (95% CI 2%-16%)
difference in CRP level between people at the 80th and the 20th
percentiles of the scale.

Subjects with higher levels of chronic stress tended to have
elevated concentrations of IL-6 and C-reactive protein. The
percentage differences comparing two or more stressful circumstances
against none were 4% (95% CI 1%-8%) for IL-6 and 5% (95% CI 1%-11%)
for C-reactive protein.

Those whose depression scores were >21 had 7% (95% CI 1.0%-14%)
higher IL-6 than those whose scores were <21.

¡§We hypothesized that inflammation may be the one of the pathways
linking psychological factors to CVD. And it was interesting that
much of this association of was accounted for by obesity and
diabetes,¡¨ she said in interview with heartwire.

The researchers stopped short of concluding that stress causes heart
disease.

The findings are based on a cross-sectional analysis. Determining
the independent effect of the behavioral factors will require a
longitudinal study, noted the investigators.

However, Ranjit said the results point to a ¡§plausible set of
pathways¡¨ for stress and other psychosocial problems to contribute
to heart disease.

According to Dr Valentin Fuster (Mount Sinai Medical Center;
Cardiovascular Institute Mount Sinai Heart, New York, NY), it is
well known that there are common aspects to obesity, diabetes, and
inflammation. But this study is the first to ¡§put all the
ingredients together¡¨ and explain the interactions with stress and
other psychological risk factors.

The research was funded with grants and contracts from the National,
Heart, Lung, and Blood Institute and the National Institute of Child
Health and Human Development.

Ranjit N, Diez-Roux AV, Shea S, et al. Psychosocial factors and
inflammation in the Multi-Ethnic Study of Atherosclerosis. Arch
Intern Med 2007; 167:174-181

Endothelial dysfunction might be a factor linking preeclampsia,
recurrent pregnancy loss and cardiovascular disease latter in life,
researchers report in the January issue of Hypertension.

Dr. Gloria Valdes of Universidad Catolica de Chile in Santiago and
colleagues point out that there is evidence that preeclampsia
predisposes women to an increased risk of cardiovascular disease.
This also appears to be true in women with recurrent pregnancy loss.

In search of a common underlying mechanism, the researchers studied
22 women with a previous healthy pregnancy, 25 who had had severe
preeclampsia and 29 who had had recurrent pregnancy loss. The women
were examined at day 10 of the luteal phase of an ovulatory cycle 11
to 37 months after pregnancy.

Compared with controls, those with placental disorders had a
significantly decrease in endothelium-dependent dilatation, a higher
rate of endothelial dysfunction, lower serum nitrites and higher
cholesterol.

Patients who had had preeclampsia also had higher, although normal,
blood pressure and their parental history showed an elevated
prevalence of cardiovascular disease.

Overall, the investigators conclude that "endothelial dysfunction
was present far from pregnancy in about 50% of subjects with
recurrent abortions or with a history of previous severe
preeclampsia."

The researchers hypothesize that these conditions and subsequent
cardiovascular disease are linked, and they suggest
the "identification and correction of endothelial dysfunction
detected during the reproductive stage on obstetric outcome and on
cardiovascular diseases needs to be elucidated."

Hypertension 2007;49:90-95