The
information in this column is intended for informational
purposes only, and does not constitute medical advice or
recommendations by the author. Please consult with your
physician before making any lifestyle or medication changes, or if you
have any other concerns regarding your health.
CAN
STATINS REVERSE
CORONARY ARTERY DISEASE?
As
regular
readers already know, there is a huge (and growing) body of research
related to
the use of the so-called statin drugs, which block a key enzyme in the
liver necessary
for the synthesis of cholesterol.
Generally, these medications lower the level of “bad
cholesterol” (LDL)
in the body while also increasing the level of the “good cholesterol”
(HDL). In the
process, total cholesterol levels are
also usually reduced. As
with most
medications, statins can result in adverse side effects, including
inflammation
of both the liver and muscles (for this reason, patients taking statins
are
advised to undergo regular blood tests to rule-out these potential side
effects).
Many
laudable
claims have been made about the potential clinical benefits of statin
therapy,
including their still-debated effects, if any, on cancer risk (please
review my
Archives for my discussion of several research papers related to this
topic). However,
there is little doubt but that statin
therapy significantly slows down the progression of artery-clogging
plaques
(atherosclerosis) in the coronary arteries of the heart, and in other
important
arteries in the body, or that long-term statin usage has been
correlated with a
decreased risk of cardiovascular events (e.g., angina, heart attack,
and some
types of stroke) and death in high-risk patients.
Whether or not statin drugs can actually reverse
atherosclerotic plaques in the
body’s critical arteries, including the coronary arteries, has been a
hot topic
of debate, although there is very little high-level clinical research
evidence
to shed light on this important question.
Now, a new research paper in the journal Circulation
addresses this very question.
This
study, rather
whimsically-named “A
Study to Evaluate
the Effect of Rosuvastatin on Intravascular
Ultrasound-Derived Coronary Atheroma Burden
(ASTEROID),” was conducted by researchers
at the Baylor College of Medicine and the Methodist DeBakey Heart and Vascular Center
in Houston, the Cleveland Clinic, the Montreal Heart Institute in Quebec, and the University
Clinic in Essen,
Germany. It should be noted that
this research was
also financially supported by the manufacturer of the drug used in this
study
(rosuvastatin, also known as Crestor®),
AstraZeneca Pharmaceuticals.
In this study,
507 patients with at least 25% narrowing of their coronary arteries
were all
placed on rosuvastatin for a period of 24 months.
All patients then underwent coronary
arteriograms and intravascular ultrasound evaluation of the coronary
arteries (via
heart catheterization) with quantitative measurements of the degree of
coronary
artery narrowing, as well as coronary artery diameter.
These invasive coronary artery studies were
performed at the beginning of the research study, and at the end of the
study
once again. After
matching patients
according to the severity and extent of coronary artery narrowing, a
total of
292 patients were found to have comparable abnormalities of their
coronary
arteries, and these patients were utilized to report the results of
this study.
Overall,
24
months of rosuvastatin therapy was associated with a 53% reduction in
the blood
levels of LDL, and a 14% average increase in the levels of HDL. The average degree of
coronary artery
narrowing decreased from 37% at the beginning of the study to 36% at
the end of
the study, while the average diameter of these same diseased coronary
arteries
increased from 1.65 millimeters to 1.68 millimeters.
This
is an
important study, albeit with some limitations.
The use of invasive and highly accurate techniques to
obtain
quantitative measurements of coronary artery atherosclerosis and
luminal
diameter in this study allowed these researchers to clearly identify
small but
meaningful changes in these critical, small-diameter arteries after 24
months
of statin therapy. On
the other hand,
the absence of a placebo (“sugar pill”) control group, and the lack of
a
“double-blinded” design (i.e., where neither patients nor the people
conducting
the research know which pills are placebos and which are
statin
pills), somewhat reduce the significance of this study’s findings. This is because we cannot
know whether or not
other factors might also have played a role in the favorable
morphologic
changes observed in the coronary arteries of the volunteers in this
study (such
as improved diet or exercise, for example).
Thus, the next logical step would be to repeat this study,
but with a
double-blinded, placebo-controlled design this time.
It should also be noted that various statin
drugs, and at varying doses, have been shown to have different degrees
of
LDL-lowering effects, and different capabilities in terms of decreasing
cardiovascular events, including death.
Moreover, recent studies of medications that combine a
statin with other
types of cholesterol-lowering drugs have shown no improved benefit over
statins
alone. Despite the
limitations of
this—and other—statin research studies, however, this particular study
offers
intriguing evidence that statin drugs may not only be able to slow down
the
progression of coronary artery atherosclerosis, but may actually be
able to
induce regression of heart- and life-threatening coronary artery
plaques.
DOES
BREAST ULTRASOUND IMPROVE
BREAST CANCER DETECTION?
Current
breast
cancer screening guidelines call for annual screening mammograms to be
performed, starting at about age 40 for women of average risk, and at
least 10
years earlier for women with one or more increased risk factors for
breast
cancer. Over the
past 2 or 3 years, MRI
scans have also become increasingly important in screening high-risk
women,
although cost factors and the erroneously positive (“false positive”)
results
often associated with MRI scans of the breast continue to stimulate
debate
about the role of MRI in breast cancer screening and detection. Ultrasound, on the other
had, has been in use
for decades. Ultrasound
is non-invasive,
does not expose the patient to ionizing radiation (like mammograms) or
to
high-level magnetic fields (like MRI), and is relatively inexpensive. Ultrasound examinations
utilize special
probes that transmit harmless sound waves through the body’s tissues. These sound waves are
reflected back to the
probe proportionally according to the density of the tissues and
structures
being imaged. The
ultrasound machine
processes these “echoes” to form images of the organs and tissues being
studied, including tumors, cysts, and other anatomic abnormalities. Today’s ultrasound
machines are very
sophisticated devices, and many of them can produce amazingly accurate
images
of tissues and structures beneath the skin.
There
are a few
significant downsides associated with ultrasound, however. First of all, acquiring
ultrasound images is
a rather subjective process when compared to other radiological
examinations
(including mammograms, CT scans, and MRI scans).
Secondly, the interpretation of ultrasound
images, with their black and grey and white smudges and shadows, is,
likewise,
a more subjective undertaking than for other types of radiological
studies. Also,
because of the physics of
sound waves, as they travel through tissues and structures of varying
density,
there are certain areas of the body that are either inaccessible to an
external
ultrasound probe, or that cannot be accurately imaged (for example,
many areas
deep in the abdomen cannot be imaged with ultrasound because gas in the
GI
tract prevents transmission of the sound waves).
Despite
its
limitations, ultrasound has long been used to image the breast, and
particularly the breasts of younger women, which are often too dense
for
mammograms, with their low-dose x-rays, to accurately image (overall,
mammograms are thought to miss 10 to 15% of breast cancers). Many of us who work
extensively with cancer
patients, and with breast cancer screening in particular, have observed
cases
where a malignant breast tumor was detected by ultrasound after being
missed by
mammography. There
have also been
previous clinical studies (most of them retrospective in nature)
suggesting
that the use of breast ultrasound, particularly in women at increased
risk for
breast cancer, probably improves diagnostic accuracy when added to
screening
mammography. At
last, however, a
prospective, randomized, multi-institutional clinical research trial
has been
performed, giving us a quantitative look at the diagnostic impact of
breast
ultrasound, when added to mammography, in high-risk women with dense
breasts.
This
study, just
published in the Journal of the American
Medical Association, enlisted 2,809 female patient volunteers
at 21
different institutions, including the Allegheny-Singer Research
Institute in
Pittsburgh, Johns Hopkins University in Baltimore, Beth Israel
Deaconess
Medical Center in Boston, Duke University in North Carolina, the Mayo
Clinic in
Minnesota, UCLA Medical Center in Los Angeles, USC Medical Center in
Los Angeles,
and multiple other US and international sites.
Participating
patients were randomized to undergo only standard screening mammography
versus
mammography plus breast ultrasound, and 97% of the patients were
followed for
at least 12 months at the time that the results of this study were
reported. All women
with abnormal
findings, by either mammography or/and ultrasound, were managed
according to
current clinical guidelines.
Among
the 2,637
women with at least 1 year of follow-up, 40 were diagnosed with breast
cancer. Eight of
these 40 women had
suspicious findings on both
mammography and ultrasound, 12 women were diagnosed with ultrasound
alone, and
another 12 were diagnosed by mammography alone.
When the researchers analyzed their data, they found that
mammography
alone, when applied to high-risk women with dense breast tissue,
detected
breast cancers at a rate of 7.6 cases per 1,000 women screened. The addition of breast
ultrasound to
mammography, in this select group of patients, increased the breast
cancer
diagnostic yield to 11.8 cases detected per 1,000 women screened. Thus, using the
combination of mammography
and ultrasound, 4.2 additional cases of breast cancer were detected,
per 1,000
women screened, than would have been identified with mammography alone. The diagnostic accuracy of
mammogram alone,
among these generally younger women with dense breasts, was only 78%. When breast ultrasound was
added to
mammography, the accuracy of this combined approach to breast cancer
screening
increased to 91%.
The
downside of
this combined modality approach to breast cancer detection is that, as
with MRI
of the breast, significantly more lesions were detected in the breasts
of these
women volunteers that, upon biopsy, were proven to be benign lesions
(for you
statistics geeks out there, the sensitivity was significantly greater
with
combined mammogram and ultrasound screening, but at the expense of
poorer
specificity, although overall diagnostic accuracy was still
significantly
greater with the combined approach).
Indeed, fewer than 10% of the suspicious lesions
identified by
ultrasound proved to be breast cancer upon biopsy.
This
well-performed prospective, randomized clinical study offers a
tremendous
degree of clinical insight into the strengths and limitations of
current
screening approaches for breast cancer.
One important caveat is that the women who were evaluated
in this study
were all considered to be at increased risk of breast cancer, based
upon
screening with one of two validated breast cancer risk assessment tools
(the
Gail and Claus breast cancer risk assessment models), and all of them
had
increased breast tissue density, which is known to decrease the
sensitivity of
mammography. However,
at least within
this very important subgroup of women undergoing annual breast cancer
screening, the addition of ultrasound to mammography significantly
increased
the yield of breast cancer diagnoses in this study.
Importantly, almost all of the cases of
breast cancer that were detected by this combined approach to screening
were
very early stage cancers (AJCC Stage I), which are associated with a
> 90%
chance of cure.
An
important
limitation of this combined modality approach to breast cancer
screening, at
least in this high-risk group of patients, was the very high “false
positive”
rate (fewer than 1 in 10 of the abnormalities detected by breast
ultrasound
turned out, upon biopsy, to actually be a breast cancer). For this reason alone, the
routine use of
combined ultrasound and mammography is not likely to be a
cost-effective or
efficient strategy for breast cancer screening in the general
population. However,
until more accurate breast cancer
screening tests become available, and with a much lower “false
positive” rate
than is currently associated with mammography, and with ultrasound and
MRI, it
still seems prudent to consider these three imaging technologies for
those patients
known to be at significantly increased risk of developing breast cancer. Whether such an approach
can be proven to
actually save lives is not clear from this research study, or from the
recent
explosion of studies looking at the use of MRI in selected patients. In our current strained
(if not broken)
healthcare system, the “cost-to-benefit ratio of enhanced approaches to
breast
cancer screening remains uncertain at this time, unfortunately.
PREVENTIVE
CARE SERVICES
AT VETERANS ADMINISTRATION (VA) MEDICAL CENTERS
The
Veterans
Administration has, for decades, been an easy target of criticism. Chronically under-funded
during both times of
peace and war, the VA is expected to provide healthcare resources to
nearly 6
million patients in 2009, including almost 4 million veterans who have
served
in the Iraq and Afghanistan theaters, as well as vets with
service-connected
disabilities, low incomes, and veterans with other special healthcare
needs. The
tremendous strain that is already being
experienced at most VA medical centers, due to the historically
unprecedented
rate of battle-injury survival in Iraq and Afghanistan, and the
resulting very
high incidence of traumatic brain and extremity injuries, and a
tremendous
surge of post-traumatic stress disorder (PTSD) cases, all present a
particularly grave set of challenges for what is, arguably, the largest
healthcare system in the United States.
The
VA healthcare
system does have a rather dark history of providing less than optimal
care, at
some of its facilities, in the past.
But
what is often overlooked is that, as a result of past concerns about
healthcare
quality at many of its facilities, the VA healthcare system has
actually
become, in recent years, both a pioneer and a leader in healthcare
quality
improvement. Indeed,
many of its
internal performance and quality improvement programs have been so
successful
that they have become, increasingly, adopted by the civilian healthcare
system,
including Medicare and Medicaid.
I
should also
note that (both as a disclaimer and as a matter of some personal
experience
with this topic) I, myself, have been a beneficiary of VA healthcare
services. As a
28-year Army veteran, I
retired from the Army with several significant service-related health
issues
for which I occasionally have sought care for at VA facilities.
As
much of the
news about veterans’ healthcare in the popular media is uniformly
negative, I
think that it is important to present the available clinical data on
care at VA
facilities in as objective a manner as possible.
A new clinical research study, just published
in the Archives of Internal Medicine,
has compared the quality and extent of preventive and chronic disease
healthcare services at VA healthcare facilities with the same services
provided
at civilian health care organizations in the United States, and the
results are
a welcome respite from the nearly constant drumbeat of negative
reporting about
VA medical facilities in the popular media.
This
study was
conducted by researchers from the Bronx (NY) VA Medical Center, the
Mount Sinai
School of Medicine in New York City,
and the Yale
University School of Medicine in New Haven, Connecticut.
Data
was
collected from a national survey in both 2000 and 2004 (152,310 and
251,570
adults participated, respectively).
The
researchers asked these hundreds of thousands of insured adults to
report on
their use of 17 recommended outpatient health screening and treatment
services
at both VA and civilian healthcare facilities.
These ambulatory healthcare services primarily included
nationally-recommended
examinations and clinical management services for cancer prevention and
detection, cardiovascular disease prevention and detection, diabetes
management, and infectious disease prevention.
The data was then analyzed in an effort to objectively
contrast the
extent to which these services were afforded to patients receiving care
at VA
medical centers and civilian medical centers.
A
total of 2,852
insured adults received their healthcare services at VA medial centers
in 2000,
while 7,155 of the patients responding to the 2004 survey received
their care
at VA facilities (1.9% and 2.4% of the total study populations in 2000
and
2004, respectively). Despite
the
increasing demands placed upon the VA healthcare system since the start
of the
Iraq war 5 years ago, veterans received more of the recommended
healthcare
services in 2004, at VA facilities, than they did in 2000. Moreover, when compared to
its civilian
counterparts, the VA offered greater access to 6 of the 17 recommended
services
in 2000, and in 9 of these 17 critical outpatient services in 2004. For example, based upon
the 2004 survey
results, when compared to civilian healthcare facilities, the patients
using a
VA healthcare facility reported a 10% greater use of cholesterol
testing and a
whopping 40% increase in the use of colorectal cancer screening
examinations.
When
comparing
the trend for increased use of specific services between the 2000 and
2004
surveys, this study determined that there was a significant shift in
favor of
the VA facilities, over the civilian medical centers, in offering
breast cancer
screening, eye examinations in diabetic patients, and vaccinations
against the
flu and pneumonia between 2000 and 2004, suggesting that the VA further
improved its services to its patients during this 4-year period (or,
perhaps,
the civilian healthcare community did a progressively poorer job in
these areas
over this timeframe, or even, perhaps, both explanations might be
simultaneously true).
On
the basis of
this study, at least based upon the self-reporting of, literally,
hundreds of
thousands of insured adults from across the country, the VA healthcare
system
would appear to have surpassed the civilian healthcare community in
terms of
actually providing vital outpatient healthcare services for disease
prevention
and management in areas that have been shown, by numerous public health
studies, to reduce premature death and disability from the most common
causes
of mortality in the United States (i.e., cardiovascular disease,
cancer, and
diabetes). While
all survey-based
studies are potentially at risk of “reporting bias,” by both the
volunteers
taking the surveys and the researchers who are actually collecting the
information, the very large cross section of the country that was
sampled by
this clinically validated survey increases the probability that the
resulting
data is accurate and representative of the US
population.
As
a purely personal (and, therefore,
subjective) anecdote, I can attest to the thoroughness of the
outpatient
primary care that I have recently received from VA facilities. No healthcare system is
perfect, and all
health care systems and facilities in the US
are struggling to provide
comprehensive preventive care and disease management services within a
broken
and increasingly bankrupted national healthcare service delivery
environment
(and the VA is no exception). But
the VA
has, by the estimation of many national and international public health
experts, transformed itself from a case study in poor quality medical
care to a
pioneer and leader in healthcare quality improvement, and across
multiple
different areas of medical and surgical care.
This Surgical Oncologist (and retired Army Colonel),
therefore, believes
that this is a very important study for the public to read. I, and millions of other
American veterans,
salute the Veterans Administration for their tireless efforts to
provide
excellent care to some of our society’s most vulnerable patients, each
and
every day, and despite its chronic and enormous budgetary shortfalls.
Disclaimer:
As always, my advice to readers is to seek the advice of your physician
before making any significant changes in
medications, diet, or level of physical activity.
