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.
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
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.
conducted by researchers from the Bronx (NY) VA Medical Center, the
School of Medicine in
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).
the basis of
this study, at least based upon the self-reporting of, literally,
thousands of insured adults from across the country, the VA healthcare
would appear to have surpassed the civilian healthcare community in
actually providing vital outpatient healthcare services for disease
and management in areas that have been shown, by numerous public health
studies, to reduce premature death and disability from the most common
of mortality in the United States (i.e., cardiovascular disease,
studies are potentially at risk of “reporting bias,” by both the
taking the surveys and the researchers who are actually collecting the
information, the very large cross section of the country that was
this clinically validated survey increases the probability that the
data is accurate and representative of the
Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center
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Copyright 2008. Robert A. Wascher, MD, FACS. All rights reserved.
Dr. Wascher's Archives:
4-27-2008: Stents vs. Bypass Surgery for Coronary Artery Disease; The “DASH” Hypertension Diet & Cardiovascular Disease Prevention; Testosterone Therapy for Women with Decreased Sexual Desire & Function
4-6-2008: Human Papilloma Virus (HPV), Pap Smear Results & Cervical Cancer; Human Papilloma Virus (HPV) Infection & Oral Cancer; Hormone Replacement Therapy (HRT) & the Risk of Gastroesophageal Reflux Disorder (GERD)
12-16-2007: Honey vs. Dextromethorphan vs. No Treatment for Kids with Night-Time Cough, Acupuncture & Hot Flashes in Women with Breast Cancer, Physical Activity & the Risk of Death, Mediterranean Diet & Mortality