Predicting Treatment Outcomes in Patients With Peripheral Artery Disease

Leg Bypass Surgery, Angioplasty and Stents Currently Fail Up to 50 Percent of the Time

Vascular Cures, a leading nonprofit investing in research to develop breakthrough treatments for vascular disease, recently announced results that indicate there may be a genetic basis for the varying outcomes of bypass surgery in the legs. Results were presented by Michael S. Conte, MD, of the University of California, San Francisco, at the 2011 Society for Vascular Surgery Annual Meeting.

pipesBypass surgery, angioplasty and stents are all used to treat blockages caused by peripheral artery disease (PAD). Current estimates are that more than 8 million Americans have PAD, a condition that can produce severe disability and lead to amputation. Hundreds of thousands of procedures are performed each year in the U.S. to improve leg circulation in patients suffering from PAD, yet up to half of these fail within a few years due to excessive scarring that leads to reduced blood flow. The reasons for the variability in the outcome of PAD treatments have been poorly understood.

Led by vascular surgeons Dr. Conte and Alec Clowes, MD, at the University of Washington, the team demonstrated a potential genetic basis for why some patients experience blockage of their bypass grafts faster and more frequently than others.

“The results of this study, together with similar findings in a Dutch study of patients who underwent coronary stent angioplasty (van Tiel et al, 2009), strongly support the hypothesis that the formation of scar tissue in blood vessels is genetically regulated by the gene p27,” stated Dr. Conte.

Dr. Conte is chief of UCSF’s Division of Vascular and Endovascular Surgery and chief medical officer of Vascular Cures. Dr. Clowes is professor of surgery at the University of Washington and vice chair for research in the Department of Surgery.

“These studies represent a major breakthrough in our understanding of arteries closing after angioplasty and bypass grafting,” added Dr. Clowes. “More importantly, they may help us identify patients at increased risk of treatment failures. These results may also accelerate drug development to prevent renarrowing of vascular reconstructions.”

Members of the Vascular Cures Research Network, Dr. Conte and Dr. Clowes performed a gene association study in a group of 204 patients who had undergone leg vein bypass grafting, testing them for a common variation of the gene p27, which is known to control how cells grow. Patients with the -838AA genotype (17% of the patients) were 2.5 times more likely to have a successful graft over patients with either of the more common -838AC or -838CC genotypes. This result remained significant even when controlling for age, gender, diabetes and other clinical factors known to influence surgical outcomes. The study was funded partially by the National Heart, Lung and Blood Institute and Vascular Cures.

About PAD

Peripheral artery disease (PAD) is a build-up of plaque in the arteries of the leg and is a rapidly growing problem. PAD can cause significant pain and disability and affects more than 8 million Americans, requiring hundreds of thousands of surgeries and leading to over 80,000 amputations each year. The treatments used today to improve blood flow in patients with PAD are bypass surgery, angioplasty and stents. While often successful initially, these interventions frequently need to be repeated due to abnormal scar formation that causes re-narrowing of the artery or graft. The failure rates of angioplasty and stents are as high as 50 percent within one to two years, and half of all bypass procedures fail within five years.

About the Vascular Cures Research Network

The Vascular Cures Research Network is a national research consortium of up to 12 world-class medical institutions. Members of this collaborative team share information and results in order to substantially accelerate the development of new drugs, technologies and predictive tools to improve treatments for vascular disease.

Advances in genomics are putting the dream of individualized medicine within reach, identifying genetic profiles and biomarkers that predict disease or response to treatment. These discoveries rely on specialized analyses of tissue from large numbers of patients, maintained in a “biobank.” Vascular Cures is building the first national vascular biobank of blood and tissues from thousands of patients. The Vascular Cures Research Network and biobank will be a resource for researchers throughout the world for decades to come.

About Vascular Cures

A leader in vascular research, Vascular Cures invests in the development of breakthrough treatments to prevent disability and death from vascular disease. As an entrepreneurial nonprofit, Vascular Cures specifically designs its programs to speed the process of getting results to patients. Research by our network of leading vascular surgeon-scientists is advancing the development of powerful new ways to predict, treat and prevent vascular disease.

To Fix Diabetic Nerve Damage, Blood Vessels and Support Cells May Be the Real Targets of Treatment, Johns Hopkins Study Suggests

Results may provide new strategy to prevent amputations

Blood vessels and supporting cells appear to be pivotal partners in repairing nerves ravaged by diabetic neuropathy, and nurturing their partnership with nerve cells might make the difference between success and failure in experimental efforts to regrow damaged nerves, Johns Hopkins researchers reported in a recent study.

NetworkAbout 20 percent of people with diabetes experience neuropathy, a painful tingling, burning or numbness in the hands and feet that reflects damage to nerves and sometimes leads to infections and amputation of the toes, fingers, hands and feet  over time. Current treatments for diabetic neuropathy focus on relieving symptoms, but don’t address the root cause by repairing nerve damage. Previous research has shown that nerve cells’ long extensions, known as axons, regenerate slowly in people with diabetes, scuttling various experiments to regrow healthy nerves, explains study leader Michael Polydefkis, MD, MHS, associate professor of neurology at the Johns Hopkins University School of Medicine.

Searching for the reasons behind this slow regeneration, Polydefkis, along with Johns Hopkins assistant professor of neurology Gigi Ebenezer, MBBS, MD, and their colleagues recruited 10 patients with diabetic neuropathy and 10 healthy people of similar ages and took tiny (3 millimeters) “punch” biopsies from the skin of each participant’s thigh. Several months later, they took 4 mm biopsies from the same site to see how the nerves, blood vessels and nerve-supporting cells, called Schwann cells, were growing back into the healing biopsy site.

In both the neuropathy patients and the healthy individuals, results reported in the June issue of Brain showed that the first to grow into the healing skin were  blood vessels, followed soon after by Schwann cells and then axons, which appeared to use the blood vessels as scaffolds. However, the entire process was significantly delayed for the neuropathy patients. Not only was axon regeneration slower compared to the healthy patients, as expected, but blood vessel growth rate was also slower, and fewer Schwann cells accompanied the growing axons into the healing skin.

“Our results suggest that regenerative abnormalities associated with diabetes are widespread,” Polydefkis says. “They’re not just affecting nerves — they’re also affecting blood vessel growth and Schwann cell proliferation.”

Additionally, he says, the findings could explain why blood vessel-related problems, such as heart attacks and strokes, often accompany diabetes. Slowed regeneration of damaged blood vessels could contribute to these conditions as well, he explains.

Polydefkis says the findings provide potential new targets for treating neuropathy and vascular problems. By promoting blood vessel and Schwann cell growth, researchers might be able to speed up axon regeneration and successfully repair damaged nerves and blood vessels, potentially combating diabetic neuropathy and vascular complications simultaneously.

To Hop or Not to Hop

by John A. Tata, MD, Medical Director, Hartford Walking Systems, Inc.

crutches

Photo by amneziak


Individuals who live with limb loss make many choices each day having to do with their mobility. Do I choose to move today or do I simply stay put? Do I use my walker, wheelchair, crutches, or prosthetic device? Or do I hop on my sound side as my primary mode of mobility?

Unfortunately, many younger individuals choose to hop on their sound side unaware of the potential damage they may be doing to the joints. The reasons are simple: it is fast, easy, seemingly painless. There is no need to get into a wheelchair or take the time to put on a prosthetic device. Most think of themselves as invincible. They seldom consider the future consequences to their hip, knee or ankle because of their choice to hop. The potential risks to their sound side joints are real and individuals with limb loss owe it to themselves to learn what they are.

Why Not Hop?

LegSim

LegSim Photo courtesy of Hartford Walking Systems

As you can imagine, the loss of a limb from amputation affects all the other weight bearing joints in the body. The vector forces of gravity must now be redistributed to the joints of our sound side: hip, knee, ankle and pelvis. This process is even more acute when an individual chooses to hop on their sound side. Now the increased vector forces are being “felt” on one side instead of being equally distributed between two limbs. This added workload to the sound side joints can cause accelerated thinning of the cartilage surfaces which line our joint spaces. The cartilage thinning and resultant bone remodeling create “degenerative arthritis.”

We are fortunate today to have a wide variety of options for mobility to avoid the necessity of the “hop.” Crutches, walkers, wheelchairs and various prosthetic devices including the LegSim all provide useful, viable options. Each device has its own strengths and weaknesses. No one device is likely to suit all of an individual’s needs. Protecting our joints from premature or accelerated cartilage thinning and damage SHOULD be a major priority of ALL individuals. This is especially true for those who live with limb loss. Physicians, physical therapists and prosthetists all need to discourage patients from “hopping around on one foot.”

Conclusion

Each and every one of us has choice in our lives. Individuals living with limb loss can choose to hop or use any one of many assist devices to move from point A to point B. The reasons why an individual chooses one device over another are many and personal. They may change from one day to the next. The most important mandate is to protect our joints each day we use them.

KEEP MOVING:  SAFELY, COMFORTABLY AND PRUDENTLY

This article was used with the permission of Hartford Walking Systems, Inc.

 

American Association of Clinical Endocrinologists (AACE) Declares Obesity a Disease State

bathroom scale with apple and tape measureThe American Association of Clinical Endocrinologists (AACE) has declared that there is significant clinical evidence to declare obesity as a disease state. The Association believes that the declaration will help lead the way for more effective therapies and treatments to help the 34 percent of Americans currently suffering with obesity.

An AACE Task Force on Obesity, chaired by AACE vice-president, Alan Garber, MD, PhD, FACE, and W. Timothy Garvey, MD, professor and chair, Department of Nutrition Sciences at the University of Alabama-Birmingham, reviewed available clinical data and determined that there is sufficient data to suggest that obesity is not just a condition but is actually a disease state.

“Whereas obesity was formerly viewed largely as the consequence of consistently poor lifestyle choices, sufficient evidence has accumulated to implicate a number of heterogeneous hormonal and regulatory disorders in the pathogenesis and progression of the obese state,” said Dr. Garber. “Thus, multiple therapeutic interventions may be necessary lifelong to delay or reverse obesity in patients. Certainly, current efforts have not prevented the proliferation of obesity in the U.S. population as well as elsewhere. Additional interventions and alternative approaches are clearly necessary.”

This is not the first time AACE has taken the lead in calling for recognition of the metabolic consequences medical conditions. In 2003, the Association published a position statement defining Insulin Resistance metabolic syndrome as risk for diabetes and cardiovascular disease . Current AACE president, Yehuda Handelsman, MD, FACP, FACE, FNLA, participated in that Task Force, as well as the current Task Force on Obesity.

“We are witnessing the global epidemic of obesity accelerating progression to diabetes and CVD and reversing the reduction in heart disease, which we witnessed in the late 20th Century,” said Dr. Handelsman. “AACE has already included obesity in its strategic plan to combat diabetes. Recognizing the endocrine hormonal roots of obesity, AACE has vowed to be in the forefront of the clinical management of obesity and its dire consequences.”

As a result of the declaration of obesity as a disease state, AACE plans to develop resources for the various modalities of obesity management, including behavioral, nutritional, pharmacological and surgical. These efforts will be part of a comprehensive campaign that will include sociopolitical, public, and educational outreach. Additionally, AACE will interact with other professional medical societies and the FDA regarding obesity research and the consideration of anti-obesity drugs and their approval pathways.

According to the Centers for Disease Control and Prevention (CDC), more than one-third of all Americans are obese. The condition, as it is currently defined, is indicated by a Body Mass index greater than 30. CDC data shows that more than 12.5 million children and adolescents, ages 2-19, are also obese. Obesity is the second leading cause of preventable death in the United States, with an estimated $147 billion dollars in associated medical costs per year.

 

Podiatrist Appointments Could Save Limbs, Lives and $3.5 Billion in U.S. Healthcare Costs Per Year

Feet and HandsIf every American at risk for developing a diabetic foot ulcer visited a podiatrist once before complications set in, the U.S. healthcare system could save $3.5 billion in one year. Closing this gap in podiatric care would reduce healthcare waste on preventable conditions, which reportedly starts at $25 billion, by 14 percent.

This estimation is a projection based on findings from a Thomson Reuters study published in the March/April 2011 issue of the Journal of the American Podiatric Medical Association (JAPMA).

The study’s numbers were based upon the American population that has either commercial insurance (116 million) or Medicare (46 million) in the Thomson Reuters MarketScan Research Database. Sponsored by the American Podiatric Medical Association (APMA) and independently conducted by Thomson Reuters, the study measured the healthcare records of nearly 500,000 patients with commercial insurance and/or Medicare.

“The study’s findings are astounding. If just one individual at risk for a foot ulcer sees a podiatrist once before a foot ulcer becomes apparent, they will have single-handedly saved our country nearly $20,000 over three years,” said Kathleen Stone, DPM, president of APMA. “This data does not even include the 47 million uninsured Americans or the 58 million currently on Medicaid, who have a higher incidence of diabetes and complications. The bottom line is that seeing a podiatrist saves limbs and lives and equates to billions of needed dollars saved for America’s healthcare system.”

After comparing health and risk factors for those who had seen a podiatrist for care to those who did not, the commercial insurance group saved $19,686 per patient over a three-year period. The Medicare group saved $4,271 per patient over the same three years. Conservatively projected, these per-patient numbers support an estimated $10.5 billion in savings over three years ($3.5 billion a year).

Including today’s podiatrist in the diabetes management team is a vital step to preventing ulcers and amputation. Recent Centers for Disease Control and Prevention statistics show that, in 2006, more than 65,000 lower-limb amputations were performed in the U.S. due to diabetes-related complications.

Diabetes currently affects nearly 26 million people in the U.S., seven million of whom are undiagnosed.

For additional information on the study, visit apma.org/study-summary.