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Genetic Cause of Rare Vascular Disease Identified

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Researchers have identified the genetic cause of a rare and debilitating vascular disorder not previously explained in the medical literature. The adult-onset condition is associated with progressive and painful arterial calcification affecting the lower extremities, yet spares patients’ coronary arteries. The new disease finding was published today in the New England Journal of Medicine.

The rare arterial condition caused by calcium buildup in arteries below the waist and in the joints of patient’s hands and feet has been observed in nine individuals from three unrelated families, who are the only people known to have the disorder. The researchers refer to the condition as ACDC, or arterial calcification due to CD73 deficiency. Although symptoms of the disorder include leg and joint discomfort, medical evaluations of the patients ruled out rheumatoid arthritis or other joint-related problems. Genetic analyses performed by the NIH researchers suggested a novel disorder and pinpointed the cause of the condition as mutations, or variants, in the NT5E gene. [Read more…]

Hispanic Life Expectancy Statistics Report Released

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CDC’s National Center for Health Statistics has issued “United States Life Tables by Hispanic Origin,” which provides life tables by Hispanic origin based on 2006 death rate data.

Life expectancy at birth for the total population in 2006 was 77.7 years; 80.6 years for the Hispanic population, 78.1 years for the non-Hispanic white population, and 72.9 years for the non-Hispanic black population.

The Hispanic population has a life expectancy advantage at birth of 2.5 years over the non-Hispanic white population and 7.7 years over the non-Hispanic black population. The reasons behind the lower mortality are not known.

Source: CDC (10/13/2010)

Heart Disease Hospitalization Rates in the U.S.

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Heart disease hospitalization rates among Americans aged 65 years and older vary substantially depending on where they live, according to a report released today by the Centers for Disease Control and Prevention.

The “Atlas of Heart Disease Hospitalizations Among Medicare Beneficiaries” shows that the highest hospitalization rates occur among blacks compared to other racial and ethnic groups.  Hospitalization rates were also highest in counties located primarily in Appalachia, the Mississippi Delta, Texas and Oklahoma. A significant number of Medicare beneficiaries live in counties without hospitals capable of providing specialized heart disease treatment.

The atlas provides for the first time statistics about heart disease hospitalizations at the county level.  Data came from the Medicare records of more than 28 million people each year between 2000 and 2006 in the 50 states, Washington, D.C., Puerto Rico and the U.S. Virgin Islands. The report documented an average of 2.1 million hospitalizations for heart disease each year.

“These data bring into sharp focus the differences in heart disease hospitalization rates that exist across this country,” said Michele Casper, Ph.D., epidemiologist in CDC’s Division for Heart Disease and Stroke Prevention.  “Importantly, with county–level information, health professionals at the local, state and national levels will be able to tailor heart disease prevention programs and polices to the needs of people living in communities with high rates of heart disease.”

Heart disease is the nation’s leading cause of death. In 2010, it is estimated to cost the United States $316.4 billion in health care services, medications and lost productivity.

In states with the highest heart disease hospitalization rate, the burden is generally two times higher than states with the lowest rates.  For instance, in Louisiana there were 95.2 hospitalizations for every 1,000 Medicare beneficiaries, compared with 44.8 in Hawaii over the same six–year period.

The atlas also brings to light significant racial and ethnic disparities. The heart disease hospitalization rate is much higher among blacks (85.3 hospitalizations per 1,000 beneficiaries) than for whites (74.4 per 1,000) or Hispanics (73.6 per 1,000).  While these rates declined slowly between 2000 and 2006 for Hispanic and white Americans aged 65 years and older, they remained steady among older black Americans.

The atlas also points out geographical differences in access to hospitals with the capability to treat heart disease patients. In 2005, 21 percent of all counties in the United States had no hospital, and 31 percent lacked a hospital with an emergency room.  Specialized cardiac services are even more limited, with 63 percent of U.S. counties lacking a cardiologist outside the Veterans Affairs system.

“Heart disease is largely preventable, and reducing the toll of this disease on society is a national priority,” said Darwin Labarthe, M.D., Ph.D., director of CDC’s Division for Heart Disease and Stroke Prevention. “With targeted public health efforts, such as prevention and early identification of risk factors, and increased access to appropriate medical care, the burden of heart disease can be reduced.”

Source: CDC (March 1, 2010)

Undiagnosed Diabetes Patients May Also Have Undiagnosed Kidney Disease

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Millions of Americans may have chronic kidney disease (CKD) and not know it, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN).

“Our research indicates that much of the CKD burden in the United States is in persons with prediabetes and undiagnosed diabetes, who are not being screened for CKD,” comments Laura C. Plantinga, ScM (University of California, San Francisco). The researchers believe that broader screening may be needed to detect patients with these two “relatively silent yet harmful diseases.”

In a study funded by the Centers for Disease Control and Prevention, Plantinga and colleagues analyzed a nationally representative sample of about 8,200 Americans from the National Health and Nutrition Examination Survey. Standard laboratory tests were used to assess the rate of CKD, focusing on people with undiagnosed diabetes or prediabetes (sometimes called “borderline” diabetes).

Based on lab tests, 42 percent of subjects with undiagnosed diabetes had CKD—similar to the 40 percent rate in those with diagnosed diabetes. “Only a small percentage of participants were aware of the diagnosis of CKD,” says Plantinga.

In addition, CKD was present in nearly 18 percent of subjects with prediabetes. Among participants without diabetes or prediabetes, the rate of CKD was about 11 percent.

“Based on these results, there may be a substantial number of individuals in the United States—up to 13 million—who have undiagnosed diabetes or prediabetes and who already have signs of kidney damage and/or reduced kidney function,” says Plantinga. Such patients would be at high risk for worsening kidney disease and diabetes, and for the poor outcomes associated with both conditions—including cardiovascular disease and death.

Diabetes is the most important risk factor for kidney disease, but the new results suggest that harmful effects on the kidneys may be occurring even before diabetes is diagnosed. “Persons at risk for diabetes and their health care providers should be aware that earlier screening for both diabetes and kidney disease may be warranted,” says Plantinga. “Earlier screening would allow for appropriate, timely medical care to prevent further progression and poor outcomes.”

In an accompanying editorial, Gary C. Curhan, MD, ScD (Brigham and Women’s Hospital, Boston, MA) calls for CKD screening to be extended to patients with prediabetes. Curhan also suggests that it may be time to consider the concept of “pre-CKD”—identifying patients at a very early stage of CKD when the disease may still be preventable or reversible.

Although the study shows an association, it cannot determine whether the development of CKD followed the development of diabetes, or whether CKD was actually caused by diabetes. There is also likely some misclassification of both diseases, although the association remained significant when tested under a range of different assumptions.

Study co-authors include Deidra C. Crews, Josef Coresh, Edgar R. Miller III (Johns Hopkins University, Baltimore, MD), Rajiv Saran, Elizabeth Hedgeman (University of Michigan, Ann Arbor), Jerry Yee (Henry Ford Hospital, Detroit, MI), Meda Pavkov, Mark S. Eberhardt, Desmond E. Williams (Centers for Disease Control and Prevention, Atlanta, GA), and Neil R. Powe (University of California, San Francisco) on behalf of the Centers for Disease Control and Prevention Chronic Kidney Disease Surveillance Team.

Disclosures: The authors reported no financial disclosures.

Source: Clinical Journal of the American Society Nephrology (CJASN), “Prevalence of Chronic Kidney Disease in US Adults with Undiagnosed Diabetes or Prediabetes,” (doi 10.2215/CJN.07891109) and the accompanying editorial,” Pre-Diabetes, Pre-Hypertension…is it time for Pre-CKD?” (doi 10.2215/CJN.01650210)

Avosentan Reduces Urinary Protein Loss but May Cause Serious Side Effects, Says Study

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The drug avosentan substantially reduces urinary protein loss in people with type 2 diabetes and kidney disease, but the drug causes serious side effects, according to a study appearing in an upcoming issue of the Journal of the American Society Nephrology (JASN). The results suggest that lower doses of avosentan may have a more favorable risk/benefit ratio for patients.

Despite aggressive treatments, individuals with kidney disease often experience proteinuria, or excessive loss of protein in the urine, which increases kidney damage. A key factor in the development of proteinuria is endothelin, which by constricting blood vessels and raising blood pressure, causes the kidney’s filtering function to deteriorate. Researchers suspect that blocking the endothelin peptide could be a promising new treatment strategy for patients who develop proteinuria. Endothelin antagonists such as oral avosentan are already available and are prescribed for patients with cardiovascular conditions.

Johannes Mann, MD (Schwabing General Hospital and KfH Kidney Centre, in Munchen, Germany) and his colleagues examined the effects of avosentan on proteinuria and kidney function in patients with type 2 diabetes and kidney disease through a multicenter, multinational, double-blind, controlled trial. The Avosentan ASCEND study enrolled 1392 patients already being treated for kidney disease and randomized them to receive avosentan 25 mg, avosentan 50 mg, or placebo.

While avosentan at either dose lowered patients’ urinary protein excretion by 40%-50% (compared with less than 10% in patients taking placebo), individuals taking the drug experienced a high incidence of serious, sometimes life-threatening side effects. These included complications of fluid overload such as pulmonary edema, as well as congestive heart failure. In addition, there were more deaths in the groups taking avosentan (21 and 17) than in the group taking placebo (12).

Dr. Mann noted that the findings from the ASCEND trial highlight the risks and potential benefits of endothelin antagonists in kidney disease patients with proteinuria and will help investigators design future studies to test the drugs’ potential. Specifically, lower doses of avosentan may generate more positive results.

Speedel Pharma Ltd, Switzerland, sponsored the study and appointed the contract research organization Quintiles Ltd for study set-up, initiation, management, and analysis. (Disclosures: Susan Kuranoff and Thomas Littke were employees of the sponsor, and all other authors have consulting funds from Speedel Pharma Ltd.

Source: Journal of the American Society Nephrology, “Avosentan for Overt Diabetic Nephropathy,” online ed. (February 18, 2010, doi 10.1681/ASN.2009060593); American Society of Nephrology (ASN).

Robotic Surgery Faster in Repairing Kidney Blockages

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A comparison of two types of minimally invasive surgery to repair kidney blockages that prevent urine from draining normally to the bladder found that robot-assisted surgery was faster and resulted in less blood loss and shorter hospital stays.

Reporting in the Canadian Journal of Urology, Ashok Hemal, M.D., a urologic surgeon from Wake Forest University Baptist Medical Center, compared laparoscopic and robot-assisted surgery for repairing the blockage, known as uretero-pelvic junction obstruction. Following the patients for 18 months showed that both options were equally successful, but the robot-assisted technique had several advantages.

On average, robot-assisted surgery was 50 percent faster (98-minute versus 145-minute average), resulted in 60 percent less blood loss (40ml versus 101ml average), and required a two-day hospital stay, versus 3.5 days for laparoscopic surgery.

“This was one of the first studies where a single surgeon at one center performed both types of surgery and compared the results,” said Hemal, director of the Robotic and Minimally Invasive Urologic Surgery Program at Wake Forest Baptist. “It allows for a more accurate comparison of surgical options than multiple physicians performing the surgeries. The results showed that robot-assisted surgery had significant advantages for this condition. It is also generally easier for surgeons to learn.”

All 60 patients had a procedure known as pyeloplasty that involves reconstructing the narrow area where part of the kidney meets the ureter, the tube that carries the urine from the renal pelvis into the bladder. Blockages in this area can be the result of birth defects or, in adults, from injury, previous surgery or disorders that can cause inflammation of the upper urinary tract.

Previously the repair required a large incision. New technology led to minimally invasive approaches that require only small incisions — laparoscopic surgery, in which the surgeon directly manipulates a viewing device and operating instruments inserted into the abdomen, and robot-assisted surgery, in which the surgeon sits at a console and uses hand and finger movements to control centimeter-size instruments while viewing the surgical site on a screen.

Various studies have reported on the results of the options, but this is one of the first studies in which a surgeon with expertise in both options compared them. Hemal treated 30 patients with laparoscopic surgery and 30 with robot-assisted surgery.

“The evolution of laparoscopic surgery in urology has been limited because it is technically challenging and requires the surgeon to be proficient in advanced suturing,” said Hemal. “Robot-assisted surgery offers a way of overcoming some of the major impediments of laparoscopic surgery. This study shows the two options are equally effective and that robot-assisted surgery has several advantages.”

Hemal’s colleagues on the report are Satyadip Mukherjee, M.D., and Kaku Singh, M.D., both with the All India Institute of Medical Sciences in New Delhi, where the surgeries were performed.

Source: Canadian Journal of Uroloygy, Wake Forest University Baptist Medical Center (2/18/2010)

Twenty Percent of American Teens Have Abnormal Lipid Levels

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Twenty percent of young people aged 12-19 years in the United States have at least one abnormal lipid level, according to a study from the Centers for Disease Control and Prevention.  Abnormal lipid levels are major risk factors for heart disease, the leading cause of death among adults in the United States.

The report, “Prevalence of Abnormal Lipid Levels among Youths —United States, 1999–2006,” was published today in CDC’s Morbidity and Mortality Weekly Report (MMWR).

The report examined data for 1999–2006 from the National Health and Nutrition Examination Survey (NHANES), an ongoing study that explores the health and nutritional status of about 6,000 participants every year.  Researchers analyzed measurements of low-density lipoprotein, or “bad,” cholesterol (LDL-C); high-density lipoprotein, or “good,” cholesterol (HDL-C); and triglycerides.

The researchers found that young people who were overweight or obese were more likely to have one or more abnormal lipid levels compared to normal weight youth.  Fourteen percent of normal weight, 22 percent of overweight, and 43 percent of obese youth had one or more abnormal lipid levels.

The study also found that 32 percent of these young people would be candidates for lipid screening based on American Academy of Pediatrics (AAP) guidelines.  The AAP recommends lipid screening for young people with a family history of high blood cholesterol or premature cardiovascular disease, or the presence of at least one major risk factor for heart disease, such as smoking, high blood pressure, diabetes, or overweight/obesity.

Reviewing health indicators for 3,125 youths, researchers found that differences in lipid levels were associated with sex, age, and race/ethnicity. Specifically:

  • More boys (24 percent) than girls (16 percent) had at least one abnormal lipid level.
  • Fourteen- and 15-year-olds (9 percent) and 18- and 19-year-olds (10 percent) were more likely to have low HDL cholesterol levels than 12- and 13-year-olds (5 percent).
  • Non-Hispanic white youths were more likely to have low levels of HDL cholesterol (8 percent) and high triglycerides (12 percent), compared to non-Hispanic black youths (5 percent and 4 percent, respectively).

Typically, heart disease develops in adulthood. But its risk factors, such as abnormal lipid levels and overweight/obesity often emerge during childhood and adolescence.

“Overweight and obese young people are at far greater risk of having abnormal lipid levels than are youths with normal weights,” said Ashleigh May, Ph.D.,  Epidemic Intelligence Service Officer in CDC’s Division for Heart Disease and Stroke Prevention, and lead author of the report.  “The current epidemic of childhood obesity makes this a matter of significant and urgent concern.”

In the past three decades, obesity among American youths has increased from 5 percent to more than 17 percent.  In light of this, the study’s authors suggested that clinicians should be aware of guidelines for lipid screening and treatment among youths.

Source: Centers for Disease Control (Jan. 21, 2010)

40% of Emergency Room Visits Billed to Public Insurance, Says Report

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More than 40 percent of the 120 million visits that Americans made to hospital emergency departments in 2006 were billed to public insurance, according to the latest News and Numbers from the Agency for Healthcare Research and Quality.

According to the analysis by the federal agency, about 50 million emergency department visits were billed to Medicaid and Medicare. The uninsured accounted for another 18 percent of visits for emergency care, while 34 percent of the visits were billed to private insurance companies and the rest were billed to workers compensation, military health plan administrator Tricare and other payers.

The agency’s study of hospital emergency department use in 2006 also found that:

  • About 38 percent of the 24.2 million visits billed to Medicare ended with the patients being admitted, compared with 11 percent of the 41.5 million visits billed to private insurers, 9.5 percent of the 26 million visits billed to Medicaid and 7 percent of the 21.2 million visits by the uninsured.
  • The uninsured were the most frequent users of hospital emergency departments. Their rate was 1.2 times greater than that of people with public or private insurance – 452 visits per 1,000 population vs. 367 visits per 1,000 population, respectively.
  • The uninsured were also the most likely to be treated and released – a possible indication of their use of hospital emergency departments as their usual source of care. Their "treat-and-release" rate was 421 visits per 1,000 population vs. 301 per 1,000 population for the insured.

Source: Agency for Healthcare Research and Quality (AHRQ)

Sun Exposure May Trigger Auto Immune Disease in Women

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Ultraviolet (UV) radiation from sunlight may be associated with the development of certain autoimmune diseases, particularly in women, according to a study by researchers at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.

“This study found that women who lived in areas with higher levels of UV exposure when they developed an autoimmune muscle disease called myositis were more likely to develop the form known as dermatomyositis, which weakens the muscles and causes distinctive rashes, instead of the form called polymyositis that does not have a rash,” said Frederick W. Miller, M.D., Ph.D., chief of the Environmental Autoimmunity Group, Program of Clinical Research, at NIEHS. “Although we have not shown a direct cause and effect link between UV exposure and this particular autoimmune disease, this study confirms the association between UV levels and the frequency of dermatomyositis that we found in a previous investigation,” said Miller.

The study, published in the August issue of Arthritis & Rheumatism, is also the first to evaluate and find a possible UV radiation association in autoimmune diseases in women.

According to Miller, women are more likely than men to develop many autoimmune diseases, but the reasons for this have not been clear. “We only found the association between UV exposure and dermatomyositis in women and not in men, and it could be that inherent differences in how women and men respond to UV radiation may play a role in the development of certain autoimmune diseases,” said Dr. Miller. Miller also noted that other researchers have shown that female mice develop more skin inflammation after UV light exposure compared to male mice and these effects may be related to the new findings in dermatomyositis.

The study was designed to determine if there was a relationship between the level of UV exposure at the onset of the disease and the type of myositis and autoantibodies that people developed. Dermatomyositis and polymyositis are the two major forms of myositis and both are considered autoimmune diseases, in which the body’s immune system attacks muscle or skin and sometimes other tissues. Dermatomyositis is typically accompanied by a distinctive reddish-purple rash on the upper eyelids or over the knuckles and is often made worse with sun exposure.

To conduct the study, the NIEHS researchers collaborated with myositis centers across the country that had seen 380 patients who had been diagnosed with dermatomyositis or polymyositis and determined their autoantibodies. “Patients with autoimmune diseases make a variety of autoantibodies that are unique to different conditions. One autoantibody specifically associated with dermatomyositis is called the anti-Mi-2 autoantibody and we know from our previous research that UV radiation increases levels of the Mi-2 protein that this autoantibody binds to,” said Miller.

In addition to finding an association between the level of UV radiation and the proportion of women who developed dermatomyositis compared to polymyositis, the researchers found an association between UV levels and the proportion of women with the anti-Mi-2 autoantibody. “More research is clearly needed to understand the potential links between UV radiation and the development of autoimmune diseases and autoantibodies in women,” said Miller.

“While the causes of autoimmune diseases are not known, we suspect from emerging research that they develop after one or more environmental exposures in genetically susceptible people,” said NIEHS Director Linda Birnbaum, Ph.D. “This study adds UV radiation to the growing list of environmental exposures possibly important in the development of autoimmune diseases.”

Source: National Institute of Environmental Health Sciences (NIEHS), July 30, 2009

Multiple Scleroris (MS) Disease Progression Risk Predictors

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Cognitive testing may help people with inactive or benign multiple sclerosis (MS) better predict their future with the disease, according to a study published in the July 29, 2009, online issue of Neurology®, the medical journal of the American Academy of Neurology. Gender and brain lesions may also determine the risk of progression of MS years after diagnosis.

By current definition, people with benign MS are those who remain “fully functional” after 15 or more years from disease onset. However, people with benign MS occasionally develop renewed disease activity or progression, and can experience severe symptoms.

For the study, researchers looked at the cognitive test results and brain scans of 63 people with benign MS during a period of five years. Of those, 43 were women and 20 were men.

The cognitive tests included verbal and visual memory, attention, concentration and the speed at which the participant processed information. Brain scans revealed the number of lesions associated with MS on the person’s brain. Follow-up neurologic exams were done every six months.

The study found that nearly 30 percent of people with benign MS significantly worsened over the course of five years. People who failed more than two cognitive tests (out of 10 total) were 20 percent more likely to progress over time. Men with benign MS were nearly three times more likely to later experience signs of MS compared to women. People with more brain lesions detected on scans were also more likely to develop signs of the disease.

“Our findings strongly suggest that a person’s gender, cognitive state and amount of lesions on the brain are important factors for predicting MS progression,” said study author Maria Pia Amato, MD, with the University of Florence in Italy. “Our study highlights the importance of cognitively testing people with benign MS who appear to be healthy. This information might be important in tailoring the patient’s treatment.”

Source: Neurology; American Academy of Neurology (AAN), July 29, 2009