Mitchel L. Zoler, PhD

PHILADELPHIA — The Framingham risk score does a poor job of estimating future risk for cardiovascular disease events in patients with rheumatoid arthritis, according to a review of 550 unselected patients drawn from the general population.

Results from a second study reported at the annual meeting of the American College of Rheumatology suggested that adding three more risk markers (carotid disease assessment with ultrasound, erythrocyte sedimentation rate, and cumulative steroid dose) to the standard Framingham risk score (FRS) could significantly improve prognostic accuracy for coronary disease in patients with RA. And findings from a third study presented at the meeting indicated that treatment with methotrexate is an effective way to cut coronary disease risk in RA patients.

To assess the prognostic value of the FRS, Cynthia S. Crowson and her associates at the Mayo Clinic in Rochester, Minn., used data collected for the Rochester Epidemiology Project.

They included 550 people who presented during 1988–2008 with incident RA that matched the 1987 RA criteria and who also had no history of cardiovascular disease at the time of their initial RA diagnosis. The researchers calculated an FRS for each of these patients based on their medical records and usedia revised FRS (introduced in 2008) that predicted risk for cardiovascular disease events including stroke and peripheral artery disease as well as coronary disease (Circulation 2008;117:743–53). The FRS estimates a person's risk for an event during the subsequent 10 years.

The Mayo researchers then compared the predicted rate of cardiovascular disease events against the actual rate observed during the first 10 years following RA diagnosis.

The study group included 491 RA patients who were aged 30–74 years, and 59 others who were aged 75 years or older. The FRS is designed for application to adults younger than 75.

Among the 341 women aged 30–74 years, the average predicted event rate was 5%, and the actual observed rate was 11%. Among the 150 men in this age range, the predicted rate was 12% and the observed rate was 26%, reported Ms. Crowson in a poster.

The researchers used a regression model to calculate a standard incidence ratio, in which the ratio of actual to expected events was 79% in women and 56% in men. Both differences were statistically significant. Further analysis showed that the largest differences between observed and expected rates were in women aged 55 years or older and in men aged 45 or older.

Although the FRS is not designed for use on people older than 74 years, Ms. Crowson and her associates applied the same analysis to the 59 RA patients in this age group. The results again showed a significant excess of observed events over expected events. In women, the observed event rate was 57%, compared with an expected 14% rate. In men, the observed rate was 87%, compared with an expected rate of 37%.

One way to improve cardiovascular risk assessment in RA patients may be to add additional risk factors to the FRS. A poster presented by Dr. Inmaculada del Rincon, a rheumatologist at the University of Texas Health Sciences Center in San Antonio, and her associates explored one way to do this. They compared the correlation between standard FRS assessment and an enhanced assessment model for predicting the risk of acute coronary syndrome events in 599 RA patients. During an average 5-year follow-up, 66 patients had acute coronary syndrome events.

To enhance the FRS predictive power, they added measures of carotid plaque and intima-media thickness by carotid ultrasonography, erythrocyte sedimentation rate, and cumulative glucocorticoid dose. The analysis showed that the standard FRS accounted for 70% of the events observed in the patients. The three additional risk markers boosted this rate to 76%, a statistically significant improvement, reported Dr. del Rincon and her associates in their poster.

A third poster at the meeting reviewed the ability of treatment with methotrexate to reduce cardiovascular risk in RA patients.

Dr. Janice Gupta, a rheumatologist at Tufts Medical Center in Boston, and her associates reviewed the literature for studies that compared the ability of methotrexate to lower cardiovascular events against other RA treatments. They identified six studies that involved a total of about 162,000 RA patients. The results showed a consistent pattern of reduced cardiovascular events in the patients who received methotrexate. The event risk was generally reduced by 15%–20%, compared with other RA treatments; the researchers did not calculate an overall summary risk-reduction rate.

Disclosures: None of the investigators in the three studies had financial relationships to disclose.

PHILADELPHIA — The Framingham risk score does a poor job of estimating future risk for cardiovascular disease events in patients with rheumatoid arthritis, according to a review of 550 unselected patients drawn from the general population.

Results from a second study reported at the annual meeting of the American College of Rheumatology suggested that adding three more risk markers (carotid disease assessment with ultrasound, erythrocyte sedimentation rate, and cumulative steroid dose) to the standard Framingham risk score (FRS) could significantly improve prognostic accuracy for coronary disease in patients with RA. And findings from a third study presented at the meeting indicated that treatment with methotrexate is an effective way to cut coronary disease risk in RA patients.

To assess the prognostic value of the FRS, Cynthia S. Crowson and her associates at the Mayo Clinic in Rochester, Minn., used data collected for the Rochester Epidemiology Project.

They included 550 people who presented during 1988–2008 with incident RA that matched the 1987 RA criteria and who also had no history of cardiovascular disease at the time of their initial RA diagnosis. The researchers calculated an FRS for each of these patients based on their medical records and usedia revised FRS (introduced in 2008) that predicted risk for cardiovascular disease events including stroke and peripheral artery disease as well as coronary disease (Circulation 2008;117:743–53). The FRS estimates a person's risk for an event during the subsequent 10 years.

The Mayo researchers then compared the predicted rate of cardiovascular disease events against the actual rate observed during the first 10 years following RA diagnosis.

The study group included 491 RA patients who were aged 30–74 years, and 59 others who were aged 75 years or older. The FRS is designed for application to adults younger than 75.

Among the 341 women aged 30–74 years, the average predicted event rate was 5%, and the actual observed rate was 11%. Among the 150 men in this age range, the predicted rate was 12% and the observed rate was 26%, reported Ms. Crowson in a poster.

The researchers used a regression model to calculate a standard incidence ratio, in which the ratio of actual to expected events was 79% in women and 56% in men. Both differences were statistically significant. Further analysis showed that the largest differences between observed and expected rates were in women aged 55 years or older and in men aged 45 or older.

Although the FRS is not designed for use on people older than 74 years, Ms. Crowson and her associates applied the same analysis to the 59 RA patients in this age group. The results again showed a significant excess of observed events over expected events. In women, the observed event rate was 57%, compared with an expected 14% rate. In men, the observed rate was 87%, compared with an expected rate of 37%.

One way to improve cardiovascular risk assessment in RA patients may be to add additional risk factors to the FRS. A poster presented by Dr. Inmaculada del Rincon, a rheumatologist at the University of Texas Health Sciences Center in San Antonio, and her associates explored one way to do this. They compared the correlation between standard FRS assessment and an enhanced assessment model for predicting the risk of acute coronary syndrome events in 599 RA patients. During an average 5-year follow-up, 66 patients had acute coronary syndrome events.

To enhance the FRS predictive power, they added measures of carotid plaque and intima-media thickness by carotid ultrasonography, erythrocyte sedimentation rate, and cumulative glucocorticoid dose. The analysis showed that the standard FRS accounted for 70% of the events observed in the patients. The three additional risk markers boosted this rate to 76%, a statistically significant improvement, reported Dr. del Rincon and her associates in their poster.

A third poster at the meeting reviewed the ability of treatment with methotrexate to reduce cardiovascular risk in RA patients.

Dr. Janice Gupta, a rheumatologist at Tufts Medical Center in Boston, and her associates reviewed the literature for studies that compared the ability of methotrexate to lower cardiovascular events against other RA treatments. They identified six studies that involved a total of about 162,000 RA patients. The results showed a consistent pattern of reduced cardiovascular events in the patients who received methotrexate. The event risk was generally reduced by 15%–20%, compared with other RA treatments; the researchers did not calculate an overall summary risk-reduction rate.

Disclosures: None of the investigators in the three studies had financial relationships to disclose.

PHILADELPHIA — The Framingham risk score does a poor job of estimating future risk for cardiovascular disease events in patients with rheumatoid arthritis, according to a review of 550 unselected patients drawn from the general population.

Results from a second study reported at the annual meeting of the American College of Rheumatology suggested that adding three more risk markers (carotid disease assessment with ultrasound, erythrocyte sedimentation rate, and cumulative steroid dose) to the standard Framingham risk score (FRS) could significantly improve prognostic accuracy for coronary disease in patients with RA. And findings from a third study presented at the meeting indicated that treatment with methotrexate is an effective way to cut coronary disease risk in RA patients.

To assess the prognostic value of the FRS, Cynthia S. Crowson and her associates at the Mayo Clinic in Rochester, Minn., used data collected for the Rochester Epidemiology Project.

They included 550 people who presented during 1988–2008 with incident RA that matched the 1987 RA criteria and who also had no history of cardiovascular disease at the time of their initial RA diagnosis. The researchers calculated an FRS for each of these patients based on their medical records and usedia revised FRS (introduced in 2008) that predicted risk for cardiovascular disease events including stroke and peripheral artery disease as well as coronary disease (Circulation 2008;117:743–53). The FRS estimates a person's risk for an event during the subsequent 10 years.

The Mayo researchers then compared the predicted rate of cardiovascular disease events against the actual rate observed during the first 10 years following RA diagnosis.

The study group included 491 RA patients who were aged 30–74 years, and 59 others who were aged 75 years or older. The FRS is designed for application to adults younger than 75.

Among the 341 women aged 30–74 years, the average predicted event rate was 5%, and the actual observed rate was 11%. Among the 150 men in this age range, the predicted rate was 12% and the observed rate was 26%, reported Ms. Crowson in a poster.

The researchers used a regression model to calculate a standard incidence ratio, in which the ratio of actual to expected events was 79% in women and 56% in men. Both differences were statistically significant. Further analysis showed that the largest differences between observed and expected rates were in women aged 55 years or older and in men aged 45 or older.

Although the FRS is not designed for use on people older than 74 years, Ms. Crowson and her associates applied the same analysis to the 59 RA patients in this age group. The results again showed a significant excess of observed events over expected events. In women, the observed event rate was 57%, compared with an expected 14% rate. In men, the observed rate was 87%, compared with an expected rate of 37%.

One way to improve cardiovascular risk assessment in RA patients may be to add additional risk factors to the FRS. A poster presented by Dr. Inmaculada del Rincon, a rheumatologist at the University of Texas Health Sciences Center in San Antonio, and her associates explored one way to do this. They compared the correlation between standard FRS assessment and an enhanced assessment model for predicting the risk of acute coronary syndrome events in 599 RA patients. During an average 5-year follow-up, 66 patients had acute coronary syndrome events.

To enhance the FRS predictive power, they added measures of carotid plaque and intima-media thickness by carotid ultrasonography, erythrocyte sedimentation rate, and cumulative glucocorticoid dose. The analysis showed that the standard FRS accounted for 70% of the events observed in the patients. The three additional risk markers boosted this rate to 76%, a statistically significant improvement, reported Dr. del Rincon and her associates in their poster.

A third poster at the meeting reviewed the ability of treatment with methotrexate to reduce cardiovascular risk in RA patients.

Dr. Janice Gupta, a rheumatologist at Tufts Medical Center in Boston, and her associates reviewed the literature for studies that compared the ability of methotrexate to lower cardiovascular events against other RA treatments. They identified six studies that involved a total of about 162,000 RA patients. The results showed a consistent pattern of reduced cardiovascular events in the patients who received methotrexate. The event risk was generally reduced by 15%–20%, compared with other RA treatments; the researchers did not calculate an overall summary risk-reduction rate.

Disclosures: None of the investigators in the three studies had financial relationships to disclose.

An expert panel convened by the American Heart Association issued a call to action for the creation of U.S. regional systems of care for patients resuscitated from out-of-hospital cardiac arrest.

“We believe that the time has come for a call to develop and implement standards for regional systems of care for those with restoration of circulation after OOHCA [out-of-hospital cardiac arrest],” wrote the 19-member panel convened by the American Heart Association, the American College of Emergency Physicians, and the National Association of State EMS Officials.

“Successful implementation and maintenance of cardiac resuscitation systems of care would have a significant and important impact on the third-leading cause of death in the United States. The time to implement these systems of care is now,” the panel said in its statement (Circulation 2010 Jan. 14 [doi:10.1161/CIR.0b013e3181cdb7db

“It will take action by the American Heart Association, which endorsed the statement, as well as by the other organizations that endorsed this, to work together to make sure this happens,” Dr. Graham Nichol, chairman of the panel, said in an interview. “There is pent-up demand [among physicians] to help these patients, and it is already happening in some places” in the United States, said Dr. Nichol, professor of medicine at the University of Washington in Seattle.

“The trauma system of care is a good model,” Dr. Nichol said. “Prehospital providers, trauma surgeons, and emergency doctors worked together for many years to create a certification process. That's the model we're advocating for.”

OOHCA affects an estimated 300,000 Americans annually, and is the third-leading cause of U.S. deaths. The panel cited a fivefold regional variation in the outcome of OOHCA patients treated by emergency medical services among sites in the Resuscitation Outcomes Consortium. This regional variation “demonstrates that it is a treatable condition,” said Dr. Nichol, who is also director and chair of the Medic One Foundation of the Harborview Center for Prehospital Emergency Care in Seattle.

Regional systems of care for these patients exist in a few locations, including Seattle, the state of Arizona, and areas of Minnesota, New York, Ohio, Texas, and Virginia. In Seattle, the survival-to-hospital-discharge rate among OOHCA patients is 16% for patients with any type of initial rhythm disturbance, and 40% among patients with ventricular fibrillation. For North America overall, the median survival rate is 8%.

Proven, effective interventions for OOHCA patients include therapeutic hypothermia, early percutaneous coronary intervention, early prognostication of patient outcomes, and use of implantable cardioverter defibrillators. Promising interventions that require special expertise to ensure their successful use include glucose control, seizure control, cardiopulmonary support, and hemofiltration, the statement said.

The proposal envisions three levels of care within a regional system: emergency medical services, level 2 cardiac resuscitation centers, and level 1 cardiac resuscitation centers. Level 1 centers would have the capability to perform primary percutaneous coronary interventions, electrophysiology testing, and placement of implantable cardioverter-defibrillators; assess prognosis; provide all services 24/7; and treat at least 40 patients resuscitated from OOHCA annually. Level 2 centers would not have these features and services, but would be capable of initiating hypothermia and providing CPR and advanced cardiac life support training for staff. In addition, they would be mandated to quickly transport patients to a level 1 facility.

Both level 1 and 2 centers as well as emergency medical services would receive external certification.

Starting such a regional system of coordinated care for OOHCA patients will take “a large group of individuals from different specialties to come together,” Dr. Nichol said. The stakeholders who need to be involved in creating these systems include emergency medical services physicians, emergency physicians, cardiologists, and critical care physicians, as well as nurses and medics.

“Each community likely needs a local champion who can implement and maintain a culture of change to achieve broad and sustained improvement in outcomes. But one person cannot do this alone,” he added.

Disclosures: Dr. Nichol reported relationships with Laerdal Inc., Physio-Control Inc., and Channing Bele Inc. Other members of the panel reported a variety of commercial relationships.

My Take

ICUs Could End Up Treating More Cardiac Arrest Survivors

It's reasonable to expect that regional systems of care, which have improved the outcomes of trauma and stroke patients, also could produce benefits for cardiac arrest patients. The cardiac arrest system could be built on top of the existing trauma and stroke regional systems. Several elements that the AHA calls for in level 1 cardiac arrest centers, such as 24/7 availability of percutaneous coronary intervention and electrophysiology services, are already in place at level 1 trauma centers. But most trauma and stroke centers lack the capability to deliver therapeutic hypothermia.

For hospitalists, the potential impact from improved cardiac arrest care would occur downstream, as more cardiac arrest patients survive their acute episode and require intensive care during their recovery.

An expert panel convened by the American Heart Association issued a call to action for the creation of U.S. regional systems of care for patients resuscitated from out-of-hospital cardiac arrest.

“We believe that the time has come for a call to develop and implement standards for regional systems of care for those with restoration of circulation after OOHCA [out-of-hospital cardiac arrest],” wrote the 19-member panel convened by the American Heart Association, the American College of Emergency Physicians, and the National Association of State EMS Officials.

“Successful implementation and maintenance of cardiac resuscitation systems of care would have a significant and important impact on the third-leading cause of death in the United States. The time to implement these systems of care is now,” the panel said in its statement (Circulation 2010 Jan. 14 [doi:10.1161/CIR.0b013e3181cdb7db

“It will take action by the American Heart Association, which endorsed the statement, as well as by the other organizations that endorsed this, to work together to make sure this happens,” Dr. Graham Nichol, chairman of the panel, said in an interview. “There is pent-up demand [among physicians] to help these patients, and it is already happening in some places” in the United States, said Dr. Nichol, professor of medicine at the University of Washington in Seattle.

“The trauma system of care is a good model,” Dr. Nichol said. “Prehospital providers, trauma surgeons, and emergency doctors worked together for many years to create a certification process. That's the model we're advocating for.”

OOHCA affects an estimated 300,000 Americans annually, and is the third-leading cause of U.S. deaths. The panel cited a fivefold regional variation in the outcome of OOHCA patients treated by emergency medical services among sites in the Resuscitation Outcomes Consortium. This regional variation “demonstrates that it is a treatable condition,” said Dr. Nichol, who is also director and chair of the Medic One Foundation of the Harborview Center for Prehospital Emergency Care in Seattle.

Regional systems of care for these patients exist in a few locations, including Seattle, the state of Arizona, and areas of Minnesota, New York, Ohio, Texas, and Virginia. In Seattle, the survival-to-hospital-discharge rate among OOHCA patients is 16% for patients with any type of initial rhythm disturbance, and 40% among patients with ventricular fibrillation. For North America overall, the median survival rate is 8%.

Proven, effective interventions for OOHCA patients include therapeutic hypothermia, early percutaneous coronary intervention, early prognostication of patient outcomes, and use of implantable cardioverter defibrillators. Promising interventions that require special expertise to ensure their successful use include glucose control, seizure control, cardiopulmonary support, and hemofiltration, the statement said.

The proposal envisions three levels of care within a regional system: emergency medical services, level 2 cardiac resuscitation centers, and level 1 cardiac resuscitation centers. Level 1 centers would have the capability to perform primary percutaneous coronary interventions, electrophysiology testing, and placement of implantable cardioverter-defibrillators; assess prognosis; provide all services 24/7; and treat at least 40 patients resuscitated from OOHCA annually. Level 2 centers would not have these features and services, but would be capable of initiating hypothermia and providing CPR and advanced cardiac life support training for staff. In addition, they would be mandated to quickly transport patients to a level 1 facility.

Both level 1 and 2 centers as well as emergency medical services would receive external certification.

Starting such a regional system of coordinated care for OOHCA patients will take “a large group of individuals from different specialties to come together,” Dr. Nichol said. The stakeholders who need to be involved in creating these systems include emergency medical services physicians, emergency physicians, cardiologists, and critical care physicians, as well as nurses and medics.

“Each community likely needs a local champion who can implement and maintain a culture of change to achieve broad and sustained improvement in outcomes. But one person cannot do this alone,” he added.

Disclosures: Dr. Nichol reported relationships with Laerdal Inc., Physio-Control Inc., and Channing Bele Inc. Other members of the panel reported a variety of commercial relationships.

My Take

ICUs Could End Up Treating More Cardiac Arrest Survivors

It's reasonable to expect that regional systems of care, which have improved the outcomes of trauma and stroke patients, also could produce benefits for cardiac arrest patients. The cardiac arrest system could be built on top of the existing trauma and stroke regional systems. Several elements that the AHA calls for in level 1 cardiac arrest centers, such as 24/7 availability of percutaneous coronary intervention and electrophysiology services, are already in place at level 1 trauma centers. But most trauma and stroke centers lack the capability to deliver therapeutic hypothermia.

For hospitalists, the potential impact from improved cardiac arrest care would occur downstream, as more cardiac arrest patients survive their acute episode and require intensive care during their recovery.

An expert panel convened by the American Heart Association issued a call to action for the creation of U.S. regional systems of care for patients resuscitated from out-of-hospital cardiac arrest.

“We believe that the time has come for a call to develop and implement standards for regional systems of care for those with restoration of circulation after OOHCA [out-of-hospital cardiac arrest],” wrote the 19-member panel convened by the American Heart Association, the American College of Emergency Physicians, and the National Association of State EMS Officials.

“Successful implementation and maintenance of cardiac resuscitation systems of care would have a significant and important impact on the third-leading cause of death in the United States. The time to implement these systems of care is now,” the panel said in its statement (Circulation 2010 Jan. 14 [doi:10.1161/CIR.0b013e3181cdb7db

“It will take action by the American Heart Association, which endorsed the statement, as well as by the other organizations that endorsed this, to work together to make sure this happens,” Dr. Graham Nichol, chairman of the panel, said in an interview. “There is pent-up demand [among physicians] to help these patients, and it is already happening in some places” in the United States, said Dr. Nichol, professor of medicine at the University of Washington in Seattle.

“The trauma system of care is a good model,” Dr. Nichol said. “Prehospital providers, trauma surgeons, and emergency doctors worked together for many years to create a certification process. That's the model we're advocating for.”

OOHCA affects an estimated 300,000 Americans annually, and is the third-leading cause of U.S. deaths. The panel cited a fivefold regional variation in the outcome of OOHCA patients treated by emergency medical services among sites in the Resuscitation Outcomes Consortium. This regional variation “demonstrates that it is a treatable condition,” said Dr. Nichol, who is also director and chair of the Medic One Foundation of the Harborview Center for Prehospital Emergency Care in Seattle.

Regional systems of care for these patients exist in a few locations, including Seattle, the state of Arizona, and areas of Minnesota, New York, Ohio, Texas, and Virginia. In Seattle, the survival-to-hospital-discharge rate among OOHCA patients is 16% for patients with any type of initial rhythm disturbance, and 40% among patients with ventricular fibrillation. For North America overall, the median survival rate is 8%.

Proven, effective interventions for OOHCA patients include therapeutic hypothermia, early percutaneous coronary intervention, early prognostication of patient outcomes, and use of implantable cardioverter defibrillators. Promising interventions that require special expertise to ensure their successful use include glucose control, seizure control, cardiopulmonary support, and hemofiltration, the statement said.

The proposal envisions three levels of care within a regional system: emergency medical services, level 2 cardiac resuscitation centers, and level 1 cardiac resuscitation centers. Level 1 centers would have the capability to perform primary percutaneous coronary interventions, electrophysiology testing, and placement of implantable cardioverter-defibrillators; assess prognosis; provide all services 24/7; and treat at least 40 patients resuscitated from OOHCA annually. Level 2 centers would not have these features and services, but would be capable of initiating hypothermia and providing CPR and advanced cardiac life support training for staff. In addition, they would be mandated to quickly transport patients to a level 1 facility.

Both level 1 and 2 centers as well as emergency medical services would receive external certification.

Starting such a regional system of coordinated care for OOHCA patients will take “a large group of individuals from different specialties to come together,” Dr. Nichol said. The stakeholders who need to be involved in creating these systems include emergency medical services physicians, emergency physicians, cardiologists, and critical care physicians, as well as nurses and medics.

“Each community likely needs a local champion who can implement and maintain a culture of change to achieve broad and sustained improvement in outcomes. But one person cannot do this alone,” he added.

Disclosures: Dr. Nichol reported relationships with Laerdal Inc., Physio-Control Inc., and Channing Bele Inc. Other members of the panel reported a variety of commercial relationships.

My Take

ICUs Could End Up Treating More Cardiac Arrest Survivors

It's reasonable to expect that regional systems of care, which have improved the outcomes of trauma and stroke patients, also could produce benefits for cardiac arrest patients. The cardiac arrest system could be built on top of the existing trauma and stroke regional systems. Several elements that the AHA calls for in level 1 cardiac arrest centers, such as 24/7 availability of percutaneous coronary intervention and electrophysiology services, are already in place at level 1 trauma centers. But most trauma and stroke centers lack the capability to deliver therapeutic hypothermia.

For hospitalists, the potential impact from improved cardiac arrest care would occur downstream, as more cardiac arrest patients survive their acute episode and require intensive care during their recovery.

ORLANDO — Patients who experienced sudden cardiac death had a significantly higher rate of treatment with a sodium channel–blocking, anticonvulsant drug, compared with people who did not have sudden death, in a case-control study of more than 10,000 people.

“This finding may explain a proportion of the sudden deaths seen in epilepsy patients,” Dr. Abdennasser Bardai said at the annual scientific sessions of the American Heart Association.

About 10% of epilepsy patients have an unexpected death unrelated to seizure, a phenomenon so common that it's been named “sudden unexplained death in epilepsy.” Dr. Bardai and his associates hypothesized that many of these deaths might be triggered by anticonvulsant drugs, especially those that block sodium channels such as carbamazepine, lamotrigine, and phenytoin. Although the sodium-channel blockade these drugs cause is aimed at neurons, the same property can affect cardiac cells and may potentially cause arrhythmia.

To explore a possible link between anticonvulsant use and sudden death, the researchers used data collected in the Integrated Primary Care Information database, which has records for more than 1 million residents of the Netherlands. They focused on medical records for people aged 18 or older during 1995-2007 in cases for which at least 1 year's record existed.

Among the more than 478,000 people who met these criteria, 926 experienced sudden death, defined as a natural death heralded by a sudden loss of consciousness within 1 hour after the onset of acute symptoms, or an unwitnessed, unexpected death of someone seen in stable medical condition less than 24 hours before, with no evidence of a noncardiac cause. The researchers matched each case with about 20 other people from the database of the same gender and of similar age, reaching a total of 9,832 controls. The mean age of the cases and controls was 72 years; 26% were men.

In a multivariate analysis that controlled for age, gender, smoking, alcohol abuse, concomitant medications, cardiovascular disease, arrhythmia, hypertension, diabetes, heart failure, and hypercholesterolemia, people who died from sudden death were 2.5-fold more likely to be on treatment with an anticonvulsant drug than were controls, a statistically significant difference, reported Dr. Bardai, a cardiovascular diseases researcher at the Academic Medical Center in Amsterdam.

In a second adjusted analysis that divided anticonvulsant drug use into agents that block sodium channels and those that don't, the sudden death cases were 2.9-fold more likely to be on a sodium channel–blocking anticonvulsant, compared with controls, a statistically significant difference. In contrast, the fraction of sudden death cases on treatment with an anticonvulsant that does not block sodium channels was not significantly different from the rate at which these drugs were used by the controls.

In a final set of analyses, Dr. Bardai and his associates calculated the use of specific anticonvulsant drugs among the sudden death cases and controls. The only significant relationship they found was that the sudden death cases were 3.4-fold more likely to be on treatment with carbamazepine, a sodium channel–blocking anticonvulsant, compared with the controls.

Disclosures: Dr. Bardai said that he and his associates had no financial disclosures.

ORLANDO — Patients who experienced sudden cardiac death had a significantly higher rate of treatment with a sodium channel–blocking, anticonvulsant drug, compared with people who did not have sudden death, in a case-control study of more than 10,000 people.

“This finding may explain a proportion of the sudden deaths seen in epilepsy patients,” Dr. Abdennasser Bardai said at the annual scientific sessions of the American Heart Association.

About 10% of epilepsy patients have an unexpected death unrelated to seizure, a phenomenon so common that it's been named “sudden unexplained death in epilepsy.” Dr. Bardai and his associates hypothesized that many of these deaths might be triggered by anticonvulsant drugs, especially those that block sodium channels such as carbamazepine, lamotrigine, and phenytoin. Although the sodium-channel blockade these drugs cause is aimed at neurons, the same property can affect cardiac cells and may potentially cause arrhythmia.

To explore a possible link between anticonvulsant use and sudden death, the researchers used data collected in the Integrated Primary Care Information database, which has records for more than 1 million residents of the Netherlands. They focused on medical records for people aged 18 or older during 1995-2007 in cases for which at least 1 year's record existed.

Among the more than 478,000 people who met these criteria, 926 experienced sudden death, defined as a natural death heralded by a sudden loss of consciousness within 1 hour after the onset of acute symptoms, or an unwitnessed, unexpected death of someone seen in stable medical condition less than 24 hours before, with no evidence of a noncardiac cause. The researchers matched each case with about 20 other people from the database of the same gender and of similar age, reaching a total of 9,832 controls. The mean age of the cases and controls was 72 years; 26% were men.

In a multivariate analysis that controlled for age, gender, smoking, alcohol abuse, concomitant medications, cardiovascular disease, arrhythmia, hypertension, diabetes, heart failure, and hypercholesterolemia, people who died from sudden death were 2.5-fold more likely to be on treatment with an anticonvulsant drug than were controls, a statistically significant difference, reported Dr. Bardai, a cardiovascular diseases researcher at the Academic Medical Center in Amsterdam.

In a second adjusted analysis that divided anticonvulsant drug use into agents that block sodium channels and those that don't, the sudden death cases were 2.9-fold more likely to be on a sodium channel–blocking anticonvulsant, compared with controls, a statistically significant difference. In contrast, the fraction of sudden death cases on treatment with an anticonvulsant that does not block sodium channels was not significantly different from the rate at which these drugs were used by the controls.

In a final set of analyses, Dr. Bardai and his associates calculated the use of specific anticonvulsant drugs among the sudden death cases and controls. The only significant relationship they found was that the sudden death cases were 3.4-fold more likely to be on treatment with carbamazepine, a sodium channel–blocking anticonvulsant, compared with the controls.

Disclosures: Dr. Bardai said that he and his associates had no financial disclosures.

ORLANDO — Patients who experienced sudden cardiac death had a significantly higher rate of treatment with a sodium channel–blocking, anticonvulsant drug, compared with people who did not have sudden death, in a case-control study of more than 10,000 people.

“This finding may explain a proportion of the sudden deaths seen in epilepsy patients,” Dr. Abdennasser Bardai said at the annual scientific sessions of the American Heart Association.

About 10% of epilepsy patients have an unexpected death unrelated to seizure, a phenomenon so common that it's been named “sudden unexplained death in epilepsy.” Dr. Bardai and his associates hypothesized that many of these deaths might be triggered by anticonvulsant drugs, especially those that block sodium channels such as carbamazepine, lamotrigine, and phenytoin. Although the sodium-channel blockade these drugs cause is aimed at neurons, the same property can affect cardiac cells and may potentially cause arrhythmia.

To explore a possible link between anticonvulsant use and sudden death, the researchers used data collected in the Integrated Primary Care Information database, which has records for more than 1 million residents of the Netherlands. They focused on medical records for people aged 18 or older during 1995-2007 in cases for which at least 1 year's record existed.

Among the more than 478,000 people who met these criteria, 926 experienced sudden death, defined as a natural death heralded by a sudden loss of consciousness within 1 hour after the onset of acute symptoms, or an unwitnessed, unexpected death of someone seen in stable medical condition less than 24 hours before, with no evidence of a noncardiac cause. The researchers matched each case with about 20 other people from the database of the same gender and of similar age, reaching a total of 9,832 controls. The mean age of the cases and controls was 72 years; 26% were men.

In a multivariate analysis that controlled for age, gender, smoking, alcohol abuse, concomitant medications, cardiovascular disease, arrhythmia, hypertension, diabetes, heart failure, and hypercholesterolemia, people who died from sudden death were 2.5-fold more likely to be on treatment with an anticonvulsant drug than were controls, a statistically significant difference, reported Dr. Bardai, a cardiovascular diseases researcher at the Academic Medical Center in Amsterdam.

In a second adjusted analysis that divided anticonvulsant drug use into agents that block sodium channels and those that don't, the sudden death cases were 2.9-fold more likely to be on a sodium channel–blocking anticonvulsant, compared with controls, a statistically significant difference. In contrast, the fraction of sudden death cases on treatment with an anticonvulsant that does not block sodium channels was not significantly different from the rate at which these drugs were used by the controls.

In a final set of analyses, Dr. Bardai and his associates calculated the use of specific anticonvulsant drugs among the sudden death cases and controls. The only significant relationship they found was that the sudden death cases were 3.4-fold more likely to be on treatment with carbamazepine, a sodium channel–blocking anticonvulsant, compared with the controls.

Disclosures: Dr. Bardai said that he and his associates had no financial disclosures.

PHILADELPHIA — Administering two or more vaccines simultaneously was safe and immunogenic in results from two separate studies reported at the annual meeting of the Infectious Diseases Society of America.

One study assessed the immune response when healthy girls received concomitant vaccination with a human papillomavirus (HPV) vaccine along with a vaccine for tetanus, diphtheria, and pertussis (Tdap), and a third vaccine with a quadrivalent, conjugated meningococcal formulation (MCV4). The second study tested coadministration of the 2007-2008 seasonal influenza vaccine with an investigational, 13-valent, conjugated pneumococcal vaccine in adults aged 50-59 years.

The first study enrolled 1,283 healthy girls aged 11-18 years at 48 U.S. centers. The researchers randomized the participants to one of six different treatment schemes: HPV vaccine only at months 0, 1, and 6; HPV with Tdap at month 0 followed by HPV only at months 1 and 6; HPV with the meningococcal vaccine at month 0 followed by HPV only at months 1 and 6; all three vaccines at month 0 followed by HPV only at months 1 and 6; Tdap only at month 0 followed by HPV only at months 1, 2, and 7; and MCV4 only at month 0 and then HPV only at months 1, 2, and 7, said Cosette M. Wheeler, Ph.D., professor of pathology and obstetrics and gynecology at the University of New Mexico in Albuquerque.

Her study used the Cervarix formulation of HPV vaccine, the Boostrix formulation of Tdap, and the Menactra formulation of meningococcal vaccine. The Cervarix and Boostrix vaccines are marketed by GlaxoSmithKline, which funded the study. Menactra is marketed by Sanofi Pasteur.

The results showed that 1 month after the subjects received any of the concomitant doses, their immune responses all fell within the prespecified criteria for noninferiority, compared with the responses when the vaccines were administered individually. Also, the immune responses to the HPV vaccine 6 months after the final dose, when one dose was given in combination with one or two of the other vaccines, were noninferior to the responses to the HPV vaccine given by itself. The recipients of two or more simultaneous vaccines also had similar incidence rates for adverse events.

The second study examined concomitant administration of an investigational, 13-valent, conjugated pneumococcal vaccine and the trivalent, seasonal influenza vaccine of 2007-2008 in 1,106 healthy adults aged 50-59 years who had no history of previously receiving a pneumococcal vaccine, said Dr. Robert W. Frenck Jr., professor of pediatrics at Cincinnati Children's Hospital Medical Center.

He and his associates randomized subjects to receive either the pneumococcal and flu vaccines together at month 0 followed by placebo at month 1, or the flu vaccine and placebo at month 0 followed by the pneumococcal vaccine at month 1.

One month after vaccination, the immune responses to both vaccines in people who received them simultaneously fell within the prespecified noninferiority limit, compared with the responses in people who received the two vaccines 1 month apart, Dr. Frenck reported. Simultaneous administration also resulted in similar rates of local and systemic reactions compared with giving the vaccines 1 month apart.

Disclosures: Dr. Wheeler has received research support from GlaxoSmithKline, Merck (which markets the HPV vaccine Gardasil), and Roche Molecular Systems. Dr. Frenck's study was funded by Wyeth, which developed the pneumococcal vaccine; he had no other disclosures.

Simultaneous administration of more than one vaccine did not impair immunogenicity.

Source Joyce Frieden/Elsevier Global Medical News

PHILADELPHIA — Administering two or more vaccines simultaneously was safe and immunogenic in results from two separate studies reported at the annual meeting of the Infectious Diseases Society of America.

One study assessed the immune response when healthy girls received concomitant vaccination with a human papillomavirus (HPV) vaccine along with a vaccine for tetanus, diphtheria, and pertussis (Tdap), and a third vaccine with a quadrivalent, conjugated meningococcal formulation (MCV4). The second study tested coadministration of the 2007-2008 seasonal influenza vaccine with an investigational, 13-valent, conjugated pneumococcal vaccine in adults aged 50-59 years.

The first study enrolled 1,283 healthy girls aged 11-18 years at 48 U.S. centers. The researchers randomized the participants to one of six different treatment schemes: HPV vaccine only at months 0, 1, and 6; HPV with Tdap at month 0 followed by HPV only at months 1 and 6; HPV with the meningococcal vaccine at month 0 followed by HPV only at months 1 and 6; all three vaccines at month 0 followed by HPV only at months 1 and 6; Tdap only at month 0 followed by HPV only at months 1, 2, and 7; and MCV4 only at month 0 and then HPV only at months 1, 2, and 7, said Cosette M. Wheeler, Ph.D., professor of pathology and obstetrics and gynecology at the University of New Mexico in Albuquerque.

Her study used the Cervarix formulation of HPV vaccine, the Boostrix formulation of Tdap, and the Menactra formulation of meningococcal vaccine. The Cervarix and Boostrix vaccines are marketed by GlaxoSmithKline, which funded the study. Menactra is marketed by Sanofi Pasteur.

The results showed that 1 month after the subjects received any of the concomitant doses, their immune responses all fell within the prespecified criteria for noninferiority, compared with the responses when the vaccines were administered individually. Also, the immune responses to the HPV vaccine 6 months after the final dose, when one dose was given in combination with one or two of the other vaccines, were noninferior to the responses to the HPV vaccine given by itself. The recipients of two or more simultaneous vaccines also had similar incidence rates for adverse events.

The second study examined concomitant administration of an investigational, 13-valent, conjugated pneumococcal vaccine and the trivalent, seasonal influenza vaccine of 2007-2008 in 1,106 healthy adults aged 50-59 years who had no history of previously receiving a pneumococcal vaccine, said Dr. Robert W. Frenck Jr., professor of pediatrics at Cincinnati Children's Hospital Medical Center.

He and his associates randomized subjects to receive either the pneumococcal and flu vaccines together at month 0 followed by placebo at month 1, or the flu vaccine and placebo at month 0 followed by the pneumococcal vaccine at month 1.

One month after vaccination, the immune responses to both vaccines in people who received them simultaneously fell within the prespecified noninferiority limit, compared with the responses in people who received the two vaccines 1 month apart, Dr. Frenck reported. Simultaneous administration also resulted in similar rates of local and systemic reactions compared with giving the vaccines 1 month apart.

Disclosures: Dr. Wheeler has received research support from GlaxoSmithKline, Merck (which markets the HPV vaccine Gardasil), and Roche Molecular Systems. Dr. Frenck's study was funded by Wyeth, which developed the pneumococcal vaccine; he had no other disclosures.

Simultaneous administration of more than one vaccine did not impair immunogenicity.

Source Joyce Frieden/Elsevier Global Medical News

PHILADELPHIA — Administering two or more vaccines simultaneously was safe and immunogenic in results from two separate studies reported at the annual meeting of the Infectious Diseases Society of America.

One study assessed the immune response when healthy girls received concomitant vaccination with a human papillomavirus (HPV) vaccine along with a vaccine for tetanus, diphtheria, and pertussis (Tdap), and a third vaccine with a quadrivalent, conjugated meningococcal formulation (MCV4). The second study tested coadministration of the 2007-2008 seasonal influenza vaccine with an investigational, 13-valent, conjugated pneumococcal vaccine in adults aged 50-59 years.

The first study enrolled 1,283 healthy girls aged 11-18 years at 48 U.S. centers. The researchers randomized the participants to one of six different treatment schemes: HPV vaccine only at months 0, 1, and 6; HPV with Tdap at month 0 followed by HPV only at months 1 and 6; HPV with the meningococcal vaccine at month 0 followed by HPV only at months 1 and 6; all three vaccines at month 0 followed by HPV only at months 1 and 6; Tdap only at month 0 followed by HPV only at months 1, 2, and 7; and MCV4 only at month 0 and then HPV only at months 1, 2, and 7, said Cosette M. Wheeler, Ph.D., professor of pathology and obstetrics and gynecology at the University of New Mexico in Albuquerque.

Her study used the Cervarix formulation of HPV vaccine, the Boostrix formulation of Tdap, and the Menactra formulation of meningococcal vaccine. The Cervarix and Boostrix vaccines are marketed by GlaxoSmithKline, which funded the study. Menactra is marketed by Sanofi Pasteur.

The results showed that 1 month after the subjects received any of the concomitant doses, their immune responses all fell within the prespecified criteria for noninferiority, compared with the responses when the vaccines were administered individually. Also, the immune responses to the HPV vaccine 6 months after the final dose, when one dose was given in combination with one or two of the other vaccines, were noninferior to the responses to the HPV vaccine given by itself. The recipients of two or more simultaneous vaccines also had similar incidence rates for adverse events.

The second study examined concomitant administration of an investigational, 13-valent, conjugated pneumococcal vaccine and the trivalent, seasonal influenza vaccine of 2007-2008 in 1,106 healthy adults aged 50-59 years who had no history of previously receiving a pneumococcal vaccine, said Dr. Robert W. Frenck Jr., professor of pediatrics at Cincinnati Children's Hospital Medical Center.

He and his associates randomized subjects to receive either the pneumococcal and flu vaccines together at month 0 followed by placebo at month 1, or the flu vaccine and placebo at month 0 followed by the pneumococcal vaccine at month 1.

One month after vaccination, the immune responses to both vaccines in people who received them simultaneously fell within the prespecified noninferiority limit, compared with the responses in people who received the two vaccines 1 month apart, Dr. Frenck reported. Simultaneous administration also resulted in similar rates of local and systemic reactions compared with giving the vaccines 1 month apart.

Disclosures: Dr. Wheeler has received research support from GlaxoSmithKline, Merck (which markets the HPV vaccine Gardasil), and Roche Molecular Systems. Dr. Frenck's study was funded by Wyeth, which developed the pneumococcal vaccine; he had no other disclosures.

Simultaneous administration of more than one vaccine did not impair immunogenicity.

Source Joyce Frieden/Elsevier Global Medical News

ORLANDO — High blood levels of a brain natriuretic peptide were associated with poor cognitive function in a study of 950 community-dwelling, healthy, elderly adults.

“This is the first time this [association] has been shown,” Dr. Lori B. Daniels said at the annual scientific sessions of the American Heart Association.

Elevated levels of natriuretic peptide mark the presence of a variety of disease states, especially heart failure, Dr. Daniels said.

Mechanisms that might link production of natriuretic peptide to poor cognitive function include reduced cardiac output that decreases oxygen or nutrient supplies to the brain, atrial fibrillation that creates microemboli, microcirculation deficits that harm both the heart and brain, and genetic predisposition, said Dr. Daniels, a cardiologist at the University of California, San Diego.

Patients analyzed were enrolled in the Rancho Bernardo study in the early 1970s. Of the more than 5,000 community-dwelling adults in the study, 950 underwent a battery of cognitive function tests in 1997-1999 and had blood specimens drawn; they were the focus of the new analysis.

The average age of the 950 participants was 77 years; 61% were women. Two-thirds were hypertensive, 4% were current smokers, 49% drank three or more alcoholic drinks per week, 41% were college graduates, 12% had diabetes, 6% had a history of stroke, and 20% a history of cardiovascular disease.

Three tests were used to evaluate cognitive function: the Mini-Mental State Examination (MMSE), which assessed orientation, attention, calculation, and recall (a score of 24 or less indicated poor cognitive function); the Trail-Making Test B, which gauged executive function (a score of 132 seconds or more indicated poor function); and a category fluency test that asked participants to name as many animals as they could in 1 minute (a score of 12 or less indicated poor function).

MMSE results identified poor function in 7%, the Trail-Making Test B identified poor function in 30%, and category fluency identified poor function in 15%.

Natriuretic peptide levels in the blood specimens were measured using a test that detects N-terminal pro-B-type natriuretic peptide (NT-proBNP). A level less than 450 pg/mL was considered low, Among the 950 participants, 79% had a low level and 21% had a high level.

People with high levels of NT-proBNP had significantly worse results on all three cognitive function tests, compared with those who had low levels. In the low-level group, 5%, 23%, and 12% of patients had poor cognitive scores on the MMSE, 23% scored low on the Trail-Making Test B, and 12% had low scores on the category fluency test. In the high-level group, 17%, 54%, and 26% of patients scored poorly on the three tests.

When the results were adjusted for age, education, body mass index, exercise, alcohol use, and smoking, participants with high NT-proBNP levels had significantly worse cognitive function scores on the MMSE and the Trail-Making Test B. Poor scores for category fluency were lower in people with high NT-proBNP in the fully adjusted model, but the difference fell short of statistical significance relative to those with low NT-proBNP.

In the fully adjusted model, people with high levels of NT-proBNP were 82%, 75%, and 37% more likely to have poor cognitive function on the three tests, respectively, compared with people with low levels.

Disclosures: Dr. Daniels received research support from Roche Diagnostics, which markets an NT-proBNP assay.

People with high levels of NT-proBNP were more likely to have poor cognitive function.

Source DR. DANIELS

ORLANDO — High blood levels of a brain natriuretic peptide were associated with poor cognitive function in a study of 950 community-dwelling, healthy, elderly adults.

“This is the first time this [association] has been shown,” Dr. Lori B. Daniels said at the annual scientific sessions of the American Heart Association.

Elevated levels of natriuretic peptide mark the presence of a variety of disease states, especially heart failure, Dr. Daniels said.

Mechanisms that might link production of natriuretic peptide to poor cognitive function include reduced cardiac output that decreases oxygen or nutrient supplies to the brain, atrial fibrillation that creates microemboli, microcirculation deficits that harm both the heart and brain, and genetic predisposition, said Dr. Daniels, a cardiologist at the University of California, San Diego.

Patients analyzed were enrolled in the Rancho Bernardo study in the early 1970s. Of the more than 5,000 community-dwelling adults in the study, 950 underwent a battery of cognitive function tests in 1997-1999 and had blood specimens drawn; they were the focus of the new analysis.

The average age of the 950 participants was 77 years; 61% were women. Two-thirds were hypertensive, 4% were current smokers, 49% drank three or more alcoholic drinks per week, 41% were college graduates, 12% had diabetes, 6% had a history of stroke, and 20% a history of cardiovascular disease.

Three tests were used to evaluate cognitive function: the Mini-Mental State Examination (MMSE), which assessed orientation, attention, calculation, and recall (a score of 24 or less indicated poor cognitive function); the Trail-Making Test B, which gauged executive function (a score of 132 seconds or more indicated poor function); and a category fluency test that asked participants to name as many animals as they could in 1 minute (a score of 12 or less indicated poor function).

MMSE results identified poor function in 7%, the Trail-Making Test B identified poor function in 30%, and category fluency identified poor function in 15%.

Natriuretic peptide levels in the blood specimens were measured using a test that detects N-terminal pro-B-type natriuretic peptide (NT-proBNP). A level less than 450 pg/mL was considered low, Among the 950 participants, 79% had a low level and 21% had a high level.

People with high levels of NT-proBNP had significantly worse results on all three cognitive function tests, compared with those who had low levels. In the low-level group, 5%, 23%, and 12% of patients had poor cognitive scores on the MMSE, 23% scored low on the Trail-Making Test B, and 12% had low scores on the category fluency test. In the high-level group, 17%, 54%, and 26% of patients scored poorly on the three tests.

When the results were adjusted for age, education, body mass index, exercise, alcohol use, and smoking, participants with high NT-proBNP levels had significantly worse cognitive function scores on the MMSE and the Trail-Making Test B. Poor scores for category fluency were lower in people with high NT-proBNP in the fully adjusted model, but the difference fell short of statistical significance relative to those with low NT-proBNP.

In the fully adjusted model, people with high levels of NT-proBNP were 82%, 75%, and 37% more likely to have poor cognitive function on the three tests, respectively, compared with people with low levels.

Disclosures: Dr. Daniels received research support from Roche Diagnostics, which markets an NT-proBNP assay.

People with high levels of NT-proBNP were more likely to have poor cognitive function.

Source DR. DANIELS

ORLANDO — High blood levels of a brain natriuretic peptide were associated with poor cognitive function in a study of 950 community-dwelling, healthy, elderly adults.

“This is the first time this [association] has been shown,” Dr. Lori B. Daniels said at the annual scientific sessions of the American Heart Association.

Elevated levels of natriuretic peptide mark the presence of a variety of disease states, especially heart failure, Dr. Daniels said.

Mechanisms that might link production of natriuretic peptide to poor cognitive function include reduced cardiac output that decreases oxygen or nutrient supplies to the brain, atrial fibrillation that creates microemboli, microcirculation deficits that harm both the heart and brain, and genetic predisposition, said Dr. Daniels, a cardiologist at the University of California, San Diego.

Patients analyzed were enrolled in the Rancho Bernardo study in the early 1970s. Of the more than 5,000 community-dwelling adults in the study, 950 underwent a battery of cognitive function tests in 1997-1999 and had blood specimens drawn; they were the focus of the new analysis.

The average age of the 950 participants was 77 years; 61% were women. Two-thirds were hypertensive, 4% were current smokers, 49% drank three or more alcoholic drinks per week, 41% were college graduates, 12% had diabetes, 6% had a history of stroke, and 20% a history of cardiovascular disease.

Three tests were used to evaluate cognitive function: the Mini-Mental State Examination (MMSE), which assessed orientation, attention, calculation, and recall (a score of 24 or less indicated poor cognitive function); the Trail-Making Test B, which gauged executive function (a score of 132 seconds or more indicated poor function); and a category fluency test that asked participants to name as many animals as they could in 1 minute (a score of 12 or less indicated poor function).

MMSE results identified poor function in 7%, the Trail-Making Test B identified poor function in 30%, and category fluency identified poor function in 15%.

Natriuretic peptide levels in the blood specimens were measured using a test that detects N-terminal pro-B-type natriuretic peptide (NT-proBNP). A level less than 450 pg/mL was considered low, Among the 950 participants, 79% had a low level and 21% had a high level.

People with high levels of NT-proBNP had significantly worse results on all three cognitive function tests, compared with those who had low levels. In the low-level group, 5%, 23%, and 12% of patients had poor cognitive scores on the MMSE, 23% scored low on the Trail-Making Test B, and 12% had low scores on the category fluency test. In the high-level group, 17%, 54%, and 26% of patients scored poorly on the three tests.

When the results were adjusted for age, education, body mass index, exercise, alcohol use, and smoking, participants with high NT-proBNP levels had significantly worse cognitive function scores on the MMSE and the Trail-Making Test B. Poor scores for category fluency were lower in people with high NT-proBNP in the fully adjusted model, but the difference fell short of statistical significance relative to those with low NT-proBNP.

In the fully adjusted model, people with high levels of NT-proBNP were 82%, 75%, and 37% more likely to have poor cognitive function on the three tests, respectively, compared with people with low levels.

Disclosures: Dr. Daniels received research support from Roche Diagnostics, which markets an NT-proBNP assay.

People with high levels of NT-proBNP were more likely to have poor cognitive function.

Source DR. DANIELS

ORLANDO — Higher serum levels of high-density lipoprotein cholesterol were linked with lower risk for incident cancer in a meta-analysis of 21 randomized, controlled trials involving nearly 140,000 people.

An unadjusted analysis of cancer incidence rates in the 21 studies relative to baseline levels of high-density lipoprotein (HDL) cholesterol showed that every 10-mg/dL increment in HDL was linked with a 24% relative reduction in new-onset cancers.

The association was statistically stronger in a multivariate analysis that adjusted for baseline levels of low-density lipoprotein (LDL) cholesterol, age, body mass index, and smoking status. In this model, every 10-mg/dL increment in baseline HDL cholesterol correlated with a 21% drop in incident cancers, Dr. Haseeb Jafri and his associates reported in a poster at the annual scientific sessions of the American Heart Association.

This is the first report of a strong and significant inverse relationship between serum level of HDL cholesterol at baseline and subsequent development of cancer, according to Dr. Jafri, an internal medicine physician at Tufts Medical Center in Boston, and his coauthors.

The antioxidant and anti-inflammatory effects of HDL cholesterol particles is one hypothesized mechanism for the link between HDL cholesterol levels and cancer susceptibility, said Dr. Richard H. Karas, director of preventive cardiology and vice chairman of the department of medicine at Tufts and senior investigator on the report.

For example, HDL cholesterol particles carry the antioxidant enzyme paraoxonase, Dr. Karas said in an interview.

The 21 lipid-intervention trials included in the meta-analysis appeared in journal articles published during 1987-2009, and included more than 73,000 people allocated to lipid interventions and more than 66,000 in the control arms.

For inclusion in the analysis, published reports had to contain data on both baseline HDL cholesterol levels and incident cancer rates. The median duration of follow-up was 5 years, and the cumulative exposure studied totaled 586,000 person-years.

The median serum level of HDL cholesterol at baseline was about 45 mg/dL. During follow-up, the study participants developed 7,928 new-onset cancers.

In the multivariate model, baseline levels of LDL cholesterol and age also were significantly related to the rate of incident cancers.

Future studies should look at the relationship between HDL cholesterol and cancer incidence in other databases, Dr. Karas said.

Disclosures: Dr. Karas disclosed receiving research support from AstraZeneca, and honoraria from Abbott and Merck. Dr. Jafri reported no financial relationships.

ORLANDO — Higher serum levels of high-density lipoprotein cholesterol were linked with lower risk for incident cancer in a meta-analysis of 21 randomized, controlled trials involving nearly 140,000 people.

An unadjusted analysis of cancer incidence rates in the 21 studies relative to baseline levels of high-density lipoprotein (HDL) cholesterol showed that every 10-mg/dL increment in HDL was linked with a 24% relative reduction in new-onset cancers.

The association was statistically stronger in a multivariate analysis that adjusted for baseline levels of low-density lipoprotein (LDL) cholesterol, age, body mass index, and smoking status. In this model, every 10-mg/dL increment in baseline HDL cholesterol correlated with a 21% drop in incident cancers, Dr. Haseeb Jafri and his associates reported in a poster at the annual scientific sessions of the American Heart Association.

This is the first report of a strong and significant inverse relationship between serum level of HDL cholesterol at baseline and subsequent development of cancer, according to Dr. Jafri, an internal medicine physician at Tufts Medical Center in Boston, and his coauthors.

The antioxidant and anti-inflammatory effects of HDL cholesterol particles is one hypothesized mechanism for the link between HDL cholesterol levels and cancer susceptibility, said Dr. Richard H. Karas, director of preventive cardiology and vice chairman of the department of medicine at Tufts and senior investigator on the report.

For example, HDL cholesterol particles carry the antioxidant enzyme paraoxonase, Dr. Karas said in an interview.

The 21 lipid-intervention trials included in the meta-analysis appeared in journal articles published during 1987-2009, and included more than 73,000 people allocated to lipid interventions and more than 66,000 in the control arms.

For inclusion in the analysis, published reports had to contain data on both baseline HDL cholesterol levels and incident cancer rates. The median duration of follow-up was 5 years, and the cumulative exposure studied totaled 586,000 person-years.

The median serum level of HDL cholesterol at baseline was about 45 mg/dL. During follow-up, the study participants developed 7,928 new-onset cancers.

In the multivariate model, baseline levels of LDL cholesterol and age also were significantly related to the rate of incident cancers.

Future studies should look at the relationship between HDL cholesterol and cancer incidence in other databases, Dr. Karas said.

Disclosures: Dr. Karas disclosed receiving research support from AstraZeneca, and honoraria from Abbott and Merck. Dr. Jafri reported no financial relationships.

ORLANDO — Higher serum levels of high-density lipoprotein cholesterol were linked with lower risk for incident cancer in a meta-analysis of 21 randomized, controlled trials involving nearly 140,000 people.

An unadjusted analysis of cancer incidence rates in the 21 studies relative to baseline levels of high-density lipoprotein (HDL) cholesterol showed that every 10-mg/dL increment in HDL was linked with a 24% relative reduction in new-onset cancers.

The association was statistically stronger in a multivariate analysis that adjusted for baseline levels of low-density lipoprotein (LDL) cholesterol, age, body mass index, and smoking status. In this model, every 10-mg/dL increment in baseline HDL cholesterol correlated with a 21% drop in incident cancers, Dr. Haseeb Jafri and his associates reported in a poster at the annual scientific sessions of the American Heart Association.

This is the first report of a strong and significant inverse relationship between serum level of HDL cholesterol at baseline and subsequent development of cancer, according to Dr. Jafri, an internal medicine physician at Tufts Medical Center in Boston, and his coauthors.

The antioxidant and anti-inflammatory effects of HDL cholesterol particles is one hypothesized mechanism for the link between HDL cholesterol levels and cancer susceptibility, said Dr. Richard H. Karas, director of preventive cardiology and vice chairman of the department of medicine at Tufts and senior investigator on the report.

For example, HDL cholesterol particles carry the antioxidant enzyme paraoxonase, Dr. Karas said in an interview.

The 21 lipid-intervention trials included in the meta-analysis appeared in journal articles published during 1987-2009, and included more than 73,000 people allocated to lipid interventions and more than 66,000 in the control arms.

For inclusion in the analysis, published reports had to contain data on both baseline HDL cholesterol levels and incident cancer rates. The median duration of follow-up was 5 years, and the cumulative exposure studied totaled 586,000 person-years.

The median serum level of HDL cholesterol at baseline was about 45 mg/dL. During follow-up, the study participants developed 7,928 new-onset cancers.

In the multivariate model, baseline levels of LDL cholesterol and age also were significantly related to the rate of incident cancers.

Future studies should look at the relationship between HDL cholesterol and cancer incidence in other databases, Dr. Karas said.

Disclosures: Dr. Karas disclosed receiving research support from AstraZeneca, and honoraria from Abbott and Merck. Dr. Jafri reported no financial relationships.

ORLANDO — Gout boosted the risk of death or hospitalization for heart failure in an observational, case-control study of more than 150,000 patients with heart failure.

The analysis also showed that patients with heart failure and gout who were on long-term allopurinol treatment had a significantly reduced risk for death or heart failure hospitalization, Dr. George Thanassoulis said at the annual scientific sessions of the American Heart Association.

These findings do not warrant the use of allopurinol in heart failure patients without gout, but the data suggest that if such patients are candidates for allopurinol because of coexisting gout, the new results “increase the reasons to treat them,” said Dr. Thanassoulis, a cardiologist at Boston University and the Framingham Heart Study.

He hypothesized that allopurinol exerts its benefit for heart failure outcomes not by lowering blood levels of uric acid, but by inhibiting oxidative stress and the endothelial dysfunction that oxidative stress produces. Dr. Thanassoulis suggested that allopurinol inhibits xanthine oxidase, the same action that also blunts uric acid production.

The study used administrative health-record data from residents of the province of Quebec who were aged older than 65 years. Cases were 14,327 people hospitalized for heart failure but without another heart failure hospitalization during the 3 years before the index episode, a restriction that helped ensure a uniform level of heart failure severity among the patients. Controls were 143,255 people in the Quebec database matched to the cases by follow-up duration and by calendar year.

The average age was 79 years among the cases and 77 years among the controls. Both groups were evenly split among men and women. Identification of gout relied on hospitalization, a physician visit, or a diagnostic code in the medical record.

During an average follow-up of 2 years, the rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout, a statistically significant difference in an analysis that controlled for several demographic and clinical variables including age, gender, comorbidities, and medications.

The risk for death or heart failure hospitalization was even higher in patients who had acute gout, with a twofold higher risk in the adjusted analysis. The researchers defined acute gout as hospitalization or a physician visit for gout within 60 days of the index heart failure event.

Another pair of analyses looked at the impact of allopurinol treatment. Among patients with an index heart failure event who also had gout treatment with allopurinol, there was a significant 31% reduction in the subsequent rate of death or heart failure hospitalization in the adjusted analysis. This benefit was limited to the patients on chronic allopurinol treatment for more than 30 days. Patients on allopurinol for 30 days or less showed no significant reduction in mortality or new heart failure hospitalizations.

The allopurinol analysis also showed no link between the drug and outcomes for the entire heart failure population studied, suggesting that benefit from allopurinol is not general for all heart failure patients, only those with gout.

The next step is to assess the relationship between heart failure, gout, and allopurinol treatment in a prospective, controlled study, Dr. Thanassoulis said.

Disclosures: Dr. Thanassoulis and his associates have no conflicts of interest.

ORLANDO — Gout boosted the risk of death or hospitalization for heart failure in an observational, case-control study of more than 150,000 patients with heart failure.

The analysis also showed that patients with heart failure and gout who were on long-term allopurinol treatment had a significantly reduced risk for death or heart failure hospitalization, Dr. George Thanassoulis said at the annual scientific sessions of the American Heart Association.

These findings do not warrant the use of allopurinol in heart failure patients without gout, but the data suggest that if such patients are candidates for allopurinol because of coexisting gout, the new results “increase the reasons to treat them,” said Dr. Thanassoulis, a cardiologist at Boston University and the Framingham Heart Study.

He hypothesized that allopurinol exerts its benefit for heart failure outcomes not by lowering blood levels of uric acid, but by inhibiting oxidative stress and the endothelial dysfunction that oxidative stress produces. Dr. Thanassoulis suggested that allopurinol inhibits xanthine oxidase, the same action that also blunts uric acid production.

The study used administrative health-record data from residents of the province of Quebec who were aged older than 65 years. Cases were 14,327 people hospitalized for heart failure but without another heart failure hospitalization during the 3 years before the index episode, a restriction that helped ensure a uniform level of heart failure severity among the patients. Controls were 143,255 people in the Quebec database matched to the cases by follow-up duration and by calendar year.

The average age was 79 years among the cases and 77 years among the controls. Both groups were evenly split among men and women. Identification of gout relied on hospitalization, a physician visit, or a diagnostic code in the medical record.

During an average follow-up of 2 years, the rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout, a statistically significant difference in an analysis that controlled for several demographic and clinical variables including age, gender, comorbidities, and medications.

The risk for death or heart failure hospitalization was even higher in patients who had acute gout, with a twofold higher risk in the adjusted analysis. The researchers defined acute gout as hospitalization or a physician visit for gout within 60 days of the index heart failure event.

Another pair of analyses looked at the impact of allopurinol treatment. Among patients with an index heart failure event who also had gout treatment with allopurinol, there was a significant 31% reduction in the subsequent rate of death or heart failure hospitalization in the adjusted analysis. This benefit was limited to the patients on chronic allopurinol treatment for more than 30 days. Patients on allopurinol for 30 days or less showed no significant reduction in mortality or new heart failure hospitalizations.

The allopurinol analysis also showed no link between the drug and outcomes for the entire heart failure population studied, suggesting that benefit from allopurinol is not general for all heart failure patients, only those with gout.

The next step is to assess the relationship between heart failure, gout, and allopurinol treatment in a prospective, controlled study, Dr. Thanassoulis said.

Disclosures: Dr. Thanassoulis and his associates have no conflicts of interest.

ORLANDO — Gout boosted the risk of death or hospitalization for heart failure in an observational, case-control study of more than 150,000 patients with heart failure.

The analysis also showed that patients with heart failure and gout who were on long-term allopurinol treatment had a significantly reduced risk for death or heart failure hospitalization, Dr. George Thanassoulis said at the annual scientific sessions of the American Heart Association.

These findings do not warrant the use of allopurinol in heart failure patients without gout, but the data suggest that if such patients are candidates for allopurinol because of coexisting gout, the new results “increase the reasons to treat them,” said Dr. Thanassoulis, a cardiologist at Boston University and the Framingham Heart Study.

He hypothesized that allopurinol exerts its benefit for heart failure outcomes not by lowering blood levels of uric acid, but by inhibiting oxidative stress and the endothelial dysfunction that oxidative stress produces. Dr. Thanassoulis suggested that allopurinol inhibits xanthine oxidase, the same action that also blunts uric acid production.

The study used administrative health-record data from residents of the province of Quebec who were aged older than 65 years. Cases were 14,327 people hospitalized for heart failure but without another heart failure hospitalization during the 3 years before the index episode, a restriction that helped ensure a uniform level of heart failure severity among the patients. Controls were 143,255 people in the Quebec database matched to the cases by follow-up duration and by calendar year.

The average age was 79 years among the cases and 77 years among the controls. Both groups were evenly split among men and women. Identification of gout relied on hospitalization, a physician visit, or a diagnostic code in the medical record.

During an average follow-up of 2 years, the rate of death or new heart failure hospitalization was 63% higher in the patients with gout than in those without gout, a statistically significant difference in an analysis that controlled for several demographic and clinical variables including age, gender, comorbidities, and medications.

The risk for death or heart failure hospitalization was even higher in patients who had acute gout, with a twofold higher risk in the adjusted analysis. The researchers defined acute gout as hospitalization or a physician visit for gout within 60 days of the index heart failure event.

Another pair of analyses looked at the impact of allopurinol treatment. Among patients with an index heart failure event who also had gout treatment with allopurinol, there was a significant 31% reduction in the subsequent rate of death or heart failure hospitalization in the adjusted analysis. This benefit was limited to the patients on chronic allopurinol treatment for more than 30 days. Patients on allopurinol for 30 days or less showed no significant reduction in mortality or new heart failure hospitalizations.

The allopurinol analysis also showed no link between the drug and outcomes for the entire heart failure population studied, suggesting that benefit from allopurinol is not general for all heart failure patients, only those with gout.

The next step is to assess the relationship between heart failure, gout, and allopurinol treatment in a prospective, controlled study, Dr. Thanassoulis said.

Disclosures: Dr. Thanassoulis and his associates have no conflicts of interest.

ORLANDO — Patients with heart failure had a greater than twofold increased risk of subsequently developing diabetes, compared with people without heart failure in a review of more than 4,600 individuals in the Framingham Offspring Study.

The analysis also showed a strong association between the severity of heart failure symptoms and the risk for new-onset diabetes: Patients with higher New York Heart Association–class heart failure faced a greater risk for developing diabetes than did patients with less severe heart failure symptoms, Dr. Ankit Rathod reported at the annual scientific sessions of the American Heart Association.

The implications are that patients with heart failure should undergo more intensive surveillance for development of insulin resistance and diabetes. The findings also present a new reason for optimized heart failure treatment to minimize symptom severity because this may cut the patient's risk for developing diabetes, Dr. Rathod said in an interview.

The hypothesized causal link between heart failure and diabetes is the neurohormonal, sympathetic activation that characterizes heart failure. This leads to norepinephrine release, which can trigger insulin resistance and hence increased susceptibility to developing diabetes, said Dr. Rathod, an internal medicine physician at Wayne State University in Detroit. In addition, patients with more severe heart failure symptoms have reduced activity, which might exacerbate insulin resistance and the risk for developing diabetes.

“I believe the connections between insulin resistance and neurohormonal activation are a real phenomenon,” said Dr. Clyde W. Yancy, medical director of the Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas. He cited study results showing that treatment with drugs that block neurohormonal activation also cut development of diabetes, such as with ramipril in the HOPE study (N. Engl. J. Med 2000;342:145-53) and treatment with carvedilol in the CAPRICORN study (Lancet 2001;357:1385-90).

Dr. Rathod's study used data collected from the more than 4,900 people enrolled in the Framingham Offspring Study in 1971. He and his associates excluded people with a history of diabetes or heart failure at the time of enrollment, as well as those who had missing data on their subsequent rate of new-onset diabetes. The 4,614 people included in the study had an average age of 35 years, and about half were women.

During an average follow-up of 24 years, 123 developed heart failure and 468 developed new-onset diabetes. Forty-one of the 123 patients (33%) who developed heart failure later developed diabetes, compared with 427 new cases of diabetes among the other 4,491 people (10%).

In a multivariate analysis that adjusted for baseline demographic and clinical differences, including drug treatments and baseline blood glucose levels, patients who first developed heart failure had a statistically significant 2.5-fold increased risk for later developing diabetes, compared with the people who did not have heart failure.

The link between heart failure and diabetes should be examined in other databases, Dr. Rathod said.

Disclosures: Dr. Rathod and Dr. Yancy both reported having no financial disclosures.

Patients who first developed heart failure had a 2.5-fold increased risk for later developing diabetes.

Source DR. RATHOD

ORLANDO — Patients with heart failure had a greater than twofold increased risk of subsequently developing diabetes, compared with people without heart failure in a review of more than 4,600 individuals in the Framingham Offspring Study.

The analysis also showed a strong association between the severity of heart failure symptoms and the risk for new-onset diabetes: Patients with higher New York Heart Association–class heart failure faced a greater risk for developing diabetes than did patients with less severe heart failure symptoms, Dr. Ankit Rathod reported at the annual scientific sessions of the American Heart Association.

The implications are that patients with heart failure should undergo more intensive surveillance for development of insulin resistance and diabetes. The findings also present a new reason for optimized heart failure treatment to minimize symptom severity because this may cut the patient's risk for developing diabetes, Dr. Rathod said in an interview.

The hypothesized causal link between heart failure and diabetes is the neurohormonal, sympathetic activation that characterizes heart failure. This leads to norepinephrine release, which can trigger insulin resistance and hence increased susceptibility to developing diabetes, said Dr. Rathod, an internal medicine physician at Wayne State University in Detroit. In addition, patients with more severe heart failure symptoms have reduced activity, which might exacerbate insulin resistance and the risk for developing diabetes.

“I believe the connections between insulin resistance and neurohormonal activation are a real phenomenon,” said Dr. Clyde W. Yancy, medical director of the Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas. He cited study results showing that treatment with drugs that block neurohormonal activation also cut development of diabetes, such as with ramipril in the HOPE study (N. Engl. J. Med 2000;342:145-53) and treatment with carvedilol in the CAPRICORN study (Lancet 2001;357:1385-90).

Dr. Rathod's study used data collected from the more than 4,900 people enrolled in the Framingham Offspring Study in 1971. He and his associates excluded people with a history of diabetes or heart failure at the time of enrollment, as well as those who had missing data on their subsequent rate of new-onset diabetes. The 4,614 people included in the study had an average age of 35 years, and about half were women.

During an average follow-up of 24 years, 123 developed heart failure and 468 developed new-onset diabetes. Forty-one of the 123 patients (33%) who developed heart failure later developed diabetes, compared with 427 new cases of diabetes among the other 4,491 people (10%).

In a multivariate analysis that adjusted for baseline demographic and clinical differences, including drug treatments and baseline blood glucose levels, patients who first developed heart failure had a statistically significant 2.5-fold increased risk for later developing diabetes, compared with the people who did not have heart failure.

The link between heart failure and diabetes should be examined in other databases, Dr. Rathod said.

Disclosures: Dr. Rathod and Dr. Yancy both reported having no financial disclosures.

Patients who first developed heart failure had a 2.5-fold increased risk for later developing diabetes.

Source DR. RATHOD

ORLANDO — Patients with heart failure had a greater than twofold increased risk of subsequently developing diabetes, compared with people without heart failure in a review of more than 4,600 individuals in the Framingham Offspring Study.

The analysis also showed a strong association between the severity of heart failure symptoms and the risk for new-onset diabetes: Patients with higher New York Heart Association–class heart failure faced a greater risk for developing diabetes than did patients with less severe heart failure symptoms, Dr. Ankit Rathod reported at the annual scientific sessions of the American Heart Association.

The implications are that patients with heart failure should undergo more intensive surveillance for development of insulin resistance and diabetes. The findings also present a new reason for optimized heart failure treatment to minimize symptom severity because this may cut the patient's risk for developing diabetes, Dr. Rathod said in an interview.

The hypothesized causal link between heart failure and diabetes is the neurohormonal, sympathetic activation that characterizes heart failure. This leads to norepinephrine release, which can trigger insulin resistance and hence increased susceptibility to developing diabetes, said Dr. Rathod, an internal medicine physician at Wayne State University in Detroit. In addition, patients with more severe heart failure symptoms have reduced activity, which might exacerbate insulin resistance and the risk for developing diabetes.

“I believe the connections between insulin resistance and neurohormonal activation are a real phenomenon,” said Dr. Clyde W. Yancy, medical director of the Baylor Heart and Vascular Institute at Baylor University Medical Center in Dallas. He cited study results showing that treatment with drugs that block neurohormonal activation also cut development of diabetes, such as with ramipril in the HOPE study (N. Engl. J. Med 2000;342:145-53) and treatment with carvedilol in the CAPRICORN study (Lancet 2001;357:1385-90).

Dr. Rathod's study used data collected from the more than 4,900 people enrolled in the Framingham Offspring Study in 1971. He and his associates excluded people with a history of diabetes or heart failure at the time of enrollment, as well as those who had missing data on their subsequent rate of new-onset diabetes. The 4,614 people included in the study had an average age of 35 years, and about half were women.

During an average follow-up of 24 years, 123 developed heart failure and 468 developed new-onset diabetes. Forty-one of the 123 patients (33%) who developed heart failure later developed diabetes, compared with 427 new cases of diabetes among the other 4,491 people (10%).

In a multivariate analysis that adjusted for baseline demographic and clinical differences, including drug treatments and baseline blood glucose levels, patients who first developed heart failure had a statistically significant 2.5-fold increased risk for later developing diabetes, compared with the people who did not have heart failure.

The link between heart failure and diabetes should be examined in other databases, Dr. Rathod said.

Disclosures: Dr. Rathod and Dr. Yancy both reported having no financial disclosures.

Patients who first developed heart failure had a 2.5-fold increased risk for later developing diabetes.

Source DR. RATHOD

ORLANDO — Replacing the generator and lead from cardiac antiarrhythmia devices carries a substantial risk for causing a major complication, a study of registry data from 713 patients has shown.

Patients who underwent generator replacement for a pacemaker or implantable cardioverter defibrillator (ICD) along with a planned lead addition or revision had a major complication rate of 15% during the 6 months following the procedure, Dr. Jeanne E. Poole said at the annual scientific sessions of the American Heart Association. When combined with minor complications, the total rate of patients having any complication during the 6 months following generator replacement and planned lead addition or revision reached 21%.

Among the subgroup of patients who underwent a left ventricular lead addition or revision, the major complication rate reached 19%, said Dr. Poole, professor and director of the electrophysiology service at the University of Washington in Seattle, and principal investigator of the registry.

“These prospectively collected data provide comprehensive risk rates for physicians to consider when planning to upgrade pacemaker or ICD systems,” Dr. Poole said. The strikingly high major complication rate found in this series contrasts with the 4% major complication rate found for 1,031 patients who underwent pacemaker or ICD generator replacement without a planned lead change in the same registry. An initial report of those data was presented last May at the annual meeting of the Heart Rhythm Society in Boston.

The complication rates reported in the new study are “sobering,” said Dr. Alan H. Kadish, professor and director of cardiac electrophysiology at Northwestern University in Chicago. “The findings suggest that for some indications, we should continue to practice as we have, but for other indications we should take a long and hard look before adding or revising a lead, especially when an atrial lead is added for 'soft' indications. A left ventricular lead addition is still quite reasonable for overt congestive heart failure, but prophylactic addition of a left ventricular lead is something that must be carefully thought about in light of the results of this study,” he said.

The Implantable Cardiac Pulse Generator Replacement Registry (REPLACE) enrolled 713 patients in the planned lead addition or revision arm of the study at 69 U.S. sites—37 academic centers and 32 private hospitals—during July 2007–November 2008, with follow-up through July 2009.

The average age of the 713 patients in this arm of the registry was 70 years; 24% were women. Heart failure was present in 83%. Pacemakers were implanted in 46%, ICDs in 45%, and cardiac resynchronization devices in 9%. The devices had been in place for an average of 4 years.

The most common procedure was a planned upgrade to a cardiac resynchronization device, in 57%.

The study used a predefined list of major and minor complications. Major complications included 14 items, including death within 30 days as a direct result of the procedure, stroke within 30 days, infection requiring intravenous antibiotics or device removal, deep vein thrombosis, pulmonary embolism, and pneumothorax or hemothorax.

During the first 24 hours after the procedure, 17 patients (2%) had major complications including 5 with cardiac perforations and 4 with pneumothorax. There were no deaths in this perioperative period. During the subsequent 6 months, 100 patients (14%) had major complications, most commonly a malfunction that required reopening the pocket, in 7%, followed by an unplanned lead addition or removal, in 4%.

Eight patients (1%) died. Overall, 109 patients (15%) had one or more major complications during the 6 months following the index intervention.

A reassuring finding was that the infection rate was low. Six patients (0.8%) had a major infection and another two (0.3%) had minor infections.

“All patients received intravenous antibiotics and appropriate skin prep,” Dr. Poole said.

Disclosures: The registry was sponsored by Biotronik, a company that markets cardiac pulse generators and leads, but it enrolled patients with any type of commercially available pacemaker or ICD.

Dr. Poole has received research grants from Biotronik, as well as honoraria from Boston Scientific, Medtronic, and St. Jude Medical.

Dr. Kadish has received grant support from St. Jude Medical and Baird. He also has consulted for and received honoraria from several companies, including Baird, Medtronic, Impulse Dynamics, Lifewatch, and Sanofi.

Two Factors Tied to Complications

Cardiac device type and procedure volume emerged from the REPLACE registry as the only variables significantly linked with complication rates.

In data collected from the first arm of the registry, limited to patients who had a generator replacement for an existing pacemaker or ICD but without a planned lead addition or revision, patients with an ICD were 60% more likely to have a major complication than were patients with a pacemaker, Dr. Theofanie Mela said at the annual scientific sessions of the American Heart Association.

In the same cohort, patients who underwent generator replacement at a center that did 250 or more procedures per year were 45% less likely to have any type of complication, compared with patients who were treated at centers that did fewer procedures each year, said Dr. Mela, director of the pacemaker laboratory at Massachusetts General Hospital in Boston.

Other variables examined that did not have a significant bearing on complication rates included age, gender, number and severity of comorbidities as measured by the Charlson Comorbidity Index, specialty of the physician performing the procedure (electrophysiologist compared with nonelectrophysiologist), and type of practice (academic center compared with private hospital).

The analysis used data from the first arm of REPLACE, in which 1,031 patients were enrolled at 68 U.S. centers (34 academic and 34 private) during July 2007–March 2008, and tallied the number of complications during 6 months' follow-up. The researchers reported a 4% major complication rate, a 7.4% minor complication rate, and an overall complication rate of 10.9% at the annual meeting of the Heart Rhythm Society in Boston last May.

Subsequent analysis examined potential determinants of the complication rate. Patients with a pacemaker had a major complication rate of 2.3%, compared with a rate of 5.8% in patients with an ICD (the registry included roughly equal numbers of patients with each device type). The 68 sites had a median annual procedure volume of 250. High-volume sites had an overall complication rate of 8.6%; low-volume centers had an overall rate of 14.9%.

Dr. Mela said that she has received honoraria from Boston Scientific, Medtronic, and St. Jude Medical.

ORLANDO — Replacing the generator and lead from cardiac antiarrhythmia devices carries a substantial risk for causing a major complication, a study of registry data from 713 patients has shown.

Patients who underwent generator replacement for a pacemaker or implantable cardioverter defibrillator (ICD) along with a planned lead addition or revision had a major complication rate of 15% during the 6 months following the procedure, Dr. Jeanne E. Poole said at the annual scientific sessions of the American Heart Association. When combined with minor complications, the total rate of patients having any complication during the 6 months following generator replacement and planned lead addition or revision reached 21%.

Among the subgroup of patients who underwent a left ventricular lead addition or revision, the major complication rate reached 19%, said Dr. Poole, professor and director of the electrophysiology service at the University of Washington in Seattle, and principal investigator of the registry.

“These prospectively collected data provide comprehensive risk rates for physicians to consider when planning to upgrade pacemaker or ICD systems,” Dr. Poole said. The strikingly high major complication rate found in this series contrasts with the 4% major complication rate found for 1,031 patients who underwent pacemaker or ICD generator replacement without a planned lead change in the same registry. An initial report of those data was presented last May at the annual meeting of the Heart Rhythm Society in Boston.

The complication rates reported in the new study are “sobering,” said Dr. Alan H. Kadish, professor and director of cardiac electrophysiology at Northwestern University in Chicago. “The findings suggest that for some indications, we should continue to practice as we have, but for other indications we should take a long and hard look before adding or revising a lead, especially when an atrial lead is added for 'soft' indications. A left ventricular lead addition is still quite reasonable for overt congestive heart failure, but prophylactic addition of a left ventricular lead is something that must be carefully thought about in light of the results of this study,” he said.

The Implantable Cardiac Pulse Generator Replacement Registry (REPLACE) enrolled 713 patients in the planned lead addition or revision arm of the study at 69 U.S. sites—37 academic centers and 32 private hospitals—during July 2007–November 2008, with follow-up through July 2009.

The average age of the 713 patients in this arm of the registry was 70 years; 24% were women. Heart failure was present in 83%. Pacemakers were implanted in 46%, ICDs in 45%, and cardiac resynchronization devices in 9%. The devices had been in place for an average of 4 years.

The most common procedure was a planned upgrade to a cardiac resynchronization device, in 57%.

The study used a predefined list of major and minor complications. Major complications included 14 items, including death within 30 days as a direct result of the procedure, stroke within 30 days, infection requiring intravenous antibiotics or device removal, deep vein thrombosis, pulmonary embolism, and pneumothorax or hemothorax.

During the first 24 hours after the procedure, 17 patients (2%) had major complications including 5 with cardiac perforations and 4 with pneumothorax. There were no deaths in this perioperative period. During the subsequent 6 months, 100 patients (14%) had major complications, most commonly a malfunction that required reopening the pocket, in 7%, followed by an unplanned lead addition or removal, in 4%.

Eight patients (1%) died. Overall, 109 patients (15%) had one or more major complications during the 6 months following the index intervention.

A reassuring finding was that the infection rate was low. Six patients (0.8%) had a major infection and another two (0.3%) had minor infections.

“All patients received intravenous antibiotics and appropriate skin prep,” Dr. Poole said.

Disclosures: The registry was sponsored by Biotronik, a company that markets cardiac pulse generators and leads, but it enrolled patients with any type of commercially available pacemaker or ICD.

Dr. Poole has received research grants from Biotronik, as well as honoraria from Boston Scientific, Medtronic, and St. Jude Medical.

Dr. Kadish has received grant support from St. Jude Medical and Baird. He also has consulted for and received honoraria from several companies, including Baird, Medtronic, Impulse Dynamics, Lifewatch, and Sanofi.

Two Factors Tied to Complications

Cardiac device type and procedure volume emerged from the REPLACE registry as the only variables significantly linked with complication rates.

In data collected from the first arm of the registry, limited to patients who had a generator replacement for an existing pacemaker or ICD but without a planned lead addition or revision, patients with an ICD were 60% more likely to have a major complication than were patients with a pacemaker, Dr. Theofanie Mela said at the annual scientific sessions of the American Heart Association.

In the same cohort, patients who underwent generator replacement at a center that did 250 or more procedures per year were 45% less likely to have any type of complication, compared with patients who were treated at centers that did fewer procedures each year, said Dr. Mela, director of the pacemaker laboratory at Massachusetts General Hospital in Boston.

Other variables examined that did not have a significant bearing on complication rates included age, gender, number and severity of comorbidities as measured by the Charlson Comorbidity Index, specialty of the physician performing the procedure (electrophysiologist compared with nonelectrophysiologist), and type of practice (academic center compared with private hospital).

The analysis used data from the first arm of REPLACE, in which 1,031 patients were enrolled at 68 U.S. centers (34 academic and 34 private) during July 2007–March 2008, and tallied the number of complications during 6 months' follow-up. The researchers reported a 4% major complication rate, a 7.4% minor complication rate, and an overall complication rate of 10.9% at the annual meeting of the Heart Rhythm Society in Boston last May.

Subsequent analysis examined potential determinants of the complication rate. Patients with a pacemaker had a major complication rate of 2.3%, compared with a rate of 5.8% in patients with an ICD (the registry included roughly equal numbers of patients with each device type). The 68 sites had a median annual procedure volume of 250. High-volume sites had an overall complication rate of 8.6%; low-volume centers had an overall rate of 14.9%.

Dr. Mela said that she has received honoraria from Boston Scientific, Medtronic, and St. Jude Medical.

ORLANDO — Replacing the generator and lead from cardiac antiarrhythmia devices carries a substantial risk for causing a major complication, a study of registry data from 713 patients has shown.

Patients who underwent generator replacement for a pacemaker or implantable cardioverter defibrillator (ICD) along with a planned lead addition or revision had a major complication rate of 15% during the 6 months following the procedure, Dr. Jeanne E. Poole said at the annual scientific sessions of the American Heart Association. When combined with minor complications, the total rate of patients having any complication during the 6 months following generator replacement and planned lead addition or revision reached 21%.

Among the subgroup of patients who underwent a left ventricular lead addition or revision, the major complication rate reached 19%, said Dr. Poole, professor and director of the electrophysiology service at the University of Washington in Seattle, and principal investigator of the registry.

“These prospectively collected data provide comprehensive risk rates for physicians to consider when planning to upgrade pacemaker or ICD systems,” Dr. Poole said. The strikingly high major complication rate found in this series contrasts with the 4% major complication rate found for 1,031 patients who underwent pacemaker or ICD generator replacement without a planned lead change in the same registry. An initial report of those data was presented last May at the annual meeting of the Heart Rhythm Society in Boston.

The complication rates reported in the new study are “sobering,” said Dr. Alan H. Kadish, professor and director of cardiac electrophysiology at Northwestern University in Chicago. “The findings suggest that for some indications, we should continue to practice as we have, but for other indications we should take a long and hard look before adding or revising a lead, especially when an atrial lead is added for 'soft' indications. A left ventricular lead addition is still quite reasonable for overt congestive heart failure, but prophylactic addition of a left ventricular lead is something that must be carefully thought about in light of the results of this study,” he said.

The Implantable Cardiac Pulse Generator Replacement Registry (REPLACE) enrolled 713 patients in the planned lead addition or revision arm of the study at 69 U.S. sites—37 academic centers and 32 private hospitals—during July 2007–November 2008, with follow-up through July 2009.

The average age of the 713 patients in this arm of the registry was 70 years; 24% were women. Heart failure was present in 83%. Pacemakers were implanted in 46%, ICDs in 45%, and cardiac resynchronization devices in 9%. The devices had been in place for an average of 4 years.

The most common procedure was a planned upgrade to a cardiac resynchronization device, in 57%.

The study used a predefined list of major and minor complications. Major complications included 14 items, including death within 30 days as a direct result of the procedure, stroke within 30 days, infection requiring intravenous antibiotics or device removal, deep vein thrombosis, pulmonary embolism, and pneumothorax or hemothorax.

During the first 24 hours after the procedure, 17 patients (2%) had major complications including 5 with cardiac perforations and 4 with pneumothorax. There were no deaths in this perioperative period. During the subsequent 6 months, 100 patients (14%) had major complications, most commonly a malfunction that required reopening the pocket, in 7%, followed by an unplanned lead addition or removal, in 4%.

Eight patients (1%) died. Overall, 109 patients (15%) had one or more major complications during the 6 months following the index intervention.

A reassuring finding was that the infection rate was low. Six patients (0.8%) had a major infection and another two (0.3%) had minor infections.

“All patients received intravenous antibiotics and appropriate skin prep,” Dr. Poole said.

Disclosures: The registry was sponsored by Biotronik, a company that markets cardiac pulse generators and leads, but it enrolled patients with any type of commercially available pacemaker or ICD.

Dr. Poole has received research grants from Biotronik, as well as honoraria from Boston Scientific, Medtronic, and St. Jude Medical.

Dr. Kadish has received grant support from St. Jude Medical and Baird. He also has consulted for and received honoraria from several companies, including Baird, Medtronic, Impulse Dynamics, Lifewatch, and Sanofi.

Two Factors Tied to Complications

Cardiac device type and procedure volume emerged from the REPLACE registry as the only variables significantly linked with complication rates.

In data collected from the first arm of the registry, limited to patients who had a generator replacement for an existing pacemaker or ICD but without a planned lead addition or revision, patients with an ICD were 60% more likely to have a major complication than were patients with a pacemaker, Dr. Theofanie Mela said at the annual scientific sessions of the American Heart Association.

In the same cohort, patients who underwent generator replacement at a center that did 250 or more procedures per year were 45% less likely to have any type of complication, compared with patients who were treated at centers that did fewer procedures each year, said Dr. Mela, director of the pacemaker laboratory at Massachusetts General Hospital in Boston.

Other variables examined that did not have a significant bearing on complication rates included age, gender, number and severity of comorbidities as measured by the Charlson Comorbidity Index, specialty of the physician performing the procedure (electrophysiologist compared with nonelectrophysiologist), and type of practice (academic center compared with private hospital).

The analysis used data from the first arm of REPLACE, in which 1,031 patients were enrolled at 68 U.S. centers (34 academic and 34 private) during July 2007–March 2008, and tallied the number of complications during 6 months' follow-up. The researchers reported a 4% major complication rate, a 7.4% minor complication rate, and an overall complication rate of 10.9% at the annual meeting of the Heart Rhythm Society in Boston last May.

Subsequent analysis examined potential determinants of the complication rate. Patients with a pacemaker had a major complication rate of 2.3%, compared with a rate of 5.8% in patients with an ICD (the registry included roughly equal numbers of patients with each device type). The 68 sites had a median annual procedure volume of 250. High-volume sites had an overall complication rate of 8.6%; low-volume centers had an overall rate of 14.9%.

Dr. Mela said that she has received honoraria from Boston Scientific, Medtronic, and St. Jude Medical.

ORLANDO — Patients who had their coronary calcium levels imaged by CT angiography had substantially better survival than did similar patients who underwent standard management, an observational study has shown.

The findings, which involved more than 4,000 patients followed for more than 6 years, could have implications for insurance reimbursement of CT angiography, Dr. Matthew J. Budoff said at the annual scientific sessions of the American Heart Association. He hypothesized that the mortality difference between patients who underwent CT imaging and those who did not may be explained by improved compliance with therapy among patients who were able to see the extent of their calcified coronary disease.

Although several payers including United Healthcare, Aetna, Medicare, and Medicaid currently reimburse for CT angiography, the national policy of Blue Cross/Blue Shield is not to cover these examinations. The Blues' stated policy is that they will not cover new diagnostic tests until their value in improving patient outcomes is proved, Dr. Budoff said. He believes the new data mean this standard has now been met, but he acknowledged that the study was observational and not a prospective, randomized trial. Nonetheless, the size and duration of the study, as well as the striking magnitude of beneficial effect, should be persuasive, said Dr. Budoff, program director of cardiology at the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center.

In his study, 2,538 symptomatic patients referred for assessment of possible coronary disease and evaluated by coronary CT had a 52% reduced risk of all-cause death during an average 6.7-year follow-up, compared with a similar group of 1,706 patients whose work-up did not include CT angiography.

“Increased awareness of coronary artery disease severity among people undergoing CT angiography may have contributed to their survival,” Dr. Budoff said. “Probable mechanisms include increased adherence to and use of antiatherosclerotic therapies, such as statins, angiotensin-converting enzyme inhibitors, and antiplatelet drugs” such as aspirin, he added.

Dr. Budoff shows his patients six images of their coronary arteries that depict the calcium deposits and stenoses. “I think that this is something that leads to compliance. It's very black and white. Patients can see their plaque and stenosis and know they need treatment,” he said in an interview.

The total of 4,244 symptomatic patients in the study had an average age of 58, and 62% did not have known coronary artery disease. The patients who underwent coronary CT and those who received standard care without coronary CT imaging were treated in the academic cardiology clinic at Harbor-UCLA. The two groups were matched by age, gender, the time when they were first seen, and their conventional cardiac risk factors.

All patients undergoing coronary CT had the examination covered by their insurance providers; however, the patients who did not undergo CT angiography may have been, as a group, somewhat poorer than those who had CT examinations, Dr. Budoff said.

During an average 80-month follow-up the all-cause mortality rate was 3% in patients who had CT examinations and 11% in those who did not, a statistically significant difference. Mortality rates began to diverge between the two groups after about 3 years, and then continued to diverge.

In a multivariate analysis that controlled for age, gender, and coronary risk factors, patients who had standard care had a fourfold higher risk of dying than did those who had CT angiography.

Disclosures: Dr. Budoff has served on the speakers bureau for GE, a company that markets CT equipment.

'Patients can see their plaque and stenosis and know they need treatment.'

Source DR. BUDOFF

Patients evaluated for coronary calcium levels and possible coronary disease using CT angiography had a 52% reduced risk of all-cause death during a mean of 6.7 years.

Source Images courtesy Dr. Matthew J. Budoff

ORLANDO — Patients who had their coronary calcium levels imaged by CT angiography had substantially better survival than did similar patients who underwent standard management, an observational study has shown.

The findings, which involved more than 4,000 patients followed for more than 6 years, could have implications for insurance reimbursement of CT angiography, Dr. Matthew J. Budoff said at the annual scientific sessions of the American Heart Association. He hypothesized that the mortality difference between patients who underwent CT imaging and those who did not may be explained by improved compliance with therapy among patients who were able to see the extent of their calcified coronary disease.

Although several payers including United Healthcare, Aetna, Medicare, and Medicaid currently reimburse for CT angiography, the national policy of Blue Cross/Blue Shield is not to cover these examinations. The Blues' stated policy is that they will not cover new diagnostic tests until their value in improving patient outcomes is proved, Dr. Budoff said. He believes the new data mean this standard has now been met, but he acknowledged that the study was observational and not a prospective, randomized trial. Nonetheless, the size and duration of the study, as well as the striking magnitude of beneficial effect, should be persuasive, said Dr. Budoff, program director of cardiology at the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center.

In his study, 2,538 symptomatic patients referred for assessment of possible coronary disease and evaluated by coronary CT had a 52% reduced risk of all-cause death during an average 6.7-year follow-up, compared with a similar group of 1,706 patients whose work-up did not include CT angiography.

“Increased awareness of coronary artery disease severity among people undergoing CT angiography may have contributed to their survival,” Dr. Budoff said. “Probable mechanisms include increased adherence to and use of antiatherosclerotic therapies, such as statins, angiotensin-converting enzyme inhibitors, and antiplatelet drugs” such as aspirin, he added.

Dr. Budoff shows his patients six images of their coronary arteries that depict the calcium deposits and stenoses. “I think that this is something that leads to compliance. It's very black and white. Patients can see their plaque and stenosis and know they need treatment,” he said in an interview.

The total of 4,244 symptomatic patients in the study had an average age of 58, and 62% did not have known coronary artery disease. The patients who underwent coronary CT and those who received standard care without coronary CT imaging were treated in the academic cardiology clinic at Harbor-UCLA. The two groups were matched by age, gender, the time when they were first seen, and their conventional cardiac risk factors.

All patients undergoing coronary CT had the examination covered by their insurance providers; however, the patients who did not undergo CT angiography may have been, as a group, somewhat poorer than those who had CT examinations, Dr. Budoff said.

During an average 80-month follow-up the all-cause mortality rate was 3% in patients who had CT examinations and 11% in those who did not, a statistically significant difference. Mortality rates began to diverge between the two groups after about 3 years, and then continued to diverge.

In a multivariate analysis that controlled for age, gender, and coronary risk factors, patients who had standard care had a fourfold higher risk of dying than did those who had CT angiography.

Disclosures: Dr. Budoff has served on the speakers bureau for GE, a company that markets CT equipment.

'Patients can see their plaque and stenosis and know they need treatment.'

Source DR. BUDOFF

Patients evaluated for coronary calcium levels and possible coronary disease using CT angiography had a 52% reduced risk of all-cause death during a mean of 6.7 years.

Source Images courtesy Dr. Matthew J. Budoff

ORLANDO — Patients who had their coronary calcium levels imaged by CT angiography had substantially better survival than did similar patients who underwent standard management, an observational study has shown.

The findings, which involved more than 4,000 patients followed for more than 6 years, could have implications for insurance reimbursement of CT angiography, Dr. Matthew J. Budoff said at the annual scientific sessions of the American Heart Association. He hypothesized that the mortality difference between patients who underwent CT imaging and those who did not may be explained by improved compliance with therapy among patients who were able to see the extent of their calcified coronary disease.

Although several payers including United Healthcare, Aetna, Medicare, and Medicaid currently reimburse for CT angiography, the national policy of Blue Cross/Blue Shield is not to cover these examinations. The Blues' stated policy is that they will not cover new diagnostic tests until their value in improving patient outcomes is proved, Dr. Budoff said. He believes the new data mean this standard has now been met, but he acknowledged that the study was observational and not a prospective, randomized trial. Nonetheless, the size and duration of the study, as well as the striking magnitude of beneficial effect, should be persuasive, said Dr. Budoff, program director of cardiology at the Los Angeles Biomedical Research Institute at Harbor–UCLA Medical Center.

In his study, 2,538 symptomatic patients referred for assessment of possible coronary disease and evaluated by coronary CT had a 52% reduced risk of all-cause death during an average 6.7-year follow-up, compared with a similar group of 1,706 patients whose work-up did not include CT angiography.

“Increased awareness of coronary artery disease severity among people undergoing CT angiography may have contributed to their survival,” Dr. Budoff said. “Probable mechanisms include increased adherence to and use of antiatherosclerotic therapies, such as statins, angiotensin-converting enzyme inhibitors, and antiplatelet drugs” such as aspirin, he added.

Dr. Budoff shows his patients six images of their coronary arteries that depict the calcium deposits and stenoses. “I think that this is something that leads to compliance. It's very black and white. Patients can see their plaque and stenosis and know they need treatment,” he said in an interview.

The total of 4,244 symptomatic patients in the study had an average age of 58, and 62% did not have known coronary artery disease. The patients who underwent coronary CT and those who received standard care without coronary CT imaging were treated in the academic cardiology clinic at Harbor-UCLA. The two groups were matched by age, gender, the time when they were first seen, and their conventional cardiac risk factors.

All patients undergoing coronary CT had the examination covered by their insurance providers; however, the patients who did not undergo CT angiography may have been, as a group, somewhat poorer than those who had CT examinations, Dr. Budoff said.

During an average 80-month follow-up the all-cause mortality rate was 3% in patients who had CT examinations and 11% in those who did not, a statistically significant difference. Mortality rates began to diverge between the two groups after about 3 years, and then continued to diverge.

In a multivariate analysis that controlled for age, gender, and coronary risk factors, patients who had standard care had a fourfold higher risk of dying than did those who had CT angiography.

Disclosures: Dr. Budoff has served on the speakers bureau for GE, a company that markets CT equipment.

'Patients can see their plaque and stenosis and know they need treatment.'

Source DR. BUDOFF

Patients evaluated for coronary calcium levels and possible coronary disease using CT angiography had a 52% reduced risk of all-cause death during a mean of 6.7 years.

Source Images courtesy Dr. Matthew J. Budoff