Denise Napoli

Up to 37% of resistant office hypertension is actually white-coat hypertension, according to an analysis of ambulatory blood pressure monitoring data from more than 8,000 patients published online March 28 in Hypertension.

Meanwhile, the remaining 63% who are truly resistant have a starkly worse clinical profile than do their white-coat counterparts, including significantly higher likelihoods of smoking, and having diabetes, left ventricular hypertrophy, microalbuminuria, and cardiovascular disease.

Dr. Alejandro de la Sierra of the University of Barcelona, and colleagues, looked at 2009 data from the Spanish Ambulatory Blood Pressure Monitoring Registry (ABPM), which included 68,045 patients with good quality office BP data, ambulatory BP data, and information about prescribed antihypertensives, including at least one diuretic.

Ambulatory BP measurements were acquired using an automated, noninvasive oscillometric device placed by a physician, and which registered BP at 20-minute intervals over a 24-hour period.

"Valid registries had to fulfill a series of pre-established criteria, including greater than or equal to 80% of systolic BP (SBP) and diastolic BP (DBP) successful recordings during the daytime and nighttime periods, 24-hour duration, and at least one BP measurement per hour," wrote the authors.

Patients returned the following day to their doctors for removal of the device.

Overall, 12% of participants in the registry (8,295 patients; 51% male, mean age 64 years) met Dr. de la Sierra’s criteria for resistant hypertension: office BP greater than or equal to 140 mm Hg systolic and/or 90 mm Hg diastolic while being treated with three or more antihypertensive agents at "appropriate" doses.

ABPM patients were classified in two groups: 5,182 patients (62.5%) had ambulatory 24-hour BP values greater than or equal to 130 and/or 80 mm Hg and were diagnosed as true RH, and 3,113 patients (37.5%) showed 24-hour BP values below this limit and were considered as having white-coat RH, wrote the authors (Hypertension 2011 March 28 [doi: 10.1161/HYPERTENSIONAHA.110.168948]).

White-coat RH patients were slightly but significantly older (65 versus 64 years), and more likely to be female (54%).

Truly resistant patients, however, were more likely to be smokers (15% versus 10%), to be diabetic (35% versus 28%), and to have cardiovascular disease (19% versus 16%), compared with the white-coat RH patients.

Moreover, 19% of the true RH patients had left ventricular hypertrophy, as seen on electrocardiogram, versus 14% of white-coat patients.

They also had higher creatinine levels than did their white-coat counterparts (75 versus 72 micromol/L), higher urinary albumin excretion (11 versus 7 mg/g), and a higher percentage of patients with a urinary albumin excretion greater than 30 mg/g (30% versus 20%).

Circadian BP patterns also showed slight differences between groups, with a higher proportion of risers – who have an increase in BP during nighttime – among the true RH cohort, based on either systolic (22% versus 18%) or diastolic (12% versus 10%) measurements.

Body mass index and total cholesterol did not vary significantly between groups.

According to the authors, the study represents the first time that the prevalence of resistant hypertension was assessed in such a large cohort of patients.

However, the researchers pointed to one major weakness of the study: the inability to confirm that patients prescribed antihypertensive drugs were adherent to their medication regimen, "thus possibly overestimating the true prevalence of RH."

And despite the findings of significant differences in clinical characteristics between groups, "their discriminating value in clinical practice is probably low," cautioned the authors.

The authors disclosed that the Spanish ABPM Registry was initiated and is maintained by Lacer Laboratories, which makes valsartan. The authors also disclosed having attended meetings funded by Lacer.

Up to 37% of resistant office hypertension is actually white-coat hypertension, according to an analysis of ambulatory blood pressure monitoring data from more than 8,000 patients published online March 28 in Hypertension.

Meanwhile, the remaining 63% who are truly resistant have a starkly worse clinical profile than do their white-coat counterparts, including significantly higher likelihoods of smoking, and having diabetes, left ventricular hypertrophy, microalbuminuria, and cardiovascular disease.

Dr. Alejandro de la Sierra of the University of Barcelona, and colleagues, looked at 2009 data from the Spanish Ambulatory Blood Pressure Monitoring Registry (ABPM), which included 68,045 patients with good quality office BP data, ambulatory BP data, and information about prescribed antihypertensives, including at least one diuretic.

Ambulatory BP measurements were acquired using an automated, noninvasive oscillometric device placed by a physician, and which registered BP at 20-minute intervals over a 24-hour period.

"Valid registries had to fulfill a series of pre-established criteria, including greater than or equal to 80% of systolic BP (SBP) and diastolic BP (DBP) successful recordings during the daytime and nighttime periods, 24-hour duration, and at least one BP measurement per hour," wrote the authors.

Patients returned the following day to their doctors for removal of the device.

Overall, 12% of participants in the registry (8,295 patients; 51% male, mean age 64 years) met Dr. de la Sierra’s criteria for resistant hypertension: office BP greater than or equal to 140 mm Hg systolic and/or 90 mm Hg diastolic while being treated with three or more antihypertensive agents at "appropriate" doses.

ABPM patients were classified in two groups: 5,182 patients (62.5%) had ambulatory 24-hour BP values greater than or equal to 130 and/or 80 mm Hg and were diagnosed as true RH, and 3,113 patients (37.5%) showed 24-hour BP values below this limit and were considered as having white-coat RH, wrote the authors (Hypertension 2011 March 28 [doi: 10.1161/HYPERTENSIONAHA.110.168948]).

White-coat RH patients were slightly but significantly older (65 versus 64 years), and more likely to be female (54%).

Truly resistant patients, however, were more likely to be smokers (15% versus 10%), to be diabetic (35% versus 28%), and to have cardiovascular disease (19% versus 16%), compared with the white-coat RH patients.

Moreover, 19% of the true RH patients had left ventricular hypertrophy, as seen on electrocardiogram, versus 14% of white-coat patients.

They also had higher creatinine levels than did their white-coat counterparts (75 versus 72 micromol/L), higher urinary albumin excretion (11 versus 7 mg/g), and a higher percentage of patients with a urinary albumin excretion greater than 30 mg/g (30% versus 20%).

Circadian BP patterns also showed slight differences between groups, with a higher proportion of risers – who have an increase in BP during nighttime – among the true RH cohort, based on either systolic (22% versus 18%) or diastolic (12% versus 10%) measurements.

Body mass index and total cholesterol did not vary significantly between groups.

According to the authors, the study represents the first time that the prevalence of resistant hypertension was assessed in such a large cohort of patients.

However, the researchers pointed to one major weakness of the study: the inability to confirm that patients prescribed antihypertensive drugs were adherent to their medication regimen, "thus possibly overestimating the true prevalence of RH."

And despite the findings of significant differences in clinical characteristics between groups, "their discriminating value in clinical practice is probably low," cautioned the authors.

The authors disclosed that the Spanish ABPM Registry was initiated and is maintained by Lacer Laboratories, which makes valsartan. The authors also disclosed having attended meetings funded by Lacer.

Up to 37% of resistant office hypertension is actually white-coat hypertension, according to an analysis of ambulatory blood pressure monitoring data from more than 8,000 patients published online March 28 in Hypertension.

Meanwhile, the remaining 63% who are truly resistant have a starkly worse clinical profile than do their white-coat counterparts, including significantly higher likelihoods of smoking, and having diabetes, left ventricular hypertrophy, microalbuminuria, and cardiovascular disease.

Dr. Alejandro de la Sierra of the University of Barcelona, and colleagues, looked at 2009 data from the Spanish Ambulatory Blood Pressure Monitoring Registry (ABPM), which included 68,045 patients with good quality office BP data, ambulatory BP data, and information about prescribed antihypertensives, including at least one diuretic.

Ambulatory BP measurements were acquired using an automated, noninvasive oscillometric device placed by a physician, and which registered BP at 20-minute intervals over a 24-hour period.

"Valid registries had to fulfill a series of pre-established criteria, including greater than or equal to 80% of systolic BP (SBP) and diastolic BP (DBP) successful recordings during the daytime and nighttime periods, 24-hour duration, and at least one BP measurement per hour," wrote the authors.

Patients returned the following day to their doctors for removal of the device.

Overall, 12% of participants in the registry (8,295 patients; 51% male, mean age 64 years) met Dr. de la Sierra’s criteria for resistant hypertension: office BP greater than or equal to 140 mm Hg systolic and/or 90 mm Hg diastolic while being treated with three or more antihypertensive agents at "appropriate" doses.

ABPM patients were classified in two groups: 5,182 patients (62.5%) had ambulatory 24-hour BP values greater than or equal to 130 and/or 80 mm Hg and were diagnosed as true RH, and 3,113 patients (37.5%) showed 24-hour BP values below this limit and were considered as having white-coat RH, wrote the authors (Hypertension 2011 March 28 [doi: 10.1161/HYPERTENSIONAHA.110.168948]).

White-coat RH patients were slightly but significantly older (65 versus 64 years), and more likely to be female (54%).

Truly resistant patients, however, were more likely to be smokers (15% versus 10%), to be diabetic (35% versus 28%), and to have cardiovascular disease (19% versus 16%), compared with the white-coat RH patients.

Moreover, 19% of the true RH patients had left ventricular hypertrophy, as seen on electrocardiogram, versus 14% of white-coat patients.

They also had higher creatinine levels than did their white-coat counterparts (75 versus 72 micromol/L), higher urinary albumin excretion (11 versus 7 mg/g), and a higher percentage of patients with a urinary albumin excretion greater than 30 mg/g (30% versus 20%).

Circadian BP patterns also showed slight differences between groups, with a higher proportion of risers – who have an increase in BP during nighttime – among the true RH cohort, based on either systolic (22% versus 18%) or diastolic (12% versus 10%) measurements.

Body mass index and total cholesterol did not vary significantly between groups.

According to the authors, the study represents the first time that the prevalence of resistant hypertension was assessed in such a large cohort of patients.

However, the researchers pointed to one major weakness of the study: the inability to confirm that patients prescribed antihypertensive drugs were adherent to their medication regimen, "thus possibly overestimating the true prevalence of RH."

And despite the findings of significant differences in clinical characteristics between groups, "their discriminating value in clinical practice is probably low," cautioned the authors.

The authors disclosed that the Spanish ABPM Registry was initiated and is maintained by Lacer Laboratories, which makes valsartan. The authors also disclosed having attended meetings funded by Lacer.

More than half of atrial fibrillation is likely attributable to modifiable risk factors, including high blood pressure, obesity, and smoking, according to an analysis of the Atherosclerosis Risk in Communities Study.

The finding, which was based on a cohort of middle-aged American adults from communities in the ARIC study, highlights the need for primary prevention among this population.

"Moreover, because improvement in these behaviors would also favorably affect other AF risk factors, such as diabetes mellitus and impaired glucose tolerance, the reduction in the incidence of AF would be even greater than expected through BP lowering alone," wrote Rachel R. Huxley, D.Phil., in the journal Circulation, published online March 28.

Dr. Huxley, an epidemiologist at the University of Minnesota, Minneapolis, and colleagues looked at nearly 20 years of follow-up from the ARIC survey, a prospective cohort study of atherosclerotic diseases in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis.

At baseline in 1987-1989, it included 15,792 men and women aged 45-64 years, selected by area probability sampling.

All patients underwent three triennial visits, and in the present study, AF cases were counted as those diagnosed at an incident study visit (not baseline assessment) by 12-lead electrocardiogram, or during follow-up with an ICD code for AF in a hospital discharge, or when AF was listed as any cause of death on a death certificate.

Those with baseline AF on electrocardiogram or history of AF were excluded, as were those with missing data.

The researchers of the current study characterized participants into one of three risk profiles. An "optimal" group had no history of cardiac disease, systolic BP less than 120 mm Hg and diastolic less than 80 mm Hg without antihypertensive drugs; a body mass index less than 25 kg/m²; fasting serum glucose less than 100 mg/dL without antidiabetic drugs or history of diabetes; and no history of smoking.

"Borderline" participants had any of the following criteria: systolic BP 120-139 and/or diastolic BP 80-89 mm Hg without antihypertensives; BMI 25-30; fasting glucose 100-125 mg/dL without use of antidiabetics and no history of diabetes; and former smoker status.

Finally, participants regarded as having "elevated" risk profiles had any of the following: history of cardiac disease (heart failure or coronary heart disease); systolic BP at least 140 mm Hg, diastolic BP at least 90 mm Hg, or use of antihypertensives; BMI greater than 30; fasting serum glucose greater than or equal to 126, or use of antidiabetic drugs; history of diabetes; or current smoker status.

Among the 14,598 subjects (55% women; 25% black; mean age, 54.2 years) over a mean 17.1 years of follow-up who were included in the current analysis, there were 1,520 cases of incident AF.

Compared with those with no risk factors, the age-adjusted incidence rates were three times higher in those with one or more elevated risk factors (2.19 vs. 6.59 per 1,000 person-years, respectively), wrote the authors (relative hazard for optimal patient group, 0.33).

For the borderline group, the incidence rate was 3.68, for a relative hazard of 0.50, compared with participants who had one or more elevated risk factors.

"Overall, the [population-attributable fraction] estimates indicated that having [one or more] elevated risk factor levels could explain 50% ... of AF events," added the authors (Circulation 2011:10.1161/CIRCULATIONAHA.110.009035).

Adding elevated and borderline levels together, that number jumped to 57%.

The authors also sought to determine which of the relevant risk factors played the biggest role in incident AF.

Elevated blood pressure, experienced by 39% of the entire cohort, accounted for roughly one in five cases of AF (21.6%). "This rose to 24.5% if borderline levels of BP, which affected another 22.7% of the cohort, were also included," wrote the authors.

"Obesity and overweight explained 17.9% of all AF cases, and diabetes mellitus and impaired glucose tolerance combined accounted for the smallest fraction [3.9%] of the AF burden in this cohort," they added.

According to the authors, this study is the second to look at the relationship between modifiable risk factors and atrial fibrillation. A 1994 analysis, using data from the Framingham cohort, found that smoking, diabetes, hypertension, and prevalent coronary heart disease combined explained 44% of the AF burden in men and 58% in women, a conclusion that Dr. Huxley called "broadly comparable" to that of the current study.

They added that the study was limited by its inability to differentiate subtypes of AF, as well as by its reliance on hospital discharge codes to ascertain more than 98% of AF cases recorded in this cohort. However, if anything, this fact likely led to the "underascertainment of cases that perhaps were not severe enough to warrant hospitalization."

The study was funded by the National Heart, Lung, and Blood Institute as well as the American Heart Association. The investigators reported having no other disclosures related to this study.

More than half of atrial fibrillation is likely attributable to modifiable risk factors, including high blood pressure, obesity, and smoking, according to an analysis of the Atherosclerosis Risk in Communities Study.

The finding, which was based on a cohort of middle-aged American adults from communities in the ARIC study, highlights the need for primary prevention among this population.

"Moreover, because improvement in these behaviors would also favorably affect other AF risk factors, such as diabetes mellitus and impaired glucose tolerance, the reduction in the incidence of AF would be even greater than expected through BP lowering alone," wrote Rachel R. Huxley, D.Phil., in the journal Circulation, published online March 28.

Dr. Huxley, an epidemiologist at the University of Minnesota, Minneapolis, and colleagues looked at nearly 20 years of follow-up from the ARIC survey, a prospective cohort study of atherosclerotic diseases in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis.

At baseline in 1987-1989, it included 15,792 men and women aged 45-64 years, selected by area probability sampling.

All patients underwent three triennial visits, and in the present study, AF cases were counted as those diagnosed at an incident study visit (not baseline assessment) by 12-lead electrocardiogram, or during follow-up with an ICD code for AF in a hospital discharge, or when AF was listed as any cause of death on a death certificate.

Those with baseline AF on electrocardiogram or history of AF were excluded, as were those with missing data.

The researchers of the current study characterized participants into one of three risk profiles. An "optimal" group had no history of cardiac disease, systolic BP less than 120 mm Hg and diastolic less than 80 mm Hg without antihypertensive drugs; a body mass index less than 25 kg/m²; fasting serum glucose less than 100 mg/dL without antidiabetic drugs or history of diabetes; and no history of smoking.

"Borderline" participants had any of the following criteria: systolic BP 120-139 and/or diastolic BP 80-89 mm Hg without antihypertensives; BMI 25-30; fasting glucose 100-125 mg/dL without use of antidiabetics and no history of diabetes; and former smoker status.

Finally, participants regarded as having "elevated" risk profiles had any of the following: history of cardiac disease (heart failure or coronary heart disease); systolic BP at least 140 mm Hg, diastolic BP at least 90 mm Hg, or use of antihypertensives; BMI greater than 30; fasting serum glucose greater than or equal to 126, or use of antidiabetic drugs; history of diabetes; or current smoker status.

Among the 14,598 subjects (55% women; 25% black; mean age, 54.2 years) over a mean 17.1 years of follow-up who were included in the current analysis, there were 1,520 cases of incident AF.

Compared with those with no risk factors, the age-adjusted incidence rates were three times higher in those with one or more elevated risk factors (2.19 vs. 6.59 per 1,000 person-years, respectively), wrote the authors (relative hazard for optimal patient group, 0.33).

For the borderline group, the incidence rate was 3.68, for a relative hazard of 0.50, compared with participants who had one or more elevated risk factors.

"Overall, the [population-attributable fraction] estimates indicated that having [one or more] elevated risk factor levels could explain 50% ... of AF events," added the authors (Circulation 2011:10.1161/CIRCULATIONAHA.110.009035).

Adding elevated and borderline levels together, that number jumped to 57%.

The authors also sought to determine which of the relevant risk factors played the biggest role in incident AF.

Elevated blood pressure, experienced by 39% of the entire cohort, accounted for roughly one in five cases of AF (21.6%). "This rose to 24.5% if borderline levels of BP, which affected another 22.7% of the cohort, were also included," wrote the authors.

"Obesity and overweight explained 17.9% of all AF cases, and diabetes mellitus and impaired glucose tolerance combined accounted for the smallest fraction [3.9%] of the AF burden in this cohort," they added.

According to the authors, this study is the second to look at the relationship between modifiable risk factors and atrial fibrillation. A 1994 analysis, using data from the Framingham cohort, found that smoking, diabetes, hypertension, and prevalent coronary heart disease combined explained 44% of the AF burden in men and 58% in women, a conclusion that Dr. Huxley called "broadly comparable" to that of the current study.

They added that the study was limited by its inability to differentiate subtypes of AF, as well as by its reliance on hospital discharge codes to ascertain more than 98% of AF cases recorded in this cohort. However, if anything, this fact likely led to the "underascertainment of cases that perhaps were not severe enough to warrant hospitalization."

The study was funded by the National Heart, Lung, and Blood Institute as well as the American Heart Association. The investigators reported having no other disclosures related to this study.

More than half of atrial fibrillation is likely attributable to modifiable risk factors, including high blood pressure, obesity, and smoking, according to an analysis of the Atherosclerosis Risk in Communities Study.

The finding, which was based on a cohort of middle-aged American adults from communities in the ARIC study, highlights the need for primary prevention among this population.

"Moreover, because improvement in these behaviors would also favorably affect other AF risk factors, such as diabetes mellitus and impaired glucose tolerance, the reduction in the incidence of AF would be even greater than expected through BP lowering alone," wrote Rachel R. Huxley, D.Phil., in the journal Circulation, published online March 28.

Dr. Huxley, an epidemiologist at the University of Minnesota, Minneapolis, and colleagues looked at nearly 20 years of follow-up from the ARIC survey, a prospective cohort study of atherosclerotic diseases in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis.

At baseline in 1987-1989, it included 15,792 men and women aged 45-64 years, selected by area probability sampling.

All patients underwent three triennial visits, and in the present study, AF cases were counted as those diagnosed at an incident study visit (not baseline assessment) by 12-lead electrocardiogram, or during follow-up with an ICD code for AF in a hospital discharge, or when AF was listed as any cause of death on a death certificate.

Those with baseline AF on electrocardiogram or history of AF were excluded, as were those with missing data.

The researchers of the current study characterized participants into one of three risk profiles. An "optimal" group had no history of cardiac disease, systolic BP less than 120 mm Hg and diastolic less than 80 mm Hg without antihypertensive drugs; a body mass index less than 25 kg/m²; fasting serum glucose less than 100 mg/dL without antidiabetic drugs or history of diabetes; and no history of smoking.

"Borderline" participants had any of the following criteria: systolic BP 120-139 and/or diastolic BP 80-89 mm Hg without antihypertensives; BMI 25-30; fasting glucose 100-125 mg/dL without use of antidiabetics and no history of diabetes; and former smoker status.

Finally, participants regarded as having "elevated" risk profiles had any of the following: history of cardiac disease (heart failure or coronary heart disease); systolic BP at least 140 mm Hg, diastolic BP at least 90 mm Hg, or use of antihypertensives; BMI greater than 30; fasting serum glucose greater than or equal to 126, or use of antidiabetic drugs; history of diabetes; or current smoker status.

Among the 14,598 subjects (55% women; 25% black; mean age, 54.2 years) over a mean 17.1 years of follow-up who were included in the current analysis, there were 1,520 cases of incident AF.

Compared with those with no risk factors, the age-adjusted incidence rates were three times higher in those with one or more elevated risk factors (2.19 vs. 6.59 per 1,000 person-years, respectively), wrote the authors (relative hazard for optimal patient group, 0.33).

For the borderline group, the incidence rate was 3.68, for a relative hazard of 0.50, compared with participants who had one or more elevated risk factors.

"Overall, the [population-attributable fraction] estimates indicated that having [one or more] elevated risk factor levels could explain 50% ... of AF events," added the authors (Circulation 2011:10.1161/CIRCULATIONAHA.110.009035).

Adding elevated and borderline levels together, that number jumped to 57%.

The authors also sought to determine which of the relevant risk factors played the biggest role in incident AF.

Elevated blood pressure, experienced by 39% of the entire cohort, accounted for roughly one in five cases of AF (21.6%). "This rose to 24.5% if borderline levels of BP, which affected another 22.7% of the cohort, were also included," wrote the authors.

"Obesity and overweight explained 17.9% of all AF cases, and diabetes mellitus and impaired glucose tolerance combined accounted for the smallest fraction [3.9%] of the AF burden in this cohort," they added.

According to the authors, this study is the second to look at the relationship between modifiable risk factors and atrial fibrillation. A 1994 analysis, using data from the Framingham cohort, found that smoking, diabetes, hypertension, and prevalent coronary heart disease combined explained 44% of the AF burden in men and 58% in women, a conclusion that Dr. Huxley called "broadly comparable" to that of the current study.

They added that the study was limited by its inability to differentiate subtypes of AF, as well as by its reliance on hospital discharge codes to ascertain more than 98% of AF cases recorded in this cohort. However, if anything, this fact likely led to the "underascertainment of cases that perhaps were not severe enough to warrant hospitalization."

The study was funded by the National Heart, Lung, and Blood Institute as well as the American Heart Association. The investigators reported having no other disclosures related to this study.

More than half of atrial fibrillation is likely attributable to modifiable risk factors, including high blood pressure, obesity, and smoking, according to an analysis of the Atherosclerosis Risk in Communities Study.

The finding, which was based on a cohort of middle-aged American adults from communities in the ARIC study, highlights the need for primary prevention among this population.

"Moreover, because improvement in these behaviors would also favorably affect other AF risk factors, such as diabetes mellitus and impaired glucose tolerance, the reduction in the incidence of AF would be even greater than expected through BP lowering alone," wrote Rachel R. Huxley, D.Phil., in the journal Circulation, published online March 28.

Dr. Huxley, an epidemiologist at the University of Minnesota, Minneapolis, and colleagues looked at nearly 20 years of follow-up from the ARIC survey, a prospective cohort study of atherosclerotic diseases in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis.

At baseline in 1987-1989, it included 15,792 men and women aged 45-64 years, selected by area probability sampling.

All patients underwent three triennial visits, and in the present study, AF cases were counted as those diagnosed at an incident study visit (not baseline assessment) by 12-lead electrocardiogram, or during follow-up with an ICD code for AF in a hospital discharge, or when AF was listed as any cause of death on a death certificate.

Those with baseline AF on electrocardiogram or history of AF were excluded, as were those with missing data.

The researchers of the current study characterized participants into one of three risk profiles. An "optimal" group had no history of cardiac disease, systolic BP less than 120 mm Hg and diastolic less than 80 mm Hg without antihypertensive drugs; a body mass index less than 25 kg/m²; fasting serum glucose less than 100 mg/dL without antidiabetic drugs or history of diabetes; and no history of smoking.

"Borderline" participants had any of the following criteria: systolic BP 120-139 and/or diastolic BP 80-89 mm Hg without antihypertensives; BMI 25-30; fasting glucose 100-125 mg/dL without use of antidiabetics and no history of diabetes; and former smoker status.

Finally, participants regarded as having "elevated" risk profiles had any of the following: history of cardiac disease (heart failure or coronary heart disease); systolic BP at least 140 mm Hg, diastolic BP at least 90 mm Hg, or use of antihypertensives; BMI greater than 30; fasting serum glucose greater than or equal to 126, or use of antidiabetic drugs; history of diabetes; or current smoker status.

Among the 14,598 subjects (55% women; 25% black; mean age, 54.2 years) over a mean 17.1 years of follow-up who were included in the current analysis, there were 1,520 cases of incident AF.

Compared with those with no risk factors, the age-adjusted incidence rates were three times higher in those with one or more elevated risk factors (2.19 vs. 6.59 per 1,000 person-years, respectively), wrote the authors (relative hazard for optimal patient group, 0.33).

For the borderline group, the incidence rate was 3.68, for a relative hazard of 0.50, compared with participants who had one or more elevated risk factors.

"Overall, the [population-attributable fraction] estimates indicated that having [one or more] elevated risk factor levels could explain 50% ... of AF events," added the authors (Circulation 2011:10.1161/CIRCULATIONAHA.110.009035).

Adding elevated and borderline levels together, that number jumped to 57%.

The authors also sought to determine which of the relevant risk factors played the biggest role in incident AF.

Elevated blood pressure, experienced by 39% of the entire cohort, accounted for roughly one in five cases of AF (21.6%). "This rose to 24.5% if borderline levels of BP, which affected another 22.7% of the cohort, were also included," wrote the authors.

"Obesity and overweight explained 17.9% of all AF cases, and diabetes mellitus and impaired glucose tolerance combined accounted for the smallest fraction [3.9%] of the AF burden in this cohort," they added.

According to the authors, this study is the second to look at the relationship between modifiable risk factors and atrial fibrillation. A 1994 analysis, using data from the Framingham cohort, found that smoking, diabetes, hypertension, and prevalent coronary heart disease combined explained 44% of the AF burden in men and 58% in women, a conclusion that Dr. Huxley called "broadly comparable" to that of the current study.

They added that the study was limited by its inability to differentiate subtypes of AF, as well as by its reliance on hospital discharge codes to ascertain more than 98% of AF cases recorded in this cohort. However, if anything, this fact likely led to the "underascertainment of cases that perhaps were not severe enough to warrant hospitalization."

The study was funded by the National Heart, Lung, and Blood Institute as well as the American Heart Association. The investigators reported having no other disclosures related to this study.

More than half of atrial fibrillation is likely attributable to modifiable risk factors, including high blood pressure, obesity, and smoking, according to an analysis of the Atherosclerosis Risk in Communities Study.

The finding, which was based on a cohort of middle-aged American adults from communities in the ARIC study, highlights the need for primary prevention among this population.

"Moreover, because improvement in these behaviors would also favorably affect other AF risk factors, such as diabetes mellitus and impaired glucose tolerance, the reduction in the incidence of AF would be even greater than expected through BP lowering alone," wrote Rachel R. Huxley, D.Phil., in the journal Circulation, published online March 28.

Dr. Huxley, an epidemiologist at the University of Minnesota, Minneapolis, and colleagues looked at nearly 20 years of follow-up from the ARIC survey, a prospective cohort study of atherosclerotic diseases in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis.

At baseline in 1987-1989, it included 15,792 men and women aged 45-64 years, selected by area probability sampling.

All patients underwent three triennial visits, and in the present study, AF cases were counted as those diagnosed at an incident study visit (not baseline assessment) by 12-lead electrocardiogram, or during follow-up with an ICD code for AF in a hospital discharge, or when AF was listed as any cause of death on a death certificate.

Those with baseline AF on electrocardiogram or history of AF were excluded, as were those with missing data.

The researchers of the current study characterized participants into one of three risk profiles. An "optimal" group had no history of cardiac disease, systolic BP less than 120 mm Hg and diastolic less than 80 mm Hg without antihypertensive drugs; a body mass index less than 25 kg/m²; fasting serum glucose less than 100 mg/dL without antidiabetic drugs or history of diabetes; and no history of smoking.

"Borderline" participants had any of the following criteria: systolic BP 120-139 and/or diastolic BP 80-89 mm Hg without antihypertensives; BMI 25-30; fasting glucose 100-125 mg/dL without use of antidiabetics and no history of diabetes; and former smoker status.

Finally, participants regarded as having "elevated" risk profiles had any of the following: history of cardiac disease (heart failure or coronary heart disease); systolic BP at least 140 mm Hg, diastolic BP at least 90 mm Hg, or use of antihypertensives; BMI greater than 30; fasting serum glucose greater than or equal to 126, or use of antidiabetic drugs; history of diabetes; or current smoker status.

Among the 14,598 subjects (55% women; 25% black; mean age, 54.2 years) over a mean 17.1 years of follow-up who were included in the current analysis, there were 1,520 cases of incident AF.

Compared with those with no risk factors, the age-adjusted incidence rates were three times higher in those with one or more elevated risk factors (2.19 vs. 6.59 per 1,000 person-years, respectively), wrote the authors (relative hazard for optimal patient group, 0.33).

For the borderline group, the incidence rate was 3.68, for a relative hazard of 0.50, compared with participants who had one or more elevated risk factors.

"Overall, the [population-attributable fraction] estimates indicated that having [one or more] elevated risk factor levels could explain 50% ... of AF events," added the authors (Circulation 2011:10.1161/CIRCULATIONAHA.110.009035).

Adding elevated and borderline levels together, that number jumped to 57%.

The authors also sought to determine which of the relevant risk factors played the biggest role in incident AF.

Elevated blood pressure, experienced by 39% of the entire cohort, accounted for roughly one in five cases of AF (21.6%). "This rose to 24.5% if borderline levels of BP, which affected another 22.7% of the cohort, were also included," wrote the authors.

"Obesity and overweight explained 17.9% of all AF cases, and diabetes mellitus and impaired glucose tolerance combined accounted for the smallest fraction [3.9%] of the AF burden in this cohort," they added.

According to the authors, this study is the second to look at the relationship between modifiable risk factors and atrial fibrillation. A 1994 analysis, using data from the Framingham cohort, found that smoking, diabetes, hypertension, and prevalent coronary heart disease combined explained 44% of the AF burden in men and 58% in women, a conclusion that Dr. Huxley called "broadly comparable" to that of the current study.

They added that the study was limited by its inability to differentiate subtypes of AF, as well as by its reliance on hospital discharge codes to ascertain more than 98% of AF cases recorded in this cohort. However, if anything, this fact likely led to the "underascertainment of cases that perhaps were not severe enough to warrant hospitalization."

The study was funded by the National Heart, Lung, and Blood Institute as well as the American Heart Association. The investigators reported having no other disclosures related to this study.

More than half of atrial fibrillation is likely attributable to modifiable risk factors, including high blood pressure, obesity, and smoking, according to an analysis of the Atherosclerosis Risk in Communities Study.

The finding, which was based on a cohort of middle-aged American adults from communities in the ARIC study, highlights the need for primary prevention among this population.

"Moreover, because improvement in these behaviors would also favorably affect other AF risk factors, such as diabetes mellitus and impaired glucose tolerance, the reduction in the incidence of AF would be even greater than expected through BP lowering alone," wrote Rachel R. Huxley, D.Phil., in the journal Circulation, published online March 28.

Dr. Huxley, an epidemiologist at the University of Minnesota, Minneapolis, and colleagues looked at nearly 20 years of follow-up from the ARIC survey, a prospective cohort study of atherosclerotic diseases in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis.

At baseline in 1987-1989, it included 15,792 men and women aged 45-64 years, selected by area probability sampling.

All patients underwent three triennial visits, and in the present study, AF cases were counted as those diagnosed at an incident study visit (not baseline assessment) by 12-lead electrocardiogram, or during follow-up with an ICD code for AF in a hospital discharge, or when AF was listed as any cause of death on a death certificate.

Those with baseline AF on electrocardiogram or history of AF were excluded, as were those with missing data.

The researchers of the current study characterized participants into one of three risk profiles. An "optimal" group had no history of cardiac disease, systolic BP less than 120 mm Hg and diastolic less than 80 mm Hg without antihypertensive drugs; a body mass index less than 25 kg/m²; fasting serum glucose less than 100 mg/dL without antidiabetic drugs or history of diabetes; and no history of smoking.

"Borderline" participants had any of the following criteria: systolic BP 120-139 and/or diastolic BP 80-89 mm Hg without antihypertensives; BMI 25-30; fasting glucose 100-125 mg/dL without use of antidiabetics and no history of diabetes; and former smoker status.

Finally, participants regarded as having "elevated" risk profiles had any of the following: history of cardiac disease (heart failure or coronary heart disease); systolic BP at least 140 mm Hg, diastolic BP at least 90 mm Hg, or use of antihypertensives; BMI greater than 30; fasting serum glucose greater than or equal to 126, or use of antidiabetic drugs; history of diabetes; or current smoker status.

Among the 14,598 subjects (55% women; 25% black; mean age, 54.2 years) over a mean 17.1 years of follow-up who were included in the current analysis, there were 1,520 cases of incident AF.

Compared with those with no risk factors, the age-adjusted incidence rates were three times higher in those with one or more elevated risk factors (2.19 vs. 6.59 per 1,000 person-years, respectively), wrote the authors (relative hazard for optimal patient group, 0.33).

For the borderline group, the incidence rate was 3.68, for a relative hazard of 0.50, compared with participants who had one or more elevated risk factors.

"Overall, the [population-attributable fraction] estimates indicated that having [one or more] elevated risk factor levels could explain 50% ... of AF events," added the authors (Circulation 2011:10.1161/CIRCULATIONAHA.110.009035).

Adding elevated and borderline levels together, that number jumped to 57%.

The authors also sought to determine which of the relevant risk factors played the biggest role in incident AF.

Elevated blood pressure, experienced by 39% of the entire cohort, accounted for roughly one in five cases of AF (21.6%). "This rose to 24.5% if borderline levels of BP, which affected another 22.7% of the cohort, were also included," wrote the authors.

"Obesity and overweight explained 17.9% of all AF cases, and diabetes mellitus and impaired glucose tolerance combined accounted for the smallest fraction [3.9%] of the AF burden in this cohort," they added.

According to the authors, this study is the second to look at the relationship between modifiable risk factors and atrial fibrillation. A 1994 analysis, using data from the Framingham cohort, found that smoking, diabetes, hypertension, and prevalent coronary heart disease combined explained 44% of the AF burden in men and 58% in women, a conclusion that Dr. Huxley called "broadly comparable" to that of the current study.

They added that the study was limited by its inability to differentiate subtypes of AF, as well as by its reliance on hospital discharge codes to ascertain more than 98% of AF cases recorded in this cohort. However, if anything, this fact likely led to the "underascertainment of cases that perhaps were not severe enough to warrant hospitalization."

The study was funded by the National Heart, Lung, and Blood Institute as well as the American Heart Association. The investigators reported having no other disclosures related to this study.

More than half of atrial fibrillation is likely attributable to modifiable risk factors, including high blood pressure, obesity, and smoking, according to an analysis of the Atherosclerosis Risk in Communities Study.

The finding, which was based on a cohort of middle-aged American adults from communities in the ARIC study, highlights the need for primary prevention among this population.

"Moreover, because improvement in these behaviors would also favorably affect other AF risk factors, such as diabetes mellitus and impaired glucose tolerance, the reduction in the incidence of AF would be even greater than expected through BP lowering alone," wrote Rachel R. Huxley, D.Phil., in the journal Circulation, published online March 28.

Dr. Huxley, an epidemiologist at the University of Minnesota, Minneapolis, and colleagues looked at nearly 20 years of follow-up from the ARIC survey, a prospective cohort study of atherosclerotic diseases in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis.

At baseline in 1987-1989, it included 15,792 men and women aged 45-64 years, selected by area probability sampling.

All patients underwent three triennial visits, and in the present study, AF cases were counted as those diagnosed at an incident study visit (not baseline assessment) by 12-lead electrocardiogram, or during follow-up with an ICD code for AF in a hospital discharge, or when AF was listed as any cause of death on a death certificate.

Those with baseline AF on electrocardiogram or history of AF were excluded, as were those with missing data.

The researchers of the current study characterized participants into one of three risk profiles. An "optimal" group had no history of cardiac disease, systolic BP less than 120 mm Hg and diastolic less than 80 mm Hg without antihypertensive drugs; a body mass index less than 25 kg/m²; fasting serum glucose less than 100 mg/dL without antidiabetic drugs or history of diabetes; and no history of smoking.

"Borderline" participants had any of the following criteria: systolic BP 120-139 and/or diastolic BP 80-89 mm Hg without antihypertensives; BMI 25-30; fasting glucose 100-125 mg/dL without use of antidiabetics and no history of diabetes; and former smoker status.

Finally, participants regarded as having "elevated" risk profiles had any of the following: history of cardiac disease (heart failure or coronary heart disease); systolic BP at least 140 mm Hg, diastolic BP at least 90 mm Hg, or use of antihypertensives; BMI greater than 30; fasting serum glucose greater than or equal to 126, or use of antidiabetic drugs; history of diabetes; or current smoker status.

Among the 14,598 subjects (55% women; 25% black; mean age, 54.2 years) over a mean 17.1 years of follow-up who were included in the current analysis, there were 1,520 cases of incident AF.

Compared with those with no risk factors, the age-adjusted incidence rates were three times higher in those with one or more elevated risk factors (2.19 vs. 6.59 per 1,000 person-years, respectively), wrote the authors (relative hazard for optimal patient group, 0.33).

For the borderline group, the incidence rate was 3.68, for a relative hazard of 0.50, compared with participants who had one or more elevated risk factors.

"Overall, the [population-attributable fraction] estimates indicated that having [one or more] elevated risk factor levels could explain 50% ... of AF events," added the authors (Circulation 2011:10.1161/CIRCULATIONAHA.110.009035).

Adding elevated and borderline levels together, that number jumped to 57%.

The authors also sought to determine which of the relevant risk factors played the biggest role in incident AF.

Elevated blood pressure, experienced by 39% of the entire cohort, accounted for roughly one in five cases of AF (21.6%). "This rose to 24.5% if borderline levels of BP, which affected another 22.7% of the cohort, were also included," wrote the authors.

"Obesity and overweight explained 17.9% of all AF cases, and diabetes mellitus and impaired glucose tolerance combined accounted for the smallest fraction [3.9%] of the AF burden in this cohort," they added.

According to the authors, this study is the second to look at the relationship between modifiable risk factors and atrial fibrillation. A 1994 analysis, using data from the Framingham cohort, found that smoking, diabetes, hypertension, and prevalent coronary heart disease combined explained 44% of the AF burden in men and 58% in women, a conclusion that Dr. Huxley called "broadly comparable" to that of the current study.

They added that the study was limited by its inability to differentiate subtypes of AF, as well as by its reliance on hospital discharge codes to ascertain more than 98% of AF cases recorded in this cohort. However, if anything, this fact likely led to the "underascertainment of cases that perhaps were not severe enough to warrant hospitalization."

The study was funded by the National Heart, Lung, and Blood Institute as well as the American Heart Association. The investigators reported having no other disclosures related to this study.

More than half of atrial fibrillation is likely attributable to modifiable risk factors, including high blood pressure, obesity, and smoking, according to an analysis of the Atherosclerosis Risk in Communities Study.

The finding, which was based on a cohort of middle-aged American adults from communities in the ARIC study, highlights the need for primary prevention among this population.

"Moreover, because improvement in these behaviors would also favorably affect other AF risk factors, such as diabetes mellitus and impaired glucose tolerance, the reduction in the incidence of AF would be even greater than expected through BP lowering alone," wrote Rachel R. Huxley, D.Phil., in the journal Circulation, published online March 28.

Dr. Huxley, an epidemiologist at the University of Minnesota, Minneapolis, and colleagues looked at nearly 20 years of follow-up from the ARIC survey, a prospective cohort study of atherosclerotic diseases in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis.

At baseline in 1987-1989, it included 15,792 men and women aged 45-64 years, selected by area probability sampling.

All patients underwent three triennial visits, and in the present study, AF cases were counted as those diagnosed at an incident study visit (not baseline assessment) by 12-lead electrocardiogram, or during follow-up with an ICD code for AF in a hospital discharge, or when AF was listed as any cause of death on a death certificate.

Those with baseline AF on electrocardiogram or history of AF were excluded, as were those with missing data.

The researchers of the current study characterized participants into one of three risk profiles. An "optimal" group had no history of cardiac disease, systolic BP less than 120 mm Hg and diastolic less than 80 mm Hg without antihypertensive drugs; a body mass index less than 25 kg/m²; fasting serum glucose less than 100 mg/dL without antidiabetic drugs or history of diabetes; and no history of smoking.

"Borderline" participants had any of the following criteria: systolic BP 120-139 and/or diastolic BP 80-89 mm Hg without antihypertensives; BMI 25-30; fasting glucose 100-125 mg/dL without use of antidiabetics and no history of diabetes; and former smoker status.

Finally, participants regarded as having "elevated" risk profiles had any of the following: history of cardiac disease (heart failure or coronary heart disease); systolic BP at least 140 mm Hg, diastolic BP at least 90 mm Hg, or use of antihypertensives; BMI greater than 30; fasting serum glucose greater than or equal to 126, or use of antidiabetic drugs; history of diabetes; or current smoker status.

Among the 14,598 subjects (55% women; 25% black; mean age, 54.2 years) over a mean 17.1 years of follow-up who were included in the current analysis, there were 1,520 cases of incident AF.

Compared with those with no risk factors, the age-adjusted incidence rates were three times higher in those with one or more elevated risk factors (2.19 vs. 6.59 per 1,000 person-years, respectively), wrote the authors (relative hazard for optimal patient group, 0.33).

For the borderline group, the incidence rate was 3.68, for a relative hazard of 0.50, compared with participants who had one or more elevated risk factors.

"Overall, the [population-attributable fraction] estimates indicated that having [one or more] elevated risk factor levels could explain 50% ... of AF events," added the authors (Circulation 2011:10.1161/CIRCULATIONAHA.110.009035).

Adding elevated and borderline levels together, that number jumped to 57%.

The authors also sought to determine which of the relevant risk factors played the biggest role in incident AF.

Elevated blood pressure, experienced by 39% of the entire cohort, accounted for roughly one in five cases of AF (21.6%). "This rose to 24.5% if borderline levels of BP, which affected another 22.7% of the cohort, were also included," wrote the authors.

"Obesity and overweight explained 17.9% of all AF cases, and diabetes mellitus and impaired glucose tolerance combined accounted for the smallest fraction [3.9%] of the AF burden in this cohort," they added.

According to the authors, this study is the second to look at the relationship between modifiable risk factors and atrial fibrillation. A 1994 analysis, using data from the Framingham cohort, found that smoking, diabetes, hypertension, and prevalent coronary heart disease combined explained 44% of the AF burden in men and 58% in women, a conclusion that Dr. Huxley called "broadly comparable" to that of the current study.

They added that the study was limited by its inability to differentiate subtypes of AF, as well as by its reliance on hospital discharge codes to ascertain more than 98% of AF cases recorded in this cohort. However, if anything, this fact likely led to the "underascertainment of cases that perhaps were not severe enough to warrant hospitalization."

The study was funded by the National Heart, Lung, and Blood Institute as well as the American Heart Association. The investigators reported having no other disclosures related to this study.

More than half of atrial fibrillation is likely attributable to modifiable risk factors, including high blood pressure, obesity, and smoking, according to an analysis of the Atherosclerosis Risk in Communities Study.

The finding, which was based on a cohort of middle-aged American adults from communities in the ARIC study, highlights the need for primary prevention among this population.

"Moreover, because improvement in these behaviors would also favorably affect other AF risk factors, such as diabetes mellitus and impaired glucose tolerance, the reduction in the incidence of AF would be even greater than expected through BP lowering alone," wrote Rachel R. Huxley, D.Phil., in the journal Circulation, published online March 28.

Dr. Huxley, an epidemiologist at the University of Minnesota, Minneapolis, and colleagues looked at nearly 20 years of follow-up from the ARIC survey, a prospective cohort study of atherosclerotic diseases in Forsyth County, N.C.; Jackson, Miss.; Washington County, Md.; and the suburbs of Minneapolis.

At baseline in 1987-1989, it included 15,792 men and women aged 45-64 years, selected by area probability sampling.

All patients underwent three triennial visits, and in the present study, AF cases were counted as those diagnosed at an incident study visit (not baseline assessment) by 12-lead electrocardiogram, or during follow-up with an ICD code for AF in a hospital discharge, or when AF was listed as any cause of death on a death certificate.

Those with baseline AF on electrocardiogram or history of AF were excluded, as were those with missing data.

The researchers of the current study characterized participants into one of three risk profiles. An "optimal" group had no history of cardiac disease, systolic BP less than 120 mm Hg and diastolic less than 80 mm Hg without antihypertensive drugs; a body mass index less than 25 kg/m²; fasting serum glucose less than 100 mg/dL without antidiabetic drugs or history of diabetes; and no history of smoking.

"Borderline" participants had any of the following criteria: systolic BP 120-139 and/or diastolic BP 80-89 mm Hg without antihypertensives; BMI 25-30; fasting glucose 100-125 mg/dL without use of antidiabetics and no history of diabetes; and former smoker status.

Finally, participants regarded as having "elevated" risk profiles had any of the following: history of cardiac disease (heart failure or coronary heart disease); systolic BP at least 140 mm Hg, diastolic BP at least 90 mm Hg, or use of antihypertensives; BMI greater than 30; fasting serum glucose greater than or equal to 126, or use of antidiabetic drugs; history of diabetes; or current smoker status.

Among the 14,598 subjects (55% women; 25% black; mean age, 54.2 years) over a mean 17.1 years of follow-up who were included in the current analysis, there were 1,520 cases of incident AF.

Compared with those with no risk factors, the age-adjusted incidence rates were three times higher in those with one or more elevated risk factors (2.19 vs. 6.59 per 1,000 person-years, respectively), wrote the authors (relative hazard for optimal patient group, 0.33).

For the borderline group, the incidence rate was 3.68, for a relative hazard of 0.50, compared with participants who had one or more elevated risk factors.

"Overall, the [population-attributable fraction] estimates indicated that having [one or more] elevated risk factor levels could explain 50% ... of AF events," added the authors (Circulation 2011:10.1161/CIRCULATIONAHA.110.009035).

Adding elevated and borderline levels together, that number jumped to 57%.

The authors also sought to determine which of the relevant risk factors played the biggest role in incident AF.

Elevated blood pressure, experienced by 39% of the entire cohort, accounted for roughly one in five cases of AF (21.6%). "This rose to 24.5% if borderline levels of BP, which affected another 22.7% of the cohort, were also included," wrote the authors.

"Obesity and overweight explained 17.9% of all AF cases, and diabetes mellitus and impaired glucose tolerance combined accounted for the smallest fraction [3.9%] of the AF burden in this cohort," they added.

According to the authors, this study is the second to look at the relationship between modifiable risk factors and atrial fibrillation. A 1994 analysis, using data from the Framingham cohort, found that smoking, diabetes, hypertension, and prevalent coronary heart disease combined explained 44% of the AF burden in men and 58% in women, a conclusion that Dr. Huxley called "broadly comparable" to that of the current study.

They added that the study was limited by its inability to differentiate subtypes of AF, as well as by its reliance on hospital discharge codes to ascertain more than 98% of AF cases recorded in this cohort. However, if anything, this fact likely led to the "underascertainment of cases that perhaps were not severe enough to warrant hospitalization."

The study was funded by the National Heart, Lung, and Blood Institute as well as the American Heart Association. The investigators reported having no other disclosures related to this study.

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, is from the "largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy" to date, according to the authors.

Despite its relatively large size, however, the study was unable to control for the looming possibility that disease severity itself plays a role in adverse pregnancy outcomes, as the authors readily admitted.

Nevertheless, "no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain," recommended the authors.

The study was led by Dr. Suzanne M. M. Verstappen of the University of Manchester’s Arthritis Research UK Epidemiology Unit and was published online in Annals of the Rheumatic Diseases.

Dr. Verstappen and her colleagues looked at women in the registry who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs, two drugs with a "known risk of adverse pregnancy outcomes," according to the authors.

A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822]).

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb).

Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post-20 weeks).

There was also one neonatal death registered.

The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death.

Finally, among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

In all cohorts, the majority of patients had RA, and the majority took etanercept.

The baseline disease activity score-28 (DAS28) was significantly higher in the anti-TNF cohorts, vs. cohort III: 6.5, 6.1, and 6.0 in cohorts Ia, Ib, and II, respectively, vs. 5.1 in cohort III.

Dr. H. Michael Belmont, medical director of New York University’s Hospital for Joint Diseases, as well as the director of the lupus clinic at Bellevue Hospital, New York, commented that, until more data are available, "The default choice would be to avoid these drugs during pregnancy. Certainly starting their use in a women contemplating conception should be delayed based on the data on hand."

Dr. Belmont, who was not affiliated with this study, joined the authors in pointing to a 2009 study by Carter et al., which found an increased observed: expected incidence of VACTERL defects (vertebral abnormalities, anal atresia, and/or cardiac, trachea, esophageal, renal, and limb abnormalities) in children born to women taking anti-TNFs (J. Rheumatol. 2009;36:635-41).

However, "The total observed number [of children born with VACTERL abnormalities] was small, 19 newborns, and the actual rate could not be calculated, as the authors relied on the [Food & Drug Administration] base of adverse events but did not know the [actual] number of exposed pregnancies, having to rely instead on historical controls to determine the expected ratio," he conceded.

On the other hand, Dr. Arthur Kavanaugh, a rheumatologist and director of the at the University of California San Diego’s Center for Innovative Therapy pointed to flaws in the current study’s analysis.

"The other explanation [for the finding of increased spontaneous abortion among anti-TNF users] is that it’s the disease more than the drug, so that people who have worse RA are going to have pregnancy outcomes that are not necessarily as good, and you just don’t know that from this because there’s only 10 people in the DMARD-only arm," he said in an interview.

"That’s just incredibly small. If you have one different outcome in that group, it would make a humongous difference in how you look at the data."

He added: "You can’t ignore the disease, and it’s the disease itself that’s going to affect the outcome as well."

Dr. Kavanaugh, like Dr. Belmont, was not affiliated with the study.

The study investigators disclosed that the British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. They added that they had no personal competing interests in relation to this study.

Dr. Kavanaugh disclosed that he has done research for the makers of TNF inhibitors, including Abbot Laboratories, Amgen, Centocor, and UCB. Dr. Belmont did not make any disclosures relevant to this study.

The British Society for Rheumatology receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, is from the "largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy" to date, according to the authors.

Despite its relatively large size, however, the study was unable to control for the looming possibility that disease severity itself plays a role in adverse pregnancy outcomes, as the authors readily admitted.

Nevertheless, "no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain," recommended the authors.

The study was led by Dr. Suzanne M. M. Verstappen of the University of Manchester’s Arthritis Research UK Epidemiology Unit and was published online in Annals of the Rheumatic Diseases.

Dr. Verstappen and her colleagues looked at women in the registry who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs, two drugs with a "known risk of adverse pregnancy outcomes," according to the authors.

A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822]).

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb).

Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post-20 weeks).

There was also one neonatal death registered.

The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death.

Finally, among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

In all cohorts, the majority of patients had RA, and the majority took etanercept.

The baseline disease activity score-28 (DAS28) was significantly higher in the anti-TNF cohorts, vs. cohort III: 6.5, 6.1, and 6.0 in cohorts Ia, Ib, and II, respectively, vs. 5.1 in cohort III.

Dr. H. Michael Belmont, medical director of New York University’s Hospital for Joint Diseases, as well as the director of the lupus clinic at Bellevue Hospital, New York, commented that, until more data are available, "The default choice would be to avoid these drugs during pregnancy. Certainly starting their use in a women contemplating conception should be delayed based on the data on hand."

Dr. Belmont, who was not affiliated with this study, joined the authors in pointing to a 2009 study by Carter et al., which found an increased observed: expected incidence of VACTERL defects (vertebral abnormalities, anal atresia, and/or cardiac, trachea, esophageal, renal, and limb abnormalities) in children born to women taking anti-TNFs (J. Rheumatol. 2009;36:635-41).

However, "The total observed number [of children born with VACTERL abnormalities] was small, 19 newborns, and the actual rate could not be calculated, as the authors relied on the [Food & Drug Administration] base of adverse events but did not know the [actual] number of exposed pregnancies, having to rely instead on historical controls to determine the expected ratio," he conceded.

On the other hand, Dr. Arthur Kavanaugh, a rheumatologist and director of the at the University of California San Diego’s Center for Innovative Therapy pointed to flaws in the current study’s analysis.

"The other explanation [for the finding of increased spontaneous abortion among anti-TNF users] is that it’s the disease more than the drug, so that people who have worse RA are going to have pregnancy outcomes that are not necessarily as good, and you just don’t know that from this because there’s only 10 people in the DMARD-only arm," he said in an interview.

"That’s just incredibly small. If you have one different outcome in that group, it would make a humongous difference in how you look at the data."

He added: "You can’t ignore the disease, and it’s the disease itself that’s going to affect the outcome as well."

Dr. Kavanaugh, like Dr. Belmont, was not affiliated with the study.

The study investigators disclosed that the British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. They added that they had no personal competing interests in relation to this study.

Dr. Kavanaugh disclosed that he has done research for the makers of TNF inhibitors, including Abbot Laboratories, Amgen, Centocor, and UCB. Dr. Belmont did not make any disclosures relevant to this study.

The British Society for Rheumatology receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, is from the "largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy" to date, according to the authors.

Despite its relatively large size, however, the study was unable to control for the looming possibility that disease severity itself plays a role in adverse pregnancy outcomes, as the authors readily admitted.

Nevertheless, "no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain," recommended the authors.

The study was led by Dr. Suzanne M. M. Verstappen of the University of Manchester’s Arthritis Research UK Epidemiology Unit and was published online in Annals of the Rheumatic Diseases.

Dr. Verstappen and her colleagues looked at women in the registry who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs, two drugs with a "known risk of adverse pregnancy outcomes," according to the authors.

A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822]).

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb).

Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post-20 weeks).

There was also one neonatal death registered.

The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death.

Finally, among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

In all cohorts, the majority of patients had RA, and the majority took etanercept.

The baseline disease activity score-28 (DAS28) was significantly higher in the anti-TNF cohorts, vs. cohort III: 6.5, 6.1, and 6.0 in cohorts Ia, Ib, and II, respectively, vs. 5.1 in cohort III.

Dr. H. Michael Belmont, medical director of New York University’s Hospital for Joint Diseases, as well as the director of the lupus clinic at Bellevue Hospital, New York, commented that, until more data are available, "The default choice would be to avoid these drugs during pregnancy. Certainly starting their use in a women contemplating conception should be delayed based on the data on hand."

Dr. Belmont, who was not affiliated with this study, joined the authors in pointing to a 2009 study by Carter et al., which found an increased observed: expected incidence of VACTERL defects (vertebral abnormalities, anal atresia, and/or cardiac, trachea, esophageal, renal, and limb abnormalities) in children born to women taking anti-TNFs (J. Rheumatol. 2009;36:635-41).

However, "The total observed number [of children born with VACTERL abnormalities] was small, 19 newborns, and the actual rate could not be calculated, as the authors relied on the [Food & Drug Administration] base of adverse events but did not know the [actual] number of exposed pregnancies, having to rely instead on historical controls to determine the expected ratio," he conceded.

On the other hand, Dr. Arthur Kavanaugh, a rheumatologist and director of the at the University of California San Diego’s Center for Innovative Therapy pointed to flaws in the current study’s analysis.

"The other explanation [for the finding of increased spontaneous abortion among anti-TNF users] is that it’s the disease more than the drug, so that people who have worse RA are going to have pregnancy outcomes that are not necessarily as good, and you just don’t know that from this because there’s only 10 people in the DMARD-only arm," he said in an interview.

"That’s just incredibly small. If you have one different outcome in that group, it would make a humongous difference in how you look at the data."

He added: "You can’t ignore the disease, and it’s the disease itself that’s going to affect the outcome as well."

Dr. Kavanaugh, like Dr. Belmont, was not affiliated with the study.

The study investigators disclosed that the British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. They added that they had no personal competing interests in relation to this study.

Dr. Kavanaugh disclosed that he has done research for the makers of TNF inhibitors, including Abbot Laboratories, Amgen, Centocor, and UCB. Dr. Belmont did not make any disclosures relevant to this study.

The British Society for Rheumatology receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

Major Finding: Patients taking mycophenolate mofetil had a 1.80 adjusted hazard ratio for relapse of ANCA-associated vasculitis, compared with azathioprine patients.

Data Source: The International Mycophenolate Mofetil Protocol to Reduce Outbreaks of Vasculitides (IMPROVE) trial, an open-label, randomized controlled study.

Disclosures: Dr. Hiemstra reported receiving honoraria from Amgen, and several coinvestigators disclosed financial relationships with other drug makers. The study was partially funded by Hoffmann-La Roche Ltd., which markets mycophenolate mofetil as CellCept.

Azathioprine was more effective than was mycophenolate mofetil for the prevention of relapse in antineutrophil cytoplasmic antibody–associated vasculitis.

“Although mycophenolate mofetil may be considered in refractory cases, it should not be considered the first-line remission maintenance therapy in AAV,” according to Dr. Thomas F. Hiemstra and colleagues (doi:10.1001/jama.2010.1658).

Dr. Hiemstra of the University of Cambridge, England, looked at 156 patients in an open-label, multicenter, randomized controlled trial known as IMPROVE (International Mycophenolate Mofetil Protocol to Reduce Outbreaks of Vasculitides).

Patients were newly diagnosed with Wegener granulomatosis or microscopic polyangiitis. All had a positive indirect immunofluorescence or enzyme-linked immunosorbent assay for antineutrophil cytoplasmic antibodies, or ANCAs.

Initially, all study participants received cyclophosphamide and glucocorticoids for induction of remission. Once remission was established, patients were divided into two groups, to receive either azathioprine or mycophenolate mofetil.

A total of 80 patients in the azathioprine group were given 2 mg/kg per day of azathioprine, up to 200 mg. The dose was titrated to 1.5 mg/kg per day after 12 months of treatment, down to 1 mg/kg per day after 18 months, and discontinued after 42 months.

The remaining 76 patients received mycophenolate mofetil at 2,000 mg/day. The dose was reduced to 1,500 mg/day after 12 months, to 1,000 mg/day after 18 months and withdrawn after 42 months.

The median follow-up for both groups was 39 months. All participants were counted in an intent-to-treat analysis.

Dr. Hiemstra recorded 42 relapses in the mycophenolate mofetil group, out of 76 patients (55%), compared with the azathioprine group, which had 30 relapses out of 80 patients (38%).

That amounted to an unadjusted hazard ratio for relapse of 1.69 among mycophenolate mofetil users (95% confidence interval, 1.06-2.70; P = .03).

After adjustment for age, sex, diagnostic subtype, route of cyclophosphamide administration [during initial treatment], and baseline creatinine level, the HR for relapses associated with mycophenolate mofetil use was 1.80 (95% CI, 1.10-2.93; P = .02).

There were no significant adverse event rate differences between the groups. According to Dr. Hiemstra, there were 22 severe adverse events in 13 patients in the azathioprine group, and 8 events in 8 patients in the mycophenolate mofetil group.

These included severe infection (8 in the azathioprine group and 3 in the mycophenolate mofetil group); leukopenia (11 episodes in the azathioprine group and 5 in the mycophenolate mofetil group); and malignancies (2 bladder cancers and 3 skin cancers in the azathioprine group, versus 1 skin malignancy among mycophenolate mofetil users).

View on the News

Study Needed on Classification, Tx

Dr. Gary S. Hoffman of the Cleveland Clinic wrote that while there have been “major contributions” in the field of vasculitis over the last several decades, data on these rare diseases are still lacking.

“The difficulty inherent in the organization of this trial is implied by noting that recruitment of 175 newly diagnosed patients with [antineutrophil cytoplasmic antibody]-positive Wegener's granulomatosis and microscopic polyangiitis required 42 centers from 11 European countries over 7 years,” he said.

Indeed, while the current trial “provides important and reliable new knowledge for the clinician,” several issues remain unresolved, he added.

For one, “as in other trials involving patients with WG and MPA, severe infections and leukopenia continue to be a major concern,” Dr. Hoffman pointed out.

Moreover, the authors only included ANCA-positive patients.

“Approximately 10% of patients with identical clinical phenotypes might be ANCA-negative and also respond to all anti-inflammatory or immunosuppressive therapies shown to be effective for those who are seropositive,” he wrote.

Finally, given the side-effect profile, “the risk-benefit formulas of long-term maintenance therapy vs. discontinuation and treatment of relapses require further study.”

“Although the therapeutic options have expanded, clinicians face difficult treatment decisions when patients in remission are unable to tolerate or have contraindications to maintenance agents such as methotrexate or azathioprine,” he concluded.

DR. HOFFMAN holds the Harold C. Schott Chair for Rheumatic and Immunologic Diseases at the Cleveland Clinic, and is director of the Center for Vasculitis Care and Research at the Cleveland Clinic Foundation. His comments were taken from an editorial accompanying the study (JAMA 2010 Nov. 8 [doi:10.1001/jama.2010.1676]). He reported having no financial disclosures.

Major Finding: Patients taking mycophenolate mofetil had a 1.80 adjusted hazard ratio for relapse of ANCA-associated vasculitis, compared with azathioprine patients.

Data Source: The International Mycophenolate Mofetil Protocol to Reduce Outbreaks of Vasculitides (IMPROVE) trial, an open-label, randomized controlled study.

Disclosures: Dr. Hiemstra reported receiving honoraria from Amgen, and several coinvestigators disclosed financial relationships with other drug makers. The study was partially funded by Hoffmann-La Roche Ltd., which markets mycophenolate mofetil as CellCept.

Azathioprine was more effective than was mycophenolate mofetil for the prevention of relapse in antineutrophil cytoplasmic antibody–associated vasculitis.

“Although mycophenolate mofetil may be considered in refractory cases, it should not be considered the first-line remission maintenance therapy in AAV,” according to Dr. Thomas F. Hiemstra and colleagues (doi:10.1001/jama.2010.1658).

Dr. Hiemstra of the University of Cambridge, England, looked at 156 patients in an open-label, multicenter, randomized controlled trial known as IMPROVE (International Mycophenolate Mofetil Protocol to Reduce Outbreaks of Vasculitides).

Patients were newly diagnosed with Wegener granulomatosis or microscopic polyangiitis. All had a positive indirect immunofluorescence or enzyme-linked immunosorbent assay for antineutrophil cytoplasmic antibodies, or ANCAs.

Initially, all study participants received cyclophosphamide and glucocorticoids for induction of remission. Once remission was established, patients were divided into two groups, to receive either azathioprine or mycophenolate mofetil.

A total of 80 patients in the azathioprine group were given 2 mg/kg per day of azathioprine, up to 200 mg. The dose was titrated to 1.5 mg/kg per day after 12 months of treatment, down to 1 mg/kg per day after 18 months, and discontinued after 42 months.

The remaining 76 patients received mycophenolate mofetil at 2,000 mg/day. The dose was reduced to 1,500 mg/day after 12 months, to 1,000 mg/day after 18 months and withdrawn after 42 months.

The median follow-up for both groups was 39 months. All participants were counted in an intent-to-treat analysis.

Dr. Hiemstra recorded 42 relapses in the mycophenolate mofetil group, out of 76 patients (55%), compared with the azathioprine group, which had 30 relapses out of 80 patients (38%).

That amounted to an unadjusted hazard ratio for relapse of 1.69 among mycophenolate mofetil users (95% confidence interval, 1.06-2.70; P = .03).

After adjustment for age, sex, diagnostic subtype, route of cyclophosphamide administration [during initial treatment], and baseline creatinine level, the HR for relapses associated with mycophenolate mofetil use was 1.80 (95% CI, 1.10-2.93; P = .02).

There were no significant adverse event rate differences between the groups. According to Dr. Hiemstra, there were 22 severe adverse events in 13 patients in the azathioprine group, and 8 events in 8 patients in the mycophenolate mofetil group.

These included severe infection (8 in the azathioprine group and 3 in the mycophenolate mofetil group); leukopenia (11 episodes in the azathioprine group and 5 in the mycophenolate mofetil group); and malignancies (2 bladder cancers and 3 skin cancers in the azathioprine group, versus 1 skin malignancy among mycophenolate mofetil users).

View on the News

Study Needed on Classification, Tx

Dr. Gary S. Hoffman of the Cleveland Clinic wrote that while there have been “major contributions” in the field of vasculitis over the last several decades, data on these rare diseases are still lacking.

“The difficulty inherent in the organization of this trial is implied by noting that recruitment of 175 newly diagnosed patients with [antineutrophil cytoplasmic antibody]-positive Wegener's granulomatosis and microscopic polyangiitis required 42 centers from 11 European countries over 7 years,” he said.

Indeed, while the current trial “provides important and reliable new knowledge for the clinician,” several issues remain unresolved, he added.

For one, “as in other trials involving patients with WG and MPA, severe infections and leukopenia continue to be a major concern,” Dr. Hoffman pointed out.

Moreover, the authors only included ANCA-positive patients.

“Approximately 10% of patients with identical clinical phenotypes might be ANCA-negative and also respond to all anti-inflammatory or immunosuppressive therapies shown to be effective for those who are seropositive,” he wrote.

Finally, given the side-effect profile, “the risk-benefit formulas of long-term maintenance therapy vs. discontinuation and treatment of relapses require further study.”

“Although the therapeutic options have expanded, clinicians face difficult treatment decisions when patients in remission are unable to tolerate or have contraindications to maintenance agents such as methotrexate or azathioprine,” he concluded.

DR. HOFFMAN holds the Harold C. Schott Chair for Rheumatic and Immunologic Diseases at the Cleveland Clinic, and is director of the Center for Vasculitis Care and Research at the Cleveland Clinic Foundation. His comments were taken from an editorial accompanying the study (JAMA 2010 Nov. 8 [doi:10.1001/jama.2010.1676]). He reported having no financial disclosures.

Major Finding: Patients taking mycophenolate mofetil had a 1.80 adjusted hazard ratio for relapse of ANCA-associated vasculitis, compared with azathioprine patients.

Data Source: The International Mycophenolate Mofetil Protocol to Reduce Outbreaks of Vasculitides (IMPROVE) trial, an open-label, randomized controlled study.

Disclosures: Dr. Hiemstra reported receiving honoraria from Amgen, and several coinvestigators disclosed financial relationships with other drug makers. The study was partially funded by Hoffmann-La Roche Ltd., which markets mycophenolate mofetil as CellCept.

Azathioprine was more effective than was mycophenolate mofetil for the prevention of relapse in antineutrophil cytoplasmic antibody–associated vasculitis.

“Although mycophenolate mofetil may be considered in refractory cases, it should not be considered the first-line remission maintenance therapy in AAV,” according to Dr. Thomas F. Hiemstra and colleagues (doi:10.1001/jama.2010.1658).

Dr. Hiemstra of the University of Cambridge, England, looked at 156 patients in an open-label, multicenter, randomized controlled trial known as IMPROVE (International Mycophenolate Mofetil Protocol to Reduce Outbreaks of Vasculitides).

Patients were newly diagnosed with Wegener granulomatosis or microscopic polyangiitis. All had a positive indirect immunofluorescence or enzyme-linked immunosorbent assay for antineutrophil cytoplasmic antibodies, or ANCAs.

Initially, all study participants received cyclophosphamide and glucocorticoids for induction of remission. Once remission was established, patients were divided into two groups, to receive either azathioprine or mycophenolate mofetil.

A total of 80 patients in the azathioprine group were given 2 mg/kg per day of azathioprine, up to 200 mg. The dose was titrated to 1.5 mg/kg per day after 12 months of treatment, down to 1 mg/kg per day after 18 months, and discontinued after 42 months.

The remaining 76 patients received mycophenolate mofetil at 2,000 mg/day. The dose was reduced to 1,500 mg/day after 12 months, to 1,000 mg/day after 18 months and withdrawn after 42 months.

The median follow-up for both groups was 39 months. All participants were counted in an intent-to-treat analysis.

Dr. Hiemstra recorded 42 relapses in the mycophenolate mofetil group, out of 76 patients (55%), compared with the azathioprine group, which had 30 relapses out of 80 patients (38%).

That amounted to an unadjusted hazard ratio for relapse of 1.69 among mycophenolate mofetil users (95% confidence interval, 1.06-2.70; P = .03).

After adjustment for age, sex, diagnostic subtype, route of cyclophosphamide administration [during initial treatment], and baseline creatinine level, the HR for relapses associated with mycophenolate mofetil use was 1.80 (95% CI, 1.10-2.93; P = .02).

There were no significant adverse event rate differences between the groups. According to Dr. Hiemstra, there were 22 severe adverse events in 13 patients in the azathioprine group, and 8 events in 8 patients in the mycophenolate mofetil group.

These included severe infection (8 in the azathioprine group and 3 in the mycophenolate mofetil group); leukopenia (11 episodes in the azathioprine group and 5 in the mycophenolate mofetil group); and malignancies (2 bladder cancers and 3 skin cancers in the azathioprine group, versus 1 skin malignancy among mycophenolate mofetil users).

View on the News

Study Needed on Classification, Tx

Dr. Gary S. Hoffman of the Cleveland Clinic wrote that while there have been “major contributions” in the field of vasculitis over the last several decades, data on these rare diseases are still lacking.

“The difficulty inherent in the organization of this trial is implied by noting that recruitment of 175 newly diagnosed patients with [antineutrophil cytoplasmic antibody]-positive Wegener's granulomatosis and microscopic polyangiitis required 42 centers from 11 European countries over 7 years,” he said.

Indeed, while the current trial “provides important and reliable new knowledge for the clinician,” several issues remain unresolved, he added.

For one, “as in other trials involving patients with WG and MPA, severe infections and leukopenia continue to be a major concern,” Dr. Hoffman pointed out.

Moreover, the authors only included ANCA-positive patients.

“Approximately 10% of patients with identical clinical phenotypes might be ANCA-negative and also respond to all anti-inflammatory or immunosuppressive therapies shown to be effective for those who are seropositive,” he wrote.

Finally, given the side-effect profile, “the risk-benefit formulas of long-term maintenance therapy vs. discontinuation and treatment of relapses require further study.”

“Although the therapeutic options have expanded, clinicians face difficult treatment decisions when patients in remission are unable to tolerate or have contraindications to maintenance agents such as methotrexate or azathioprine,” he concluded.

DR. HOFFMAN holds the Harold C. Schott Chair for Rheumatic and Immunologic Diseases at the Cleveland Clinic, and is director of the Center for Vasculitis Care and Research at the Cleveland Clinic Foundation. His comments were taken from an editorial accompanying the study (JAMA 2010 Nov. 8 [doi:10.1001/jama.2010.1676]). He reported having no financial disclosures.

Although percutaneous radiofrequency ablation and surgical resection for small hepatocellular carcinomas have similar survival rates, ablation patients have a higher rate of cancer recurrence, compared with surgical resection patients, reported Dr. Hung-Hsu Hung and colleagues in the January issue of Clinical Gastroenterology and Hepatology.

Dr. Hung, of Taipei (Taiwan) Veterans General Hospital and the National Yang-Ming University, also in Taipei, looked at 419 consecutive patients who underwent radiofrequency ablation (RFA) or surgical resection (SR) at the hospital in 2002-2007. All patients had no more than three small (5 cm or less) liver tumors without extrahepatic metastasis (Clin. Gastroenterol. Hepatol. 2011 January [doi:10.1016/j.cgh.2010.08.018]).

In all, 190 patients underwent RFA and the remaining 229 underwent SR to treat their liver cancer. Patients who chose SR were on average slightly younger (60 years vs. 67 years; P less than .001). This was expected, given the invasive nature of the surgery.

Additionally, the authors found that there was a higher proportion of patients with chronic hepatitis B in the SR group than in the RFA group (59.8% vs. 46.3%; P = .004), whereas chronic hepatitis C was more common in the RFA group (44.7% vs. 26.6%; P less than .001).

This was also an expected finding, because in chronic HBV infection, hepatocellular carcinomas tend to occur at a younger age, the researchers wrote.

Regarding survival, 83 patients had died after a median follow-up of more than 42 months. "Among the 190 patients [who] underwent RFA, 41 (21.6%) died during the follow-up period; 97 (51.1%) were alive with regular visits" until Jan. 31, 2010, and the remaining 52 (27.4%) were lost to follow-up sometime before 2010.

In comparison, there were 42 deaths (18.3%) among the SR group, with 120 patients known to be alive through Jan. 31, 2010 (52.4%), and the remaining 67 patients (29.3%) lost to follow-up.

"The cumulative overall survival rates at 1, 2, 3, and 5 years were 97.3%, 92.2%, 88.2%, and 79.3% in the SR group and 96.6%, 86.7%, 77.3%, and 67.4% in the RFA group, respectively," a significant difference in univariate analysis (P less than 0.009), wrote the authors.

However, after controlling for the older age and comorbidities of the RFA group in multivariate analysis, the authors found that RFA was not an independent risk factor associated with poor survival.

Next, the authors looked at factors associated with cancer recurrence. Overall, 244 patients had experienced tumor recurrence at a median of 14.5 months following RFA or SR.

"The cumulative recurrence rates at 1, 2, 3, and 5 years were 17.4%, 30.5%, 43.9%, and 59.1% in the SR group and 37.4%, 54.1%, 71.0%, and 79.5% in the RFA group, respectively (P less than .001)," they reported.

As with survival, that translated to a significantly higher univariate risk of recurrence among RFA patients (hazard ratio, 2.05; 95% confidence interval, 1.58-2.65). When assessed in a multivariate analysis, RFA was still significantly associated with cancer recurrence (HR, 1.95; 95% CI, 1.48-2.57; P less than .001).

The finding of equal survival but greater recurrence among RFA patients persisted in a third propensity analysis, which employed nearest-neighbor one-to-one matching of 84 patients in each group in terms of age, sex, tumor size, tumor number, platelet counts, hepatitis status, and several other parameters.

The only subgroup for which RFA was equal to SR in terms of both survival and tumor recurrence was patients with solitary hepatocellular carcinoma less than 2 cm in size, known as "very early small HCC (Barcelona Clinic Liver Cancer stage 0)" tumors.

According to the authors, their study "highlights the importance of close surveillance after local ablation therapy." Additionally, the authors concluded that RFA may be a good alternative to surgical resection for BCLC stage 0 HCC, although prospective study is needed.

Dr. Hung and colleagues disclosed no conflicts of interest related to this study.

Although percutaneous radiofrequency ablation and surgical resection for small hepatocellular carcinomas have similar survival rates, ablation patients have a higher rate of cancer recurrence, compared with surgical resection patients, reported Dr. Hung-Hsu Hung and colleagues in the January issue of Clinical Gastroenterology and Hepatology.

Dr. Hung, of Taipei (Taiwan) Veterans General Hospital and the National Yang-Ming University, also in Taipei, looked at 419 consecutive patients who underwent radiofrequency ablation (RFA) or surgical resection (SR) at the hospital in 2002-2007. All patients had no more than three small (5 cm or less) liver tumors without extrahepatic metastasis (Clin. Gastroenterol. Hepatol. 2011 January [doi:10.1016/j.cgh.2010.08.018]).

In all, 190 patients underwent RFA and the remaining 229 underwent SR to treat their liver cancer. Patients who chose SR were on average slightly younger (60 years vs. 67 years; P less than .001). This was expected, given the invasive nature of the surgery.

Additionally, the authors found that there was a higher proportion of patients with chronic hepatitis B in the SR group than in the RFA group (59.8% vs. 46.3%; P = .004), whereas chronic hepatitis C was more common in the RFA group (44.7% vs. 26.6%; P less than .001).

This was also an expected finding, because in chronic HBV infection, hepatocellular carcinomas tend to occur at a younger age, the researchers wrote.

Regarding survival, 83 patients had died after a median follow-up of more than 42 months. "Among the 190 patients [who] underwent RFA, 41 (21.6%) died during the follow-up period; 97 (51.1%) were alive with regular visits" until Jan. 31, 2010, and the remaining 52 (27.4%) were lost to follow-up sometime before 2010.

In comparison, there were 42 deaths (18.3%) among the SR group, with 120 patients known to be alive through Jan. 31, 2010 (52.4%), and the remaining 67 patients (29.3%) lost to follow-up.

"The cumulative overall survival rates at 1, 2, 3, and 5 years were 97.3%, 92.2%, 88.2%, and 79.3% in the SR group and 96.6%, 86.7%, 77.3%, and 67.4% in the RFA group, respectively," a significant difference in univariate analysis (P less than 0.009), wrote the authors.

However, after controlling for the older age and comorbidities of the RFA group in multivariate analysis, the authors found that RFA was not an independent risk factor associated with poor survival.

Next, the authors looked at factors associated with cancer recurrence. Overall, 244 patients had experienced tumor recurrence at a median of 14.5 months following RFA or SR.

"The cumulative recurrence rates at 1, 2, 3, and 5 years were 17.4%, 30.5%, 43.9%, and 59.1% in the SR group and 37.4%, 54.1%, 71.0%, and 79.5% in the RFA group, respectively (P less than .001)," they reported.

As with survival, that translated to a significantly higher univariate risk of recurrence among RFA patients (hazard ratio, 2.05; 95% confidence interval, 1.58-2.65). When assessed in a multivariate analysis, RFA was still significantly associated with cancer recurrence (HR, 1.95; 95% CI, 1.48-2.57; P less than .001).

The finding of equal survival but greater recurrence among RFA patients persisted in a third propensity analysis, which employed nearest-neighbor one-to-one matching of 84 patients in each group in terms of age, sex, tumor size, tumor number, platelet counts, hepatitis status, and several other parameters.

The only subgroup for which RFA was equal to SR in terms of both survival and tumor recurrence was patients with solitary hepatocellular carcinoma less than 2 cm in size, known as "very early small HCC (Barcelona Clinic Liver Cancer stage 0)" tumors.

According to the authors, their study "highlights the importance of close surveillance after local ablation therapy." Additionally, the authors concluded that RFA may be a good alternative to surgical resection for BCLC stage 0 HCC, although prospective study is needed.

Dr. Hung and colleagues disclosed no conflicts of interest related to this study.

Although percutaneous radiofrequency ablation and surgical resection for small hepatocellular carcinomas have similar survival rates, ablation patients have a higher rate of cancer recurrence, compared with surgical resection patients, reported Dr. Hung-Hsu Hung and colleagues in the January issue of Clinical Gastroenterology and Hepatology.

Dr. Hung, of Taipei (Taiwan) Veterans General Hospital and the National Yang-Ming University, also in Taipei, looked at 419 consecutive patients who underwent radiofrequency ablation (RFA) or surgical resection (SR) at the hospital in 2002-2007. All patients had no more than three small (5 cm or less) liver tumors without extrahepatic metastasis (Clin. Gastroenterol. Hepatol. 2011 January [doi:10.1016/j.cgh.2010.08.018]).

In all, 190 patients underwent RFA and the remaining 229 underwent SR to treat their liver cancer. Patients who chose SR were on average slightly younger (60 years vs. 67 years; P less than .001). This was expected, given the invasive nature of the surgery.

Additionally, the authors found that there was a higher proportion of patients with chronic hepatitis B in the SR group than in the RFA group (59.8% vs. 46.3%; P = .004), whereas chronic hepatitis C was more common in the RFA group (44.7% vs. 26.6%; P less than .001).

This was also an expected finding, because in chronic HBV infection, hepatocellular carcinomas tend to occur at a younger age, the researchers wrote.

Regarding survival, 83 patients had died after a median follow-up of more than 42 months. "Among the 190 patients [who] underwent RFA, 41 (21.6%) died during the follow-up period; 97 (51.1%) were alive with regular visits" until Jan. 31, 2010, and the remaining 52 (27.4%) were lost to follow-up sometime before 2010.

In comparison, there were 42 deaths (18.3%) among the SR group, with 120 patients known to be alive through Jan. 31, 2010 (52.4%), and the remaining 67 patients (29.3%) lost to follow-up.

"The cumulative overall survival rates at 1, 2, 3, and 5 years were 97.3%, 92.2%, 88.2%, and 79.3% in the SR group and 96.6%, 86.7%, 77.3%, and 67.4% in the RFA group, respectively," a significant difference in univariate analysis (P less than 0.009), wrote the authors.

However, after controlling for the older age and comorbidities of the RFA group in multivariate analysis, the authors found that RFA was not an independent risk factor associated with poor survival.

Next, the authors looked at factors associated with cancer recurrence. Overall, 244 patients had experienced tumor recurrence at a median of 14.5 months following RFA or SR.

"The cumulative recurrence rates at 1, 2, 3, and 5 years were 17.4%, 30.5%, 43.9%, and 59.1% in the SR group and 37.4%, 54.1%, 71.0%, and 79.5% in the RFA group, respectively (P less than .001)," they reported.

As with survival, that translated to a significantly higher univariate risk of recurrence among RFA patients (hazard ratio, 2.05; 95% confidence interval, 1.58-2.65). When assessed in a multivariate analysis, RFA was still significantly associated with cancer recurrence (HR, 1.95; 95% CI, 1.48-2.57; P less than .001).

The finding of equal survival but greater recurrence among RFA patients persisted in a third propensity analysis, which employed nearest-neighbor one-to-one matching of 84 patients in each group in terms of age, sex, tumor size, tumor number, platelet counts, hepatitis status, and several other parameters.

The only subgroup for which RFA was equal to SR in terms of both survival and tumor recurrence was patients with solitary hepatocellular carcinoma less than 2 cm in size, known as "very early small HCC (Barcelona Clinic Liver Cancer stage 0)" tumors.

According to the authors, their study "highlights the importance of close surveillance after local ablation therapy." Additionally, the authors concluded that RFA may be a good alternative to surgical resection for BCLC stage 0 HCC, although prospective study is needed.

Dr. Hung and colleagues disclosed no conflicts of interest related to this study.

Although percutaneous radiofrequency ablation and surgical resection for small hepatocellular carcinomas have similar survival rates, ablation patients have a higher rate of cancer recurrence, compared with surgical resection patients, reported Dr. Hung-Hsu Hung and colleagues in the January issue of Clinical Gastroenterology and Hepatology.

Dr. Hung, of Taipei (Taiwan) Veterans General Hospital and the National Yang-Ming University, also in Taipei, looked at 419 consecutive patients who underwent radiofrequency ablation (RFA) or surgical resection (SR) at the hospital in 2002-2007. All patients had no more than three small (5 cm or less) liver tumors without extrahepatic metastasis (Clin. Gastroenterol. Hepatol. 2011 January [doi:10.1016/j.cgh.2010.08.018]).

In all, 190 patients underwent RFA and the remaining 229 underwent SR to treat their liver cancer. Patients who chose SR were on average slightly younger (60 years vs. 67 years; P less than .001). This was expected, given the invasive nature of the surgery.

Additionally, the authors found that there was a higher proportion of patients with chronic hepatitis B in the SR group than in the RFA group (59.8% vs. 46.3%; P = .004), whereas chronic hepatitis C was more common in the RFA group (44.7% vs. 26.6%; P less than .001).

This was also an expected finding, because in chronic HBV infection, hepatocellular carcinomas tend to occur at a younger age, the researchers wrote.

Regarding survival, 83 patients had died after a median follow-up of more than 42 months. "Among the 190 patients [who] underwent RFA, 41 (21.6%) died during the follow-up period; 97 (51.1%) were alive with regular visits" until Jan. 31, 2010, and the remaining 52 (27.4%) were lost to follow-up sometime before 2010.

In comparison, there were 42 deaths (18.3%) among the SR group, with 120 patients known to be alive through Jan. 31, 2010 (52.4%), and the remaining 67 patients (29.3%) lost to follow-up.

"The cumulative overall survival rates at 1, 2, 3, and 5 years were 97.3%, 92.2%, 88.2%, and 79.3% in the SR group and 96.6%, 86.7%, 77.3%, and 67.4% in the RFA group, respectively," a significant difference in univariate analysis (P less than 0.009), wrote the authors.

However, after controlling for the older age and comorbidities of the RFA group in multivariate analysis, the authors found that RFA was not an independent risk factor associated with poor survival.

Next, the authors looked at factors associated with cancer recurrence. Overall, 244 patients had experienced tumor recurrence at a median of 14.5 months following RFA or SR.

"The cumulative recurrence rates at 1, 2, 3, and 5 years were 17.4%, 30.5%, 43.9%, and 59.1% in the SR group and 37.4%, 54.1%, 71.0%, and 79.5% in the RFA group, respectively (P less than .001)," they reported.

As with survival, that translated to a significantly higher univariate risk of recurrence among RFA patients (hazard ratio, 2.05; 95% confidence interval, 1.58-2.65). When assessed in a multivariate analysis, RFA was still significantly associated with cancer recurrence (HR, 1.95; 95% CI, 1.48-2.57; P less than .001).

The finding of equal survival but greater recurrence among RFA patients persisted in a third propensity analysis, which employed nearest-neighbor one-to-one matching of 84 patients in each group in terms of age, sex, tumor size, tumor number, platelet counts, hepatitis status, and several other parameters.

The only subgroup for which RFA was equal to SR in terms of both survival and tumor recurrence was patients with solitary hepatocellular carcinoma less than 2 cm in size, known as "very early small HCC (Barcelona Clinic Liver Cancer stage 0)" tumors.

According to the authors, their study "highlights the importance of close surveillance after local ablation therapy." Additionally, the authors concluded that RFA may be a good alternative to surgical resection for BCLC stage 0 HCC, although prospective study is needed.

Dr. Hung and colleagues disclosed no conflicts of interest related to this study.

Although percutaneous radiofrequency ablation and surgical resection for small hepatocellular carcinomas have similar survival rates, ablation patients have a higher rate of cancer recurrence, compared with surgical resection patients, reported Dr. Hung-Hsu Hung and colleagues in the January issue of Clinical Gastroenterology and Hepatology.

Dr. Hung, of Taipei (Taiwan) Veterans General Hospital and the National Yang-Ming University, also in Taipei, looked at 419 consecutive patients who underwent radiofrequency ablation (RFA) or surgical resection (SR) at the hospital in 2002-2007. All patients had no more than three small (5 cm or less) liver tumors without extrahepatic metastasis (Clin. Gastroenterol. Hepatol. 2011 January [doi:10.1016/j.cgh.2010.08.018]).

In all, 190 patients underwent RFA and the remaining 229 underwent SR to treat their liver cancer. Patients who chose SR were on average slightly younger (60 years vs. 67 years; P less than .001). This was expected, given the invasive nature of the surgery.

Additionally, the authors found that there was a higher proportion of patients with chronic hepatitis B in the SR group than in the RFA group (59.8% vs. 46.3%; P = .004), whereas chronic hepatitis C was more common in the RFA group (44.7% vs. 26.6%; P less than .001).

This was also an expected finding, because in chronic HBV infection, hepatocellular carcinomas tend to occur at a younger age, the researchers wrote.

Regarding survival, 83 patients had died after a median follow-up of more than 42 months. "Among the 190 patients [who] underwent RFA, 41 (21.6%) died during the follow-up period; 97 (51.1%) were alive with regular visits" until Jan. 31, 2010, and the remaining 52 (27.4%) were lost to follow-up sometime before 2010.

In comparison, there were 42 deaths (18.3%) among the SR group, with 120 patients known to be alive through Jan. 31, 2010 (52.4%), and the remaining 67 patients (29.3%) lost to follow-up.

"The cumulative overall survival rates at 1, 2, 3, and 5 years were 97.3%, 92.2%, 88.2%, and 79.3% in the SR group and 96.6%, 86.7%, 77.3%, and 67.4% in the RFA group, respectively," a significant difference in univariate analysis (P less than 0.009), wrote the authors.

However, after controlling for the older age and comorbidities of the RFA group in multivariate analysis, the authors found that RFA was not an independent risk factor associated with poor survival.

Next, the authors looked at factors associated with cancer recurrence. Overall, 244 patients had experienced tumor recurrence at a median of 14.5 months following RFA or SR.

"The cumulative recurrence rates at 1, 2, 3, and 5 years were 17.4%, 30.5%, 43.9%, and 59.1% in the SR group and 37.4%, 54.1%, 71.0%, and 79.5% in the RFA group, respectively (P less than .001)," they reported.

As with survival, that translated to a significantly higher univariate risk of recurrence among RFA patients (hazard ratio, 2.05; 95% confidence interval, 1.58-2.65). When assessed in a multivariate analysis, RFA was still significantly associated with cancer recurrence (HR, 1.95; 95% CI, 1.48-2.57; P less than .001).

The finding of equal survival but greater recurrence among RFA patients persisted in a third propensity analysis, which employed nearest-neighbor one-to-one matching of 84 patients in each group in terms of age, sex, tumor size, tumor number, platelet counts, hepatitis status, and several other parameters.

The only subgroup for which RFA was equal to SR in terms of both survival and tumor recurrence was patients with solitary hepatocellular carcinoma less than 2 cm in size, known as "very early small HCC (Barcelona Clinic Liver Cancer stage 0)" tumors.

According to the authors, their study "highlights the importance of close surveillance after local ablation therapy." Additionally, the authors concluded that RFA may be a good alternative to surgical resection for BCLC stage 0 HCC, although prospective study is needed.

Dr. Hung and colleagues disclosed no conflicts of interest related to this study.

Although percutaneous radiofrequency ablation and surgical resection for small hepatocellular carcinomas have similar survival rates, ablation patients have a higher rate of cancer recurrence, compared with surgical resection patients, reported Dr. Hung-Hsu Hung and colleagues in the January issue of Clinical Gastroenterology and Hepatology.

Dr. Hung, of Taipei (Taiwan) Veterans General Hospital and the National Yang-Ming University, also in Taipei, looked at 419 consecutive patients who underwent radiofrequency ablation (RFA) or surgical resection (SR) at the hospital in 2002-2007. All patients had no more than three small (5 cm or less) liver tumors without extrahepatic metastasis (Clin. Gastroenterol. Hepatol. 2011 January [doi:10.1016/j.cgh.2010.08.018]).

In all, 190 patients underwent RFA and the remaining 229 underwent SR to treat their liver cancer. Patients who chose SR were on average slightly younger (60 years vs. 67 years; P less than .001). This was expected, given the invasive nature of the surgery.

Additionally, the authors found that there was a higher proportion of patients with chronic hepatitis B in the SR group than in the RFA group (59.8% vs. 46.3%; P = .004), whereas chronic hepatitis C was more common in the RFA group (44.7% vs. 26.6%; P less than .001).

This was also an expected finding, because in chronic HBV infection, hepatocellular carcinomas tend to occur at a younger age, the researchers wrote.

Regarding survival, 83 patients had died after a median follow-up of more than 42 months. "Among the 190 patients [who] underwent RFA, 41 (21.6%) died during the follow-up period; 97 (51.1%) were alive with regular visits" until Jan. 31, 2010, and the remaining 52 (27.4%) were lost to follow-up sometime before 2010.

In comparison, there were 42 deaths (18.3%) among the SR group, with 120 patients known to be alive through Jan. 31, 2010 (52.4%), and the remaining 67 patients (29.3%) lost to follow-up.

"The cumulative overall survival rates at 1, 2, 3, and 5 years were 97.3%, 92.2%, 88.2%, and 79.3% in the SR group and 96.6%, 86.7%, 77.3%, and 67.4% in the RFA group, respectively," a significant difference in univariate analysis (P less than 0.009), wrote the authors.

However, after controlling for the older age and comorbidities of the RFA group in multivariate analysis, the authors found that RFA was not an independent risk factor associated with poor survival.

Next, the authors looked at factors associated with cancer recurrence. Overall, 244 patients had experienced tumor recurrence at a median of 14.5 months following RFA or SR.

"The cumulative recurrence rates at 1, 2, 3, and 5 years were 17.4%, 30.5%, 43.9%, and 59.1% in the SR group and 37.4%, 54.1%, 71.0%, and 79.5% in the RFA group, respectively (P less than .001)," they reported.

As with survival, that translated to a significantly higher univariate risk of recurrence among RFA patients (hazard ratio, 2.05; 95% confidence interval, 1.58-2.65). When assessed in a multivariate analysis, RFA was still significantly associated with cancer recurrence (HR, 1.95; 95% CI, 1.48-2.57; P less than .001).

The finding of equal survival but greater recurrence among RFA patients persisted in a third propensity analysis, which employed nearest-neighbor one-to-one matching of 84 patients in each group in terms of age, sex, tumor size, tumor number, platelet counts, hepatitis status, and several other parameters.

The only subgroup for which RFA was equal to SR in terms of both survival and tumor recurrence was patients with solitary hepatocellular carcinoma less than 2 cm in size, known as "very early small HCC (Barcelona Clinic Liver Cancer stage 0)" tumors.

According to the authors, their study "highlights the importance of close surveillance after local ablation therapy." Additionally, the authors concluded that RFA may be a good alternative to surgical resection for BCLC stage 0 HCC, although prospective study is needed.

Dr. Hung and colleagues disclosed no conflicts of interest related to this study.

Patients with concomitant inflammatory bowel disease and primary sclerosing cholangitis often develop colon cancer soon after they are found to have the two coexisting diseases, reported Dr. Erin Withers Thackeray and colleagues in the January issue of Clinical Gastroenterology and Hepatology.

The finding supports the current guideline of annual colonoscopies in these patients, and reinforces the need for counseling and education in this population, she added. The yearly colonoscopies should begin when PSC is diagnosed in an IBD patient, or when IBD is diagnosed in a PSC patient, the authors said (Clin. Gastroenterol. Hepatol. 2011 January [doi:10.1016/j.cgh.2010.09.020]).

Dr. Thackeray of the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., performed a retrospective chart review of all adult patients with both IBD and PSC who had available pathology reports from colonoscopy or surgery, and who had a biopsy showing colon cancer or dysplasia.

Patients who had undergone colon resection or had a history of previous colorectal cancer or dysplasia were excluded from the study; patients with liver transplant were not excluded.

A total of 54 patients met the study criteria of having both IBD and PSC, plus colonic neoplasia. The study included 16 women and 38 men, with a mean age of 44 years for diagnosis of both diseases.

Overall, 38 of the patients had a diagnosis of IBD that preceded PSC diagnosis by a median of 11 years (with IBD defined as Crohn’s disease, chronic ulcerative colitis, or indeterminate colitis). IBD and PSC were diagnosed simultaneously in seven patients, and nine patients developed IBD a median of 4 years following PSC diagnosis. For the current study, analysis began once both diagnoses were confirmed.

Patients were followed for a mean of 4.2 years, during which time each patient had a median of three colonoscopies (range, two to four). The breakdown of biopsy findings included 14 patients with colorectal carcinoma, 7 with high-grade dysplasia, 3 with dysplasia-associated lesions or masses, and 30 patients with low-grade dysplasia. The dysplasia grade was determined according to the Inflammatory Bowel Disease/Dysplasia Morphology Study Group (Hum. Pathol. 1983;14:931-68).

According to the authors, in the 2-year period following diagnosis of PSC and IBD, there were 21.5 occurrences of either colon cancer or dysplasia per 100 person-years, including 7.6 occurrences of cancer. That was similar to the rate of cancer or dysplasia that occurred 8-10 years after dual diagnosis (20.4 cases per 100 person-years of follow-up, including 6.8 occurrences of cancer).

The authors also sought to characterize the type and location of these early cancers in the patients with IBD and PSC. They found that all 14 cancers were adenocarcinomas, 2 of which were located in the cecum; 5 were in the ascending colon, 4 were in the transverse colon, and 3 were in the rectosigmoid colon.

Regarding the stage of the cancers, the authors noted that "according to the [American Joint Committee on Cancer] staging system for colon cancer, 2 patients had stage I cancer, 4 had stage IIA cancer, 4 had stage IIIB cancer, 2 had stage IIIC, and 2 had stage IV cancer." Four patients died of their malignancy.

In addition to confirming the early occurrence of dysplasia in this population, the study offers what the authors call the first evidence to support the current recommendation for annual colonoscopies in patients with PSC and IBD.

It also characterizes the "widespread" nature of neoplasms that do develop, the authors said, "demonstrating that colonoscopy rather than sigmoidoscopy is important for surveillance purposes in this population."

However, there were limitations, including the fact that the study depended on the accuracy of the medical record, and that the Mayo Clinic is a referral center, "which may influence our patient population and limits follow-up in some cases."

Nevertheless, "future directions for research in this population include determining specific clinical characteristics that can identify patients who are at higher risk for developing colon cancer," wrote the authors.

The authors stated that they had no disclosures relevant to this study.

Patients with concomitant inflammatory bowel disease and primary sclerosing cholangitis often develop colon cancer soon after they are found to have the two coexisting diseases, reported Dr. Erin Withers Thackeray and colleagues in the January issue of Clinical Gastroenterology and Hepatology.

The finding supports the current guideline of annual colonoscopies in these patients, and reinforces the need for counseling and education in this population, she added. The yearly colonoscopies should begin when PSC is diagnosed in an IBD patient, or when IBD is diagnosed in a PSC patient, the authors said (Clin. Gastroenterol. Hepatol. 2011 January [doi:10.1016/j.cgh.2010.09.020]).

Dr. Thackeray of the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., performed a retrospective chart review of all adult patients with both IBD and PSC who had available pathology reports from colonoscopy or surgery, and who had a biopsy showing colon cancer or dysplasia.

Patients who had undergone colon resection or had a history of previous colorectal cancer or dysplasia were excluded from the study; patients with liver transplant were not excluded.

A total of 54 patients met the study criteria of having both IBD and PSC, plus colonic neoplasia. The study included 16 women and 38 men, with a mean age of 44 years for diagnosis of both diseases.

Overall, 38 of the patients had a diagnosis of IBD that preceded PSC diagnosis by a median of 11 years (with IBD defined as Crohn’s disease, chronic ulcerative colitis, or indeterminate colitis). IBD and PSC were diagnosed simultaneously in seven patients, and nine patients developed IBD a median of 4 years following PSC diagnosis. For the current study, analysis began once both diagnoses were confirmed.

Patients were followed for a mean of 4.2 years, during which time each patient had a median of three colonoscopies (range, two to four). The breakdown of biopsy findings included 14 patients with colorectal carcinoma, 7 with high-grade dysplasia, 3 with dysplasia-associated lesions or masses, and 30 patients with low-grade dysplasia. The dysplasia grade was determined according to the Inflammatory Bowel Disease/Dysplasia Morphology Study Group (Hum. Pathol. 1983;14:931-68).

According to the authors, in the 2-year period following diagnosis of PSC and IBD, there were 21.5 occurrences of either colon cancer or dysplasia per 100 person-years, including 7.6 occurrences of cancer. That was similar to the rate of cancer or dysplasia that occurred 8-10 years after dual diagnosis (20.4 cases per 100 person-years of follow-up, including 6.8 occurrences of cancer).

The authors also sought to characterize the type and location of these early cancers in the patients with IBD and PSC. They found that all 14 cancers were adenocarcinomas, 2 of which were located in the cecum; 5 were in the ascending colon, 4 were in the transverse colon, and 3 were in the rectosigmoid colon.

Regarding the stage of the cancers, the authors noted that "according to the [American Joint Committee on Cancer] staging system for colon cancer, 2 patients had stage I cancer, 4 had stage IIA cancer, 4 had stage IIIB cancer, 2 had stage IIIC, and 2 had stage IV cancer." Four patients died of their malignancy.

In addition to confirming the early occurrence of dysplasia in this population, the study offers what the authors call the first evidence to support the current recommendation for annual colonoscopies in patients with PSC and IBD.

It also characterizes the "widespread" nature of neoplasms that do develop, the authors said, "demonstrating that colonoscopy rather than sigmoidoscopy is important for surveillance purposes in this population."

However, there were limitations, including the fact that the study depended on the accuracy of the medical record, and that the Mayo Clinic is a referral center, "which may influence our patient population and limits follow-up in some cases."

Nevertheless, "future directions for research in this population include determining specific clinical characteristics that can identify patients who are at higher risk for developing colon cancer," wrote the authors.

The authors stated that they had no disclosures relevant to this study.

Patients with concomitant inflammatory bowel disease and primary sclerosing cholangitis often develop colon cancer soon after they are found to have the two coexisting diseases, reported Dr. Erin Withers Thackeray and colleagues in the January issue of Clinical Gastroenterology and Hepatology.

The finding supports the current guideline of annual colonoscopies in these patients, and reinforces the need for counseling and education in this population, she added. The yearly colonoscopies should begin when PSC is diagnosed in an IBD patient, or when IBD is diagnosed in a PSC patient, the authors said (Clin. Gastroenterol. Hepatol. 2011 January [doi:10.1016/j.cgh.2010.09.020]).

Dr. Thackeray of the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., performed a retrospective chart review of all adult patients with both IBD and PSC who had available pathology reports from colonoscopy or surgery, and who had a biopsy showing colon cancer or dysplasia.

Patients who had undergone colon resection or had a history of previous colorectal cancer or dysplasia were excluded from the study; patients with liver transplant were not excluded.

A total of 54 patients met the study criteria of having both IBD and PSC, plus colonic neoplasia. The study included 16 women and 38 men, with a mean age of 44 years for diagnosis of both diseases.

Overall, 38 of the patients had a diagnosis of IBD that preceded PSC diagnosis by a median of 11 years (with IBD defined as Crohn’s disease, chronic ulcerative colitis, or indeterminate colitis). IBD and PSC were diagnosed simultaneously in seven patients, and nine patients developed IBD a median of 4 years following PSC diagnosis. For the current study, analysis began once both diagnoses were confirmed.

Patients were followed for a mean of 4.2 years, during which time each patient had a median of three colonoscopies (range, two to four). The breakdown of biopsy findings included 14 patients with colorectal carcinoma, 7 with high-grade dysplasia, 3 with dysplasia-associated lesions or masses, and 30 patients with low-grade dysplasia. The dysplasia grade was determined according to the Inflammatory Bowel Disease/Dysplasia Morphology Study Group (Hum. Pathol. 1983;14:931-68).

According to the authors, in the 2-year period following diagnosis of PSC and IBD, there were 21.5 occurrences of either colon cancer or dysplasia per 100 person-years, including 7.6 occurrences of cancer. That was similar to the rate of cancer or dysplasia that occurred 8-10 years after dual diagnosis (20.4 cases per 100 person-years of follow-up, including 6.8 occurrences of cancer).

The authors also sought to characterize the type and location of these early cancers in the patients with IBD and PSC. They found that all 14 cancers were adenocarcinomas, 2 of which were located in the cecum; 5 were in the ascending colon, 4 were in the transverse colon, and 3 were in the rectosigmoid colon.

Regarding the stage of the cancers, the authors noted that "according to the [American Joint Committee on Cancer] staging system for colon cancer, 2 patients had stage I cancer, 4 had stage IIA cancer, 4 had stage IIIB cancer, 2 had stage IIIC, and 2 had stage IV cancer." Four patients died of their malignancy.

In addition to confirming the early occurrence of dysplasia in this population, the study offers what the authors call the first evidence to support the current recommendation for annual colonoscopies in patients with PSC and IBD.

It also characterizes the "widespread" nature of neoplasms that do develop, the authors said, "demonstrating that colonoscopy rather than sigmoidoscopy is important for surveillance purposes in this population."

However, there were limitations, including the fact that the study depended on the accuracy of the medical record, and that the Mayo Clinic is a referral center, "which may influence our patient population and limits follow-up in some cases."

Nevertheless, "future directions for research in this population include determining specific clinical characteristics that can identify patients who are at higher risk for developing colon cancer," wrote the authors.

The authors stated that they had no disclosures relevant to this study.

Esophageal distensibility was significantly limited in patients with eosinophilic esophagitis, compared with healthy controls, reported Monika A. Kwiatek, Ph.D., and colleagues in the January issue of Gastroenterology.

The finding, which represents "the first quantification of reduced esophageal distensibility in EoE," could make distensibility "a useful objective measure to characterize disease severity ... [given that] solid food dysphagia and food impaction are likely dependent on the opening aperture of the esophagus," wrote the researchers (Gastroenterology 2011 January [doi:10.1053/j.gastro.2010.09.037]).

Dr. Kwiatek of the division of gastroenterology at Northwestern University, Chicago, looked at 33 patients with EoE, including 22 males and 11 females (age range, 19-67 years). Patients were from the gastroenterology clinic at Northwestern Memorial Faculty Foundation, and had current endoscopic biopsies with histopathology confirming EoE (that is, 15 or more eosinophils per high-powered field).

These patients were compared with a volunteer group of 15 healthy controls (6 males and 9 females, aged 21-68 years) who had no gastrointestinal symptoms and were not currently using gastrointestinal medications.

Esophageal volume was measured with a functional luminal imaging probe, known as the EndoFLIP, which uses impedance planimetry to determine multiple, adjacent, cross-sectional areas (CSAs) in the esophagus, according to the authors. The compliant, cylindrical bag is filled with a "specially formulated conductive solution" once it is inside the esophagus, which allows communication between electrodes inside the bag. The device is also capable of measuring intrabag pressure during distension, they added.

All subjects underwent esophagogastroduodenoscopy to evaluate for EoE and to help place the EndoFLIP across the esophagogastric junction (EGJ).

Dr. Kwiatek found that when the EndoFLIP bag was placed at the EGJ and inflated to 20 mL, controls had a median CSA of 15 mm2. That was significantly greater than EoE patients’ median CSA of 13 mm2 (P less than 0.05).

The difference was even greater when the EndoFLIP was further inflated to 30 mL. In this stage, controls had a median CSA of 22 mm2, whereas EoE patients registered a median of just 14 mm2 (P less than 0.05).

A similar – although not statistically significant – trend was seen when the EndoFLIP was used to measure pressure. With the bag inflated to 20 mL, control subjects had a median pressure of 19 mm Hg, compared with 21 mm Hg among EoE patients.

With the bag inflated to 30 mL, the pressure difference was once again even greater, although not significant (24 mm Hg among controls vs. 29 mm Hg among EoE patients).

The measures amounted to a "distensibility index" that was significantly lower among EoE patients, compared with controls, at both the 20-mL level (controls, 0.9 mm2/Hg vs. EoE patients, 0.5 mm2/Hg; P = .03) and the 30-mL threshold (controls, 0.8 mm2/Hg vs. EoE patients, 0.5 mm2/Hg; P = .01).

The authors also sought to determine whether esophageal distensibility was correlated with the degree of eosinophilic infiltration, or any other patient factors.

They found that none of the following factors were significantly related: mucosal eosinophil count, patient age and sex, and current gastrointestinal treatment at the time of the study.

The process of testing distensibility was well tolerated, according to the researchers. There were no cases of bleeding or mucosal tearing related to the subsequent esophageal biopsy.

"We hypothesize that measuring esophageal distensibility may be an important adjunct to the clinical management of EoE that potentially provides a more objective measure from which to guide medical and dilation therapy," concluded the authors.

"However, future studies done before and after therapy are required to determine whether reduced distensibility is responsive to treatment focused on reducing inflammation and fibrosis, and whether these changes are associated with improvement in patient reported symptom severity reported outcomes," they added.

The authors disclosed that the EndoFLIP equipment used in this study was provided by Crospon Ltd., maker of the device. One of the authors also disclosed serving on the advisory board for Crospon.

Esophageal distensibility was significantly limited in patients with eosinophilic esophagitis, compared with healthy controls, reported Monika A. Kwiatek, Ph.D., and colleagues in the January issue of Gastroenterology.

The finding, which represents "the first quantification of reduced esophageal distensibility in EoE," could make distensibility "a useful objective measure to characterize disease severity ... [given that] solid food dysphagia and food impaction are likely dependent on the opening aperture of the esophagus," wrote the researchers (Gastroenterology 2011 January [doi:10.1053/j.gastro.2010.09.037]).

Dr. Kwiatek of the division of gastroenterology at Northwestern University, Chicago, looked at 33 patients with EoE, including 22 males and 11 females (age range, 19-67 years). Patients were from the gastroenterology clinic at Northwestern Memorial Faculty Foundation, and had current endoscopic biopsies with histopathology confirming EoE (that is, 15 or more eosinophils per high-powered field).

These patients were compared with a volunteer group of 15 healthy controls (6 males and 9 females, aged 21-68 years) who had no gastrointestinal symptoms and were not currently using gastrointestinal medications.

Esophageal volume was measured with a functional luminal imaging probe, known as the EndoFLIP, which uses impedance planimetry to determine multiple, adjacent, cross-sectional areas (CSAs) in the esophagus, according to the authors. The compliant, cylindrical bag is filled with a "specially formulated conductive solution" once it is inside the esophagus, which allows communication between electrodes inside the bag. The device is also capable of measuring intrabag pressure during distension, they added.

All subjects underwent esophagogastroduodenoscopy to evaluate for EoE and to help place the EndoFLIP across the esophagogastric junction (EGJ).

Dr. Kwiatek found that when the EndoFLIP bag was placed at the EGJ and inflated to 20 mL, controls had a median CSA of 15 mm2. That was significantly greater than EoE patients’ median CSA of 13 mm2 (P less than 0.05).

The difference was even greater when the EndoFLIP was further inflated to 30 mL. In this stage, controls had a median CSA of 22 mm2, whereas EoE patients registered a median of just 14 mm2 (P less than 0.05).

A similar – although not statistically significant – trend was seen when the EndoFLIP was used to measure pressure. With the bag inflated to 20 mL, control subjects had a median pressure of 19 mm Hg, compared with 21 mm Hg among EoE patients.

With the bag inflated to 30 mL, the pressure difference was once again even greater, although not significant (24 mm Hg among controls vs. 29 mm Hg among EoE patients).

The measures amounted to a "distensibility index" that was significantly lower among EoE patients, compared with controls, at both the 20-mL level (controls, 0.9 mm2/Hg vs. EoE patients, 0.5 mm2/Hg; P = .03) and the 30-mL threshold (controls, 0.8 mm2/Hg vs. EoE patients, 0.5 mm2/Hg; P = .01).

The authors also sought to determine whether esophageal distensibility was correlated with the degree of eosinophilic infiltration, or any other patient factors.

They found that none of the following factors were significantly related: mucosal eosinophil count, patient age and sex, and current gastrointestinal treatment at the time of the study.

The process of testing distensibility was well tolerated, according to the researchers. There were no cases of bleeding or mucosal tearing related to the subsequent esophageal biopsy.

"We hypothesize that measuring esophageal distensibility may be an important adjunct to the clinical management of EoE that potentially provides a more objective measure from which to guide medical and dilation therapy," concluded the authors.

"However, future studies done before and after therapy are required to determine whether reduced distensibility is responsive to treatment focused on reducing inflammation and fibrosis, and whether these changes are associated with improvement in patient reported symptom severity reported outcomes," they added.

The authors disclosed that the EndoFLIP equipment used in this study was provided by Crospon Ltd., maker of the device. One of the authors also disclosed serving on the advisory board for Crospon.

Esophageal distensibility was significantly limited in patients with eosinophilic esophagitis, compared with healthy controls, reported Monika A. Kwiatek, Ph.D., and colleagues in the January issue of Gastroenterology.

The finding, which represents "the first quantification of reduced esophageal distensibility in EoE," could make distensibility "a useful objective measure to characterize disease severity ... [given that] solid food dysphagia and food impaction are likely dependent on the opening aperture of the esophagus," wrote the researchers (Gastroenterology 2011 January [doi:10.1053/j.gastro.2010.09.037]).

Dr. Kwiatek of the division of gastroenterology at Northwestern University, Chicago, looked at 33 patients with EoE, including 22 males and 11 females (age range, 19-67 years). Patients were from the gastroenterology clinic at Northwestern Memorial Faculty Foundation, and had current endoscopic biopsies with histopathology confirming EoE (that is, 15 or more eosinophils per high-powered field).

These patients were compared with a volunteer group of 15 healthy controls (6 males and 9 females, aged 21-68 years) who had no gastrointestinal symptoms and were not currently using gastrointestinal medications.

Esophageal volume was measured with a functional luminal imaging probe, known as the EndoFLIP, which uses impedance planimetry to determine multiple, adjacent, cross-sectional areas (CSAs) in the esophagus, according to the authors. The compliant, cylindrical bag is filled with a "specially formulated conductive solution" once it is inside the esophagus, which allows communication between electrodes inside the bag. The device is also capable of measuring intrabag pressure during distension, they added.

All subjects underwent esophagogastroduodenoscopy to evaluate for EoE and to help place the EndoFLIP across the esophagogastric junction (EGJ).

Dr. Kwiatek found that when the EndoFLIP bag was placed at the EGJ and inflated to 20 mL, controls had a median CSA of 15 mm2. That was significantly greater than EoE patients’ median CSA of 13 mm2 (P less than 0.05).

The difference was even greater when the EndoFLIP was further inflated to 30 mL. In this stage, controls had a median CSA of 22 mm2, whereas EoE patients registered a median of just 14 mm2 (P less than 0.05).

A similar – although not statistically significant – trend was seen when the EndoFLIP was used to measure pressure. With the bag inflated to 20 mL, control subjects had a median pressure of 19 mm Hg, compared with 21 mm Hg among EoE patients.

With the bag inflated to 30 mL, the pressure difference was once again even greater, although not significant (24 mm Hg among controls vs. 29 mm Hg among EoE patients).

The measures amounted to a "distensibility index" that was significantly lower among EoE patients, compared with controls, at both the 20-mL level (controls, 0.9 mm2/Hg vs. EoE patients, 0.5 mm2/Hg; P = .03) and the 30-mL threshold (controls, 0.8 mm2/Hg vs. EoE patients, 0.5 mm2/Hg; P = .01).

The authors also sought to determine whether esophageal distensibility was correlated with the degree of eosinophilic infiltration, or any other patient factors.

They found that none of the following factors were significantly related: mucosal eosinophil count, patient age and sex, and current gastrointestinal treatment at the time of the study.

The process of testing distensibility was well tolerated, according to the researchers. There were no cases of bleeding or mucosal tearing related to the subsequent esophageal biopsy.

"We hypothesize that measuring esophageal distensibility may be an important adjunct to the clinical management of EoE that potentially provides a more objective measure from which to guide medical and dilation therapy," concluded the authors.

"However, future studies done before and after therapy are required to determine whether reduced distensibility is responsive to treatment focused on reducing inflammation and fibrosis, and whether these changes are associated with improvement in patient reported symptom severity reported outcomes," they added.

The authors disclosed that the EndoFLIP equipment used in this study was provided by Crospon Ltd., maker of the device. One of the authors also disclosed serving on the advisory board for Crospon.