Sharon Worcester

MIAMI BEACH — All patients with nonalcoholic steatohepatitis, as well as those at risk for developing the condition, should be counseled about the importance of diet and exercise, while more aggressive therapy should be considered in those who fail to achieve 10% weight loss with diet and exercise alone, Dr. Stephen A. Harrison said at a meeting on hepatobiliary disease sponsored by the University of Miami.

Studies suggest that people who are overweight or obese have a substantially higher risk of nonalcoholic steatohepatitis (NASH). For example, about 3% of the general population has NASH, compared with 20%–40% of those with body mass index greater than 35 mg/kg2, said Dr. Harrison, chief of hepatology at Brooke Army Medical Center, San Antonio. Female gender, Hispanic ethnicity, diabetes, metabolic syndrome, age over 50, and elevated aspartate transaminase level are among other factors that have been associated with NASH risk.

Weight loss is the accepted standard for treatment, Dr. Harrison said. Studies consistently show that substantial weight loss results in improved histo- pathology. For example, in a recent randomized study evaluating the use of orlistat to augment weight loss, Dr. Harrison showed that patients in both the treatment and control groups who achieved greater than 9% weight loss had improvements in insulin resistance, steatosis, and inflammation, as well as significant reductions in NASH activity scores.

Control patients who were treated with dietary restrictions and vitamin E lost a mean of 6% of their body weight, compared with 8% weight loss in those also treated with orlistat, and no differences were seen between the groups with regard to histopathological outcomes. Orlistat can be considered a tool to help augment weight loss, but it is those patients who achieve greater than 9% weight loss who will benefit, Dr. Harrison noted.

Exercise has also been shown to be helpful in these patients. In one study of more than 1,500 individuals who exercised at a gym at least 1 day per week and who followed a diet low in processed carbohydrates, 6% of patients lost at least 5% of body weight, and nearly half of all patients with abnormal alanine transaminase (ALT) levels had ALT normalization at 1 year. Every 5% decrease in weight was associated with a 3.6-fold decrease in ALT, and participants also experienced reductions in triglycerides, blood pressure, and fasting glucose.

Data on adjustable gastric banding are quite provocative in terms of its effects on NASH, Dr. Harrison said. In one study of 36 patients who lost an average of 75 pounds by 25 months, 23 patients had NASH, and 82% of them had resolution of NASH.

Recent studies also appear to dispel the notion that the kind of rapid weight loss often associated with surgery can lead to worsening of steatohepatitis. Older data based on a single follow-up liver biopsy suggested that rapid weight loss was associated with increasing inflammation, but studies that are more recent have used serial biopsies, which showed an initial increase in inflammation, followed by resolution over time, he explained.

Pharmacotherapy is another option in those who can't or won't lose weight, Dr. Harrison said. Thiazolidinediones (glitazones) will form the foundation of therapy in the future in these patients, he said.

Studies of pioglitazone and rosiglitazone, for example, are very promising in regard to their effects on plasma glucose, hepatic insulin sensitivity, adiponectin levels, hepatic fat content, inflammation, steatosis, and fibrosis.

Other drugs, such as metformin, also show promise, but studies suggest that metformin is not associated with the histopathological improvements seen with the glitazones. Combination therapy, however, may be beneficial; metformin appears to mitigate the weight gain that can occur with the glitazones, he explained.

MIAMI BEACH — All patients with nonalcoholic steatohepatitis, as well as those at risk for developing the condition, should be counseled about the importance of diet and exercise, while more aggressive therapy should be considered in those who fail to achieve 10% weight loss with diet and exercise alone, Dr. Stephen A. Harrison said at a meeting on hepatobiliary disease sponsored by the University of Miami.

Studies suggest that people who are overweight or obese have a substantially higher risk of nonalcoholic steatohepatitis (NASH). For example, about 3% of the general population has NASH, compared with 20%–40% of those with body mass index greater than 35 mg/kg2, said Dr. Harrison, chief of hepatology at Brooke Army Medical Center, San Antonio. Female gender, Hispanic ethnicity, diabetes, metabolic syndrome, age over 50, and elevated aspartate transaminase level are among other factors that have been associated with NASH risk.

Weight loss is the accepted standard for treatment, Dr. Harrison said. Studies consistently show that substantial weight loss results in improved histo- pathology. For example, in a recent randomized study evaluating the use of orlistat to augment weight loss, Dr. Harrison showed that patients in both the treatment and control groups who achieved greater than 9% weight loss had improvements in insulin resistance, steatosis, and inflammation, as well as significant reductions in NASH activity scores.

Control patients who were treated with dietary restrictions and vitamin E lost a mean of 6% of their body weight, compared with 8% weight loss in those also treated with orlistat, and no differences were seen between the groups with regard to histopathological outcomes. Orlistat can be considered a tool to help augment weight loss, but it is those patients who achieve greater than 9% weight loss who will benefit, Dr. Harrison noted.

Exercise has also been shown to be helpful in these patients. In one study of more than 1,500 individuals who exercised at a gym at least 1 day per week and who followed a diet low in processed carbohydrates, 6% of patients lost at least 5% of body weight, and nearly half of all patients with abnormal alanine transaminase (ALT) levels had ALT normalization at 1 year. Every 5% decrease in weight was associated with a 3.6-fold decrease in ALT, and participants also experienced reductions in triglycerides, blood pressure, and fasting glucose.

Data on adjustable gastric banding are quite provocative in terms of its effects on NASH, Dr. Harrison said. In one study of 36 patients who lost an average of 75 pounds by 25 months, 23 patients had NASH, and 82% of them had resolution of NASH.

Recent studies also appear to dispel the notion that the kind of rapid weight loss often associated with surgery can lead to worsening of steatohepatitis. Older data based on a single follow-up liver biopsy suggested that rapid weight loss was associated with increasing inflammation, but studies that are more recent have used serial biopsies, which showed an initial increase in inflammation, followed by resolution over time, he explained.

Pharmacotherapy is another option in those who can't or won't lose weight, Dr. Harrison said. Thiazolidinediones (glitazones) will form the foundation of therapy in the future in these patients, he said.

Studies of pioglitazone and rosiglitazone, for example, are very promising in regard to their effects on plasma glucose, hepatic insulin sensitivity, adiponectin levels, hepatic fat content, inflammation, steatosis, and fibrosis.

Other drugs, such as metformin, also show promise, but studies suggest that metformin is not associated with the histopathological improvements seen with the glitazones. Combination therapy, however, may be beneficial; metformin appears to mitigate the weight gain that can occur with the glitazones, he explained.

MIAMI BEACH — All patients with nonalcoholic steatohepatitis, as well as those at risk for developing the condition, should be counseled about the importance of diet and exercise, while more aggressive therapy should be considered in those who fail to achieve 10% weight loss with diet and exercise alone, Dr. Stephen A. Harrison said at a meeting on hepatobiliary disease sponsored by the University of Miami.

Studies suggest that people who are overweight or obese have a substantially higher risk of nonalcoholic steatohepatitis (NASH). For example, about 3% of the general population has NASH, compared with 20%–40% of those with body mass index greater than 35 mg/kg2, said Dr. Harrison, chief of hepatology at Brooke Army Medical Center, San Antonio. Female gender, Hispanic ethnicity, diabetes, metabolic syndrome, age over 50, and elevated aspartate transaminase level are among other factors that have been associated with NASH risk.

Weight loss is the accepted standard for treatment, Dr. Harrison said. Studies consistently show that substantial weight loss results in improved histo- pathology. For example, in a recent randomized study evaluating the use of orlistat to augment weight loss, Dr. Harrison showed that patients in both the treatment and control groups who achieved greater than 9% weight loss had improvements in insulin resistance, steatosis, and inflammation, as well as significant reductions in NASH activity scores.

Control patients who were treated with dietary restrictions and vitamin E lost a mean of 6% of their body weight, compared with 8% weight loss in those also treated with orlistat, and no differences were seen between the groups with regard to histopathological outcomes. Orlistat can be considered a tool to help augment weight loss, but it is those patients who achieve greater than 9% weight loss who will benefit, Dr. Harrison noted.

Exercise has also been shown to be helpful in these patients. In one study of more than 1,500 individuals who exercised at a gym at least 1 day per week and who followed a diet low in processed carbohydrates, 6% of patients lost at least 5% of body weight, and nearly half of all patients with abnormal alanine transaminase (ALT) levels had ALT normalization at 1 year. Every 5% decrease in weight was associated with a 3.6-fold decrease in ALT, and participants also experienced reductions in triglycerides, blood pressure, and fasting glucose.

Data on adjustable gastric banding are quite provocative in terms of its effects on NASH, Dr. Harrison said. In one study of 36 patients who lost an average of 75 pounds by 25 months, 23 patients had NASH, and 82% of them had resolution of NASH.

Recent studies also appear to dispel the notion that the kind of rapid weight loss often associated with surgery can lead to worsening of steatohepatitis. Older data based on a single follow-up liver biopsy suggested that rapid weight loss was associated with increasing inflammation, but studies that are more recent have used serial biopsies, which showed an initial increase in inflammation, followed by resolution over time, he explained.

Pharmacotherapy is another option in those who can't or won't lose weight, Dr. Harrison said. Thiazolidinediones (glitazones) will form the foundation of therapy in the future in these patients, he said.

Studies of pioglitazone and rosiglitazone, for example, are very promising in regard to their effects on plasma glucose, hepatic insulin sensitivity, adiponectin levels, hepatic fat content, inflammation, steatosis, and fibrosis.

Other drugs, such as metformin, also show promise, but studies suggest that metformin is not associated with the histopathological improvements seen with the glitazones. Combination therapy, however, may be beneficial; metformin appears to mitigate the weight gain that can occur with the glitazones, he explained.

DESTIN, FLA. — The incidence of gout is on the rise, and lifestyle factors are largely to blame, Dr. N. Lawrence Edwards said at the annual Rheumatology on the Beach.

For example, one study showed that between 1977–1978 and 1995–1996, the annual rate of primary gout more than doubled, from about 16 cases/100,000 population to nearly 42 cases/100,000 population. Factors that appear to play a role in this incidence spike are greater longevity, widespread diuretic and aspirin use, hypertension incidence, obesity, metabolic syndrome, and dietary trends, said Dr. Edwards, professor and vice chairman of the department of medicine at the University of Florida, Gainesville.

Weight reduction, decreased alcohol consumption, and reduced intake of purine-rich foods (which have been linked with gout) will reduce urate levels only by about 1 mg/dL. Medical treatment should be considered early in patients presenting with acute attacks, he said.

Urate-lowering therapy, which 15 years ago was reserved for use in patients with chronic gout, now is considered warranted following the first one or two acute attacks.

Uricosuric agents, such a probenecid, and the xanthine oxidase inhibitor allopurinol are used for reducing urate levels, but uricosuric agents increase the risk of uric acid crystallization in the urine and associated stone formation. There are a number of other agents, such as ampicillin, penicillin, cephradine, heparin, and rifampicin, that can potentially affect the action of uricosuric agents, Dr. Edwards said.

Allopurinol, which is a purine analog that is both a substrate and inhibitor of xanthine oxidase, is effective both for people who overproduce and for those who underexcrete xanthine oxidase. The drug also has the convenience of single daily dosing, and it can be efficacious in patients with renal insufficiency.

However, allopurinol isn't always effective for achieving target serum urate levels and concerns about intolerance based on reports of severe hypersensitivity syndrome, rash, gastrointestinal problems, increases in liver enzymes, and bone marrow suppression, tend to scare physicians away from prescribing higher doses, he noted.

As with uricosuric agents, drug-drug interactions also are a problem with allopurinol.

Keys to effective treatment with this drug include dosing allopurinol to achieve a serum urate level between 5.0 and 6.0 mg/dL, which allows reduction of total body urate pool and mobilization of deposited crystals, Dr. Edwards said, stressing the need to start at a low dose of 50–100 mg/day, with close monitoring of escalation.

DESTIN, FLA. — The incidence of gout is on the rise, and lifestyle factors are largely to blame, Dr. N. Lawrence Edwards said at the annual Rheumatology on the Beach.

For example, one study showed that between 1977–1978 and 1995–1996, the annual rate of primary gout more than doubled, from about 16 cases/100,000 population to nearly 42 cases/100,000 population. Factors that appear to play a role in this incidence spike are greater longevity, widespread diuretic and aspirin use, hypertension incidence, obesity, metabolic syndrome, and dietary trends, said Dr. Edwards, professor and vice chairman of the department of medicine at the University of Florida, Gainesville.

Weight reduction, decreased alcohol consumption, and reduced intake of purine-rich foods (which have been linked with gout) will reduce urate levels only by about 1 mg/dL. Medical treatment should be considered early in patients presenting with acute attacks, he said.

Urate-lowering therapy, which 15 years ago was reserved for use in patients with chronic gout, now is considered warranted following the first one or two acute attacks.

Uricosuric agents, such a probenecid, and the xanthine oxidase inhibitor allopurinol are used for reducing urate levels, but uricosuric agents increase the risk of uric acid crystallization in the urine and associated stone formation. There are a number of other agents, such as ampicillin, penicillin, cephradine, heparin, and rifampicin, that can potentially affect the action of uricosuric agents, Dr. Edwards said.

Allopurinol, which is a purine analog that is both a substrate and inhibitor of xanthine oxidase, is effective both for people who overproduce and for those who underexcrete xanthine oxidase. The drug also has the convenience of single daily dosing, and it can be efficacious in patients with renal insufficiency.

However, allopurinol isn't always effective for achieving target serum urate levels and concerns about intolerance based on reports of severe hypersensitivity syndrome, rash, gastrointestinal problems, increases in liver enzymes, and bone marrow suppression, tend to scare physicians away from prescribing higher doses, he noted.

As with uricosuric agents, drug-drug interactions also are a problem with allopurinol.

Keys to effective treatment with this drug include dosing allopurinol to achieve a serum urate level between 5.0 and 6.0 mg/dL, which allows reduction of total body urate pool and mobilization of deposited crystals, Dr. Edwards said, stressing the need to start at a low dose of 50–100 mg/day, with close monitoring of escalation.

DESTIN, FLA. — The incidence of gout is on the rise, and lifestyle factors are largely to blame, Dr. N. Lawrence Edwards said at the annual Rheumatology on the Beach.

For example, one study showed that between 1977–1978 and 1995–1996, the annual rate of primary gout more than doubled, from about 16 cases/100,000 population to nearly 42 cases/100,000 population. Factors that appear to play a role in this incidence spike are greater longevity, widespread diuretic and aspirin use, hypertension incidence, obesity, metabolic syndrome, and dietary trends, said Dr. Edwards, professor and vice chairman of the department of medicine at the University of Florida, Gainesville.

Weight reduction, decreased alcohol consumption, and reduced intake of purine-rich foods (which have been linked with gout) will reduce urate levels only by about 1 mg/dL. Medical treatment should be considered early in patients presenting with acute attacks, he said.

Urate-lowering therapy, which 15 years ago was reserved for use in patients with chronic gout, now is considered warranted following the first one or two acute attacks.

Uricosuric agents, such a probenecid, and the xanthine oxidase inhibitor allopurinol are used for reducing urate levels, but uricosuric agents increase the risk of uric acid crystallization in the urine and associated stone formation. There are a number of other agents, such as ampicillin, penicillin, cephradine, heparin, and rifampicin, that can potentially affect the action of uricosuric agents, Dr. Edwards said.

Allopurinol, which is a purine analog that is both a substrate and inhibitor of xanthine oxidase, is effective both for people who overproduce and for those who underexcrete xanthine oxidase. The drug also has the convenience of single daily dosing, and it can be efficacious in patients with renal insufficiency.

However, allopurinol isn't always effective for achieving target serum urate levels and concerns about intolerance based on reports of severe hypersensitivity syndrome, rash, gastrointestinal problems, increases in liver enzymes, and bone marrow suppression, tend to scare physicians away from prescribing higher doses, he noted.

As with uricosuric agents, drug-drug interactions also are a problem with allopurinol.

Keys to effective treatment with this drug include dosing allopurinol to achieve a serum urate level between 5.0 and 6.0 mg/dL, which allows reduction of total body urate pool and mobilization of deposited crystals, Dr. Edwards said, stressing the need to start at a low dose of 50–100 mg/day, with close monitoring of escalation.

MIAMI BEACH — All patients with nonalcoholic steatohepatitis, as well as those at risk for developing the condition, should be counseled about the importance of diet and exercise, while more aggressive therapy should be considered in those who fail to achieve 10% weight loss with diet and exercise alone, Dr. Stephen A. Harrison said at a meeting on hepatobiliary disease sponsored by the University of Miami.

Studies suggest that people who are overweight or obese have a substantially higher risk of nonalcoholic steatohepatitis (NASH). For example, about 3% of the general population has NASH, compared with 20%–40% of those with body mass index greater than 35 mg/kg

Weight loss is the accepted standard for treatment, Dr. Harrison said. Studies consistently show that substantial weight loss results in improved histopathology. For example, in a recent randomized study evaluating the use of orlistat to augment weight loss, Dr. Harrison showed that patients in both the treatment and control groups who achieved greater than 9% weight loss had improvements in insulin resistance, steatosis, and inflammation, as well as significant reductions in NASH activity scores.

Control patients who were treated with dietary restrictions and vitamin E lost a mean of 6% of their body weight, compared with 8% weight loss in those also treated with orlistat, and no differences were seen between the groups with regard to histopathologic outcomes. Orlistat can be considered a tool to help augment weight loss, but it is those patients who achieve greater than 9% weight loss who will benefit, Dr. Harrison noted.

Exercise has also been shown to be helpful in these patients. In one study of more than 1,500 individuals who exercised at a gym at least 1 day per week and who followed a diet low in processed carbohydrates, 6% of patients lost at least 5% of body weight, and nearly half of all patients with abnormal alanine transaminase (ALT) levels had ALT normalization at 1 year. Every 5% decrease in weight was associated with a 3.6-fold decrease in ALT, and participants also experienced reductions in triglycerides, blood pressure, and fasting glucose.

Weight loss surgery is also an option, particularly for morbidly obese patients and those who are not able to lose enough weight through diet and exercise alone.

Data on adjustable gastric banding are quite provocative in terms of its effects on NASH, Dr. Harrison said. In one study of 36 patients who lost an average of 75 pounds by 25 months, 23 patients had NASH, and 82% of them had resolution of NASH.

Recent studies also appear to dispel the notion that the kind of rapid weight loss often associated with surgery can lead to worsening of steatohepatitis. Older data based on a single follow-up liver biopsy suggested that rapid weight loss was associated with increasing inflammation, but studies that are more recent have used serial biopsies, which showed an initial increase in inflammation, followed by resolution over time, he explained.

Pharmacotherapy is another option in those who can't or won't lose weight, Dr. Harrison said. Thiazolidinediones (glitazones) will form the foundation of therapy in the future in these patients, he said.

Studies of pioglitazone and rosiglitazone, are promising in regard to their effects on plasma glucose, hepatic insulin sensitivity, adiponectin levels, hepatic fat content, inflammation, steatosis, and fibrosis.

Other drugs, such as metformin, show promise, but studies suggest that metformin is not associated with the histopathologic improvements seen with the glitazones. Combination therapy, however, may be beneficial; metformin appears to mitigate the weight gain that can occur with the glitazones, Dr. Harrison said.

Who's at Risk for a NASH Diagnosis?

A composite index based on clinical and laboratory findings can help identify patients at risk of having NASH, Dr. Harrison said.

A study of 80 patients with biopsy-proven nonalcoholic fatty liver disease, including 39 with simple steatosis and 41 with NASH, showed that the index—including three of five of the following factors—has 74% sensitivity and 66% specificity for identifying patients at risk of NASH. The factors are aspartate transaminase (AST) of 45 U/L or over, body mass index of 30 kg/m

“So for instance, if you have a female over age 50 that's obese, her probability of having steatohepatitis is certainly greater than 50%,” he said.

In addition, in a recent study of 97 severely obese patients undergoing bariatric surgery, insulin resistance was shown to be more severe in patients with NASH, compared with those without NASH, and both AST level and the presence of diabetes were independently associated with a NASH diagnosis (Am. J. Gastroenterol. 2007;102:399–408).

Other studies have also shown an association between metabolic syndrome and NASH; one study found that 88% of patients with NASH had metabolic syndrome, Dr. Harrison noted.

MIAMI BEACH — All patients with nonalcoholic steatohepatitis, as well as those at risk for developing the condition, should be counseled about the importance of diet and exercise, while more aggressive therapy should be considered in those who fail to achieve 10% weight loss with diet and exercise alone, Dr. Stephen A. Harrison said at a meeting on hepatobiliary disease sponsored by the University of Miami.

Studies suggest that people who are overweight or obese have a substantially higher risk of nonalcoholic steatohepatitis (NASH). For example, about 3% of the general population has NASH, compared with 20%–40% of those with body mass index greater than 35 mg/kg

Weight loss is the accepted standard for treatment, Dr. Harrison said. Studies consistently show that substantial weight loss results in improved histopathology. For example, in a recent randomized study evaluating the use of orlistat to augment weight loss, Dr. Harrison showed that patients in both the treatment and control groups who achieved greater than 9% weight loss had improvements in insulin resistance, steatosis, and inflammation, as well as significant reductions in NASH activity scores.

Control patients who were treated with dietary restrictions and vitamin E lost a mean of 6% of their body weight, compared with 8% weight loss in those also treated with orlistat, and no differences were seen between the groups with regard to histopathologic outcomes. Orlistat can be considered a tool to help augment weight loss, but it is those patients who achieve greater than 9% weight loss who will benefit, Dr. Harrison noted.

Exercise has also been shown to be helpful in these patients. In one study of more than 1,500 individuals who exercised at a gym at least 1 day per week and who followed a diet low in processed carbohydrates, 6% of patients lost at least 5% of body weight, and nearly half of all patients with abnormal alanine transaminase (ALT) levels had ALT normalization at 1 year. Every 5% decrease in weight was associated with a 3.6-fold decrease in ALT, and participants also experienced reductions in triglycerides, blood pressure, and fasting glucose.

Weight loss surgery is also an option, particularly for morbidly obese patients and those who are not able to lose enough weight through diet and exercise alone.

Data on adjustable gastric banding are quite provocative in terms of its effects on NASH, Dr. Harrison said. In one study of 36 patients who lost an average of 75 pounds by 25 months, 23 patients had NASH, and 82% of them had resolution of NASH.

Recent studies also appear to dispel the notion that the kind of rapid weight loss often associated with surgery can lead to worsening of steatohepatitis. Older data based on a single follow-up liver biopsy suggested that rapid weight loss was associated with increasing inflammation, but studies that are more recent have used serial biopsies, which showed an initial increase in inflammation, followed by resolution over time, he explained.

Pharmacotherapy is another option in those who can't or won't lose weight, Dr. Harrison said. Thiazolidinediones (glitazones) will form the foundation of therapy in the future in these patients, he said.

Studies of pioglitazone and rosiglitazone, are promising in regard to their effects on plasma glucose, hepatic insulin sensitivity, adiponectin levels, hepatic fat content, inflammation, steatosis, and fibrosis.

Other drugs, such as metformin, show promise, but studies suggest that metformin is not associated with the histopathologic improvements seen with the glitazones. Combination therapy, however, may be beneficial; metformin appears to mitigate the weight gain that can occur with the glitazones, Dr. Harrison said.

Who's at Risk for a NASH Diagnosis?

A composite index based on clinical and laboratory findings can help identify patients at risk of having NASH, Dr. Harrison said.

A study of 80 patients with biopsy-proven nonalcoholic fatty liver disease, including 39 with simple steatosis and 41 with NASH, showed that the index—including three of five of the following factors—has 74% sensitivity and 66% specificity for identifying patients at risk of NASH. The factors are aspartate transaminase (AST) of 45 U/L or over, body mass index of 30 kg/m

“So for instance, if you have a female over age 50 that's obese, her probability of having steatohepatitis is certainly greater than 50%,” he said.

In addition, in a recent study of 97 severely obese patients undergoing bariatric surgery, insulin resistance was shown to be more severe in patients with NASH, compared with those without NASH, and both AST level and the presence of diabetes were independently associated with a NASH diagnosis (Am. J. Gastroenterol. 2007;102:399–408).

Other studies have also shown an association between metabolic syndrome and NASH; one study found that 88% of patients with NASH had metabolic syndrome, Dr. Harrison noted.

MIAMI BEACH — All patients with nonalcoholic steatohepatitis, as well as those at risk for developing the condition, should be counseled about the importance of diet and exercise, while more aggressive therapy should be considered in those who fail to achieve 10% weight loss with diet and exercise alone, Dr. Stephen A. Harrison said at a meeting on hepatobiliary disease sponsored by the University of Miami.

Studies suggest that people who are overweight or obese have a substantially higher risk of nonalcoholic steatohepatitis (NASH). For example, about 3% of the general population has NASH, compared with 20%–40% of those with body mass index greater than 35 mg/kg

Weight loss is the accepted standard for treatment, Dr. Harrison said. Studies consistently show that substantial weight loss results in improved histopathology. For example, in a recent randomized study evaluating the use of orlistat to augment weight loss, Dr. Harrison showed that patients in both the treatment and control groups who achieved greater than 9% weight loss had improvements in insulin resistance, steatosis, and inflammation, as well as significant reductions in NASH activity scores.

Control patients who were treated with dietary restrictions and vitamin E lost a mean of 6% of their body weight, compared with 8% weight loss in those also treated with orlistat, and no differences were seen between the groups with regard to histopathologic outcomes. Orlistat can be considered a tool to help augment weight loss, but it is those patients who achieve greater than 9% weight loss who will benefit, Dr. Harrison noted.

Exercise has also been shown to be helpful in these patients. In one study of more than 1,500 individuals who exercised at a gym at least 1 day per week and who followed a diet low in processed carbohydrates, 6% of patients lost at least 5% of body weight, and nearly half of all patients with abnormal alanine transaminase (ALT) levels had ALT normalization at 1 year. Every 5% decrease in weight was associated with a 3.6-fold decrease in ALT, and participants also experienced reductions in triglycerides, blood pressure, and fasting glucose.

Weight loss surgery is also an option, particularly for morbidly obese patients and those who are not able to lose enough weight through diet and exercise alone.

Data on adjustable gastric banding are quite provocative in terms of its effects on NASH, Dr. Harrison said. In one study of 36 patients who lost an average of 75 pounds by 25 months, 23 patients had NASH, and 82% of them had resolution of NASH.

Recent studies also appear to dispel the notion that the kind of rapid weight loss often associated with surgery can lead to worsening of steatohepatitis. Older data based on a single follow-up liver biopsy suggested that rapid weight loss was associated with increasing inflammation, but studies that are more recent have used serial biopsies, which showed an initial increase in inflammation, followed by resolution over time, he explained.

Pharmacotherapy is another option in those who can't or won't lose weight, Dr. Harrison said. Thiazolidinediones (glitazones) will form the foundation of therapy in the future in these patients, he said.

Studies of pioglitazone and rosiglitazone, are promising in regard to their effects on plasma glucose, hepatic insulin sensitivity, adiponectin levels, hepatic fat content, inflammation, steatosis, and fibrosis.

Other drugs, such as metformin, show promise, but studies suggest that metformin is not associated with the histopathologic improvements seen with the glitazones. Combination therapy, however, may be beneficial; metformin appears to mitigate the weight gain that can occur with the glitazones, Dr. Harrison said.

Who's at Risk for a NASH Diagnosis?

A composite index based on clinical and laboratory findings can help identify patients at risk of having NASH, Dr. Harrison said.

A study of 80 patients with biopsy-proven nonalcoholic fatty liver disease, including 39 with simple steatosis and 41 with NASH, showed that the index—including three of five of the following factors—has 74% sensitivity and 66% specificity for identifying patients at risk of NASH. The factors are aspartate transaminase (AST) of 45 U/L or over, body mass index of 30 kg/m

“So for instance, if you have a female over age 50 that's obese, her probability of having steatohepatitis is certainly greater than 50%,” he said.

In addition, in a recent study of 97 severely obese patients undergoing bariatric surgery, insulin resistance was shown to be more severe in patients with NASH, compared with those without NASH, and both AST level and the presence of diabetes were independently associated with a NASH diagnosis (Am. J. Gastroenterol. 2007;102:399–408).

Other studies have also shown an association between metabolic syndrome and NASH; one study found that 88% of patients with NASH had metabolic syndrome, Dr. Harrison noted.

SAN FRANCISCO – Women who have migraine with aura could be at increased risk for ischemic stroke, Leah MacClellan said at the 32nd International Stroke Conference.

She reported findings from a population-based case-control study of 386 women aged 15–49 years who presented with a first, nontraumatic ischemic stroke and 614 controls matched for age, race, and region.

The investigators stratified the odds of stroke among women with a history of migraine with aura, compared with women who did not have a history of migraine, by the presence of hypertension, diabetes, or myocardial infarction.

The associations were strongest among those with no history of these classic stroke risk factors, Ms. MacClellan explained at the conference, which was sponsored by the American Stroke Association.

For example, the odds ratio for stroke in those with migraine plus aura versus those with no history of migraine was 0.8 in those with hypertension, compared with 1.7 for those without hypertension; 1.2 in those with diabetes, compared with 1.5 in those without diabetes; and 0.2 in those with a history of MI, compared with 1.6 in those with no history of MI, said Ms. MacClellan of the University of Maryland, Baltimore. All associations were statistically significant.

“This finding is important because it suggests migraine might contribute to stroke independent of these classic risk factors,” she said.

A similar analysis stratifying stroke risk based on current smoking and oral contraceptive use in women with migraine plus aura, compared with women with no history of migraine, showed the associations between migraine with aura and stroke were the same regardless of smoking or OC use. However, the interaction between smoking and OC use was shown to be important, she reported.

Compared with women with migraine plus aura alone, those who smoked and had migraine plus aura had a significant 2.3-fold increased risk of stroke, as did those with migraine plus aura who used oral contraceptives. Women with migraine plus aura who smoked and also used OCs had a significant 7.3-fold increase in the odds of stroke.

“This finding is important because these are modifiable risk factors,” Ms. MacClellan noted.

Another finding of note from this study was that onset of migraine with aura in the past year was associated with increased stroke risk. Those with onset in the past year, compared with those with no history of migraine, had a significant 6.7-fold increased risk of stroke.

Those with a migraine history of more than 12 years had a non-statistically significant 1.4-fold increase in stroke risk. This finding contrasts with those from at least one other study showing that long-term migraine history was associated with increased stroke risk, she said.

The possibility that unrecognized disorders might explain the association between recent migraine onset and stroke risk in the current study warrants additional study, she said during a discussion that followed her presentation.

There was no evidence in the current study of a role for patent foramen ovale in mediating the association between migraine with aura and stroke, nor was there any evidence for preferential infarct location in terms of anterior and posterior circulation in those patients with migraine plus aura.

Patients in this study were identified from discharge data from 59 hospitals, and all had stroke that was confirmed by CT or MRI. Controls were ascertained by random digit dialing.

Migraine with aura was defined as headache with aura at least twice per year, with spots, lines, flashing lights, or loss of vision occurring around the time of the headache. Migraine without aura was defined as at least five headaches per year with nausea, vomiting, or sensitivity to light during headache, and no history of visual aura.

Migraine with aura was reported by 38% of patients and 29% of controls. The percentage with migraine without aura was similar in the two groups; thus the current analysis focused only on migraine with aura.

SAN FRANCISCO – Women who have migraine with aura could be at increased risk for ischemic stroke, Leah MacClellan said at the 32nd International Stroke Conference.

She reported findings from a population-based case-control study of 386 women aged 15–49 years who presented with a first, nontraumatic ischemic stroke and 614 controls matched for age, race, and region.

The investigators stratified the odds of stroke among women with a history of migraine with aura, compared with women who did not have a history of migraine, by the presence of hypertension, diabetes, or myocardial infarction.

The associations were strongest among those with no history of these classic stroke risk factors, Ms. MacClellan explained at the conference, which was sponsored by the American Stroke Association.

For example, the odds ratio for stroke in those with migraine plus aura versus those with no history of migraine was 0.8 in those with hypertension, compared with 1.7 for those without hypertension; 1.2 in those with diabetes, compared with 1.5 in those without diabetes; and 0.2 in those with a history of MI, compared with 1.6 in those with no history of MI, said Ms. MacClellan of the University of Maryland, Baltimore. All associations were statistically significant.

“This finding is important because it suggests migraine might contribute to stroke independent of these classic risk factors,” she said.

A similar analysis stratifying stroke risk based on current smoking and oral contraceptive use in women with migraine plus aura, compared with women with no history of migraine, showed the associations between migraine with aura and stroke were the same regardless of smoking or OC use. However, the interaction between smoking and OC use was shown to be important, she reported.

Compared with women with migraine plus aura alone, those who smoked and had migraine plus aura had a significant 2.3-fold increased risk of stroke, as did those with migraine plus aura who used oral contraceptives. Women with migraine plus aura who smoked and also used OCs had a significant 7.3-fold increase in the odds of stroke.

“This finding is important because these are modifiable risk factors,” Ms. MacClellan noted.

Another finding of note from this study was that onset of migraine with aura in the past year was associated with increased stroke risk. Those with onset in the past year, compared with those with no history of migraine, had a significant 6.7-fold increased risk of stroke.

Those with a migraine history of more than 12 years had a non-statistically significant 1.4-fold increase in stroke risk. This finding contrasts with those from at least one other study showing that long-term migraine history was associated with increased stroke risk, she said.

The possibility that unrecognized disorders might explain the association between recent migraine onset and stroke risk in the current study warrants additional study, she said during a discussion that followed her presentation.

There was no evidence in the current study of a role for patent foramen ovale in mediating the association between migraine with aura and stroke, nor was there any evidence for preferential infarct location in terms of anterior and posterior circulation in those patients with migraine plus aura.

Patients in this study were identified from discharge data from 59 hospitals, and all had stroke that was confirmed by CT or MRI. Controls were ascertained by random digit dialing.

Migraine with aura was defined as headache with aura at least twice per year, with spots, lines, flashing lights, or loss of vision occurring around the time of the headache. Migraine without aura was defined as at least five headaches per year with nausea, vomiting, or sensitivity to light during headache, and no history of visual aura.

Migraine with aura was reported by 38% of patients and 29% of controls. The percentage with migraine without aura was similar in the two groups; thus the current analysis focused only on migraine with aura.

SAN FRANCISCO – Women who have migraine with aura could be at increased risk for ischemic stroke, Leah MacClellan said at the 32nd International Stroke Conference.

She reported findings from a population-based case-control study of 386 women aged 15–49 years who presented with a first, nontraumatic ischemic stroke and 614 controls matched for age, race, and region.

The investigators stratified the odds of stroke among women with a history of migraine with aura, compared with women who did not have a history of migraine, by the presence of hypertension, diabetes, or myocardial infarction.

The associations were strongest among those with no history of these classic stroke risk factors, Ms. MacClellan explained at the conference, which was sponsored by the American Stroke Association.

For example, the odds ratio for stroke in those with migraine plus aura versus those with no history of migraine was 0.8 in those with hypertension, compared with 1.7 for those without hypertension; 1.2 in those with diabetes, compared with 1.5 in those without diabetes; and 0.2 in those with a history of MI, compared with 1.6 in those with no history of MI, said Ms. MacClellan of the University of Maryland, Baltimore. All associations were statistically significant.

“This finding is important because it suggests migraine might contribute to stroke independent of these classic risk factors,” she said.

A similar analysis stratifying stroke risk based on current smoking and oral contraceptive use in women with migraine plus aura, compared with women with no history of migraine, showed the associations between migraine with aura and stroke were the same regardless of smoking or OC use. However, the interaction between smoking and OC use was shown to be important, she reported.

Compared with women with migraine plus aura alone, those who smoked and had migraine plus aura had a significant 2.3-fold increased risk of stroke, as did those with migraine plus aura who used oral contraceptives. Women with migraine plus aura who smoked and also used OCs had a significant 7.3-fold increase in the odds of stroke.

“This finding is important because these are modifiable risk factors,” Ms. MacClellan noted.

Another finding of note from this study was that onset of migraine with aura in the past year was associated with increased stroke risk. Those with onset in the past year, compared with those with no history of migraine, had a significant 6.7-fold increased risk of stroke.

Those with a migraine history of more than 12 years had a non-statistically significant 1.4-fold increase in stroke risk. This finding contrasts with those from at least one other study showing that long-term migraine history was associated with increased stroke risk, she said.

The possibility that unrecognized disorders might explain the association between recent migraine onset and stroke risk in the current study warrants additional study, she said during a discussion that followed her presentation.

There was no evidence in the current study of a role for patent foramen ovale in mediating the association between migraine with aura and stroke, nor was there any evidence for preferential infarct location in terms of anterior and posterior circulation in those patients with migraine plus aura.

Patients in this study were identified from discharge data from 59 hospitals, and all had stroke that was confirmed by CT or MRI. Controls were ascertained by random digit dialing.

Migraine with aura was defined as headache with aura at least twice per year, with spots, lines, flashing lights, or loss of vision occurring around the time of the headache. Migraine without aura was defined as at least five headaches per year with nausea, vomiting, or sensitivity to light during headache, and no history of visual aura.

Migraine with aura was reported by 38% of patients and 29% of controls. The percentage with migraine without aura was similar in the two groups; thus the current analysis focused only on migraine with aura.

ORLANDO — Hypofibrinolysis is a risk factor for venous thrombosis, particularly in women, younger individuals, and those who also have Factor V Leiden, Dr. Mirjam E. Meltzer reported at the annual meeting of the American Society of Hematology.

In a study of 2,420 patients with a first episode of pulmonary embolism or deep vein thrombosis of the leg, and 2,943 controls, increased clot lysis time (CLT) was associated with increased venous thrombosis risk, said Dr. Meltzer of University Medical Center, Utrecht, the Netherlands.

Lysis of a tissue factor-induced clot by exogenous tissue-type plasminogen activator was assessed by monitoring changes in turbidity during clot formation and subsequent lysis. Quartiles of CLT were established based on values in control subjects.

Each increasing quartile of CLT was shown to be associated with an increase in venous thrombosis risk, she explained.

Individuals with hypofibrinolysis (those in the fourth quartile of CLT), compared with those in the first quartile, had an odds ratio for venous thrombosis of 1.8 after adjusting for age and sex. The risk was slightly increased in women and younger patients.

For example, women younger than 49 years had an odds ratio for venous thrombosis of 2.5, and those over age 49 years had an odds ratio of 1.7, compared with the 1.8 overall odds ratio. And women had an overall odds ratio of 2.7, compared with 1.6 for men.

Study participants were between ages 18 and 70, and were from the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based, case-control study.

Venous thrombosis risk in this analysis was determined for hypofibrinolysis alone, as well as in combination with Factor V Leiden and prothrombin 20210A mutations. The venous thrombosis risk was increased threefold in those with Factor V Leiden alone, and sevenfold in those with both hypofibrinolysis and Factor V Leiden, compared with subjects in the first quartile of CLT, Dr. Meltzer said.

A similar analysis of those with hypofibrinolysis and the prothrombin 20210A mutation showed the mutation did not enhance the risk over the threefold increased risk in those with prothrombin 20210A alone.

The findings confirm those from smaller studies showing a link between hypofibrinolysis and increased venous thrombosis risk, she noted.

ORLANDO — Hypofibrinolysis is a risk factor for venous thrombosis, particularly in women, younger individuals, and those who also have Factor V Leiden, Dr. Mirjam E. Meltzer reported at the annual meeting of the American Society of Hematology.

In a study of 2,420 patients with a first episode of pulmonary embolism or deep vein thrombosis of the leg, and 2,943 controls, increased clot lysis time (CLT) was associated with increased venous thrombosis risk, said Dr. Meltzer of University Medical Center, Utrecht, the Netherlands.

Lysis of a tissue factor-induced clot by exogenous tissue-type plasminogen activator was assessed by monitoring changes in turbidity during clot formation and subsequent lysis. Quartiles of CLT were established based on values in control subjects.

Each increasing quartile of CLT was shown to be associated with an increase in venous thrombosis risk, she explained.

Individuals with hypofibrinolysis (those in the fourth quartile of CLT), compared with those in the first quartile, had an odds ratio for venous thrombosis of 1.8 after adjusting for age and sex. The risk was slightly increased in women and younger patients.

For example, women younger than 49 years had an odds ratio for venous thrombosis of 2.5, and those over age 49 years had an odds ratio of 1.7, compared with the 1.8 overall odds ratio. And women had an overall odds ratio of 2.7, compared with 1.6 for men.

Study participants were between ages 18 and 70, and were from the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based, case-control study.

Venous thrombosis risk in this analysis was determined for hypofibrinolysis alone, as well as in combination with Factor V Leiden and prothrombin 20210A mutations. The venous thrombosis risk was increased threefold in those with Factor V Leiden alone, and sevenfold in those with both hypofibrinolysis and Factor V Leiden, compared with subjects in the first quartile of CLT, Dr. Meltzer said.

A similar analysis of those with hypofibrinolysis and the prothrombin 20210A mutation showed the mutation did not enhance the risk over the threefold increased risk in those with prothrombin 20210A alone.

The findings confirm those from smaller studies showing a link between hypofibrinolysis and increased venous thrombosis risk, she noted.

ORLANDO — Hypofibrinolysis is a risk factor for venous thrombosis, particularly in women, younger individuals, and those who also have Factor V Leiden, Dr. Mirjam E. Meltzer reported at the annual meeting of the American Society of Hematology.

In a study of 2,420 patients with a first episode of pulmonary embolism or deep vein thrombosis of the leg, and 2,943 controls, increased clot lysis time (CLT) was associated with increased venous thrombosis risk, said Dr. Meltzer of University Medical Center, Utrecht, the Netherlands.

Lysis of a tissue factor-induced clot by exogenous tissue-type plasminogen activator was assessed by monitoring changes in turbidity during clot formation and subsequent lysis. Quartiles of CLT were established based on values in control subjects.

Each increasing quartile of CLT was shown to be associated with an increase in venous thrombosis risk, she explained.

Individuals with hypofibrinolysis (those in the fourth quartile of CLT), compared with those in the first quartile, had an odds ratio for venous thrombosis of 1.8 after adjusting for age and sex. The risk was slightly increased in women and younger patients.

For example, women younger than 49 years had an odds ratio for venous thrombosis of 2.5, and those over age 49 years had an odds ratio of 1.7, compared with the 1.8 overall odds ratio. And women had an overall odds ratio of 2.7, compared with 1.6 for men.

Study participants were between ages 18 and 70, and were from the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based, case-control study.

Venous thrombosis risk in this analysis was determined for hypofibrinolysis alone, as well as in combination with Factor V Leiden and prothrombin 20210A mutations. The venous thrombosis risk was increased threefold in those with Factor V Leiden alone, and sevenfold in those with both hypofibrinolysis and Factor V Leiden, compared with subjects in the first quartile of CLT, Dr. Meltzer said.

A similar analysis of those with hypofibrinolysis and the prothrombin 20210A mutation showed the mutation did not enhance the risk over the threefold increased risk in those with prothrombin 20210A alone.

The findings confirm those from smaller studies showing a link between hypofibrinolysis and increased venous thrombosis risk, she noted.

TUCSON, ARIZ. — The graft failure rate was similar in on- and off-pump coronary artery bypass graft patients in a recent trial, but clinical outcomes at 1 year were better in the off-pump group, Dr. Mitchell J. Magee reported at the annual meeting of the Southern Thoracic Surgical Association.

The Project of Ex Vivo Vein Graft Engineering via Transfection (PREVENT) IV trial was a multicenter placebo-controlled trial of edifoligide to prevent vein graft failure from neointimal hyperplasia. A total of 3,014 patients undergoing primary isolated CABG with at least two planned saphenous vein grafts were enrolled, and the choice of surgical technique was at the surgeon's discretion. The reported study is a nonrandomized subgroup analysis of outcomes at 1 and 2 years in the on- vs. off-pump CABG patients.

A total of 2,377 patients underwent on-pump CABG, and 637 underwent off-pump CABG. One-year angiographic data in 1,920 patients who had a total of 4,736 grafts (representing 80% of the planned angiographic cohort) showed that vein graft failure, defined as 75% or greater stenosis or occlusion, was higher than expected, but similar in both groups at about 24%, said Dr. Magee.

One-year major adverse cardiac or cerebral events (MACCE) follow-up in 99.4% of enrolled patients showed that death, myocardial infarction, and/or stroke occurred in 15.4% vs. 11.3% of on- and off-pump patients, respectively. The difference remained statistically significant after adjusting for significant predictors of MACCE, including age, gender, heart failure, atrial fibrillation, and smoking (adjusted hazard ratio of 1.33). At 2-year follow-up, however, no differences in MACCE were seen between the two groups.

The findings suggest the off-pump approach offers benefits unrelated to vein graft patency, said Dr. Magee, noting that patients in the on-pump group were significantly younger, and had more COPD, congestive heart failure, lower mean ejection fraction, worse target artery quality, and longer operating times. They also were more likely to have urgent vs. elective surgery and four- or five-vessel (vs. three-vessel) CABG.

However, the effects of poor target artery quality and endoscopic (vs. open) harvest technique, which both had an adverse effect on graft patency at 1 year in both on- and off-pump patients, were more pronounced in the off-pump group, noted Dr. Magee, of the Cardiopulmonary Research Science and Technology Institute, Dallas.

With poor vs. good target artery quality, the likelihood of graft failure was 1.9 times greater in off-pump than on-pump patients. And with endoscopic harvest technique, the likelihood of failure was 1.7 times greater in off-pump vs. on-pump patients. This outcome may be the result of a propensity in off-pump patients to have a hypercoagulable condition, which when combined with the factors that had an impact on graft failure—since these factors might also aggravate endothelial injury—could adversely affect outcomes in off-pump vs. on-pump patients, he suggested.

The higher-than-expected graft failure rate seen in this large patient population (compared with others reported in the literature) likely reflects current practice with the challenging patient population and reduced target artery quality typically encountered when doing these procedures, he said.

As for the loss of overall benefit at 2 years in off- vs. on-pump CABG, he speculated that patient factors are to blame. “I can only suspect that the main benefits of off-pump surgery are primarily in the perioperative period, and that perhaps between 1 and 2 years, other patient factors, progression of comorbid disease, or development of comorbid disease, have an effect on MACCE … and offset the benefit that we see in that early perioperative period.”

In terms of how the findings will affect his management of CABG patients, Dr. Magee said that in the absence of other factors that would sway him to perform off-pump CABG he will have a lower threshold for performing on-pump CABG in patients with poor target artery quality, endoscopic harvest, and multiple targets also perceived to be of poor quality.

TUCSON, ARIZ. — The graft failure rate was similar in on- and off-pump coronary artery bypass graft patients in a recent trial, but clinical outcomes at 1 year were better in the off-pump group, Dr. Mitchell J. Magee reported at the annual meeting of the Southern Thoracic Surgical Association.

The Project of Ex Vivo Vein Graft Engineering via Transfection (PREVENT) IV trial was a multicenter placebo-controlled trial of edifoligide to prevent vein graft failure from neointimal hyperplasia. A total of 3,014 patients undergoing primary isolated CABG with at least two planned saphenous vein grafts were enrolled, and the choice of surgical technique was at the surgeon's discretion. The reported study is a nonrandomized subgroup analysis of outcomes at 1 and 2 years in the on- vs. off-pump CABG patients.

A total of 2,377 patients underwent on-pump CABG, and 637 underwent off-pump CABG. One-year angiographic data in 1,920 patients who had a total of 4,736 grafts (representing 80% of the planned angiographic cohort) showed that vein graft failure, defined as 75% or greater stenosis or occlusion, was higher than expected, but similar in both groups at about 24%, said Dr. Magee.

One-year major adverse cardiac or cerebral events (MACCE) follow-up in 99.4% of enrolled patients showed that death, myocardial infarction, and/or stroke occurred in 15.4% vs. 11.3% of on- and off-pump patients, respectively. The difference remained statistically significant after adjusting for significant predictors of MACCE, including age, gender, heart failure, atrial fibrillation, and smoking (adjusted hazard ratio of 1.33). At 2-year follow-up, however, no differences in MACCE were seen between the two groups.

The findings suggest the off-pump approach offers benefits unrelated to vein graft patency, said Dr. Magee, noting that patients in the on-pump group were significantly younger, and had more COPD, congestive heart failure, lower mean ejection fraction, worse target artery quality, and longer operating times. They also were more likely to have urgent vs. elective surgery and four- or five-vessel (vs. three-vessel) CABG.

However, the effects of poor target artery quality and endoscopic (vs. open) harvest technique, which both had an adverse effect on graft patency at 1 year in both on- and off-pump patients, were more pronounced in the off-pump group, noted Dr. Magee, of the Cardiopulmonary Research Science and Technology Institute, Dallas.

With poor vs. good target artery quality, the likelihood of graft failure was 1.9 times greater in off-pump than on-pump patients. And with endoscopic harvest technique, the likelihood of failure was 1.7 times greater in off-pump vs. on-pump patients. This outcome may be the result of a propensity in off-pump patients to have a hypercoagulable condition, which when combined with the factors that had an impact on graft failure—since these factors might also aggravate endothelial injury—could adversely affect outcomes in off-pump vs. on-pump patients, he suggested.

The higher-than-expected graft failure rate seen in this large patient population (compared with others reported in the literature) likely reflects current practice with the challenging patient population and reduced target artery quality typically encountered when doing these procedures, he said.

As for the loss of overall benefit at 2 years in off- vs. on-pump CABG, he speculated that patient factors are to blame. “I can only suspect that the main benefits of off-pump surgery are primarily in the perioperative period, and that perhaps between 1 and 2 years, other patient factors, progression of comorbid disease, or development of comorbid disease, have an effect on MACCE … and offset the benefit that we see in that early perioperative period.”

In terms of how the findings will affect his management of CABG patients, Dr. Magee said that in the absence of other factors that would sway him to perform off-pump CABG he will have a lower threshold for performing on-pump CABG in patients with poor target artery quality, endoscopic harvest, and multiple targets also perceived to be of poor quality.

TUCSON, ARIZ. — The graft failure rate was similar in on- and off-pump coronary artery bypass graft patients in a recent trial, but clinical outcomes at 1 year were better in the off-pump group, Dr. Mitchell J. Magee reported at the annual meeting of the Southern Thoracic Surgical Association.

The Project of Ex Vivo Vein Graft Engineering via Transfection (PREVENT) IV trial was a multicenter placebo-controlled trial of edifoligide to prevent vein graft failure from neointimal hyperplasia. A total of 3,014 patients undergoing primary isolated CABG with at least two planned saphenous vein grafts were enrolled, and the choice of surgical technique was at the surgeon's discretion. The reported study is a nonrandomized subgroup analysis of outcomes at 1 and 2 years in the on- vs. off-pump CABG patients.

A total of 2,377 patients underwent on-pump CABG, and 637 underwent off-pump CABG. One-year angiographic data in 1,920 patients who had a total of 4,736 grafts (representing 80% of the planned angiographic cohort) showed that vein graft failure, defined as 75% or greater stenosis or occlusion, was higher than expected, but similar in both groups at about 24%, said Dr. Magee.

One-year major adverse cardiac or cerebral events (MACCE) follow-up in 99.4% of enrolled patients showed that death, myocardial infarction, and/or stroke occurred in 15.4% vs. 11.3% of on- and off-pump patients, respectively. The difference remained statistically significant after adjusting for significant predictors of MACCE, including age, gender, heart failure, atrial fibrillation, and smoking (adjusted hazard ratio of 1.33). At 2-year follow-up, however, no differences in MACCE were seen between the two groups.

The findings suggest the off-pump approach offers benefits unrelated to vein graft patency, said Dr. Magee, noting that patients in the on-pump group were significantly younger, and had more COPD, congestive heart failure, lower mean ejection fraction, worse target artery quality, and longer operating times. They also were more likely to have urgent vs. elective surgery and four- or five-vessel (vs. three-vessel) CABG.

However, the effects of poor target artery quality and endoscopic (vs. open) harvest technique, which both had an adverse effect on graft patency at 1 year in both on- and off-pump patients, were more pronounced in the off-pump group, noted Dr. Magee, of the Cardiopulmonary Research Science and Technology Institute, Dallas.

With poor vs. good target artery quality, the likelihood of graft failure was 1.9 times greater in off-pump than on-pump patients. And with endoscopic harvest technique, the likelihood of failure was 1.7 times greater in off-pump vs. on-pump patients. This outcome may be the result of a propensity in off-pump patients to have a hypercoagulable condition, which when combined with the factors that had an impact on graft failure—since these factors might also aggravate endothelial injury—could adversely affect outcomes in off-pump vs. on-pump patients, he suggested.

The higher-than-expected graft failure rate seen in this large patient population (compared with others reported in the literature) likely reflects current practice with the challenging patient population and reduced target artery quality typically encountered when doing these procedures, he said.

As for the loss of overall benefit at 2 years in off- vs. on-pump CABG, he speculated that patient factors are to blame. “I can only suspect that the main benefits of off-pump surgery are primarily in the perioperative period, and that perhaps between 1 and 2 years, other patient factors, progression of comorbid disease, or development of comorbid disease, have an effect on MACCE … and offset the benefit that we see in that early perioperative period.”

In terms of how the findings will affect his management of CABG patients, Dr. Magee said that in the absence of other factors that would sway him to perform off-pump CABG he will have a lower threshold for performing on-pump CABG in patients with poor target artery quality, endoscopic harvest, and multiple targets also perceived to be of poor quality.

TUCSON, ARIZ. — Proximal aortic replacement performed at the time of aortic valve surgery adds no additional risk to the patient, Dr. T. Brett Reece said at the annual meeting of the Southern Thoracic Surgical Association.

A retrospective study of 430 cases involving aortic valve intervention alone and 146 cases involving aortic valve intervention with proximal aortic replacement showed that complication mortality and in-hospital mortality were similar in the two groups, said Dr. Reece of the University of Virginia, Charlottesville.

The 30-day mortality was 4% in the valve intervention-only group, and 3% in the proximal aortic replacement group. The operative complication rate was 7% vs. 9%, respectively. The differences were not statistically significant.

Neurologic, pulmonary, and renal complications, however, were significantly more common in the valve intervention-only group, compared with the proximal aortic replacement group (21% vs. 8%, 23% vs. 12%, and 8% vs. 3%, respectively), Dr. Reece noted, adding that hospital and intensive care unit stays were also significantly longer in the valve intervention-only group.

Patients included in the study were treated electively at the University of Virginia between 1996 and 2004. The mean age was significantly higher in the valve intervention-only group (68 vs. 60 years), but the groups were similar with regard to comorbidities, including rates of diabetes, pulmonary disease, hemodialysis, cerebrovascular disease, coronary artery disease, and heart failure.

Numerous studies suggest proximal aortic replacement is indicated at the time of valve intervention in patients with proximal aorta diameter greater than 5 cm, but in practice this often doesn't occur because of concern that the replacement adds risk for patients who might never need the second procedure.

But many of these patients will indeed develop a problem with their proximal aorta. These patients are at risk for aortic catastrophe and require a second operative procedure.

Recent studies have shown that proximal aortic replacement can be done with acceptable risk in patients with previous surgery, but the perioperative risk is consistently higher than with the original procedure, said Dr. Reece. When considering the risks associated with a second procedure, risks associated with both the first and second procedure should be considered, he said.

The actual numbers in terms of risk related to a single procedure vs. separated procedures are not clear in the literature, but they are high enough that there's secondary literature on revisions in patients who need proximal aortic replacement after prior intervention, he noted.

Thus, although it may be true that not all patients with an enlarged proximal aorta will require later replacement, a large population will, and therefore the findings of the current study show that concomitant replacement at the time of valve intervention is warranted, he said.

“We advocate replacement of the proximal aorta in patients undergoing an aortic valve procedure with a [proximal aorta] diameter of 5 cm,” he said.

TUCSON, ARIZ. — Proximal aortic replacement performed at the time of aortic valve surgery adds no additional risk to the patient, Dr. T. Brett Reece said at the annual meeting of the Southern Thoracic Surgical Association.

A retrospective study of 430 cases involving aortic valve intervention alone and 146 cases involving aortic valve intervention with proximal aortic replacement showed that complication mortality and in-hospital mortality were similar in the two groups, said Dr. Reece of the University of Virginia, Charlottesville.

The 30-day mortality was 4% in the valve intervention-only group, and 3% in the proximal aortic replacement group. The operative complication rate was 7% vs. 9%, respectively. The differences were not statistically significant.

Neurologic, pulmonary, and renal complications, however, were significantly more common in the valve intervention-only group, compared with the proximal aortic replacement group (21% vs. 8%, 23% vs. 12%, and 8% vs. 3%, respectively), Dr. Reece noted, adding that hospital and intensive care unit stays were also significantly longer in the valve intervention-only group.

Patients included in the study were treated electively at the University of Virginia between 1996 and 2004. The mean age was significantly higher in the valve intervention-only group (68 vs. 60 years), but the groups were similar with regard to comorbidities, including rates of diabetes, pulmonary disease, hemodialysis, cerebrovascular disease, coronary artery disease, and heart failure.

Numerous studies suggest proximal aortic replacement is indicated at the time of valve intervention in patients with proximal aorta diameter greater than 5 cm, but in practice this often doesn't occur because of concern that the replacement adds risk for patients who might never need the second procedure.

But many of these patients will indeed develop a problem with their proximal aorta. These patients are at risk for aortic catastrophe and require a second operative procedure.

Recent studies have shown that proximal aortic replacement can be done with acceptable risk in patients with previous surgery, but the perioperative risk is consistently higher than with the original procedure, said Dr. Reece. When considering the risks associated with a second procedure, risks associated with both the first and second procedure should be considered, he said.

The actual numbers in terms of risk related to a single procedure vs. separated procedures are not clear in the literature, but they are high enough that there's secondary literature on revisions in patients who need proximal aortic replacement after prior intervention, he noted.

Thus, although it may be true that not all patients with an enlarged proximal aorta will require later replacement, a large population will, and therefore the findings of the current study show that concomitant replacement at the time of valve intervention is warranted, he said.

“We advocate replacement of the proximal aorta in patients undergoing an aortic valve procedure with a [proximal aorta] diameter of 5 cm,” he said.

TUCSON, ARIZ. — Proximal aortic replacement performed at the time of aortic valve surgery adds no additional risk to the patient, Dr. T. Brett Reece said at the annual meeting of the Southern Thoracic Surgical Association.

A retrospective study of 430 cases involving aortic valve intervention alone and 146 cases involving aortic valve intervention with proximal aortic replacement showed that complication mortality and in-hospital mortality were similar in the two groups, said Dr. Reece of the University of Virginia, Charlottesville.

The 30-day mortality was 4% in the valve intervention-only group, and 3% in the proximal aortic replacement group. The operative complication rate was 7% vs. 9%, respectively. The differences were not statistically significant.

Neurologic, pulmonary, and renal complications, however, were significantly more common in the valve intervention-only group, compared with the proximal aortic replacement group (21% vs. 8%, 23% vs. 12%, and 8% vs. 3%, respectively), Dr. Reece noted, adding that hospital and intensive care unit stays were also significantly longer in the valve intervention-only group.

Patients included in the study were treated electively at the University of Virginia between 1996 and 2004. The mean age was significantly higher in the valve intervention-only group (68 vs. 60 years), but the groups were similar with regard to comorbidities, including rates of diabetes, pulmonary disease, hemodialysis, cerebrovascular disease, coronary artery disease, and heart failure.

Numerous studies suggest proximal aortic replacement is indicated at the time of valve intervention in patients with proximal aorta diameter greater than 5 cm, but in practice this often doesn't occur because of concern that the replacement adds risk for patients who might never need the second procedure.

But many of these patients will indeed develop a problem with their proximal aorta. These patients are at risk for aortic catastrophe and require a second operative procedure.

Recent studies have shown that proximal aortic replacement can be done with acceptable risk in patients with previous surgery, but the perioperative risk is consistently higher than with the original procedure, said Dr. Reece. When considering the risks associated with a second procedure, risks associated with both the first and second procedure should be considered, he said.

The actual numbers in terms of risk related to a single procedure vs. separated procedures are not clear in the literature, but they are high enough that there's secondary literature on revisions in patients who need proximal aortic replacement after prior intervention, he noted.

Thus, although it may be true that not all patients with an enlarged proximal aorta will require later replacement, a large population will, and therefore the findings of the current study show that concomitant replacement at the time of valve intervention is warranted, he said.

“We advocate replacement of the proximal aorta in patients undergoing an aortic valve procedure with a [proximal aorta] diameter of 5 cm,” he said.

ORLANDO — High-density lipoproteins, which are known protectors against arterial atherothrombosis, may also protect against recurrent venous thrombosis, Dr. Sabine Eichinger reported at the annual meeting of the American Society of Hematology.

In a prospective study of 772 patients with a first episode of spontaneous venous thromboembolism, the relationship between plasma lipoprotein parameters and recurrence of venous thrombosis was evaluated. Of the 772 patients, 100 (13%) had recurrent venous thromboembolism during an average follow-up of 4 years. Patients who had a recurrence had significantly lower mean plasma levels of apolipoprotein A-I, a major component of HDL (1.12 vs. 1.23 mg/mL), compared with those who had no recurrence, said Dr. Eichinger of the Medical University of Vienna.

The relative risk of recurrence in this study population was 0.87 for each increase of 0.1 mg/mL in plasma apolipoprotein A-I; for those patients with apolipoprotein A-I levels above the 67th percentile of the study population, compared with those with lower levels, the relative risk of recurrence was 0.51.

In addition, the HDL cholesterol levels and HDL particle concentrations in the plasma of patients with recurrence were lower, compared with those patients without recurrence, Dr. Eichinger noted.

Although HDL is known to protect against arterial atherothrombosis, venous thrombosis is a clinically distinct entity, particularly with regard to thrombus appearance, pathogenic mechanisms, and therapeutic approaches. Although it was believed that HDL is protective against recurrent venous thrombosis as a result of its multiple antithrombotic and anti-inflammatory actions, this had not been previously shown, she explained.

ORLANDO — High-density lipoproteins, which are known protectors against arterial atherothrombosis, may also protect against recurrent venous thrombosis, Dr. Sabine Eichinger reported at the annual meeting of the American Society of Hematology.

In a prospective study of 772 patients with a first episode of spontaneous venous thromboembolism, the relationship between plasma lipoprotein parameters and recurrence of venous thrombosis was evaluated. Of the 772 patients, 100 (13%) had recurrent venous thromboembolism during an average follow-up of 4 years. Patients who had a recurrence had significantly lower mean plasma levels of apolipoprotein A-I, a major component of HDL (1.12 vs. 1.23 mg/mL), compared with those who had no recurrence, said Dr. Eichinger of the Medical University of Vienna.

The relative risk of recurrence in this study population was 0.87 for each increase of 0.1 mg/mL in plasma apolipoprotein A-I; for those patients with apolipoprotein A-I levels above the 67th percentile of the study population, compared with those with lower levels, the relative risk of recurrence was 0.51.

In addition, the HDL cholesterol levels and HDL particle concentrations in the plasma of patients with recurrence were lower, compared with those patients without recurrence, Dr. Eichinger noted.

Although HDL is known to protect against arterial atherothrombosis, venous thrombosis is a clinically distinct entity, particularly with regard to thrombus appearance, pathogenic mechanisms, and therapeutic approaches. Although it was believed that HDL is protective against recurrent venous thrombosis as a result of its multiple antithrombotic and anti-inflammatory actions, this had not been previously shown, she explained.

ORLANDO — High-density lipoproteins, which are known protectors against arterial atherothrombosis, may also protect against recurrent venous thrombosis, Dr. Sabine Eichinger reported at the annual meeting of the American Society of Hematology.

In a prospective study of 772 patients with a first episode of spontaneous venous thromboembolism, the relationship between plasma lipoprotein parameters and recurrence of venous thrombosis was evaluated. Of the 772 patients, 100 (13%) had recurrent venous thromboembolism during an average follow-up of 4 years. Patients who had a recurrence had significantly lower mean plasma levels of apolipoprotein A-I, a major component of HDL (1.12 vs. 1.23 mg/mL), compared with those who had no recurrence, said Dr. Eichinger of the Medical University of Vienna.

The relative risk of recurrence in this study population was 0.87 for each increase of 0.1 mg/mL in plasma apolipoprotein A-I; for those patients with apolipoprotein A-I levels above the 67th percentile of the study population, compared with those with lower levels, the relative risk of recurrence was 0.51.

In addition, the HDL cholesterol levels and HDL particle concentrations in the plasma of patients with recurrence were lower, compared with those patients without recurrence, Dr. Eichinger noted.

Although HDL is known to protect against arterial atherothrombosis, venous thrombosis is a clinically distinct entity, particularly with regard to thrombus appearance, pathogenic mechanisms, and therapeutic approaches. Although it was believed that HDL is protective against recurrent venous thrombosis as a result of its multiple antithrombotic and anti-inflammatory actions, this had not been previously shown, she explained.

ORLANDO — High-density lipoproteins, which are known protectors against arterial atherothrombosis, also appear to protect against recurrent venous thrombosis, Dr. Sabine Eichinger reported at the annual meeting of the American Society of Hematology.

In a prospective study of 772 patients with a first episode of spontaneous venous thromboembolism, the relationship between plasma lipoprotein parameters and recurrence of venous thrombosis was evaluated. Of the 772 patients, 100 (13%) had recurrent VTE during an average follow-up of 4 years.

Compared with patients without recurrence, those with recurrence had significantly lower mean plasma levels of apolipoprotein A-I, a major component of HDL (1.12 vs. 1.23 mg/mL), said Dr. Eichinger of the Medical University of Vienna.

The relative risk of recurrence in this study population was 0.87 for each increase of 0.1 mg/mL in plasma apolipoprotein A-I; for those with apolipoprotein A-I levels above the 67th percentile, compared with those with lower levels, relative risk of recurrence was 0.51.

Further, HDL cholesterol levels and HDL particle concentrations were lower in patients with recurrence, she noted.

Although it was thought that HDL is protective against recurrent venous thrombosis as a result of its multiple antithrombotic and anti-inflammatory actions, this had not been previously shown, she explained.

Measurement of HDL parameters may be useful for predicting venous thrombosis recurrence risk, and drugs that increase HDL might be useful for reducing venous thrombotic events, she concluded.

ORLANDO — High-density lipoproteins, which are known protectors against arterial atherothrombosis, also appear to protect against recurrent venous thrombosis, Dr. Sabine Eichinger reported at the annual meeting of the American Society of Hematology.

In a prospective study of 772 patients with a first episode of spontaneous venous thromboembolism, the relationship between plasma lipoprotein parameters and recurrence of venous thrombosis was evaluated. Of the 772 patients, 100 (13%) had recurrent VTE during an average follow-up of 4 years.

Compared with patients without recurrence, those with recurrence had significantly lower mean plasma levels of apolipoprotein A-I, a major component of HDL (1.12 vs. 1.23 mg/mL), said Dr. Eichinger of the Medical University of Vienna.

The relative risk of recurrence in this study population was 0.87 for each increase of 0.1 mg/mL in plasma apolipoprotein A-I; for those with apolipoprotein A-I levels above the 67th percentile, compared with those with lower levels, relative risk of recurrence was 0.51.

Further, HDL cholesterol levels and HDL particle concentrations were lower in patients with recurrence, she noted.

Although it was thought that HDL is protective against recurrent venous thrombosis as a result of its multiple antithrombotic and anti-inflammatory actions, this had not been previously shown, she explained.

Measurement of HDL parameters may be useful for predicting venous thrombosis recurrence risk, and drugs that increase HDL might be useful for reducing venous thrombotic events, she concluded.

ORLANDO — High-density lipoproteins, which are known protectors against arterial atherothrombosis, also appear to protect against recurrent venous thrombosis, Dr. Sabine Eichinger reported at the annual meeting of the American Society of Hematology.

In a prospective study of 772 patients with a first episode of spontaneous venous thromboembolism, the relationship between plasma lipoprotein parameters and recurrence of venous thrombosis was evaluated. Of the 772 patients, 100 (13%) had recurrent VTE during an average follow-up of 4 years.

Compared with patients without recurrence, those with recurrence had significantly lower mean plasma levels of apolipoprotein A-I, a major component of HDL (1.12 vs. 1.23 mg/mL), said Dr. Eichinger of the Medical University of Vienna.

The relative risk of recurrence in this study population was 0.87 for each increase of 0.1 mg/mL in plasma apolipoprotein A-I; for those with apolipoprotein A-I levels above the 67th percentile, compared with those with lower levels, relative risk of recurrence was 0.51.

Further, HDL cholesterol levels and HDL particle concentrations were lower in patients with recurrence, she noted.

Although it was thought that HDL is protective against recurrent venous thrombosis as a result of its multiple antithrombotic and anti-inflammatory actions, this had not been previously shown, she explained.

Measurement of HDL parameters may be useful for predicting venous thrombosis recurrence risk, and drugs that increase HDL might be useful for reducing venous thrombotic events, she concluded.

ORLANDO — Hypofibrinolysis is a risk factor for venous thrombosis, particularly in women, younger individuals, and those who also have Factor V Leiden, Dr. Mirjam E. Meltzer reported at the annual meeting of the American Society of Hematology.

In a study of 2,420 patients with a first episode of pulmonary embolism or deep vein thrombosis of the leg, and 2,943 controls, increased clot lysis time (CLT) was associated with increased venous thrombosis risk, said Dr. Meltzer of University Medical Center, Utrecht, the Netherlands.

Lysis of a tissue factor-induced clot by exogenous tissue-type plasminogen activator was assessed by monitoring changes in turbidity during clot formation and subsequent lysis. Quartiles of CLT were established based on values in control subjects.

Each increasing quartile of CLT was shown to be associated with an increase in venous thrombosis risk, she explained.

Individuals with hypofibrinolysis (those in the fourth quartile of CLT), compared with those in the first quartile, had an odds ratio for venous thrombosis of 1.8 after adjusting for age and sex. The risk was slightly higher in women and younger patients.

Women younger than 49 years had an odds ratio for venous thrombosis of 2.5, and those over age 49 years had an odds ratio of 1.7, compared with the 1.8 overall odds ratio. Women had an overall odds ratio of 2.7, compared with 1.6 for men.

Participants were aged 18-70 years, and were from the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based, case-control study.

Venous thrombosis risk in this analysis was determined for hypofibrinolysis alone, and in combination with Factor V Leiden and prothrombin 20210A mutations. Risk was increased threefold in those with Factor V Leiden alone, and sevenfold in those with both hypofibrinolysis and Factor V Leiden, compared with subjects in the first quartile of CLT, Dr. Meltzer said.

A similar analysis of those with hypofibrinolysis and the prothrombin 20210A mutation showed the mutation did not enhance the risk over the threefold increased risk in those with prothrombin 20210A alone.

The findings confirm those from smaller studies showing a link between hypofibrinolysis and increased venous thrombosis risk, she noted.

ORLANDO — Hypofibrinolysis is a risk factor for venous thrombosis, particularly in women, younger individuals, and those who also have Factor V Leiden, Dr. Mirjam E. Meltzer reported at the annual meeting of the American Society of Hematology.

In a study of 2,420 patients with a first episode of pulmonary embolism or deep vein thrombosis of the leg, and 2,943 controls, increased clot lysis time (CLT) was associated with increased venous thrombosis risk, said Dr. Meltzer of University Medical Center, Utrecht, the Netherlands.

Lysis of a tissue factor-induced clot by exogenous tissue-type plasminogen activator was assessed by monitoring changes in turbidity during clot formation and subsequent lysis. Quartiles of CLT were established based on values in control subjects.

Each increasing quartile of CLT was shown to be associated with an increase in venous thrombosis risk, she explained.

Individuals with hypofibrinolysis (those in the fourth quartile of CLT), compared with those in the first quartile, had an odds ratio for venous thrombosis of 1.8 after adjusting for age and sex. The risk was slightly higher in women and younger patients.

Women younger than 49 years had an odds ratio for venous thrombosis of 2.5, and those over age 49 years had an odds ratio of 1.7, compared with the 1.8 overall odds ratio. Women had an overall odds ratio of 2.7, compared with 1.6 for men.

Participants were aged 18-70 years, and were from the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based, case-control study.

Venous thrombosis risk in this analysis was determined for hypofibrinolysis alone, and in combination with Factor V Leiden and prothrombin 20210A mutations. Risk was increased threefold in those with Factor V Leiden alone, and sevenfold in those with both hypofibrinolysis and Factor V Leiden, compared with subjects in the first quartile of CLT, Dr. Meltzer said.

A similar analysis of those with hypofibrinolysis and the prothrombin 20210A mutation showed the mutation did not enhance the risk over the threefold increased risk in those with prothrombin 20210A alone.

The findings confirm those from smaller studies showing a link between hypofibrinolysis and increased venous thrombosis risk, she noted.

ORLANDO — Hypofibrinolysis is a risk factor for venous thrombosis, particularly in women, younger individuals, and those who also have Factor V Leiden, Dr. Mirjam E. Meltzer reported at the annual meeting of the American Society of Hematology.

In a study of 2,420 patients with a first episode of pulmonary embolism or deep vein thrombosis of the leg, and 2,943 controls, increased clot lysis time (CLT) was associated with increased venous thrombosis risk, said Dr. Meltzer of University Medical Center, Utrecht, the Netherlands.

Lysis of a tissue factor-induced clot by exogenous tissue-type plasminogen activator was assessed by monitoring changes in turbidity during clot formation and subsequent lysis. Quartiles of CLT were established based on values in control subjects.

Each increasing quartile of CLT was shown to be associated with an increase in venous thrombosis risk, she explained.

Individuals with hypofibrinolysis (those in the fourth quartile of CLT), compared with those in the first quartile, had an odds ratio for venous thrombosis of 1.8 after adjusting for age and sex. The risk was slightly higher in women and younger patients.

Women younger than 49 years had an odds ratio for venous thrombosis of 2.5, and those over age 49 years had an odds ratio of 1.7, compared with the 1.8 overall odds ratio. Women had an overall odds ratio of 2.7, compared with 1.6 for men.

Participants were aged 18-70 years, and were from the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study, a population-based, case-control study.

Venous thrombosis risk in this analysis was determined for hypofibrinolysis alone, and in combination with Factor V Leiden and prothrombin 20210A mutations. Risk was increased threefold in those with Factor V Leiden alone, and sevenfold in those with both hypofibrinolysis and Factor V Leiden, compared with subjects in the first quartile of CLT, Dr. Meltzer said.

A similar analysis of those with hypofibrinolysis and the prothrombin 20210A mutation showed the mutation did not enhance the risk over the threefold increased risk in those with prothrombin 20210A alone.

The findings confirm those from smaller studies showing a link between hypofibrinolysis and increased venous thrombosis risk, she noted.