ACC 2011

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116g/m²] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116g/m²] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116g/m²] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116g/m²] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116g/m²] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116g/m²] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116g/m²] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116g/m²] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

NEW ORLEANS – Frequent periodic leg movements during sleep were associated with left ventricular hypertrophy in patients with restless legs syndrome, according to a study presented at the annual meeting of the American College of Cardiology.

Moreover, patients who had sleep disturbance due to frequent periodic leg movements and severe LVH were at increased risk for heart failure, recurrent hospitalizations, and death.

"We have known for a long time that LVH is a poor prognostic factor that increases the risk of cardiac events. What is new about this study is that it appears that restless legs syndrome is another risk factor that may predispose patients to, and lead to more complications of, LVH," Dr. Arshad Jahangir said at a press conference during the meeting.

Dr. Jahangir, principal investigator in the study and professor of medicine at the Mayo Clinic in Scottsdale, Ariz., said that the findings need to be confirmed in larger studies. Also, it will be important to evaluate whether effective treatments for restless legs syndrome can prevent adverse outcomes associated with LVH.

Approximately 12 million Americans have restless legs syndrome. The condition is increasingly common with age and is implicated in about one-third of all cases of insomnia. Up to 90% of patients also have periodic limb movement disorder, which is characterized by involuntary jerking movements during sleep. The mechanisms that drive the disorder are not fully understood, Dr. Jahangir said, but the sympathetic nervous system is involved and patients typically have increased heart rate and blood pressure.

The study enrolled 584 restless legs syndrome patients who underwent overnight polysomnography studies. Patients were stratified according to frequency of leg movements during sleep: 45% had frequent leg movements, defined as a Periodic Movement Index [PMI] of more than 35 per hour, and 55% had infrequent leg movements, defined as a PMI of 35 or fewer movements per hour. Despite having a left ventricular ejection fraction of around 60% at baseline, the group with frequent periodic limb movements had a significantly higher left ventricular mass (P=.01), mass index (P=.002), and posterior wall thickness (P=.01), indicating the presence of LVH.

At baseline, the groups with frequent versus infrequent periodic limb movements had similar clinical and echocardiographic parameters, and were comparable for the presence of cardiovascular risk factors, including hypertension, diabetes, heart failure, high cholesterol level, heart failure, or renal dysfunction. Patients with frequent periodic limb movements were older (median age 67 vs. 61 years), more often male, had more atrial fibrillation (30% vs. 17%), and more underlying coronary heart disease than those with infrequent periodic limb movements.

The presence of severe LVH [defined as left ventricular mass index >116g/m²] and atrial fibrillation led to a significantly greater likelihood of heart failure, recurrent hospitalizations, and death over a mean follow-up of 3 years. Dr. Jahangir said that even in participants with frequent periodic limb movements and no atrial fibrillation, patients with severe LVH had a greater number of cardiac events.

Severe LVH was found in 37% of those with atrial fibrillation and 20% of those without it, suggesting that underlying electrical dysfunction and restless legs syndrome may act together to lead to adverse cardiovascular outcomes.

"This is a retrospective study that points out an interesting association between RLS and LVH. This could be an important observation, but the findings need to be validated in a prospective study," said Dr. William Zoghbi, who chaired the press conference and is the chair of cardiovascular imaging at the Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the National Heart, Lung, and Blood Institute and the Angel and Paul Harvey Cardiovascular Research Endowment to CardioGerontology Research Laboratory at Mayo Clinic Arizona. Dr. Jahangir had no relevant financial disclosures.

NEW ORLEANS  – In the 10-year follow-up of a study in patients with stable coronary artery disease, the ratio of triglycerides to high-density lipoproteins was highly predictive of major adverse cardiovascular events (MACE).

Dr. Raul D. Santos of the Heart Institute at the University of Sao Paulo Medical School Hospital in Brazil reported the analysis, which was part of the Medical, Angioplasty, or Surgery Study (MASS-II). That study compared the long-term effects of medical treatment, angioplasty, or surgical strategies in patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function, determining that surgery was the optimal approach in this patient subset (J. Am. Coll. Cardiol. 2004;43:1743-51)

“After 10 years of follow-up of stable CAD patients in MASS-II, the TG/HDL [triglyceride/high-density lipoprotein] ratio was the only lipid parameter independently associated” with major adverse cardiovascular events (MACE), Dr. Santos reported in the poster presentation.

The study randomly assigned 611 patients to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Lipid-modifying therapies were equally instituted in all study patient groups. Concentrations of total cholesterol, high-density lipoprotein (HDL), non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as LDL/HDL and TG/HDL ratios, were divided according to distribution quartiles. The associations between MACE occurrence and plasma lipids at baseline and at 6 months, as well as other risk factors and randomized CAD treatment, were determined by Cox regression models.

Mean levels of lipids were 150 mg/dL for TG, 37 mg/dL for HDL cholesterol, and 140 mg/dL for LDL cholesterol.

“LDL was not well treated at the time this study began 11 years ago. Only about one third of patients were on statins, and mean levels were about 140 mg/dL,” Dr. Santos said. “Yet, even in these patients with high LDL, the TG/HDL ratio was a marker for later events.”

In the MASS-II patients followed for an average of 11.4 years (range 9-15 years), MACE were observed in 42% of the PCI arm, 59% of the medical therapy arm, and 33% of the CABG arm.

After adjustment for confounders, the investigators found the following factors to be independently associated with MACE: age greater than 65 years, randomization to CABG versus medical therapy, systemic arterial hypertension, and TG/HDL ratio determined at 6 months.

For the TG/HDL ratio, the hazard ratio for the occurrence of MACE, comparing the highest and lowest quartiles of the ratios, was significant at 1.57 (P = .015). Hazard ratios for the third versus first quartiles was 1.38 (P = .098) and for the second versus first quartiles was 0.83 (P = .445). No association was found between MACE and other plasma lipids.

Among patients with a TG/HDL ratio greater than 6, only about 45% of patients were free of MACE at 10 years, compared with greater than 70% for those with a TG/HDL ratio of less than 3. 

“The TG/HDL ratio is a marker of residual risk,” Dr. Santos said. “For clinicians, this means that you treat the LDL, of course, but you need to look at triglycerides and HDL. While the lab doesn’t give you this ratio, it’s very easy to calculate.”

Dr. Gerald S. Berenson of Tulane University School of Medicine, New Orleans, and principal investigator of the Bogalusa Heart Study, viewed the poster with interest. “This is very important information,” he said. “The TG/HDL ratio is so easy to measure. Everyone is looking at particle size, and so forth, but we routinely get these levels, so you just need to look at the ratio. It’s a good measure of insulin resistance as well.”

Dr. Santos has served on the speakers bureaus of Novartis, Merck, Biolab, and Bristol-Myers Squibb. Dr. Berenson had no relevant conflicts of interest.

NEW ORLEANS  – In the 10-year follow-up of a study in patients with stable coronary artery disease, the ratio of triglycerides to high-density lipoproteins was highly predictive of major adverse cardiovascular events (MACE).

Dr. Raul D. Santos of the Heart Institute at the University of Sao Paulo Medical School Hospital in Brazil reported the analysis, which was part of the Medical, Angioplasty, or Surgery Study (MASS-II). That study compared the long-term effects of medical treatment, angioplasty, or surgical strategies in patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function, determining that surgery was the optimal approach in this patient subset (J. Am. Coll. Cardiol. 2004;43:1743-51)

“After 10 years of follow-up of stable CAD patients in MASS-II, the TG/HDL [triglyceride/high-density lipoprotein] ratio was the only lipid parameter independently associated” with major adverse cardiovascular events (MACE), Dr. Santos reported in the poster presentation.

The study randomly assigned 611 patients to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Lipid-modifying therapies were equally instituted in all study patient groups. Concentrations of total cholesterol, high-density lipoprotein (HDL), non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as LDL/HDL and TG/HDL ratios, were divided according to distribution quartiles. The associations between MACE occurrence and plasma lipids at baseline and at 6 months, as well as other risk factors and randomized CAD treatment, were determined by Cox regression models.

Mean levels of lipids were 150 mg/dL for TG, 37 mg/dL for HDL cholesterol, and 140 mg/dL for LDL cholesterol.

“LDL was not well treated at the time this study began 11 years ago. Only about one third of patients were on statins, and mean levels were about 140 mg/dL,” Dr. Santos said. “Yet, even in these patients with high LDL, the TG/HDL ratio was a marker for later events.”

In the MASS-II patients followed for an average of 11.4 years (range 9-15 years), MACE were observed in 42% of the PCI arm, 59% of the medical therapy arm, and 33% of the CABG arm.

After adjustment for confounders, the investigators found the following factors to be independently associated with MACE: age greater than 65 years, randomization to CABG versus medical therapy, systemic arterial hypertension, and TG/HDL ratio determined at 6 months.

For the TG/HDL ratio, the hazard ratio for the occurrence of MACE, comparing the highest and lowest quartiles of the ratios, was significant at 1.57 (P = .015). Hazard ratios for the third versus first quartiles was 1.38 (P = .098) and for the second versus first quartiles was 0.83 (P = .445). No association was found between MACE and other plasma lipids.

Among patients with a TG/HDL ratio greater than 6, only about 45% of patients were free of MACE at 10 years, compared with greater than 70% for those with a TG/HDL ratio of less than 3. 

“The TG/HDL ratio is a marker of residual risk,” Dr. Santos said. “For clinicians, this means that you treat the LDL, of course, but you need to look at triglycerides and HDL. While the lab doesn’t give you this ratio, it’s very easy to calculate.”

Dr. Gerald S. Berenson of Tulane University School of Medicine, New Orleans, and principal investigator of the Bogalusa Heart Study, viewed the poster with interest. “This is very important information,” he said. “The TG/HDL ratio is so easy to measure. Everyone is looking at particle size, and so forth, but we routinely get these levels, so you just need to look at the ratio. It’s a good measure of insulin resistance as well.”

Dr. Santos has served on the speakers bureaus of Novartis, Merck, Biolab, and Bristol-Myers Squibb. Dr. Berenson had no relevant conflicts of interest.

NEW ORLEANS  – In the 10-year follow-up of a study in patients with stable coronary artery disease, the ratio of triglycerides to high-density lipoproteins was highly predictive of major adverse cardiovascular events (MACE).

Dr. Raul D. Santos of the Heart Institute at the University of Sao Paulo Medical School Hospital in Brazil reported the analysis, which was part of the Medical, Angioplasty, or Surgery Study (MASS-II). That study compared the long-term effects of medical treatment, angioplasty, or surgical strategies in patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function, determining that surgery was the optimal approach in this patient subset (J. Am. Coll. Cardiol. 2004;43:1743-51)

“After 10 years of follow-up of stable CAD patients in MASS-II, the TG/HDL [triglyceride/high-density lipoprotein] ratio was the only lipid parameter independently associated” with major adverse cardiovascular events (MACE), Dr. Santos reported in the poster presentation.

The study randomly assigned 611 patients to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Lipid-modifying therapies were equally instituted in all study patient groups. Concentrations of total cholesterol, high-density lipoprotein (HDL), non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as LDL/HDL and TG/HDL ratios, were divided according to distribution quartiles. The associations between MACE occurrence and plasma lipids at baseline and at 6 months, as well as other risk factors and randomized CAD treatment, were determined by Cox regression models.

Mean levels of lipids were 150 mg/dL for TG, 37 mg/dL for HDL cholesterol, and 140 mg/dL for LDL cholesterol.

“LDL was not well treated at the time this study began 11 years ago. Only about one third of patients were on statins, and mean levels were about 140 mg/dL,” Dr. Santos said. “Yet, even in these patients with high LDL, the TG/HDL ratio was a marker for later events.”

In the MASS-II patients followed for an average of 11.4 years (range 9-15 years), MACE were observed in 42% of the PCI arm, 59% of the medical therapy arm, and 33% of the CABG arm.

After adjustment for confounders, the investigators found the following factors to be independently associated with MACE: age greater than 65 years, randomization to CABG versus medical therapy, systemic arterial hypertension, and TG/HDL ratio determined at 6 months.

For the TG/HDL ratio, the hazard ratio for the occurrence of MACE, comparing the highest and lowest quartiles of the ratios, was significant at 1.57 (P = .015). Hazard ratios for the third versus first quartiles was 1.38 (P = .098) and for the second versus first quartiles was 0.83 (P = .445). No association was found between MACE and other plasma lipids.

Among patients with a TG/HDL ratio greater than 6, only about 45% of patients were free of MACE at 10 years, compared with greater than 70% for those with a TG/HDL ratio of less than 3. 

“The TG/HDL ratio is a marker of residual risk,” Dr. Santos said. “For clinicians, this means that you treat the LDL, of course, but you need to look at triglycerides and HDL. While the lab doesn’t give you this ratio, it’s very easy to calculate.”

Dr. Gerald S. Berenson of Tulane University School of Medicine, New Orleans, and principal investigator of the Bogalusa Heart Study, viewed the poster with interest. “This is very important information,” he said. “The TG/HDL ratio is so easy to measure. Everyone is looking at particle size, and so forth, but we routinely get these levels, so you just need to look at the ratio. It’s a good measure of insulin resistance as well.”

Dr. Santos has served on the speakers bureaus of Novartis, Merck, Biolab, and Bristol-Myers Squibb. Dr. Berenson had no relevant conflicts of interest.

NEW ORLEANS  – In the 10-year follow-up of a study in patients with stable coronary artery disease, the ratio of triglycerides to high-density lipoproteins was highly predictive of major adverse cardiovascular events (MACE).

Dr. Raul D. Santos of the Heart Institute at the University of Sao Paulo Medical School Hospital in Brazil reported the analysis, which was part of the Medical, Angioplasty, or Surgery Study (MASS-II). That study compared the long-term effects of medical treatment, angioplasty, or surgical strategies in patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function, determining that surgery was the optimal approach in this patient subset (J. Am. Coll. Cardiol. 2004;43:1743-51)

“After 10 years of follow-up of stable CAD patients in MASS-II, the TG/HDL [triglyceride/high-density lipoprotein] ratio was the only lipid parameter independently associated” with major adverse cardiovascular events (MACE), Dr. Santos reported in the poster presentation.

The study randomly assigned 611 patients to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Lipid-modifying therapies were equally instituted in all study patient groups. Concentrations of total cholesterol, high-density lipoprotein (HDL), non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as LDL/HDL and TG/HDL ratios, were divided according to distribution quartiles. The associations between MACE occurrence and plasma lipids at baseline and at 6 months, as well as other risk factors and randomized CAD treatment, were determined by Cox regression models.

Mean levels of lipids were 150 mg/dL for TG, 37 mg/dL for HDL cholesterol, and 140 mg/dL for LDL cholesterol.

“LDL was not well treated at the time this study began 11 years ago. Only about one third of patients were on statins, and mean levels were about 140 mg/dL,” Dr. Santos said. “Yet, even in these patients with high LDL, the TG/HDL ratio was a marker for later events.”

In the MASS-II patients followed for an average of 11.4 years (range 9-15 years), MACE were observed in 42% of the PCI arm, 59% of the medical therapy arm, and 33% of the CABG arm.

After adjustment for confounders, the investigators found the following factors to be independently associated with MACE: age greater than 65 years, randomization to CABG versus medical therapy, systemic arterial hypertension, and TG/HDL ratio determined at 6 months.

For the TG/HDL ratio, the hazard ratio for the occurrence of MACE, comparing the highest and lowest quartiles of the ratios, was significant at 1.57 (P = .015). Hazard ratios for the third versus first quartiles was 1.38 (P = .098) and for the second versus first quartiles was 0.83 (P = .445). No association was found between MACE and other plasma lipids.

Among patients with a TG/HDL ratio greater than 6, only about 45% of patients were free of MACE at 10 years, compared with greater than 70% for those with a TG/HDL ratio of less than 3. 

“The TG/HDL ratio is a marker of residual risk,” Dr. Santos said. “For clinicians, this means that you treat the LDL, of course, but you need to look at triglycerides and HDL. While the lab doesn’t give you this ratio, it’s very easy to calculate.”

Dr. Gerald S. Berenson of Tulane University School of Medicine, New Orleans, and principal investigator of the Bogalusa Heart Study, viewed the poster with interest. “This is very important information,” he said. “The TG/HDL ratio is so easy to measure. Everyone is looking at particle size, and so forth, but we routinely get these levels, so you just need to look at the ratio. It’s a good measure of insulin resistance as well.”

Dr. Santos has served on the speakers bureaus of Novartis, Merck, Biolab, and Bristol-Myers Squibb. Dr. Berenson had no relevant conflicts of interest.

NEW ORLEANS  – In the 10-year follow-up of a study in patients with stable coronary artery disease, the ratio of triglycerides to high-density lipoproteins was highly predictive of major adverse cardiovascular events (MACE).

Dr. Raul D. Santos of the Heart Institute at the University of Sao Paulo Medical School Hospital in Brazil reported the analysis, which was part of the Medical, Angioplasty, or Surgery Study (MASS-II). That study compared the long-term effects of medical treatment, angioplasty, or surgical strategies in patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function, determining that surgery was the optimal approach in this patient subset (J. Am. Coll. Cardiol. 2004;43:1743-51)

“After 10 years of follow-up of stable CAD patients in MASS-II, the TG/HDL [triglyceride/high-density lipoprotein] ratio was the only lipid parameter independently associated” with major adverse cardiovascular events (MACE), Dr. Santos reported in the poster presentation.

The study randomly assigned 611 patients to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Lipid-modifying therapies were equally instituted in all study patient groups. Concentrations of total cholesterol, high-density lipoprotein (HDL), non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as LDL/HDL and TG/HDL ratios, were divided according to distribution quartiles. The associations between MACE occurrence and plasma lipids at baseline and at 6 months, as well as other risk factors and randomized CAD treatment, were determined by Cox regression models.

Mean levels of lipids were 150 mg/dL for TG, 37 mg/dL for HDL cholesterol, and 140 mg/dL for LDL cholesterol.

“LDL was not well treated at the time this study began 11 years ago. Only about one third of patients were on statins, and mean levels were about 140 mg/dL,” Dr. Santos said. “Yet, even in these patients with high LDL, the TG/HDL ratio was a marker for later events.”

In the MASS-II patients followed for an average of 11.4 years (range 9-15 years), MACE were observed in 42% of the PCI arm, 59% of the medical therapy arm, and 33% of the CABG arm.

After adjustment for confounders, the investigators found the following factors to be independently associated with MACE: age greater than 65 years, randomization to CABG versus medical therapy, systemic arterial hypertension, and TG/HDL ratio determined at 6 months.

For the TG/HDL ratio, the hazard ratio for the occurrence of MACE, comparing the highest and lowest quartiles of the ratios, was significant at 1.57 (P = .015). Hazard ratios for the third versus first quartiles was 1.38 (P = .098) and for the second versus first quartiles was 0.83 (P = .445). No association was found between MACE and other plasma lipids.

Among patients with a TG/HDL ratio greater than 6, only about 45% of patients were free of MACE at 10 years, compared with greater than 70% for those with a TG/HDL ratio of less than 3. 

“The TG/HDL ratio is a marker of residual risk,” Dr. Santos said. “For clinicians, this means that you treat the LDL, of course, but you need to look at triglycerides and HDL. While the lab doesn’t give you this ratio, it’s very easy to calculate.”

Dr. Gerald S. Berenson of Tulane University School of Medicine, New Orleans, and principal investigator of the Bogalusa Heart Study, viewed the poster with interest. “This is very important information,” he said. “The TG/HDL ratio is so easy to measure. Everyone is looking at particle size, and so forth, but we routinely get these levels, so you just need to look at the ratio. It’s a good measure of insulin resistance as well.”

Dr. Santos has served on the speakers bureaus of Novartis, Merck, Biolab, and Bristol-Myers Squibb. Dr. Berenson had no relevant conflicts of interest.

NEW ORLEANS  – In the 10-year follow-up of a study in patients with stable coronary artery disease, the ratio of triglycerides to high-density lipoproteins was highly predictive of major adverse cardiovascular events (MACE).

Dr. Raul D. Santos of the Heart Institute at the University of Sao Paulo Medical School Hospital in Brazil reported the analysis, which was part of the Medical, Angioplasty, or Surgery Study (MASS-II). That study compared the long-term effects of medical treatment, angioplasty, or surgical strategies in patients with stable angina symptoms of multivessel coronary artery disease (CAD) and preserved ventricular function, determining that surgery was the optimal approach in this patient subset (J. Am. Coll. Cardiol. 2004;43:1743-51)

“After 10 years of follow-up of stable CAD patients in MASS-II, the TG/HDL [triglyceride/high-density lipoprotein] ratio was the only lipid parameter independently associated” with major adverse cardiovascular events (MACE), Dr. Santos reported in the poster presentation.

The study randomly assigned 611 patients to coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy. Lipid-modifying therapies were equally instituted in all study patient groups. Concentrations of total cholesterol, high-density lipoprotein (HDL), non-HDL cholesterol, and low-density lipoprotein (LDL) cholesterol, as well as LDL/HDL and TG/HDL ratios, were divided according to distribution quartiles. The associations between MACE occurrence and plasma lipids at baseline and at 6 months, as well as other risk factors and randomized CAD treatment, were determined by Cox regression models.

Mean levels of lipids were 150 mg/dL for TG, 37 mg/dL for HDL cholesterol, and 140 mg/dL for LDL cholesterol.

“LDL was not well treated at the time this study began 11 years ago. Only about one third of patients were on statins, and mean levels were about 140 mg/dL,” Dr. Santos said. “Yet, even in these patients with high LDL, the TG/HDL ratio was a marker for later events.”

In the MASS-II patients followed for an average of 11.4 years (range 9-15 years), MACE were observed in 42% of the PCI arm, 59% of the medical therapy arm, and 33% of the CABG arm.

After adjustment for confounders, the investigators found the following factors to be independently associated with MACE: age greater than 65 years, randomization to CABG versus medical therapy, systemic arterial hypertension, and TG/HDL ratio determined at 6 months.

For the TG/HDL ratio, the hazard ratio for the occurrence of MACE, comparing the highest and lowest quartiles of the ratios, was significant at 1.57 (P = .015). Hazard ratios for the third versus first quartiles was 1.38 (P = .098) and for the second versus first quartiles was 0.83 (P = .445). No association was found between MACE and other plasma lipids.

Among patients with a TG/HDL ratio greater than 6, only about 45% of patients were free of MACE at 10 years, compared with greater than 70% for those with a TG/HDL ratio of less than 3. 

“The TG/HDL ratio is a marker of residual risk,” Dr. Santos said. “For clinicians, this means that you treat the LDL, of course, but you need to look at triglycerides and HDL. While the lab doesn’t give you this ratio, it’s very easy to calculate.”

Dr. Gerald S. Berenson of Tulane University School of Medicine, New Orleans, and principal investigator of the Bogalusa Heart Study, viewed the poster with interest. “This is very important information,” he said. “The TG/HDL ratio is so easy to measure. Everyone is looking at particle size, and so forth, but we routinely get these levels, so you just need to look at the ratio. It’s a good measure of insulin resistance as well.”

Dr. Santos has served on the speakers bureaus of Novartis, Merck, Biolab, and Bristol-Myers Squibb. Dr. Berenson had no relevant conflicts of interest.

NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.

About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.

Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.

Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.

The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.

Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.

Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).

No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.

Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.

NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.

About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.

Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.

Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.

The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.

Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.

Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).

No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.

Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.

NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.

About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.

Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.

Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.

The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.

Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.

Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).

No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.

Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.

NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.

About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.

Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.

Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.

The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.

Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.

Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).

No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.

Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.

NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.

About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.

Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.

Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.

The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.

Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.

Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).

No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.

Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.

NEW ORLEANS – Pulse pressure measured by a physician may help discriminate between patients with "white coat" hypertension and true hypertension, according to a study presented April 4 at the annual scientific sessions of the American College of Cardiology.

About a third of the more than 1,000 patients in the study who were receiving ongoing anti-hypertensive treatment actually had white coat hypertension (WCH), suggesting that the costs and potential side effects from drug therapy could have been avoided in these patients, said Dr. Young Keun Ahn of the Chonnam National University Hospital, Gwangju, South Korea, and associates.

Twenty-four hour ambulatory blood pressure monitoring or self-blood pressure monitoring can diagnose white coat hypertension, he said, but pulse pressure is simpler to use and is suitable for patients without aortic valvular insufficiency or aortic disease, he added.

Dr. Ahn and his colleagues found that pulse pressure as measured by a physician was more significantly related to WCH than was systolic blood pressure, a value that had been shown in earlier studies to be helpful in identifying patients with WCH.

The study enrolled 1,087 patients undergoing treatment for chronic hypertension in outpatient academic hospital settings. Participants were trained to self-measure their blood pressure twice a day and record it every morning and evening for 2 weeks.

Thirty-one percent of patients were found to have WCH, which was defined as a difference above 20 mm Hg in systole or 10 mm Hg in diastole.

Pulse pressure was positively correlated with a systolic white coat effect (r=.063, P<.001) and diastolic white coat effect (r=.037, P< .001).

No association was found between a white coat effect and age or gender. However, patients with a family history of premature heart disease were more likely to experience white coat hypertension. Patients with diabetes, smokers, and those with organ damage were less likely to have it.

Dr. William Zoghbi noted that "If a stressful encounter like seeing a doctor can cause white coat hypertension, then perhaps this response would be replicated in other stressful situations. It would be useful to monitor these patients to determine if they are at risk for ongoing hypertension." Dr. Zoghbi is the chief of cardiovascular imaging at Methodist DeBakey Heart and Vascular Center in Houston.

The study was funded by the Korean Institute of Medicine; the Korea Healthcare Technology R& D Project; Korean Ministry of Health, Welfare, & Family Affairs; and the Republic of Korea.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study presented at the annual scientific sessions of the American College of Cardiology.

"In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins," said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

"LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28," Dr. Cromwell observed. "Mipomersen’s lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes."

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Dr. Cromwell noted that the drug had a more pronounced effect in females and in patients whose age was above the median. However, mipomersen’s effects in males and in younger persons were still statistically significant and clinically meaningful.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued due to on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued due to a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively.

"Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration. It’s real, and it does have to be managed," Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart. One patient had an ALT of at least 10 times the upper limit of normal.

"We don’t see this as a huge ALT signal," Dr. Cromwell pointed out. "This is against the backdrop of a statin, which is already sensitizing the liver. We think it’s reassuring."

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. "This does not represent a huge accumulation of fat. Instead, it is a signal that it’s there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase."

Dr. Patrick Moriarty, a lipid specialist who is assistant professor of medicine at the University of Kansas, Kansas City, commented, "We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down."

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, "The drug is not for every patient, but it could fill the need for an effective treatment in a small subset."

In Dr. Moriarty’s opinion, the injectable delivery will not be a barrier to acceptance. "It could be a problem for some patients and physicians, but patients can do these injections themselves, just like diabetes patients do. In studies I’ve participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves."

The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study presented at the annual scientific sessions of the American College of Cardiology.

"In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins," said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

"LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28," Dr. Cromwell observed. "Mipomersen’s lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes."

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Dr. Cromwell noted that the drug had a more pronounced effect in females and in patients whose age was above the median. However, mipomersen’s effects in males and in younger persons were still statistically significant and clinically meaningful.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued due to on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued due to a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively.

"Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration. It’s real, and it does have to be managed," Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart. One patient had an ALT of at least 10 times the upper limit of normal.

"We don’t see this as a huge ALT signal," Dr. Cromwell pointed out. "This is against the backdrop of a statin, which is already sensitizing the liver. We think it’s reassuring."

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. "This does not represent a huge accumulation of fat. Instead, it is a signal that it’s there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase."

Dr. Patrick Moriarty, a lipid specialist who is assistant professor of medicine at the University of Kansas, Kansas City, commented, "We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down."

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, "The drug is not for every patient, but it could fill the need for an effective treatment in a small subset."

In Dr. Moriarty’s opinion, the injectable delivery will not be a barrier to acceptance. "It could be a problem for some patients and physicians, but patients can do these injections themselves, just like diabetes patients do. In studies I’ve participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves."

The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.

NEW ORLEANS – In patients with hypercholesterolemia and high cardiovascular risk, the novel agent mipomersen administered as add-on therapy led to robust reductions in LDL cholesterol, based on the results of a double-blind, phase III study presented at the annual scientific sessions of the American College of Cardiology.

"In high-risk patients refractory to maximally tolerated statin therapy, the addition of mipomersen significantly reduced LDL-C and other atherogenic lipids and lipoproteins," said Dr. William C. Cromwell of the Presbyterian Cardiovascular Institute in Charlotte, N.C.

Mipomersen is the first of a new class of agents called apolipoprotein B (apoB) synthesis inhibitors. In the study, the drug was administered subcutaneously once a week. Among its side effects were injection site reactions, increases in alanine aminotransferase (ALT) levels, and steatosis.

The study included 158 patients at high risk for cardiovascular events who were unable to achieve target LDL-C levels with statins, bile-acid sequestrants, and niacin. At baseline, all patients were on maximally tolerated doses of a statin; 63 were on the maximal approved dose, and 25 were also receiving ezetimibe.

All subjects had LDL-C levels of at least 100 mg/dL and triglycerides below 200 mg/dL. They were randomized 2:1 to 200 mg subcutaneous mipomersen or placebo weekly for 26 weeks. The primary end point was percent change in LDL-C from baseline at week 28 or 2 weeks after the last dose if treatment was not completed.

LDL-C levels of less than 100 mg/dL were achieved by 77 (76%) mipomersen-treated patients, compared with 19 (38%) placebo-treated patients. LDL-C levels of less than 70 mg/dL were achieved by 51 (50%) and 4 (8%), respectively.

The percent reduction in LDL cholesterol from baseline to the primary efficacy time point was a 37% drop in the mipomersen arm and a 5% drop in the placebo arm, a significant difference.

"LDL-C levels decreased through the first 17 weeks of treatment and remained relatively low through week 28," Dr. Cromwell observed. "Mipomersen’s lipid-lowering effects were independent of baseline LDL-C or race, and were similar for patients with and without diabetes."

The effect of the drug in the diabetic subset was robust. In the diabetes cohort, the mean decline in LDL-C from baseline was 51% for the 56 patients on mipomersen and 32% for the 29 on placebo.

Dr. Cromwell noted that the drug had a more pronounced effect in females and in patients whose age was above the median. However, mipomersen’s effects in males and in younger persons were still statistically significant and clinically meaningful.

Mipomersen also was associated with significant reductions from baseline values in apoB (38%), total cholesterol (26%), non-HDL cholesterol (36%), and lipoprotein(a) (24%). HDL-C levels did not change significantly from baseline.

Sixty of the 105 mipomersen-treated patients (57%) and 44 of 52 placebo patients (85%) completed treatment. A total of 26 mipomersen-treated patients and 2 placebo-treated patients discontinued due to on-treatment adverse events. Of the mipomersen noncompleters, seven discontinued due to a liver enzyme-related adverse event, and seven stopped because of an injection site reaction.

Injection site reactions were the most common adverse event, occurring in 78% of the mipomersen group and 31% of the placebo group. Flu-like symptoms occurred in 34% and 21%, respectively.

"Injection site reaction is the biggest side effect with this drug. This ranges from induration to redness, and some patients have skin discoloration. It’s real, and it does have to be managed," Dr. Cromwell acknowledged.

ALT elevations at least 3 times the upper limit of normal were observed in 14% of patients on mipomersen, versus none receiving placebo, but this occurred without concomitant significant bilirubin elevations, he said. For 10% of patients, ALT elevations occurred on consecutive measurements at least 7 days apart. One patient had an ALT of at least 10 times the upper limit of normal.

"We don’t see this as a huge ALT signal," Dr. Cromwell pointed out. "This is against the backdrop of a statin, which is already sensitizing the liver. We think it’s reassuring."

Approximately one-third of patients had an increase in steatosis, defined as liver fat increasing by at least 5%; median percent change from baseline was 15%. "This does not represent a huge accumulation of fat. Instead, it is a signal that it’s there at 28 weeks, and it is not particularly worrying. In a series of patients with much longer exposures, there is a plateau in this increase."

Dr. Patrick Moriarty, a lipid specialist who is assistant professor of medicine at the University of Kansas, Kansas City, commented, "We treat many refractory patients, and I can tell you that a drug of this class is very much needed in this patient population. It will help get their lipid numbers down."

The fact that patients achieve good LDL-C reductions on top of statin therapy is very encouraging, he said, noting, "The drug is not for every patient, but it could fill the need for an effective treatment in a small subset."

In Dr. Moriarty’s opinion, the injectable delivery will not be a barrier to acceptance. "It could be a problem for some patients and physicians, but patients can do these injections themselves, just like diabetes patients do. In studies I’ve participated in, we offer patients the opportunity to have the nurse give them the injections but most patients learn to do [the injections] themselves."

The study was sponsored by Isis Pharmaceuticals and Genzyme Corporation. Dr. Cromwell has received consultant fees or honoraria from Isis. Dr. Moriarty has participated in clinical trials of mipomersen.